P- Reviewer: Chen W, Manguso F, Romano M S- Editor: Gou SX L- Editor: A E- Editor: Zhang DN
Published online Sep 28, 2014. doi: 10.3748/wjg.v20.i36.12818
Revised: June 10, 2014
Accepted: July 16, 2014
Published online: September 28, 2014
Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases.
Core tip:Helicobacter pylori (H. pylori) infections are intimately related to malignant gastric condictions and benign diseases in the stomach, nevertheless there are extragastric manifestations closely related with H. pylori infection. This review focuses on hematologic diseases included in international consensus and management guides for H. pylori infection; specifically iron deficiency, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and extranodal marginal zone mucosa-associated lymphoid tissue lymphoma. In addition of other hematologic diseases not included in guides and consensus as auto-immune neutropenia, antiphospholipid syndrome, and plasma cell dyscrasias.
Citation: Campuzano-Maya G. Hematologic manifestations of
Helicobacter pyloriinfection. World J Gastroenterol 2014; 20(36): 12818-12838
- URL: https://www.wjgnet.com/1007-9327/full/v20/i36/12818.htm
- DOI: https://dx.doi.org/10.3748/wjg.v20.i36.12818
Helicobacter pylori (H. pylori) is present in over 50% of all stomachs in the world population, making it the most frequent infection in humans. It displays a marked disparity in occurrence between developed countries, where its prevalence oscillates between 30% and 50%, and developing countries, where its prevalence ranges between 80% and 90%.
After 1983, when it was discovered that the stomach could be colonized by bacteria, increasing evidence has shown that H. pylori is a pathogen closely related to a variety of gastric conditions. These range from benign stomach diseases such as chronic gastritis, duodenal peptic ulcers and gastric peptic ulcers to malignant diseases such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In the 30 years that have elapsed since its discovery, more than 50 extragastric manifestations of H. pylori infection have been reported, involving a range of medical specializations including cardiology, dermatology, endocrinology, gynecology and obstetrics, pneumology, neurology, odontology, ophthalmology, otorhinolaryngology, pediatrics, and hematology[6-18]. Hematological manifestations are the subject of this review.
For practical purposes, this review was divided arbitrarily into two groups. The first is made up of hematological diseases that are recognized as extragastric manifestations of H. pylori infection by the scientific community and have been incorporated into international consensus and management guides on H. pylori infection. The second is made up of hematological diseases that are not included in the international consensus and management guides on H. pylori infection (Table 1). Despite the existence of publications that link these diseases to H. pylori infections, they are not recognized by the scientific community due to a lack of either new evidence or further analysis.
|Recognized as extragastric manifestation|
|Vitamin B12 (cobalamina) deficiency[25,27]|
|Gastric MALT lymphoma[19-37]|
|Unrecognized as extragastric manifestation|
|Plasma cell dyscrasias[284-286]|
|Other hematologic manifestation (childhood leukemia, myelo dysplastic syndrome, thrombocytosis)|
As of May 2014, the following conditions fulfill the criteria to be hematological diseases that are recognized in international consensus and management guides on H. pylori infection: (1) Unexplained iron deficiency included in the Maastricht III Consensus-2007 and subsequently ratified in several international consensus and management guides on H. pylori infection[20-28]; (2) Unexplained vitamin B12 (cobalamin) deficiency included in Maastricht IV/Florence Consensus-2012 and recently ratified in the III Spanish Consensus Conference on H. pylori infection carried out in 2013; (3) Primary immune thrombocytopenic purpura included in the Maastricht III Consensus-2007 and subsequently ratified in several international consensus and management guides of H. pylori infection[21-28]; and (4) Gastric MALT lymphoma included in the first Maastricht Consensus and subsequently ratified in all international consensus and management guides created for H. pylori infection[19-28,30-37].
It is important to note that of the extragastric diseases described in the medical literature that are possibly associated with H. pylori, only three such conditions have been incorporated into the guidelines: iron deficiency[19-28], vitamin B12 deficiency[25,27], and primary immune thrombocytopenic purpura[19,21-28].
Iron deficiency (ID) is a serious public health issue, regardless of whether it is associated with anemia. It affects a quarter of the world’s population, over two billion people, according to the World Health Organization (WHO). Importantly, ID seriously affects at-risk populations such as children and pregnant women[38,39]. ID is associated with an increase in morbidity, including increased susceptibility to infections, decreased labor productivity, and impaired physical and cognitive development, even without an associated anemia.
It is especially important to remember that ID is a chronic process with a slow onset, in which the iron imbalance may take several years to establish and manifest clinically. One of the consequences can be observed through blood characteristics such as morphological alterations of erythrocytes or the presence of anemia, according to the criteria of the WHO. ID occurs in three stages: pre-latent (stage 1), in which ferritin is between 12 and 30 μg/L, latent (stage 2) when the ferritin falls below 12 μg/L, and ID anemia (stage 3) when anemia is present in addition to diminished or depleted reservoir iron levels (determined by serum ferritin).
H. pylori and iron deficiency: The relationship between H. pylori and ID, regardless of whether the latter is accompanied by anemia, was first described by Blecker et al in 1991 in Belgium. This case described a 15-year-old patient with ID anemia due to H. pylori-positive chronic active hemorrhagic gastritis, without prior gastrointestinal manifestations. After the infection was eradicated, the hematological parameters and ferrokinetics returned to normal values, and it was not necessary to administer supplementary iron treatments. Two years later in France, Bruel et al discovered a second case of ID anemia (hemoglobin 5.6 g/dL) in an 11-year-old child with a severe digestive hemorrhage who was diagnosed with an H. pylori infection. The anemia resolved after the eradication of the H. pylori infection, without supplementary iron treatment. In the same year in Italy, Dufour et al presented the case of a 7-year-old child diagnosed with refractory ID anemia (hemoglobin 5.1 g/dL) who received oral iron treatment. The presence of H. pylori was described as in the preceding cases; however, it was asymptomatic from the gastrointestinal perspective. The infection was eradicated, and without supplementary iron treatment, there were improved hematological parameters (hemoglobin 13 g/dL) six months later.
After these pioneering reports of resolution of ID with treatment of the infection[42-44], additional isolated cases appeared during the 1990s in the medical literature[45-49] in both adolescents and adults that corroborated the association and therapeutic response after H. pylori eradication[46,50,51]. The volume of cases in the literature by the first decade of the 21st century supported the publication of five meta-analyses[52-56], that showed an association between H. pylori and ID with resolution of H. pylori-associated disease after eradication in children[57-65], male and females in puberty[66,67], prepubertal girls, adult men and women[46,51,69-80], older adults, pregnant women and nonpregnant women. All of these publications have lent scientific support to the different international consensus and management guidelines that indicate that H. pylori should be sought and eradicated in ID cases[19-28].
Pathophysiology of iron deficiency by H. pylori: The pathophysiologic mechanisms by which H. pylori is associated with the development of ID and ID anemia are not fully understood, and more questions than answers remain. Here, we summarize the proposed explanations to explain the association of H. pylori with ID and ID anemia. It is still not known why some patients manifest this association and why in other patients it is not present, or there are other associations; or why some of the infections are asymptomatic.
Over the past decade, it has been linked H. pylori and ID development with a recently discovered hormone called hepcidin. This hormone is produced in the liver and regulates iron metabolism in enterocytes and releases stored iron from macrophages of the reticuloendothelial system. Hepcidin rises after H. pylori infection, acting as an acute phase reactant in response to the inflammation produced in the gastric mucosa, resulting in pathology known as “anemia of inflammation or chronic disease”[86-90]. Preliminary studies show that serum hepcidin is elevated in patients infected with H. pylori and these levels are normalized after eradication of the infection, allowing that the iron to be absorbed by the enterocytes and released from macrophages of the reticuloendothelial system, where they are confined.
Other possible causes of iron imbalance in patients infected with H. pylori are chronic gastritis, which occurs in all individuals infected with H. pylori. This can cause bleeding when it becomes erosive gastritis, especially in patients with active bleeding peptic ulcers[93,94] and in patients who chronically ingest non-steroidal anti-inflammatory drug including aspirin[95-98]. Similar to activities of other bacteria, mechanisms that have been hypothesized to explain ID in patients infected by H. pylori are related to changes in gastric physiology, including changes in pH, and especially in the presence of achlorhydria, which significantly reduces the solubility of inorganic iron and thus its intestinal absorption.
Furthermore, highly virulent strains such as H. pylori with the cytotoxin-associated gene A (CagA) and the vacuolating cytotoxin A (VacA), act through molecular mimicry mechanisms to produce or magnify ID in patients compared with patients infected with other less virulent strains[76,99-101]. This finding could partially explain the marked differences from one region to another and the large discrepancies observed in the different studies.
Management of iron deficiency in the post-helicobacter era: It is important to note that H. pylori is not the only cause of ID, and its inclusion in the international consensus and guidelines for managing H. pylori is an indication that it “should be sought and eradicated” but does not substitute for the adequate study of the most common causes of ID. These situations are specific to each region, due to the prevalence of ID, which varies with that of H. pylori infection and is a variable problem from one area to another. More than 250 studies referenced in the medical literature have tried to clarify the relationship of H. pylori in the development of ID, along with five meta-analyses that have all shown the association of infection in the development of ID and resolution after eradication[52-56]. The recovery of hematological and ferrokinetic parameters in ID after H. pylori eradication has enabled its inclusion as an unexplained origin of ID in the international consensus and management guides of H. pylori infection put forth by the scientific community and to indicate that it should be sought and eradicated in both adults and children[19-28].
Vitamin B12 is required as a coenzyme for the metabolism of the amino acids methionine, threonine and valine and for the transformation of methyl-tetrahydrofolate to tetrahydrofolate, which is necessary for DNA synthesis. Vitamin B12 is produced by mammals, and the consumption of animal products is required for incorporation in the human body.
Vitamin B12 deficiency, also known as cobalamin deficiency, is defined by low serum values of vitamin B12 and both homocysteine and methylmalonic acid, two components of the vitamin B12 metabolic pathway. The diagnosis of vitamin B12 deficiency is established in accordance with the following criteria: (1) serum vitamin B12 levels < 150 pmol/L (< 200 pg/mL) with clinical features and/or hematological anomalies related to vitamin B12 deficiency; (2) serum vitamin B12 levels < 150 pmol/L on two separate occasions; (3) serum vitamin B12 levels < 150 pmol/L and total serum homocysteine levels > 13 μmol/L or methylmalonic acid levels > 0.4 μmol/L (in the absence of renal failure and folate and vitamin B6 deficiencies); and (4) serum holotranscobalamin levels < 35 pmol/L.
It is important to remember that vitamin B12 deficiency is a chronic process with slow onset, in which the vitamin B12 imbalance may take several years to establish and manifest clinically in blood count parameters such as erythrocyte morphological alterations or anemia, according to the criteria of the WHO. Vitamin B12 deficiency occurs in four stages: (1) decreased levels of vitamin in blood (stage I); (2) low concentration of vitamin in the cell and metabolic abnormalities (stage II); (3) increased levels of homocysteine and methylmalonic acid and decrease of DNA synthesis, with the emergence of neuropsychiatric symptoms (stage III); and (4) macrocytic anemia (stage IV).
Vitamin B12 deficiency represents a serious public health problem, and its prevalence is highly variable, depending on the ages and populations analyzed. Epidemiological studies show that in general population, vitamin B12 deficiency has a prevalence of approximately 20% in industrialized countries, with a range between 5% and 60%, depending on the vitamin B12 deficiency definition that is used[103,104]. For several years, it has been known that the prevalence of vitamin B12 deficiency, specifically pernicious anemia, is higher in Latin America than it is in the rest of the world. It also occurs in younger people, whereas in the rest of the world, it is a disease related to old age.
The etiology of pernicious anemia and subacute combined degeneration are closely related to vitamin B12 deficiency, but other diseases are also linked with the elevated homocysteine levels that are observed in vitamin B12 deficiency, such as Alzheimer’s disease[108,109], dementia[110,111], depression, cerebral stroke[113,114], pulmonary embolism[115,116] and coronary heart disease.
H. pylori and vitamin B12deficiency: Pernicious anemia, as a stage of chronic vitamin B12 deficiency, was the first extragastric disease to be associated with H. pylori infection, as postulated in the scientific community by O′Connor et al. One year later, Warren and Marshall reported to the scientific community that the stomach could be colonized by bacteria. In 1991, Fong et al carried out the first well-controlled study to clarify a possible association between pernicious anemia and H. pylori infection, after which they concluded that “patients with pernicious anemia are protected from infection with H. pylori, and H. pylori does not passively colonize mucosa inflamed by an unrelated process”. These findings were confirmed by Saito et al in Japan in 2008.
Nevertheless, when the vitamin B12 deficiency becomes clinically relevant, the bacteria are not found on the site of the lesion. H. pylori disappears as a result of histological and physiological changes induced by the chronic atrophy of the gastric mucosa in the case of gastric cancer and the changes mediated by the immunological response on the gastric mucosa in the case of vitamin B12 deficiency and pernicious anemia. This can be evidenced by the presence of antibodies against intrinsic factor and parietal cells, despite to disappearance of H. pylori on gastric mucosa at diagnosis[122,123]. Moreover, H+/K+ ATPase autoantibodies, which are closely linked to classical autoimmune gastritis, are also significant indicators for mucosa atrophy in chronic H. pylori gastritis[124,125].
H. pylori infection can cause malabsorption of different micronutrients among which included the vitamin B12[127-129]. A systematic review and meta-analysis in 17 studies involving 2454 patients showed a significantly reduction of serum levels of vitamin B12 in H. pylori infected patients than in non-infected. Marino et al demonstrated in 62 older patients a relationship between the decrease in serum levels of vitamin B12 and increase of serum homocysteine due to H. pylori infection. Likewise, H. pylori eradication in vitamin B12 deficiency patients is followed by increasing of serum levels of vitamin B12 and decreased serum levels of homocysteine.
Moreover, it was known that there was an association of H. pylori with stomach cancer, and it was already widely recognized by the scientific community that pernicious anemia was closely related to the development of stomach cancer[132-135]. This association was recently verified by Vanella et al after a systematic review and meta-analysis showed that the relative risk to develop gastric cancer in patients with pernicious anemia was elevated at 6.8 (95%CI: 2.6-18.1).
Pathophysiology of vitamin B12 deficiency: The pathophysiological mechanisms by which H. pylori infection is related to the etiology of vitamin B12 deficiency are not fully clarified at this time. It is still not known why some patients manifest this association while others may show different H. pylori-associated conditions or none at all or why some of the infections are asymptomatic. Below, we describe explanations that have been proposed to clarify the association between H. pylori and vitamin B12 deficiency.
Vitamin B12 deficiency occurs as a result of antibodies directed against gastric parietal cells and intrinsic factor, in addition to achlorhydria and a decrease in pepsinogen I and gastrin. These changes result in a histopathologic entity known as chronic gastritis type A or autoimmune. The lack of intrinsic factor, which occurs due to changes in the gastric mucosa, reduces the absorption and transport of vitamin B12 from the diet. Chronic atrophic gastritis that induced by the immune response reaches gastric atrophy and pernicious anemia over a period of 10-30 years, depleting reservoirs of vitamin B12. Additionally, chronic vitamin B12 deficiency can cause peripheral neuropathy and lesions in the lateral and posterior columns of the spinal cord; this is known as subacute combined degeneration and progresses to axial demyelination, neural degeneration, and eventually death.
Vitamin B12 deficiency management in the post-helicobacter era: Similar to ID, it is important to clarify that H. pylori is not the only cause of vitamin B12 deficiency in the post-helicobacter era of vitamin B12 deficiency. Inclusion in the international consensus and management guides is an indication to seek and eradicate H. pylori in cases of vitamin B12 deficiency, but this does not replace a proper study of the specific epidemiologic causes in each region. A recent systematic review and meta-analysis evaluated the association of H. pylori and serum levels of vitamin B12 in 17 studies involving 2454 patients. This study showed that serum vitamin B12 levels were significantly lower in infected patients than in uninfected, and H. pylori eradication revealed a significant increase in the levels of vitamin B12 after successful treatment. These publications have enabled the inclusion of vitamin B12 deficiency in the international consensus and management guides on H. pylori infection as an indication for which “H. pylori should be sought and eradicated” prior to other traditional interventions[25,27].
Primary immune thrombocytopenia (ITP), previously called idiopathic thrombocytopenic purpura and autoimmune thrombocytopenic purpura, has been defined and described in the Vicenza Consensus. ITP has been redefined as “an autoimmune disorder characterized by isolated thrombocytopenia (peripheral blood platelet count 100 × 109/L) in the absence of other causes or disorders that may be associated with thrombocytopenia. The diagnosis of primary ITP remains one of exclusion; no robust clinical or laboratory parameters are currently available to establish its diagnosis with accuracy. The main clinical problem of primary ITP is an increased risk of bleeding, although bleeding symptoms may not always be present”. In this consensus statement, it was ratified that ITP is a diagnosis of exclusion, and it is necessary to exclude causal diseases such as systemic lupus erythematous and human immunodeficiency virus/acquired immunodeficiency syndrome prior to diagnosis. In addition, it included infection by H. pylori as a new disease in the list of diseases that must be ruled out in ITP, as previously recommended by the British Society for Haematology (BSH) in 2003. Likewise, Vicenza Consensus established as substitute name for idiopathic thrombocytopenic purpura or autoimmune thrombocytopenic purpura, the term “immune thrombocytopenia” maintaining the acronym ITP to refer to the disease. Additionally, it called “primary immune thrombocytopenia” the in cases where is excluded the diseases associated, giving the name “secondary immune thrombocytopenia”, for example, in the case of infection with H. pylori. The extension “secondary immune thrombocytopenia H. pylori-associated” or “ITP H. pylori-associated” would require the demonstration of complete resolution of ITP after proven eradication of the bacteria.
ITP is the most common immune disease in hematology. The annual incidence of ITP is 5.5 per 100000 persons, when the cutoff point is 50 platelets per 109/L and 3.2 per 100000 persons, when the cutoff is 50 platelets per 109/L. The chronic form of ITP increases with age, being double in people above 60 years compared to those under 60 years[141,142], as well as with a higher incidence in women than in men, with a ratio of 2:1 to 3:1.
H. pylori and adult immune thrombocytopenia: García Pérez et al described the relationship of H. pylori with ITP for the first time in 1993 in Spain, reporting a patient with ITP in whom the platelet count was normalized after eradication of H. pylori. After this publication, the medical literature presented several case reports of ITP patients with platelet counts recovering after the eradication of H. pylori, particularly in Japan[145-149] and European countries such as Italy[150-152] and Turkey.
Since the first series corroborated the relationship of H. pylori infection with ITP, it is possible to find 40 additional case series in the medical literature in 2014 that consistently show the relationship of H. pylori eradication with the recovery of platelet counts. On the European continent, there are 10 reported cases: eight in Italy[154-160], one in Turkey and one in Serbia. The total number was 495 ITP patients, 288 (58.2%) of whom were infected with H. pylori, of which 242 received eradication treatment. This achieved a successful eradication in 222 (91.7%) patients and a platelet response in 108 (48.6%) patients. On the Asian continent, there are 28 reported case series: Twenty-three in Japan,[163-185], two in China[186,187], two in Iran[188,189] and one in South Korea, with a total number of 1525 ITP patients, of whom 1089 (71.4%) were infected with H. pylori. Eradication treatment was received by 929 patients and it was successful in 811 (87.3%), of whom 472 (58.2%) had a platelet response. On the Americas, there are reported two case series: one in Colombia and one in Canada, with a total number of 54 ITP patients, of whom 33 (90.6%) were infected with H. pylori. Eradication treatment was received by 33 patients and it was successful in 29 (87.9%), of whom 24 (82.8%) had a platelet response.
The consolidated analysis of all 41 worldwide reported series shows a total of 2074 ITP patients; 1410 (68.0%) were infected with H. pylori, and from this group, 1204 received eradication treatment. Eradication was successful in 1062 (88.2%) and platelet recovery was observed in 604 (56.9%). Further analysis shows that in almost every series where there was a platelet response after H. pylori eradication treatment, the H. pylori infection rate in ITP patients was relatively higher than in those where no association was found. Overall, the European continent showed a mean infection rate of 58.2% in ITP patients and a mean platelet response in 48.6% of them. The Asian continent showed an infection rate of 71.4% and 58.2% in the platelet response, while the Americas had both the highest prevalence of H. pylori infection (90.6%) and the highest platelet response (82.8%) of all reported series. Thus, the worldwide summary of 40 cases series showed an infection rate of 68.0% in ITP patients and a platelet response in 56.9% of the eradicated patients, as shown in Table 2.
|Ref.||Year||Country||Patients with ITP||H. pylori-infected ITP patients||Treated patients||H. pylori-eradicated patients||Patients with platelet response|
|Gasbarrini et al||1998||Italy||18||11 (61.1)||11||8 (72.7)||8 (100)|
|Emilia et al||2001||Italy||30||13 (43.3)||13||12 (92.3)||6 (50.0)|
|Emilia et al||2002||Italy||7||3 (42.9)||3||3 (100)||2 (66.7)|
|Veneri et al||2002||Italy||35||25 (71.4)||16||15 (93.8)||11 (73.3)|
|Veneri et al||2005||Italy||43||43 (100)||43||41 (95.3)||20 (48.8)|
|Stasi et al||2005||Italy||137||64 (46.7)||52||52 (100)||17 (32.7)|
|Suvajdzic et al||2006||Serbia||54||39 (72.2)||30||23 (76.7)||6 (26.1)|
|Sayan||2006||Turkey||34||20 (58.8)||20||18 (90.0)||8 (44.0)|
|Emilia et al||2007||Italy||75||38 (50.7)||38||34 (89.5)||23 (67.6)|
|Scandellari et al||2009||Italy||62||32 (51.6)||16||16 (100)||7 (43.8)|
|Subtotal European continent||495||288 (58.2)||242||222 (91.7)||108 (48.6)|
|Kohda et al||2002||Japan||40||25 (62.5)||19||19 (100)||12 (63.2)|
|Kohda et al||2003||Japan||51||31 (60.8)||26||24 (92.3)||14 (58.3)|
|Ando et al||2003||Japan||61||50 (82.0)||29||27 (93.1)||13 (48.1)|
|Hashino et al||2003||Japan||22||14 (63.6)||14||13 (92.9)||5 (38.5)|
|Hino et al||2003||Japan||30||21 (70.0)||21||18 (85.7)||10 (55.6)|
|Kato et al||2004||Japan||20||20 (100)||20||17 (85.0)||11 (64.7)|
|Ando et al||2004||Japan||20||17 (85.0)||17||15 (88.2)||10 (66.7)|
|Nomura et al||2004||Japan||42||28 (66.7)||28||28 (100)||15 (53.6)|
|Sato et al||2004||Japan||53||39 (73.6)||32||27 (84.4)||15 (55.6)|
|Takahashi et al||2004||Japan||20||15 (75.0)||15||13 (86.7)||7 (53.8)|
|Fujimura et al||2005||Japan||435||300 (69.0)||228||161 (70.6)||101 (62.7)|
|Inaba et al||2005||Japan||35||25 (71.4)||25||25 (100)||11 (44.0)|
|Tsutsumi||2005||Japan||25||17 (68.0)||9||9 (100)||6 (66.7)|
|Suzuki et al||2005||Japan||36||25 (69.4)||13||11 (84.6)||6 (54.5)|
|Asahi et al||2006||Japan||37||26 (70.3)||26||26 (100)||16 (61.5)|
|Ishiyama et al||2006||Japan||14||14 (100)||14||14 (100)||8 (57.1)|
|Satake et al||2007||Japan||38||26 (68.4)||26||23 (88.5)||13 (56.5)|
|Kodama et al||2007||Japan||116||67 (57.8)||52||44 (84.6)||27 (61.4)|
|Kong et al||2008||China||31||31 (100)||31||31 (100)||23 (74.2)|
|Rostami et al||2008||Iran||129||79 (61.2)||71||62 (87.3)||30 (48.4)|
|Asahi et al||2008||Japan||34||23 (67.6)||23||23 (100)||14 (60.9)|
|Suzuki et al||2008||Japan||36||36 (100)||36||31 (86.1)||20 (64.5)|
|Wu et al||2009||Chine||31||31 (100)||31||31 (100)||21 (67.7)|
|Tsumoto et al||2009||Japan||30||21 (70.0)||21||20 (95.2)||10 (50.0)|
|Tag et al||2010||South Korea||25||23 (92.0)||23||23 (100)||11 (47.8)|
|Sato et al||2011||Japan||31||31 (100)||31||31 (100)||18 (58.1)|
|Kikuchi et al||2011||Japan||31||19 (61.3)||19||19 (100)||10 (52.6)|
|Payandeh et al||2012||Iran||52||35 (67.3)||29||26 (89.7)||15 (57.7)|
|Subtotal Asian continent||1525||1089 (71.4)||929||811 (87.3)||472 (58.2)|
|Campuzano-Maya||2007||Colombia||32||29 (90.6)||29||26 (89.7)||21 (80.8)|
|Jackson et al||2008||Canada||22||4 (18.2)||4||3 (75.0)||3 (100)|
|Subtotal American continent||54||33 (90.6)||33||29 (87.9)||24 (82.8)|
|Total worldwide||2074||1410 (68.0)||1204||1062 (88.2)||604 (56.9)|
There are a few studies did not find any association between ITP and H. pylori infection that occurred in Spain, France, United States and Mexico. This lack of association can be explained by the low prevalence of infection in countries where studies were performed because the sample was insufficient or for other unmentioned reasons.
H. pylori and immune thrombocytopenia in children: Studies of the relationship between H. pylori and ITP in children are few and contradictory. Some groups have shown a beneficial effect of H. pylori eradication in Asian countries such as China, Japan and Iran and in European countries such as Finland, Netherlands and Italy[202,203]. These studies found a relationship between infection and ITP in children, with platelet count recovery in an average of 35.2% of the patients, as shown in Table 3. The platelet response was lower than the response rate observed in adult patients with ITP, which was above 50%[154-192,204]. However, groups in Turkey, Italy[206,207], Hungary and Thailand found a low response to eradication[207,208] or did not find a response[205,206,209]. It is important to clarify that the ITP in children has different characteristics than the clinical form of adult ITP.
|Ref.||Year||Country||Patients with ITP||H. pylori-infected ITP patients||Treated patients||H. pylori-eradicated patients||Patients with platelet response|
|Rajantie et al||2003||Finland||17||9 (52.9)||9||9 (100)||5 (55.6)|
|Neefjes et al||2007||Netherlands||47||3 (6.4)||3||3 (100)||3 (100)|
|Ferrara et al||2009||Italy||24||8 (33.3)||8||8 (100)||8 (100)|
|Russo et al||2011||Italy||244||50 (20.5)||37||33 (89.2)||13 (39.4)|
|Subtotal European continent||332||70 (21.1)||57||53 (93.0)||29 (54.7)|
|Jaing et al||2003||Taiwan||22||9 (40.9)||9||9 (100)||5 (55.6)|
|Hayashi et al||2005||Japan||10||2 (20.0)||2||1 (50.0)||1 (100)|
|Hamidieh et al||2008||Iran||31||4 (12.9)||4||4 (100)||1 (25.0)|
|Subtotal Asian continent||63||15 (23.8)||15||14 (93.3)||7 (50.0)|
|Total worldwide||395||85 (21.5)||72||67 (93.1)||36 (53.7)|
Pathophysiology of secondary ITP (H. pylori-associated): Primary ITP is associated with congenital or acquired immune disorders, leading to an autoimmune response against platelets or megakaryocytes and characterized because it is not associated with other alterations. Often found in patients with ITP are events that can lead to the development of an autoimmune response. In the case of H. pylori as a causative agent of ITP, various mechanisms involved in the development of the autoimmune response have been described. One mechanism is the change in the Fcγ receptor balance related to the activation of monocytes and their relation to the inhibitory receptor FcγRIIB. It has been reported that H. pylori infection decreases levels of the inhibitory receptor FcγRIIB in monocytes, leading to increased monocyte function with nonspecific phagocytosis and autoreactivity with B and T lymphocytes. These results were corroborated by finding a reversing effect after bacteria eradication. This finding can link H. pylori infection to autoantibody production by B-lymphocytes and the overactivation of the innate and acquired immune response against circulating platelets.
Along with monocyte overactivation, the production of autoantibodies that can opsonize platelets and induce phagocytosis mediated by antibodies in the reticuloendothelial system by spleen macrophages has been described in ITP. The molecular mimicry of bacterial infection-related proteins is responsible for this response. Amino acid sequences of virulence factors (VacA and CagA)[17,180] and urease B are present in H. pylori infection and are the major antigens associated with autoimmune response against platelets. The homology of these antigens with platelet surface glycoproteins including glycoprotein IIIa and other platelet antigens associated with antibodies anti CagA show the importance of H. pylori infection in ITP.
ITP management in the post-Helicobacter era: It is important to clarify that H. pylori is not the only cause of thrombocytopenia, and the indication that it “should be sought and eradicated” does not replace a proper study of the etiologies that are most frequently associated with the study of thrombocytopenia in each region. The 40 cases series previously described, a meta-analysis and two systematic reviews[212,213] have all shown the importance of H. pylori infection in the development of ITP and that eradicating the infection improves the platelet count by more than 50% in adult patients with chronic ITP[211-213]. Similarly, these publications have enabled the inclusion of ITP in the international consensus and management guides on H. pylori infection as an indication, wherein “H. pylori should be sought and eradicated” prior to other traditional interventions both in adults and children[19,21-28].
The American Society of Hematology (ASH) proposed a new name for idiopathic thrombocytopenia purpura or autoimmune thrombocytopenia purpura, changing it to primary immune thrombocytopenia and keeping the same acronym, ITP. The international working group of standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children created a new group for disease-associated immune thrombocytopenia, which in this case is called “secondary ITP (H. pylori-associated)”. Moreover, ASH and BSH recognized H. pylori as a new cause for ITP and noted that the presence of H. pylori should be treated and eradicated in positive cases before attempting conventional treatments for ITP in both adults and children[139,210].
Gastric MALT lymphoma is a rare form of non-Hodgkin lymphoma that affects B lymphocytes and typically develops in lymphoid tissue associated with mucous membranes and rarely in lymph nodes. It represents approximately 5% of all diagnosed non-Hodgkin lymphomas. Its annual incidence is estimated at approximately 1/313000, with a female predominance, and mainly affects adults over 50 years (mean 65 years), as it is quite rare in children.
MALT lymphoma is an extranodal non-Hodgkin’s B-cell lymphoma: Extranodal marginal zone lymphoma, better known by the acronym MALT lymphoma, is defined as a low-grade malignant lymphoma of the stomach originating from B cells and is associated with chronic infection by H. pylori. Gastric MALT lymphoma was described in 1983 by Isaacson et al, four months after the description of bacterial colonization of the gastric mucosa by H. pylori. Eight years later, it was proven to be intimately related to that lymphoma, when Wotherspoon et al, in 1991, proved their causal relationship for the first time. Two years later, the same authors proved that the eradication of H. pylori infection provided a complete cure of the lymphoma in up to 75% of the patients and that this remission was maintained over time without conventional anticancer therapy.
The first fact that showed a relationship between H. pylori and gastric MALT lymphoma was the observation that lymphoid tissue lesions in the gastric mucosa are pathognomonic with H. pylori infection and are not a normal finding in gastric mucosa without infection[222,223]. Lymphoid follicles have been described in 27% to 100% of H. pylori-infected patients[219,222-224], and this percentage would be 100% if the number and depth of biopsies were appropriate. Additionally, after eradicating the infection, these lymphoid aggregates disappear in all patients.
Pathophysiology of gastric MALT lymphoma: The mechanisms by which H. pylori produces the appearance of a lymphoma similar to gastric carcinogenesis[226-234] has not been fully clarified, but it is likely that environmental, host, and bacterial-related factors must be involved[235-240]. According to Isaacson, H. pylori infection leads to development of MALT lymphoma and can take the following course. First, the infection gives rise to a lymphocyte response that conditions a polyclonal B lymphocyte response and MALT formation through antibody production. Then, different lymphocyte populations would maintain the response provoked by the bacteria. In the polyclonal MALT proliferation, a monoclonal population of B-cells could appear and accumulate cytogenetic changes such as translocations, mutations, microsatellite instabilities, eventually evolving into a low-grade MALT lymphoma that is dependent on H. pylori-related antigen stimuli. Finally, new cytogenetic changes such as translocations, suppressor gene deactivation (p53 and p16, among others), and c-myc activation would make this neoplastic population of monoclonal B-cells escape from its dependence on T lymphocytes and H. pylori antigens and favor its transformation into a high-grade lymphoma. As a result of this sequence of events, a low- or high-grade lymphoma would ultimately develop.
There are cases of extra-gastric MALT lymphoma where the presence of H. pylori has been found and where infection eradication is followed by full remission. These include the conjunctiva[242,243], duodenum[244-246], salivary gland (parotid)[247,248] associated with Sjögren’s syndrome and H. pylori infection, larynx, nasal mucosa, lung (and respiratory tract), rectum[253,254], liver, urinary bladder[256,257], jejunum, patients with Sjögren’s syndrome[249,259] and in patients with previous heart transplants or liver transplants.
Management of gastric MALT lymphoma patients in the post-helicobacter era: The medical scientific community agrees that the therapy for gastric MALT lymphoma is H. pylori eradication and long-term observation[220,261,262]. Most of the international consensus and management guides on H. pylori infection recommend study and eradication as an indication in all patients with a histological diagnosis of gastric MALT lymphoma[19-37]. However, extra-gastric MALT lymphomas may also respond to eradication in infected patients, though the guides and consensus do not include them as an absolute indication. Physicians should eradicate the infection in such patients as good medical practice. All H. pylori infection management guides and consensus include an indication for eradication in any individual where infection is known and eradication is desired[19-37].
This group includes autoimmune neutropenia, antiphospholipid syndrome, plasma cell dyscrasia including monoclonal gammopathy of undetermined significance and multiple myeloma, Shöenlein-Henoch purpura, and other possible associations with diseases such as leukemia and hemorrhagic manifestations with a hematological origin, including congenital coagulopathies and bleeding disorders.
Gupta et al initially proposed the relationship between H. pylori infection and autoimmune neutropenia in 2002 in England, when they reported the case of a patient with neutropenia (400 neutrophils per μL) that normalized quickly after eradicating H. pylori infection. After this work, two new studies have been reported with eight and 69 patients[264,265] that corroborated the Gupta et al report. In the future, it is important that patients with suspected autoimmune neutropenia receive the option of determining their H. pylori status and treating a present infection as part of the management of their condition and good medical practice.
Antiphospholipid syndrome is an immunological hypercoagulable disorder characterized by both arterial and venous thrombosis and pregnancy-related comorbidities such as abortions, premature birth, and preeclampsia. It was proposed as an extra-gastric disease associated with H. pylori in 2001 by Cicconi et al in Italy, who published the case of a woman in which antiphospholipid syndrome disappeared after the eradication of an infection with H. pylori. There are no additional reports of this finding in the medical literature, most likely because it is not being considered and subsequently not studied. However, it is worth remembering that antiphospholipid syndrome has been associated with other H. pylori infection-related diseases including ITP[191,268,269], systemic erythematous lupus, and central serous chorioretinitis[271,272].
Plasma cell dyscrasias (PCD) are one of the most frequent clonal diseases in the elderly and include monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma, solitary plasmacytomas, plasma cell leukemia, Waldenstrom macroglobulinemia and other chronic myeloproliferative diseases of B lymphocytes. PCDs can be asymptomatic and can transform from one disease into another. For example, a fully benign and asymptomatic MGUS that does not require treatment can transform into another more serious and potentially lethal condition such as multiple myeloma.
The association of these diseases with gastric alterations was known many years before the discovery that the stomach could be colonized by bacteria. Gastrointestinal plasmacytomas were documented in 1920 by the father of modern medicine, Osler et al. The relationship between plasmacytomas and multiple myeloma with pernicious anemia[275,276] and gastric cancer[277-281] has been known for many years, both of which are entities intimately related to H. pylori infection. Furthermore, from a histological view, gastric MALT lymphoma can be difficult to distinguish from gastrointestinal plasmacytomas[282,283]. The most important evidence of the relationship of H. pylori infection with PCD is the fact that certain plasmacytomas disappear after H. pylori eradication. The authors who have analyzed this feature of H. pylori-infection recommend that all patients with these manifestations are indicated for infection studies and eradication therapy if it is found to be positive[284-286]. Gastric MALT lymphoma, a clearly recognized H. pylori associated disease, has additionally been associated with MGUS and Waldenstrom disease.
The concurrence of multiple myeloma with gastric MALT lymphoma[289-295] is a finding that was known for many years before any knowledge of H. pylori existed. Today, with the knowledge that MALT also contains plasmocytes that can be stimulated by H. pylori antigens, this association is understandable. In the case of plasmacytomas, it could be said that they are an expression of localized myeloma and if they disseminated, it would not be possible to differentiate between one and the other. Wöhrer et al demonstrated the association of gastric lymphoma with gastric myeloma. They also described the case of a plasmacytomas of the orbit that entered into full remission after H. pylori eradication. With this background, it is logical that any patient diagnosed with a plasma cell-related disease should be studied for H. pylori infection and, if positive, receive eradication treatment for H. pylori before beginning conventional treatment.
Monoclonal gammopathy is important for studying patients with PCD, and according to the work of Malik et al, it could be related to H. pylori infections as a result of chronic antigen stimulation of B lymphocytes in the gastric mucosa by the bacteria. They further suggest that gammopathy could resolve in up to 30% of cases after eradicating the bacteria. This debated relationship is supported by certain authors[287,299] but refuted by others[264,300].
Schöenlein-Henoch purpura is an immune condition of unknown etiology that presents as small vessel leukocytoclastic vasculitis with immunoglobulin A (IgA) deposits in skin, joints, gastrointestinal tract, and kidneys. Schöenlein-Henoch purpura is included in this review because it is part of the differential diagnosis of thrombocytopenia that manifests as purple skin lesions, similar to ITP, which was previously discussed. The association of Schönlein-Henoch purpura (or Henoch-Schönlein purpura) with H. pylori was described in Germany in 1996 by Rainauer et al in a 2-year-old male. After that report, additional case series have been published supporting the association both in adults[303-308] and in children and adolescents[306,309,310], with the disappearance of clinical manifestations in cases where H. pylori was eradicated[306-308].
According to the medical literature, other clinically relevant hematologic manifestations are possibly associated with H. pylori infection that are no less important, despite little published data. Lehtine et al reported that “in Iceland, H. pylori immunoglobulin G was associated with increased risk of childhood leukemia in offspring (OR = 2.8, 95%CI: 1.1-6.9). Since H. pylori immunoglobulin G indicates chronic carriage of the microorganism, early colonization of the offspring probably differs between Iceland and Finland, two affluent countries”. This study should be replicated in other countries, especially in areas with a high prevalence of H. pylori such as Asia and Latin America. Diamantidis et al reported in patients with myelodysplastic syndrome (MDS) that, “although there is no evidence for a causal relationship between H. pylori-positive and MDS, the increased prevalence of H. pylori-positive among the MDS patients is an interesting finding that deserves further investigation as it may indicate a common factor causing susceptibilities to both MDS and H. pylori-positive or that H. pylori might influence the pathophysiology of MDS”. Recently, Kawamata et al described a patient in whom there was “H. pylori-induced thrombocytosis clinically indistinguishable from essential thrombocythemia”, which disappeared after the infection was eradicated.
Another problem that arises in clinical practice is an increased risk of hemorrhage in patients with hematological diseases that carry a greater inherent risk of bleeding. H. pylori, according to preliminary studies, could be a risk factor for the occurrence of these events. This is the case of patients with acute leukemia who, if infected with H. pylori, have a greater risk of gastrointestinal hemorrhage during treatment compared with uninfected patients. This risk would be reduced if all leukemia patients were offered H. pylori screening and eradication, if found to be infected, upon starting leukemia treatment. In patients with potentially hemorrhagic genetic diseases such as hemophilias (A and B) and Von Willebrand disease, it has been observed that H. pylori infection “should be considered as an important cause of upper gastrointestinal bleeding in patients with hemophilia. We would recommend stool antigen test as a new and noninvasive screening test for diagnosis of H. pylori infection in all patients with hereditary hemorrhagic disorders”. This policy is cost-efficient for health systems if one considers that “screening, followed by treatment of all infected patients, yielded a reduction of direct costs over a 5-year period of 130 US-$ per screened patient” and, in consequence, “due to increased bleeding complications, H. pylori screening and therapy appears mandatory in patients with bleeding disorders”. This protocol would also be applicable for patients undergoing prophylactic anticoagulation, including aspirin, as analyzed previously. There is also support for its study and eradication in patients with chronic idiopathic neutropenia, in which splenomegaly is most likely associated with H. pylori and increased infection periods have been observed in patients infected by H. pylori[264,265].
The recognition of hematologic diseases associated with H. pylori infection and their inclusion as indications for study and eradication in the international consensus and management guides on H. pylori infection, represents a deep change in the management paradigm of these diseases and a great breakthrough for humanity. Many benefits can be brought by eradiation of the infection, especially those related to gastric cancer and peptic acid disease[29,267,319]. Table 4 summarizes the paradigm shifts that are discussed in this review and are being introduced into medical practice, as well as the social impact expected from these new paradigms derived from H. pylori eradication.
|Disease||Accepted paradigm||New paradigm||Medical and social impact|
|Iron deficiency1||The management of ID is palliative and is based on iron supplementation, but it often does not treat the immediate cause of ID||With the incorporation of ID in the international consensus and management guides on H. pylori infection as an indication to "seek and eradicate"[19-28], a new paradigm was generated. The etiology of ID can be infectious and eradication of H. pylori can be enough to "cure" in the strict sense of the word[52-56]||Under the new paradigm, eradication of the infection can correct ID, in addition to restoring health[52-56] and increase the productivity of the infected people. It also reduces the prevalence of H. pylori infection and associated diseases such as gastric cancer, and peptic acid disease|
|Vitamin B12 deficiency2||Vitamin B12 deficiency management is palliative and is based on the supplementation of vitamin, but often it does not treat the underlying cause of deficiency of vitamin B12||With the incorporation of vitamin B12 deficiency in the international consensus and management guides on H. pylori infection as an indication to "seek and eradicate"[25,27] a new paradigm was generated. The etiology of vitamin B12 deficiency can be infectious, and the eradication of H. pylori can be enough to "correct" in the strict sense of the word[52-56,131]||Under the new paradigm, eradication of the infection can correct the vitamin B12 deficiency, and the patient can avoid palliative treatment associated with chronic disease. These include the closely related gastric cancer and diverse diseases such as Alzheimer's disease[108,109], dementia[110,111], depression, cerebral stroke[113,114] pulmonary embolism[115,116], acute myocardial infarction and coronary heart disease. Additionally, it can prevent other manifestations of vitamin B12 deficiency and in the homocysteine pathway, which can generate high morbidity and mortality with elevated costs for health systems|
|Immune thrombocytopenia3||Treatment of immune thrombocytopenia is palliative, not curative. It is aimed to control the production of antibodies against platelets by medication or removal of organs that destroy platelets, such as the spleen[140,321]||With the incorporation of immune thrombocytopenia in the international consensus and management guides on H. pylori infection as an indication to "seek and eradicate"[19,21-28] a new paradigm was generated. The etiology of immune thrombocytopenia can be infectious and eradication of H. pylori can be enough to "cure" in the strict sense of word[154-192,204]||Under the new paradigm, where the eradication of the infection corrects the platelet count and is a definitive cure for immune thrombocytopenia, the patient avoids chronic disease and non-curative and palliative treatment. Moreover, eradication of infection in these patients reduces the prevalence of gastric cancer and peptic ulcer disease, which are closely related to high morbidity, mortality and high costs for health systems|
|Gastric MALT lymphoma||Gastric lymphoma is a manifestation of extranodal non-Hodgkin lymphoma. Treatment includes radical gastrectomy supplemented with total abdominal radiotherapy and chemotherapy, similar to the treatment that administered for other non-Hodgkin lymphomas||With the incorporation of gastric MALT lymphoma in the international consensus and management guides on H. pylori infection as an indication to "investigate and eradicate"[19-37] a new paradigm was generated. The etiology of gastric MALT lymphoma can be infectious and eradication of H. pylori may be sufficient for "cure" in the strict sense of the word[220,261,262]||Under the new paradigm, whereby the eradication of the infection induced a complete remission with a definitive cure of gastric MALT lymphoma immune, the patient avoids a chronic disease, with non-curative and palliative treatment. This change transforms a neoplastic disease with difficult and expensive management into an infectious disease with an excellent prognosis and low treatment cost|
The author gratefully acknowledges to John Fredy Castro A for her insightful discussions and help with the English translation, as well as the patient’s willingness and collaboration.
|1.||Mitchell HM. The epidemiology of Helicobacter pylori. Curr Top Microbiol Immunol. 1999;241:11-30. [PubMed] [DOI]|
|2.||Epidemiology of, and risk factors for, Helicobacter pylori infection among 3194 asymptomatic subjects in 17 populations. The EUROGAST Study Group. Gut. 1993;34:1672-1676. [PubMed] [DOI]|
|3.||Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983;1:1273-1275. [PubMed]|
|5.||Stolte M, Bayerdörffer E, Morgner A, Alpen B, Wündisch T, Thiede C, Neubauer A. Helicobacter and gastric MALT lymphoma. Gut. 2002;50 Suppl 3:III19-III24. [PubMed] [DOI]|
|6.||Gasbarrini A, Franceschi F, Armuzzi A, Ojetti V, Candelli M, Torre ES, De Lorenzo A, Anti M, Pretolani S, Gasbarrini G. Extradigestive manifestations of Helicobacter pylori gastric infection. Gut. 1999;45 Suppl 1:I9-I12. [PubMed] [DOI]|
|7.||Realdi G, Dore MP, Fastame L. Extradigestive manifestations of Helicobacter pylori infection: fact and fiction. Dig Dis Sci. 1999;44:229-236. [PubMed] [DOI]|
|8.||Carloni E, Cremonini F, Di Caro S, Padalino C, Gerardino L, Santoliquido A, Colasanti S, Pola P, Gasbarrini A. Helicobacter pylori-related extradigestive diseases and effects of eradication therapy. Dig Liver Dis. 2000;32 Suppl 3:S214-S216. [PubMed] [DOI]|
|9.||De Koster E, De Bruyne I, Langlet P, Deltenre M. Evidence based medicine and extradigestive manifestations of Helicobacter pylori. Acta Gastroenterol Belg. 2000;63:388-392. [PubMed]|
|10.||Sherman PM, Lin FY. Extradigestive manifestation of Helicobacter pylori infection in children and adolescents. Can J Gastroenterol. 2005;19:421-424. [PubMed]|
|11.||Solnick JV, Franceschi F, Roccarina D, Gasbarrini A. Extragastric manifestations of Helicobacter pylori infection--other Helicobacter species. Helicobacter. 2006;11 Suppl 1:46-51. [PubMed] [DOI]|
|12.||Bohr UR, Annibale B, Franceschi F, Roccarina D, Gasbarrini A. Extragastric manifestations of Helicobacter pylori infection -- other Helicobacters. Helicobacter. 2007;12 Suppl 1:45-53. [PubMed] [DOI]|
|13.||Moyaert H, Franceschi F, Roccarina D, Ducatelle R, Haesebrouck F, Gasbarrini A. Extragastric manifestations of Helicobacter pylori infection: other Helicobacters. Helicobacter. 2008;13 Suppl 1:47-57. [PubMed]|
|14.||Pellicano R, Franceschi F, Saracco G, Fagoonee S, Roccarina D, Gasbarrini A. Helicobacters and extragastric diseases. Helicobacter. 2009;14 Suppl 1:58-68. [PubMed] [DOI]|
|15.||Figura N, Franceschi F, Santucci A, Bernardini G, Gasbarrini G, Gasbarrini A. Extragastric manifestations of Helicobacter pylori infection. Helicobacter. 2010;15 Suppl 1:60-68. [PubMed] [DOI]|
|16.||Suzuki H, Franceschi F, Nishizawa T, Gasbarrini A. Extragastric manifestations of Helicobacter pylori infection. Helicobacter. 2011;16 Suppl 1:65-69. [PubMed] [DOI]|
|17.||Banić M, Franceschi F, Babić Z, Gasbarrini A. Extragastric manifestations of Helicobacter pylori infection. Helicobacter. 2012;17 Suppl 1:49-55. [PubMed] [DOI]|
|18.||Roubaud Baudron C, Franceschi F, Salles N, Gasbarrini A. Extragastric diseases and Helicobacter pylori. Helicobacter. 2013;18 Suppl 1:44-51. [PubMed] [DOI]|
|19.||Malfertheiner P, Megraud F, O’Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut. 2007;56:772-781. [PubMed]|
|20.||Chey WD, Wong BC. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102:1808-1825. [PubMed] [DOI]|
|21.||Caselli M, Zullo A, Maconi G, Parente F, Alvisi V, Casetti T, Sorrentino D, Gasbarrini G. “Cervia II Working Group Report 2006”: guidelines on diagnosis and treatment of Helicobacter pylori infection in Italy. Dig Liver Dis. 2007;39:782-789. [PubMed] [DOI]|
|22.||Kim N, Kim JJ, Choe YH, Kim HS, Kim JI, Chung IS. [Diagnosis and treatment guidelines for Helicobacter pylori infection in Korea]. Korean J Gastroenterol. 2009;54:269-278. [PubMed] [DOI]|
|23.||Fock KM, Katelaris P, Sugano K, Ang TL, Hunt R, Talley NJ, Lam SK, Xiao SD, Tan HJ, Wu CY. Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection. J Gastroenterol Hepatol. 2009;24:1587-1600. [PubMed]|
|24.||Asaka M, Kato M, Takahashi S, Fukuda Y, Sugiyama T, Ota H, Uemura N, Murakami K, Satoh K, Sugano K. Guidelines for the management of Helicobacter pylori infection in Japan: 2009 revised edition. Helicobacter. 2010;15:1-20. [PubMed]|
|25.||Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T. Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. Gut. 2012;61:646-664. [PubMed] [DOI]|
|26.||Coelho LG, Maguinilk I, Zaterka S, Parente JM, do Carmo Friche Passos M, Moraes-Filho JP. 3rd Brazilian Consensus on Helicobacter pylori. Arq Gastroenterol. 2013;50. [PubMed] [DOI]|
|27.||Gisbert JP, Calvet X, Bermejo F, Boixeda D, Bory F, Bujanda L, Castro-Fernández M, Dominguez-Muñoz E, Elizalde JI, Forné M. [III Spanish Consensus Conference on Helicobacter pylori infection]. Gastroenterol Hepatol. 2013;36:340-374. [PubMed] [DOI]|
|28.||Liu WZ, Xie Y, Cheng H, Lu NH, Hu FL, Zhang WD, Zhou LY, Chen Y, Zeng ZR, Wang CW. Fourth Chinese National Consensus Report on the management of Helicobacter pylori infection. J Dig Dis. 2013;14:211-221. [PubMed] [DOI]|
|29.||Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. European Helicobacter Pylori Study Group. Gut. 1997;41:8-13. [PubMed] [DOI]|
|30.||Lam SK, Talley NJ. Report of the 1997 Asia Pacific Consensus Conference on the management of Helicobacter pylori infection. J Gastroenterol Hepatol. 1998;13:1-12. [PubMed] [DOI]|
|31.||Sainz R, Borda F, Domínguez E, Gisbert JP. [Helicobacter pylori infection. The Spanish consensus report. The Spanish Consensus Conference Group]. Rev Esp Enferm Dig. 1999;91:777-784. [PubMed]|
|32.||Coelho LG, León-Barúa R, Quigley EM. Latin-American Consensus Conference on Helicobacter pylori infection. Latin-American National Gastroenterological Societies affiliated with the Inter-American Association of Gastroenterology (AIGE). Am J Gastroenterol. 2000;95:2688-2691. [PubMed] [DOI]|
|33.||Caselli M, Parente F, Palli D, Covacci A, Alvisi V, Gasbarrini G, Bianchi Porro G. “Cervia Working Group Report”: guidelines on the diagnosis and treatment of Helicobacter pylori infection. Dig Liver Dis. 2001;33:75-80. [PubMed] [DOI]|
|34.||Malfertheiner P, Mégraud F, O’Morain C, Hungin AP, Jones R, Axon A, Graham DY, Tytgat G. Current concepts in the management of Helicobacter pylori infection--the Maastricht 2-2000 Consensus Report. Aliment Pharmacol Ther. 2002;16:167-180. [PubMed] [DOI]|
|35.||Coelho LG, Zaterka S. [Second Brazilian Consensus Conference on Helicobacter pylori infection]. Arq Gastroenterol. 2005;42:128-132. [PubMed]|
|36.||Monés J, Gisbert JP, Borda F, Domínguez-Muñoz E. Indications, diagnostic tests and Helicobacter pylori eradication therapy. Recommendations by the 2nd Spanish Consensus Conference. Rev Esp Enferm Dig. 2005;97:348-374. [PubMed] [DOI]|
|37.||Hu FL, Hu PJ, Liu WZ, De Wang J, Lv NH, Xiao SD, Zhang WD, Cheng H, Xie Y. Third Chinese National Consensus Report on the management of Helicobacter pylori infection. J Dig Dis. 2008;9:178-184. [PubMed] [DOI]|
|38.||Iron deficiency anemia assessment, prevention, and control. Geneva: World Health Organization. Available from: http://www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf.|
|39.||McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005. Public Health Nutr. 2009;12:444-454. [PubMed] [DOI]|
|40.||Zimmermann MB, Hurrell RF. Nutritional iron deficiency. Lancet. 2007;370:511-520. [PubMed] [DOI]|
|41.||Goodnough LT, Nemeth E. Iron deficiency and related disorders. Wintrobe’s Clinical Hema-tology. 13th ed. Philadelphia, PA: Lippincott Williams & Wilkins 2013; 617-642.|
|42.||Blecker U, Renders F, Lanciers S, Vandenplas Y. Syncopes leading to the diagnosis of a Helicobacter pylori positive chronic active haemorrhagic gastritis. Eur J Pediatr. 1991;150:560-561. [PubMed] [DOI]|
|43.||Bruel H, Dabadie A, Pouedras P, Gambert C, Le Gall E, Jezequel C. [Helicobacter pylori gastritis manifested by acute anemia]. Ann Pediatr (Paris). 1993;40:364-367. [PubMed]|
|44.||Dufour C, Brisigotti M, Fabretti G, Luxardo P, Mori PG, Barabino A. Helicobacter pylori gastric infection and sideropenic refractory anemia. J Pediatr Gastroenterol Nutr. 1993;17:225-227. [PubMed] [DOI]|
|45.||Marignani M, Angeletti S, Bordi C, Malagnino F, Mancino C, Delle Fave G, Annibale B. Reversal of long-standing iron deficiency anaemia after eradication of Helicobacter pylori infection. Scand J Gastroenterol. 1997;32:617-622. [PubMed] [DOI]|
|46.||Milman N, Rosenstock S, Andersen L, Jørgensen T, Bonnevie O. Serum ferritin, hemoglobin, and Helicobacter pylori infection: a seroepidemiologic survey comprising 2794 Danish adults. Gastroenterology. 1998;115:268-274. [PubMed] [DOI]|
|47.||Annibale B, Marignani M, Monarca B, Antonelli G, Marcheggiano A, Martino G, Mandelli F, Caprilli R, Delle Fave G. Reversal of iron deficiency anemia after Helicobacter pylori eradication in patients with asymptomatic gastritis. Ann Intern Med. 1999;131:668-672. [PubMed]|
|48.||Barabino A, Dufour C, Marino CE, Claudiani F, De Alessandri A. Unexplained refractory iron-deficiency anemia associated with Helicobacter pylori gastric infection in children: further clinical evidence. J Pediatr Gastroenterol Nutr. 1999;28:116-119. [PubMed] [DOI]|
|49.||Capurso G, Marignani M, Delle Fave G, Annibale B. Iron-deficiency anemia in premenopausal women: why not consider atrophic body gastritis and Helicobacter pylori role? Am J Gastroenterol. 1999;94:3084-3085. [PubMed] [DOI]|
|50.||Peach HG, Bath NE, Farish SJ. Helicobacter pylori infection: an added stressor on iron status of women in the community. Med J Aust. 1998;169:188-190. [PubMed]|
|51.||Collett JA, Burt MJ, Frampton CM, Yeo KH, Chapman TM, Buttimore RC, Cook HB, Chapman BA. Seroprevalence of Helicobacter pylori in the adult population of Christchurch: risk factors and relationship to dyspeptic symptoms and iron studies. N Z Med J. 1999;112:292-295. [PubMed]|
|52.||Muhsen K, Cohen D. Helicobacter pylori infection and iron stores: a systematic review and meta-analysis. Helicobacter. 2008;13:323-340. [PubMed]|
|53.||Qu XH, Huang XL, Xiong P, Zhu CY, Huang YL, Lu LG, Sun X, Rong L, Zhong L, Sun DY. Does Helicobacter pylori infection play a role in iron deficiency anemia? A meta-analysis. World J Gastroenterol. 2010;16:886-896. [PubMed]|
|54.||Huang X, Qu X, Yan W, Huang Y, Cai M, Hu B, Wu L, Lin H, Chen Z, Zhu C. Iron deficiency anaemia can be improved after eradication of Helicobacter pylori. Postgrad Med J. 2010;86:272-278. [PubMed]|
|55.||Yuan W, Li Yumin D, Yang L. Iron deficiency anemia in Helicobacter pylori infection: meta-analysis of randomized controlled trials. Scand J Gastroenterol. 2010;45:665-676. [PubMed] [DOI]|
|56.||Zhang ZF, Yang N, Zhao G, Zhu L, Zhu Y, Wang LX. Effect of Helicobacter pylori eradication on iron deficiency. Chin Med J (Engl). 2010;123:1924-1930. [PubMed]|
|57.||Ashorn M, Ruuska T, Mäkipernaa A. Helicobacter pylori and iron deficiency anaemia in children. Scand J Gastroenterol. 2001;36:701-705. [PubMed]|
|58.||Seo JK, Ko JS, Choi KD. Serum ferritin and Helicobacter pylori infection in children: a sero-epidemiologic study in Korea. J Gastroenterol Hepatol. 2002;17:754-757. [PubMed]|
|59.||Kostaki M, Fessatou S, Karpathios T. Refractory iron-deficiency anaemia due to silent Helicobacter pylori gastritis in children. Eur J Pediatr. 2003;162:177-179. [PubMed]|
|60.||Yang YJ, Sheu BS, Lee SC, Yang HB, Wu JJ. Children of Helicobacter pylori-infected dyspeptic mothers are predisposed to H. pylori acquisition with subsequent iron deficiency and growth retardation. Helicobacter. 2005;10:249-255. [PubMed]|
|61.||Gessner BD, Baggett HC, Muth PT, Dunaway E, Gold BD, Feng Z, Parkinson AJ. A controlled, household-randomized, open-label trial of the effect that treatment of Helicobacter pylori infection has on iron deficiency in children in rural Alaska. J Infect Dis. 2006;193:537-546. [PubMed]|
|62.||Baggett HC, Parkinson AJ, Muth PT, Gold BD, Gessner BD. Endemic iron deficiency associated with Helicobacter pylori infection among school-aged children in Alaska. Pediatrics. 2006;117:e396-e404. [PubMed]|
|63.||Süoglu OD, Gökçe S, Saglam AT, Sökücü S, Saner G. Association of Helicobacter pylori infection with gastroduodenal disease, epidemiologic factors and iron-deficiency anemia in Turkish children undergoing endoscopy, and impact on growth. Pediatr Int. 2007;49:858-863. [PubMed]|
|64.||Sarker SA, Mahmud H, Davidsson L, Alam NH, Ahmed T, Alam N, Salam MA, Beglinger C, Gyr N, Fuchs GJ. Causal relationship of Helicobacter pylori with iron-deficiency anemia or failure of iron supplementation in children. Gastroenterology. 2008;135:1534-1542. [PubMed]|
|65.||Haghi-Ashtiani MT, Monajemzadeh M, Motamed F, Mahjoub F, Sharifan M, Shahsiah R, Kashef N. Anemia in children with and without Helicobacter pylori infection. Arch Med Res. 2008;39:536-540. [PubMed]|
|66.||Choe YH, Lee JE, Kim SK. Effect of helicobacter pylori eradication on sideropenic refractory anaemia in adolescent girls with Helicobacter pylori infection. Acta Paediatr. 2000;89:154-157. [PubMed]|
|67.||Choe YH, Kim SK, Hong YC. The relationship between Helicobacter pylori infection and iron deficiency: seroprevalence study in 937 pubescent children. Arch Dis Child. 2003;88:178. [PubMed]|
|68.||Hershko C, Hoffbrand AV, Keret D, Souroujon M, Maschler I, Monselise Y, Lahad A. Role of autoimmune gastritis, Helicobacter pylori and celiac disease in refractory or unexplained iron deficiency anemia. Haematologica. 2005;90:585-595. [PubMed]|
|69.||Parkinson AJ, Gold BD, Bulkow L, Wainwright RB, Swaminathan B, Khanna B, Petersen KM, Fitzgerald MA. High prevalence of Helicobacter pylori in the Alaska native population and association with low serum ferritin levels in young adults. Clin Diagn Lab Immunol. 2000;7:885-888. [PubMed]|
|70.||Berg G, Bode G, Blettner M, Boeing H, Brenner H. Helicobacter pylori infection and serum ferritin: A population-based study among 1806 adults in Germany. Am J Gastroenterol. 2001;96:1014-1018. [PubMed]|
|71.||Bini EJ. Helicobacter pylori and iron deficiency anemia: guilty as charged? Am J Med. 2001;111:495-497. [PubMed]|
|72.||Cuoco L, Cammarota G, Jorizzo RA, Santarelli L, Cianci R, Montalto M, Gasbarrini A, Gasbarrini G. Link between Helicobacter pylori infection and iron-deficiency anaemia in patients with coeliac disease. Scand J Gastroenterol. 2001;36:1284-1288. [PubMed]|
|73.||Choe YH, Kwon YS, Jung MK, Kang SK, Hwang TS, Hong YC. Helicobacter pylori-associated iron-deficiency anemia in adolescent female athletes. J Pediatr. 2001;139:100-104. [PubMed]|
|74.||Yoshimura M, Hirai M, Tanaka N, Kasahara Y, Hosokawa O. Remission of severe anemia persisting for over 20 years after eradication of Helicobacter pylori in cases of Ménètrier’s disease and atrophic gastritis: Helicobacter pylori as a pathogenic factor in iron-deficiency anemia. Intern Med. 2003;42:971-977. [PubMed]|
|75.||Nahon S, Lahmek P, Massard J, Lesgourgues B, Mariaud de Serre N, Traissac L, Bodiguel V, Adotti F, Delas N. Helicobacter pylori-associated chronic gastritis and unexplained iron deficiency anemia: a reliable association? Helicobacter. 2003;8:573-577. [PubMed]|
|76.||Ciacci C, Sabbatini F, Cavallaro R, Castiglione F, Di Bella S, Iovino P, Palumbo A, Tortora R, Amoruso D, Mazzacca G. Helicobacter pylori impairs iron absorption in infected individuals. Dig Liver Dis. 2004;36:455-460. [PubMed]|
|77.||Valiyaveettil AN, Hamide A, Bobby Z, Krishnan R. Effect of anti-Helicobacter pylori therapy on outcome of iron-deficiency anemia: a randomized, controlled study. Indian J Gastroenterol. 2005;24:155-157. [PubMed]|
|78.||Cardenas VM, Mulla ZD, Ortiz M, Graham DY. Iron deficiency and Helicobacter pylori infection in the United States. Am J Epidemiol. 2006;163:127-134. [PubMed]|
|79.||Chen LH, Luo HS. Effects of H pylori therapy on erythrocytic and iron parameters in iron deficiency anemia patients with H pylori-positive chronic gastristis. World J Gastroenterol. 2007;13:5380-5383. [PubMed]|
|80.||Vijayan G, Sundaram RC, Bobby Z, Hamide A, Selvaraj N, Dasse NR. Increased plasma malondialdehyde and fructosamine in anemic H pylori infected patients: effect of treatment. World J Gastroenterol. 2007;13:796-800. [PubMed]|
|81.||Kaffes A, Cullen J, Mitchell H, Katelaris PH. Effect of Helicobacter pylori infection and low-dose aspirin use on iron stores in the elderly. J Gastroenterol Hepatol. 2003;18:1024-1028. [PubMed]|
|82.||Mulayim B, Celik NY, Yanik FF. Helicobacter pylori infection detected by 14C-urea breath test is associated with iron deficiency anemia in pregnant women. J Obstet Gynaecol Res. 2008;34:980-985. [PubMed]|
|83.||Correa P, Piazuelo MB. Natural history of Helicobacter pylori infection. Dig Liver Dis. 2008;40:490-496. [PubMed]|
|84.||Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001;276:7806-7810. [PubMed] [DOI]|
|85.||Kroot JJ, Tjalsma H, Fleming RE, Swinkels DW. Hepcidin in human iron disorders: diagnostic implications. Clin Chem. 2011;57:1650-1669. [PubMed] [DOI]|
|86.||Cherian S, Forbes DA, Cook AG, Sanfilippo FM, Kemna EH, Swinkels DW, Burgner DP. An insight into the relationships between hepcidin, anemia, infections and inflammatory cytokines in pediatric refugees: a cross-sectional study. PLoS One. 2008;3:e4030. [PubMed] [DOI]|
|87.||Hershko C, Ronson A. Iron deficiency, Helicobacter infection and gastritis. Acta Haematol. 2009;122:97-102. [PubMed]|
|88.||Lee SY, Song EY, Yun YM, Yoon SY, Cho YH, Kim SY, Lee MH. Serum prohepcidin levels in Helicobacter pylori infected patients with iron deficiency anemia. Korean J Intern Med. 2010;25:195-200. [PubMed] [DOI]|
|89.||Schwarz P, Kübler JA, Strnad P, Müller K, Barth TF, Gerloff A, Feick P, Peyssonnaux C, Vaulont S, Adler G. Hepcidin is localised in gastric parietal cells, regulates acid secretion and is induced by Helicobacter pylori infection. Gut. 2012;61:193-201. [PubMed] [DOI]|
|90.||Ozkasap S, Yarali N, Isik P, Bay A, Kara A, Tunc B. The role of prohepcidin in anemia due to Helicobacter pylori infection. Pediatr Hematol Oncol. 2013;30:425-431. [PubMed] [DOI]|
|91.||Azab SF, Esh AM. Serum hepcidin levels in Helicobacter pylori-infected children with iron-deficiency anemia: a case-control study. Ann Hematol. 2013;92:1477-1483. [PubMed] [DOI]|
|92.||Yip R, Limburg PJ, Ahlquist DA, Carpenter HA, O’Neill A, Kruse D, Stitham S, Gold BD, Gunter EW, Looker AC. Pervasive occult gastrointestinal bleeding in an Alaska native population with prevalent iron deficiency. Role of Helicobacter pylori gastritis. JAMA. 1997;277:1135-1139. [PubMed]|
|93.||Kang JM, Kim N, Lee BH, Park HK, Jo HJ, Shin CM, Lee SH, Park YS, Hwang JH, Kim JW. Risk factors for peptic ulcer bleeding in terms of Helicobacter pylori, NSAIDs, and antiplatelet agents. Scand J Gastroenterol. 2011;46:1295-1301. [PubMed] [DOI]|
|94.||Musumba C, Jorgensen A, Sutton L, Van Eker D, Moorcroft J, Hopkins M, Pritchard DM, Pirmohamed M. The relative contribution of NSAIDs and Helicobacter pylori to the aetiology of endoscopically-diagnosed peptic ulcer disease: observations from a tertiary referral hospital in the UK between 2005 and 2010. Aliment Pharmacol Ther. 2012;36:48-56. [PubMed] [DOI]|
|95.||Vergara M, Catalán M, Gisbert JP, Calvet X. Meta-analysis: role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users. Aliment Pharmacol Ther. 2005;21:1411-1418. [PubMed]|
|96.||De Leest HT, Steen KS, Bloemena E, Lems WF, Kuipers EJ, Van de Laar MA, Bijlsma JW, Janssen M, Houben HH, Kostense PJ. Helicobacter pylori eradication in patients on long-term treatment with NSAIDs reduces the severity of gastritis: a randomized controlled trial. J Clin Gastroenterol. 2009;43:140-146. [PubMed] [DOI]|
|97.||Sokic-Milutinovic A, Krstic M, Rozer-Smolovic B, Alempijevic T. Role of Helicobacter pylori infection in gastroduodenal damage in patients starting NSAID therapy: 4 Months follow-up study. Dig Dis Sci. 2010;55:2887-2892. [PubMed] [DOI]|
|98.||Song HJ, Kwon JW, Kim N, Park YS. Cost Effectiveness Associated with Helicobacter pylori Screening and Eradication in Patients Taking Nonsteroidal Anti-Inflammatory Drugs and/or Aspirin. Gut Liver. 2013;7:182-189. [PubMed] [DOI]|
|99.||Afifi MT, Abd El-Aziz HK, Hamed NA, Barghash NA, Abdo A, Gamal M. Role of Helicobacter pylori in refractory iron deficiency anaemia. Br J Biomed Sci. 2009;66:133-136. [PubMed]|
|100.||Boyanova L. Role of Helicobacter pylori virulence factors for iron acquisition from gastric epithelial cells of the host and impact on bacterial colonization. Future Microbiol. 2011;6:843-846. [PubMed] [DOI]|
|101.||Ge R, Sun X. Iron trafficking system in Helicobacter pylori. Biometals. 2012;25:247-258. [PubMed] [DOI]|
|102.||Davis RE. Clinical chemistry of vitamin B12. Adv Clin Chem. 1985;24:163-216. [PubMed]|
|103.||Andrès E, Loukili NH, Noel E, Kaltenbach G, Abdelgheni MB, Perrin AE, Noblet-Dick M, Maloisel F, Schlienger JL, Blicklé JF. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171:251-259. [PubMed]|
|104.||Dali-Youcef N, Andrès E. An update on cobalamin deficiency in adults. QJM. 2009;102:17-28. [PubMed] [DOI]|
|105.||Herbert V. Staging vitamin B-12 (cobalamin) status in vegetarians. Am J Clin Nutr. 1994;59:1213S-1222S. [PubMed]|
|106.||Carmel R, Johnson CS, Weiner JM. Pernicious anemia in Latin Americans is not a disease of the elderly. Arch Intern Med. 1987;147:1995-1996. [PubMed]|
|107.||Carmel R. Prevalence of undiagnosed pernicious anemia in the elderly. Arch Intern Med. 1996;156:1097-1100. [PubMed]|
|108.||Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002;346:476-483. [PubMed]|
|109.||Hooshmand B, Solomon A, Kåreholt I, Leiviskä J, Rusanen M, Ahtiluoto S, Winblad B, Laatikainen T, Soininen H, Kivipelto M. Homocysteine and holotranscobalamin and the risk of Alzheimer disease: a longitudinal study. Neurology. 2010;75:1408-1414. [PubMed] [DOI]|
|110.||Werder SF. Cobalamin deficiency, hyperhomocysteinemia, and dementia. Neuropsychiatr Dis Treat. 2010;6:159-195. [PubMed]|
|111.||Hooshmand B, Solomon A, Kåreholt I, Rusanen M, Hänninen T, Leiviskä J, Winblad B, Laatikainen T, Soininen H, Kivipelto M. Associations between serum homocysteine, holotranscobalamin, folate and cognition in the elderly: a longitudinal study. J Intern Med. 2012;271:204-212. [PubMed] [DOI]|
|112.||Tiemeier H, van Tuijl HR, Hofman A, Meijer J, Kiliaan AJ, Breteler MM. Vitamin B12, folate, and homocysteine in depression: the Rotterdam Study. Am J Psychiatry. 2002;159:2099-2101. [PubMed]|
|113.||Kaptan K, Beyan C. Does hyperhomocysteinemia due to vitamin B12 deficiency associted with Helicobacter pylori infection has a role on cerebral stroke? Med Sci Monit. 2002;8:LE52-LE3; author reply LE53. [PubMed]|
|114.||Moghaddasi M, Mamarabadi M, Mirzadeh S, Freydoonnejad AA, Razjouyan H. Homocysteine, vitamin B12 and folate levels in Iranian patients with ischemic stroke. Neurol Res. 2010;32:953-956. [PubMed] [DOI]|
|115.||Caldera A, Mora J, Kotler M, Eiger G. Pulmonary embolism in a patient with pernicious anemia and hyperhomocysteinemia. Chest. 2002;122:1487-1488. [PubMed]|
|116.||Andrès E, Kurtz JE. Pulmonary embolism in pernicious anemia and hyperhomocysteinemia. Chest. 2003;124:1181. [PubMed]|
|117.||Whincup PH, Mendall MA, Perry IJ, Strachan DP. Hyperhomocysteinaemia, Helicobacter pylori, and coronary heart disease. Heart. 1997;78:524. [PubMed]|
|118.||O’Connor HJ, Axon AT, Dixon MF. Campylobacter-like organisms unusual in type A (pernicious anaemia) gastritis. Lancet. 1984;2:1091. [PubMed]|
|119.||Fong TL, Dooley CP, Dehesa M, Cohen H, Carmel R, Fitzgibbons PL, Perez-Perez GI, Blaser MJ. Helicobacter pylori infection in pernicious anemia: a prospective controlled study. Gastroenterology. 1991;100:328-332. [PubMed]|
|120.||Saito M, Mori A, Irie T, Tanaka M, Morioka M. [Helicobacter pylori infection is not associated with pernicious anemia in Japan]. Rinsho Ketsueki. 2008;49:1569-1571. [PubMed]|
|121.||Kokkola A, Kosunen TU, Puolakkainen P, Sipponen P, Harkonen M, Laxen F, Virtamo J, Haapiainen R, Rautelin H. Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis. APMIS. 2003;111:619-624. [PubMed]|
|122.||Suter PM, Golner BB, Goldin BR, Morrow FD, Russell RM. Reversal of protein-bound vitamin B12 malabsorption with antibiotics in atrophic gastritis. Gastroenterology. 1991;101:1039-1045. [PubMed]|
|123.||Valle J, Kekki M, Sipponen P, Ihamäki T, Siurala M. Long-term course and consequences of Helicobacter pylori gastritis. Results of a 32-year follow-up study. Scand J Gastroenterol. 1996;31:546-550. [PubMed]|
|124.||Ma JY, Borch K, Sjöstrand SE, Janzon L, Mårdh S. Positive correlation between H,K-adenosine triphosphatase autoantibodies and Helicobacter pylori antibodies in patients with pernicious anemia. Scand J Gastroenterol. 1994;29:961-965. [PubMed]|
|125.||Claeys D, Faller G, Appelmelk BJ, Negrini R, Kirchner T. The gastric H+,K+-ATPase is a major autoantigen in chronic Helicobacter pylori gastritis with body mucosa atrophy. Gastroenterology. 1998;115:340-347. [PubMed]|
|126.||Pietroiusti A, Galante A, Magrini A, Bergamaschi A. Helicobacter pylori interference with micronutrients and orally administered drugs: a new mechanism explaining its role in extragastric disorders. Mini Rev Med Chem. 2008;8:135-141. [PubMed]|
|127.||Kaptan K, Beyan C, Ural AU, Cetin T, Avcu F, Gülşen M, Finci R, Yalçín A. Helicobacter pylori--is it a novel causative agent in Vitamin B12 deficiency? Arch Intern Med. 2000;160:1349-1353. [PubMed]|
|128.||Carmel R, Aurangzeb I, Qian D. Associations of food-cobalamin malabsorption with ethnic origin, age, Helicobacter pylori infection, and serum markers of gastritis. Am J Gastroenterol. 2001;96:63-70. [PubMed]|
|129.||Andrès E, Federici L, Affenberger S, Vidal-Alaball J, Loukili NH, Zimmer J, Kaltenbach G. B12 deficiency: a look beyond pernicious anemia. J Fam Pract. 2007;56:537-542. [PubMed]|
|130.||Lahner E, Persechino S, Annibale B. Micronutrients (Other than iron) and Helicobacter pylori infection: a systematic review. Helicobacter. 2012;17:1-15. [PubMed] [DOI]|
|131.||Marino MC, de Oliveira CA, Rocha AM, Rocha GA, Clementino NC, Antunes LF, Oliveira RA, Martins AS, Del Puerto HL, D’Almeida V. Long-term effect of Helicobacter pylori eradication on plasma homocysteine in elderly patients with cobalamin deficiency. Gut. 2007;56:469-474. [PubMed]|
|132.||Kaplan HS, Rigler LG. Pernicious anemia and susceptibility to gastric neoplasms. J Lab Clin Med. 1947;32:644-653. [PubMed]|
|133.||Zamcheck N, Grable E, Ley A, Norman L. Occurrence of gastric cancer among patients with pernicious anemia at the Boston City Hospital. N Engl J Med. 1955;252:1103-1110. [PubMed]|
|134.||Berkson J, Butt HR, Comfort MW. Occurrence of gastric cancer in persons with achlorhydria and with pernicious anemia. Proc Staff Meet Mayo Clin. 1956;31:583-596. [PubMed]|
|135.||Payne RW. Pernicious anaemia and gastric cancer in England and Wales. Br Med J. 1961;1:1807-1809. [PubMed]|
|136.||Vannella L, Lahner E, Osborn J, Annibale B. Systematic review: gastric cancer incidence in pernicious anaemia. Aliment Pharmacol Ther. 2013;37:375-382. [PubMed] [DOI]|
|137.||Toh BH, van Driel IR, Gleeson PA. Pernicious anemia. N Engl J Med. 1997;337:1441-1448. [PubMed]|
|138.||Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113:2386-2393. [PubMed]|
|139.||British Committee for Standards in Haematology General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003;120:574-596. [PubMed]|
|140.||Liel MS, Carverley DC. Thrombopcytopenia caused by immunologic platelet destruction. Wintrobe’s Clinical Hematology. 13th ed. Philadelphia, PA: Lippincott Williams & Wilkins 2013; 1061-1076.|
|141.||Frederiksen H, Schmidt K. The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood. 1999;94:909-913. [PubMed]|
|142.||Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190-4207. [PubMed] [DOI]|
|143.||Pizzuto J, Ambriz R. Therapeutic experience on 934 adults with idiopathic thrombocytopenic purpura: Multicentric Trial of the Cooperative Latin American group on Hemostasis and Thrombosis. Blood. 1984;64:1179-1183. [PubMed]|
|144.||García Pérez A, Valverde de La Osa J, Giménez Samper M, Alonso García I. [Resolution of an autoimmune thrombocytopenic purpura after eradicating treatment of Helicobacter pylori]. Sangre (Barc). 1999;44:387-388. [PubMed]|
|145.||Tohda S, Ohkusa T. Resolution of refractory idiopathic thrombocytopenic purpura after eradication of Helicobacter pylori. Am J Hematol. 2000;65:329-330. [PubMed]|
|146.||Goto H, Kikuta T, Ota A, Tsuji H, Hino R. [Successful treatment of refractory idiopathic thrombocytopenic purpura by eradication of Helicobacter pylori]. Rinsho Ketsueki. 2001;42:1192-1194. [PubMed]|
|147.||Mukai M, Kon Y, Notoya A, Kohno M. Helicobacter pylori associated with idiopathic thrombocytopenic purpura. Am J Med. 2002;113:169-171. [PubMed]|
|148.||Asaumi N, Niiya K, Shibakura M, Yoshida C, Niiya M, Tanimoto M. Secondary eradication of Helicobacter pylori was effective against refractory idiopathic thrombocytopenic purpura. Blood Coagul Fibrinolysis. 2003;14:785-786. [PubMed]|
|149.||Takechi T, Unemoto J, Ishihara M, Hosokawa T, Zushi N, Shiraishi T, Ogura H, Wakiguchi H. Idiopathic thrombocytopenic purpura associated with Helicobacter pylori infection. Pediatr Int. 2006;48:76-78. [PubMed]|
|150.||Grimaz S, Damiani D, Brosolo P, Skert C, Geromin A, de Pretis G. Resolution of thrombocytopenia after treatment for Helicobacter pylori: a case report. Haematologica. 1999;84:283-284. [PubMed]|
|151.||Soldinger E, Pilia MC, Piubello W, Nadali G. Multi-resistant idiopathic thrombocytopenia successfully treated by eradication of Helicobacter pylori. Dig Liver Dis. 2001;33:732. [PubMed] [DOI]|
|152.||Candelli M, Nista EC, Pignataro G, Gasbarrini G, Gasbarrini A. Idiopathic thrombocytopenic purpura and Helicobacter pylori infection. Scand J Gastroenterol. 2003;38:569-570. [PubMed] [DOI]|
|153.||Kurekci AE, Atay AA, Sarici SU, Ozcan O. Complete platelet recovery after treatment of Helicobacter pylori infection in a child with chronic immune thrombocytopenic purpura: a case report. Pediatr Hematol Oncol. 2004;21:593-596. [PubMed] [DOI]|
|154.||Gasbarrini A, Franceschi F, Tartaglione R, Landolfi R, Pola P, Gasbarrini G. Regression of autoimmune thrombocytopenia after eradication of Helicobacter pylori. Lancet. 1998;352:878. [PubMed] [DOI]|
|155.||Emilia G, Longo G, Luppi M, Gandini G, Morselli M, Ferrara L, Amarri S, Cagossi K, Torelli G. Helicobacter pylori eradication can induce platelet recovery in idiopathic thrombocytopenic purpura. Blood. 2001;97:812-814. [PubMed] [DOI]|
|156.||Emilia G, Luppi M, Morselli M, Potenza L, D’Apollo N, Torelli G. Helicobacter pylori infection and idiopathic thrombocytopenic purpura. Br J Haematol. 2002;118:1198-1199. [PubMed] [DOI]|
|157.||Veneri D, Franchini M, Gottardi M, D’Adda M, Ambrosetti A, Krampera M, Zanetti F, Pizzolo G. Efficacy of Helicobacter pylori eradication in raising platelet count in adult patients with idiopathic thrombocytopenic purpura. Haematologica. 2002;87:1177-1179. [PubMed]|
|158.||Veneri D, Krampera M, Franchini M. High prevalence of sustained remission of idiopathic thrombocytopenic purpura after Helicobacter pylori eradication: a long-term follow-up study. Platelets. 2005;16:117-119. [PubMed] [DOI]|
|159.||Stasi R, Rossi Z, Stipa E, Amadori S, Newland AC, Provan D. Helicobacter pylori eradication in the management of patients with idiopathic thrombocytopenic purpura. Am J Med. 2005;118:414-419. [PubMed] [DOI]|
|160.||Emilia G, Luppi M, Zucchini P, Morselli M, Potenza L, Forghieri F, Volzone F, Jovic G, Leonardi G, Donelli A. Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles. Blood. 2007;110:3833-3841. [PubMed] [DOI]|
|161.||Sayan O, Akyol Erikci A, Ozturk A. The Efficacy of Helicobacter pylori eradication in the treatment of idiopathic thrombocytopenic purpura--the first study in Turkey. Acta Haematol. 2006;116:146-149. [PubMed] [DOI]|
|162.||Suvajdzić N, Stanković B, Artiko V, Cvejić T, Bulat V, Bakrac M, Colović M, Obradović V, Atkinson HD. Helicobacter pylori eradication can induce platelet recovery in chronic idiopathic thrombocytopenic purpura. Platelets. 2006;17:227-230. [PubMed] [DOI]|
|163.||Kohda K, Kuga T, Kogawa K, Kanisawa Y, Koike K, Kuroiwa G, Hirayama Y, Sato Y, Niitsu Y. Effect of Helicobacter pylori eradication on platelet recovery in Japanese patients with chronic idiopathic thrombocytopenic purpura and secondary autoimmune thrombocytopenic purpura. Br J Haematol. 2002;118:584-588. [PubMed] [DOI]|
|164.||Kohda K, Niitsu Y. [Helicobacter pylori infection and idiopathic thrombocytopenic purpura]. Nihon Rinsho. 2003;61:644-649. [PubMed]|
|165.||Ando K, Shimamoto T, Tauchi T, Ito Y, Kuriyama Y, Gotoh A, Miyazawa K, Kimura Y, Kawai T, Ohyashiki K. Can eradication therapy for Helicobacter pylori really improve the thrombocytopenia in idiopathic thrombocytopenic purpura? Our experience and a literature review. Int J Hematol. 2003;77:239-244. [PubMed] [DOI]|
|166.||Hashino S, Mori A, Suzuki S, Izumiyama K, Kahata K, Yonezumi M, Chiba K, Kondo T, Ota S, Toyashima N. Platelet recovery in patients with idiopathic thrombocytopenic purpura after eradication of Helicobacter pylori. Int J Hematol. 2003;77:188-191. [PubMed] [DOI]|
|167.||Hino M, Yamane T, Park K, Takubo T, Ohta K, Kitagawa S, Higuchi K, Arakawa T. Platelet recovery after eradication of Helicobacter pylori in patients with idiopathic thrombocytopenic purpura. Ann Hematol. 2003;82:30-32. [PubMed]|
|168.||Kato A, Kato H, Hirashima N, Sakamoto T, Nukaya H, Ito K, Matsunaga S, Kondo H, Tanaka Y, Sakakibara K. [Evaluation of the efficacy of an Helicobacter pylori eradication treatment for idiopathic thrombocytopenic purpura patients]. Nihon Shokakibyo Gakkai Zasshi. 2004;101:1209-1216. [PubMed]|
|169.||Ando T, Tsuzuki T, Mizuno T, Minami M, Ina K, Kusugami K, Takamatsu J, Adachi K, El-Omar E, Ohta M. Characteristics of Helicobacter pylori-induced gastritis and the effect of H. pylori eradication in patients with chronic idiopathic thrombocytopenic purpura. Helicobacter. 2004;9:443-452. [PubMed] [DOI]|
|170.||Nomura S, Inami N, Kanazawa S. The effects of Helicobacter pylori eradication on chemokine production in patients with immune thrombocytopenic purpura. Eur J Haematol. 2004;72:304-305. [PubMed] [DOI]|
|171.||Sato R, Murakami K, Watanabe K, Okimoto T, Miyajima H, Ogata M, Ohtsuka E, Kodama M, Saburi Y, Fujioka T. Effect of Helicobacter pylori eradication on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura. Arch Intern Med. 2004;164:1904-1907. [PubMed] [DOI]|
|172.||Takahashi T, Yujiri T, Shinohara K, Inoue Y, Sato Y, Fujii Y, Okubo M, Zaitsu Y, Ariyoshi K, Nakamura Y. Molecular mimicry by Helicobacter pylori CagA protein may be involved in the pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura. Br J Haematol. 2004;124:91-96. [PubMed] [DOI]|
|173.||Fujimura K, Kuwana M, Kurata Y, Imamura M, Harada H, Sakamaki H, Teramura M, Koda K, Nomura S, Sugihara S. Is eradication therapy useful as the first line of treatment in Helicobacter pylori-positive idiopathic thrombocytopenic purpura? Analysis of 207 eradicated chronic ITP cases in Japan. Int J Hematol. 2005;81:162-168. [PubMed] [DOI]|
|174.||Inaba T, Mizuno M, Take S, Suwaki K, Honda T, Kawai K, Fujita M, Tamura T, Yokota K, Oguma K. Eradication of Helicobacter pylori increases platelet count in patients with idiopathic thrombocytopenic purpura in Japan. Eur J Clin Invest. 2005;35:214-219. [PubMed] [DOI]|
|175.||Tsutsumi Y, Kanamori H, Yamato H, Ehira N, Kawamura T, Umehara S, Mori A, Obara S, Ogura N, Tanaka J. Randomized study of Helicobacter pylori eradication therapy and proton pump inhibitor monotherapy for idiopathic thrombocytopenic purpura. Ann Hematol. 2005;84:807-811. [PubMed] [DOI]|
|176.||Suzuki T, Matsushima M, Masui A, Watanabe K, Takagi A, Ogawa Y, Shirai T, Mine T. Effect of Helicobacter pylori eradication in patients with chronic idiopathic thrombocytopenic purpura-a randomized controlled trial. Am J Gastroenterol. 2005;100:1265-1270. [PubMed] [DOI]|
|177.||Asahi A, Kuwana M, Suzuki H, Hibi T, Kawakami Y, Ikeda Y. Effects of a Helicobacter pylori eradication regimen on anti-platelet autoantibody response in infected and uninfected patients with idiopathic thrombocytopenic purpura. Haematologica. 2006;91:1436-1437. [PubMed]|
|178.||Ishiyama M, Teramura M, Iwabe K, Kato T, Motoji T. Clonally expanded T-cells in the peripheral blood of patients with idiopathic Thrombocytopenic purpura and Helicobacter pylori infection. Int J Hematol. 2006;83:147-151. [PubMed] [DOI]|
|179.||Satake M, Nishikawa J, Fukagawa Y, Akashi K, Okamoto T, Yoshida T, Hirano A, Maetani N, Iida Y, Sakaida I. The long-term efficacy of Helicobacter pylori eradication therapy in patients with idiopathic thrombocytopenic purpura. J Gastroenterol Hepatol. 2007;22:2233-2237. [PubMed] [DOI]|
|180.||Kodama M, Kitadai Y, Ito M, Kai H, Masuda H, Tanaka S, Yoshihara M, Fujimura K, Chayama K. Immune response to CagA protein is associated with improved platelet count after Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura. Helicobacter. 2007;12:36-42. [PubMed] [DOI]|
|181.||Asahi A, Nishimoto T, Okazaki Y, Suzuki H, Masaoka T, Kawakami Y, Ikeda Y, Kuwana M. Helicobacter pylori eradication shifts monocyte Fcgamma receptor balance toward inhibitory FcgammaRIIB in immune thrombocytopenic purpura patients. J Clin Invest. 2008;118:2939-2949. [PubMed] [DOI]|
|182.||Suzuki T, Matsushima M, Shirakura K, Koike J, Masui A, Takagi A, Shirasugi Y, Ogawa Y, Shirai T, Mine T. Association of inflammatory cytokine gene polymorphisms with platelet recovery in idiopathic thrombocytopenic purpura patients after the eradication of Helicobacter pylori. Digestion. 2008;77:73-78. [PubMed] [DOI]|
|183.||Tsumoto C, Tominaga K, Okazaki H, Tanigawa T, Yamagami H, Watanabe K, Nakao T, Koh K, Watanabe T, Fujiwara Y. Long-term efficacy of Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura: 7-year follow-up prospective study. Ann Hematol. 2009;88:789-793. [PubMed] [DOI]|
|184.||Sato R, Murakami K, Okimoto T, Watanabe K, Kodama M, Fujioka T. Development of corpus atrophic gastritis may be associated with Helicobacter pylori-related idiopathic thrombocytopenic purpura. J Gastroenterol. 2011;46:991-997. [PubMed] [DOI]|
|185.||Kikuchi T, Kobayashi T, Yamashita T, Ohashi K, Sakamaki H, Akiyama H. Eight-year follow-up of patients with immune thrombocytopenic purpura related toH. pyloriinfection. Platelets. 2011;22:61-64. [PubMed] [DOI]|
|186.||Kong R, Qiu HC, Wu PF, Niu XH, Shen WX, Wang Y. [Clinical significance of Helicobacter pylori in pathogenesis of idiopathic thrombocytopenic purpura]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008;16:1222-1226. [PubMed]|
|187.||Wu S, Li Y, Jian Z, Tang F. [Anti-Helicobacter pylori treatment in patients with idiopathic thrombocytopenic purpura]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2009;34:1251-1254. [PubMed]|
|188.||Rostami N, Keshtkar-Jahromi M, Rahnavardi M, Keshtkar-Jahromi M, Esfahani FS. Effect of eradication of Helicobacter pylori on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura: a controlled trial. Am J Hematol. 2008;83:376-381. [PubMed] [DOI]|
|189.||Payandeh M, Sohrabi N, Zare ME, Kansestani AN, Hashemian AH. Platelet Count Response to Helicobacter pylori Eradication in Iranian Patients with Idiopathic Thrombocytopenic Purpura. Mediterr J Hematol Infect Dis. 2012;4:e2012056. [PubMed] [DOI]|
|190.||Tag HS, Lee HS, Jung SH, Kim BK, Kim SB, Lee A, Lee JS, Shin SH, Kim YS. Effects of Helicobacter pylori eradication in patients with immune thrombocytopenic purpura. Korean J Hematol. 2010;45:127-132. [PubMed] [DOI]|
|191.||Campuzano-Maya G. Proof of an association between Helicobacter pylori and idiopathic thrombocytopenic purpura in Latin America. Helicobacter. 2007;12:265-273. [PubMed] [DOI]|
|192.||Jackson SC, Beck P, Buret AG, O’Connor PM, Meddings J, Pineo G, Poon MC. Long term platelet responses to Helicobacter pylori eradication in Canadian patients with immune thrombocytopenic purpura. Int J Hematol. 2008;88:212-218. [PubMed] [DOI]|
|193.||Jarque I, Andreu R, Llopis I, De la Rubia J, Gomis F, Senent L, Jiménez C, Martín G, Martínez JA, Sanz GF. Absence of platelet response after eradication of Helicobacter pylori infection in patients with chronic idiopathic thrombocytopenic purpura. Br J Haematol. 2001;115:1002-1003. [PubMed] [DOI]|
|194.||Michel M, Khellaf M, Desforges L, Lee K, Schaeffer A, Godeau B, Bierling P. Autoimmune thrombocytopenic Purpura and Helicobacter pylori infection. Arch Intern Med. 2002;162:1033-1036. [PubMed] [DOI]|
|195.||Michel M, Cooper N, Jean C, Frissora C, Bussel JB. Does Helicobater pylori initiate or perpetuate immune thrombocytopenic purpura? Blood. 2004;103:890-896. [PubMed] [DOI]|
|196.||Estrada-Gómez RA, Parra-Ortega I, Martínez-Barreda C, Ruiz-Argüelles GJ. Helicobacter pylori infection and thrombocytopenia: a single-institution experience in Mexico. Rev Invest Clin. 2007;59:112-115. [PubMed]|
|197.||Jaing TH, Yang CP, Hung IJ, Chiu CH, Chang KW. Efficacy of Helicobacter pylori eradication on platelet recovery in children with chronic idiopathic thrombocytopenic purpura. Acta Paediatr. 2003;92:1153-1157. [PubMed] [DOI]|
|198.||Hayashi H, Okuda M, Aoyagi N, Yoshiyama M, Miyashiro E, Kounami S, Yoshikawa N. Helicobacter pylori infection in children with chronic idiopathic thrombocytopenic purpura. Pediatr Int. 2005;47:292-295. [PubMed] [DOI]|
|199.||Hamidieh AA, Arzanian MT, Gachkar L, Pasha F. Helicobacter pylori infection in children with chronic idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 2008;30:96-97. [PubMed] [DOI]|
|200.||Rajantie J, Klemola T. Helicobacter pylori and idiopathic thrombocytopenic purpura in children. Blood. 2003;101:1660. [PubMed] [DOI]|
|201.||Neefjes VM, Heijboer H, Tamminga RY. H. pylori infection in childhood chronic immune thrombocytopenic purpura. Haematologica. 2007;92:576. [PubMed] [DOI]|
|202.||Ferrara M, Capozzi L, Russo R. Effect of Helicobacter pylori eradication on platelet count in children with chronic idiopathic thrombocytopenic purpura. Hematology. 2009;14:282-285. [PubMed] [DOI]|
|203.||Russo G, Miraglia V, Branciforte F, Matarese SM, Zecca M, Bisogno G, Parodi E, Amendola G, Giordano P, Jankovic M. Effect of eradication of Helicobacter pylori in children with chronic immune thrombocytopenia: a prospective, controlled, multicenter study. Pediatr Blood Cancer. 2011;56:273-278. [PubMed] [DOI]|
|204.||Scandellari R, Allemand E, Vettore S, Plebani M, Randi ML, Fabris F. Platelet response to Helicobacter pylori eradication therapy in adult chronic idiopathic thrombocytopenic purpura seems to be related to the presence of anticytotoxin-associated gene A antibodies. Blood Coagul Fibrinolysis. 2009;20:108-113. [PubMed] [DOI]|
|205.||Yetgin S, Demir H, Arslan D, Unal S, Koçak N. Autoimmune thrombocytopenic purpura and Helicobacter pylori infection effectivity during childhood. Am J Hematol. 2005;78:318. [PubMed] [DOI]|
|206.||Loffredo G, Marzano MG, Migliorati R, Miele E, Menna F, Poggi V, Staiano A. The relationship between immune thrombocytopenic purpura and Helicobacter pylori infection in children: where is the truth? Eur J Pediatr. 2007;166:1067-1068. [PubMed] [DOI]|
|207.||Bisogno G, Errigo G, Rossetti F, Sainati L, Pusiol A, Da Dalt L, Colleselli P, Grotto P, Carli M. The role of Helicobacter pylori in children with chronic idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 2008;30:53-57. [PubMed] [DOI]|
|208.||Treepongkaruna S, Sirachainan N, Kanjanapongkul S, Winaichatsak A, Sirithorn S, Sumritsopak R, Chuansumrit A. Absence of platelet recovery following Helicobacter pylori eradication in childhood chronic idiopathic thrombocytopenic purpura: a multi-center randomized controlled trial. Pediatr Blood Cancer. 2009;53:72-77. [PubMed] [DOI]|
|209.||Veres G, Karóczkai I, Bodánszky H, Marosi A, Magyarossi E, Dezsofi A, Arató A. [The role of Helicobacter pylori infection in children with chronic immune thrombocytopenic purpura]. Orv Hetil. 2009;150:801-804. [PubMed] [DOI]|
|210.||Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115:168-186. [PubMed] [DOI]|
|211.||Franchini M, Cruciani M, Mengoli C, Pizzolo G, Veneri D. Effect of Helicobacter pylori eradication on platelet count in idiopathic thrombocytopenic purpura: a systematic review and meta-analysis. J Antimicrob Chemother. 2007;60:237-246. [PubMed] [DOI]|
|212.||Stasi R, Sarpatwari A, Segal JB, Osborn J, Evangelista ML, Cooper N, Provan D, Newland A, Amadori S, Bussel JB. Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systematic review. Blood. 2009;113:1231-1240. [PubMed] [DOI]|
|213.||Arnold DM, Bernotas A, Nazi I, Stasi R, Kuwana M, Liu Y, Kelton JG, Crowther MA. Platelet count response to H. pylori treatment in patients with immune thrombocytopenic purpura with and without H. pylori infection: a systematic review. Haematologica. 2009;94:850-856. [PubMed] [DOI]|
|214.||Wotherspoon AC. Which lessons can be drawn from study of Helicobacter pylori related MALT lymphoma? Helicobacter pylori Basic mechanims to clinical cure 2002. Dordrecht, The Netherlands: Kluwer Academic Publishers 2002; 231-239.|
|215.||Isaacson PG, Spencer J, Finn T. Primary B-cell gastric lymphoma. Hum Pathol. 1986;17:72-82. [PubMed] [DOI]|
|216.||Claviez A, Meyer U, Dominick C, Beck JF, Rister M, Tiemann M. MALT lymphoma in children: a report from the NHL-BFM Study Group. Pediatr Blood Cancer. 2006;47:210-214. [PubMed] [DOI]|
|217.||Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD. The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997. Ann Oncol. 1999;10:1419-1432. [PubMed] [DOI]|
|218.||Isaacson P, Wright DH. Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma. Cancer. 1983;52:1410-1416. [PubMed]|
|219.||Wotherspoon AC, Ortiz-Hidalgo C, Falzon MR, Isaacson PG. Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet. 1991;338:1175-1176. [PubMed] [DOI]|
|220.||Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni M, Isaacson PG. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet. 1993;342:575-577. [PubMed] [DOI]|
|221.||Isaacson PG, Diss TC, Wotherspoon AC, Barbazza R, De Boni M, Doglioni C. Long-term follow-up of gastric MALT lymphoma treated by eradication of H. pylori with antibodies. Gastroenterology. 1999;117:750-751. [PubMed] [DOI]|
|222.||Wyatt JI, Rathbone BJ. Immune response of the gastric mucosa to Campylobacter pylori. Scand J Gastroenterol Suppl. 1988;142:44-49. [PubMed] [DOI]|
|223.||Stolte M, Eidt S. Lymphoid follicles in antral mucosa: immune response to Campylobacter pylori? J Clin Pathol. 1989;42:1269-1271. [PubMed] [DOI]|
|224.||Genta RM, Hamner HW, Graham DY. Gastric lymphoid follicles in Helicobacter pylori infection: frequency, distribution, and response to triple therapy. Hum Pathol. 1993;24:577-583. [PubMed] [DOI]|
|225.||Stolte M. Helicobacter pylori gastritis and gastric MALT-lymphoma. Lancet. 1992;339:745-746. [PubMed] [DOI]|
|226.||Correa P. Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 1992;52:6735-6740. [PubMed]|
|227.||Correa P. The biological model of gastric carcinogenesis. IARC Sci Publ. 2004;301-310. [PubMed]|
|228.||Nardone G, Rocco A, Malfertheiner P. Review article: helicobacter pylori and molecular events in precancerous gastric lesions. Aliment Pharmacol Ther. 2004;20:261-270. [PubMed] [DOI]|
|229.||Crowe SE. Helicobacter infection, chronic inflammation, and the development of malignancy. Curr Opin Gastroenterol. 2005;21:32-38. [PubMed]|
|230.||Ando T, Goto Y, Maeda O, Watanabe O, Ishiguro K, Goto H. Causal role of Helicobacter pylori infection in gastric cancer. World J Gastroenterol. 2006;12:181-186. [PubMed]|
|231.||Ito M, Tanaka S, Kamada T, Haruma K, Chayama K. Causal role of Helicobacter pylori infection and eradication therapy in gastric carcinogenesis. World J Gastroenterol. 2006;12:10-16. [PubMed]|
|232.||Matysiak-Budnik T, Mégraud F. Helicobacter pylori infection and gastric cancer. Eur J Cancer. 2006;42:708-716. [PubMed] [DOI]|
|233.||Peek RM, Crabtree JE. Helicobacter infection and gastric neoplasia. J Pathol. 2006;208:233-248. [PubMed] [DOI]|
|234.||Tsuji S, Tsujii M, Murata H, Nishida T, Komori M, Yasumaru M, Ishii S, Sasayama Y, Kawano S, Hayashi N. Helicobacter pylori eradication to prevent gastric cancer: underlying molecular and cellular mechanisms. World J Gastroenterol. 2006;12:1671-1680. [PubMed]|
|235.||Hussell T, Isaacson PG, Crabtree JE, Spencer J. The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue to Helicobacter pylori. Lancet. 1993;342:571-574. [PubMed] [DOI]|
|236.||Witherell HL, Hansen S, Jellum E, Orentreich N, Vogelman JH, Parsonnet J. Risk for gastric lymphoma in persons with CagA+ and CagA- Helicobacter pylori infection. J Infect Dis. 1997;176:1641-1644. [PubMed] [DOI]|
|237.||Peng H, Ranaldi R, Diss TC, Isaacson PG, Bearzi I, Pan L. High frequency of CagA+ Helicobacter pylori infection in high-grade gastric MALT B-cell lymphomas. J Pathol. 1998;185:409-412. [PubMed]|
|238.||Morgner A, Bayerdörffer E, Neubauer A, Stolte M. Gastric MALT lymphoma and its relationship to Helicobacter pylori infection: management and pathogenesis of the disease. Microsc Res Tech. 2000;48:349-356. [PubMed]|
|239.||Nardone G, Morgner A. Helicobacter pylori and gastric malignancies. Helicobacter. 2003;8 Suppl 1:44-52. [PubMed] [DOI]|
|240.||Müller AM, Ihorst G, Mertelsmann R, Engelhardt M. Epidemiology of non-Hodgkin’s lymphoma (NHL): trends, geographic distribution, and etiology. Ann Hematol. 2005;84:1-12. [PubMed] [DOI]|
|241.||Isaacson PG. Gastric MALT lymphoma: from concept to cure. Ann Oncol. 1999;10:637-645. [PubMed]|
|242.||Minasian MC, Sharma A, Richman PI, Olver JM. Conjunctival MALT lymphoma: an usual cause of red eye. Postgrad Med J. 1999;75:423-424. [PubMed]|
|243.||Chan CC, Smith JA, Shen DF, Ursea R, LeHoang P, Grossniklaus HE. Helicobacter pylori (H. pylori) molecular signature in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma. Histol Histopathol. 2004;19:1219-1226. [PubMed]|
|244.||Nagashima R, Takeda H, Maeda K, Ohno S, Takahashi T. Regression of duodenal mucosa-associated lymphoid tissue lymphoma after eradication of Helicobacter pylori. Gastroenterology. 1996;111:1674-1678. [PubMed] [DOI]|
|245.||Fischbach W, Tacke W, Greiner A, Konrad H. Regression of immunoproliferative small intestinal disease after eradication of Helicobacter pylori. Lancet. 1997;349:31-32. [PubMed] [DOI]|
|246.||Ochi M, Tominaga K, Okazaki H, Yamamori K, Wada T, Shiba M, Sasaki E, Watanabe T, Fujiwara Y, Oshitani N. Regression of primary low-grade mucosa-associated lymphoid tissue lymphoma of duodenum after long-term treatment with clarithromycin. Scand J Gastroenterol. 2006;41:365-369. [PubMed] [DOI]|
|247.||Alkan S, Karcher DS, Newman MA, Cohen P. Regression of salivary gland MALT lymphoma after treatment for Helicobacter pylori. Lancet. 1996;348:268-269. [PubMed] [DOI]|
|248.||Berrebi D, Lescoeur B, Faye A, Faure C, Vilmer E, Peuchmaur M. MALT lymphoma of labial minor salivary gland in an immunocompetent child with a gastric Helicobacter pylori infection. J Pediatr. 1998;133:290-292. [PubMed] [DOI]|
|249.||Nishimura M, Miyajima S, Okada N. Salivary gland MALT lymphoma associated with Helicobacter pylori infection in a patient with Sjögren’s Syndrome. J Dermatol. 2000;27:450-452. [PubMed]|
|250.||Kania RE, Hartl DM, Badoual C, Le Maignan C, Brasnu DF. Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the larynx. Head Neck. 2005;27:258-262. [PubMed] [DOI]|
|251.||Gupte S, Nair R, Naresh KN, Borges AM, Soman CS, Gopal R, Advani SH. MALT lymphoma of nasal mucosa treated with antibiotics. Leuk Lymphoma. 1999;36:195-197. [PubMed] [DOI]|
|252.||Kawashima T, Nishimura H, Akiyama H, Hirai K, Yamagishi S, Okada D, Kinoshita H, Enomoto Y, Okamoto J, Nakajima Y. Primary pulmonary mucosa-associated lymphoid tissue lymphoma combined with idiopathic thrombocytopenic purpura and amyloidoma in the lung. J Nippon Med Sch. 2005;72:370-374. [PubMed] [DOI]|
|253.||Matsumoto T, Iida M, Shimizu M. Regression of mucosa-associated lymphoid-tissue lymphoma of rectum after eradication of Helicobacter pylori. Lancet. 1997;350:115-116. [PubMed] [DOI]|
|254.||Inoue F, Chiba T. Regression of MALT lymphoma of the rectum after anti-H. pylori therapy in a patient negative for H. pylori. Gastroenterology. 1999;117:514-515. [PubMed] [DOI]|
|255.||Colović M, Hadzi-Djokić J, Cemerikić V, Colović R, Janković G, Dacić M. Primary MALT lymphoma of the kidney. Hematol Cell Ther. 1999;41:229-232. [PubMed] [DOI]|
|256.||van den Bosch J, Kropman RF, Blok P, Wijermans PW. Disappearance of a mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder after treatment for Helicobacter pylori. Eur J Haematol. 2002;68:187-188. [PubMed] [DOI]|
|257.||Kröber SM, Aepinus C, Ruck P, Müller-Hermelink HK, Horny HP, Kaiserling E. Extranodal marginal zone B cell lymphoma of MALT type involving the mucosa of both the urinary bladder and stomach. J Clin Pathol. 2002;55:554-557. [PubMed] [DOI]|
|258.||Keung YK, Higgs V, Albertson DA, Cappellari JO. Mucosa-associated lymhpoid tissue (MALT) lymphoma of the jejunum and Helicobacter pylori--chance association? Leuk Lymphoma. 2003;44:1413-1416. [PubMed] [DOI]|
|259.||Shehab TM, Hsi ED, Poterucha JJ, Gunaratnam NT, Fontana RJ. Helicobacter pylori-associated gastric MALT lymphoma in liver transplant recipients. Transplantation. 2001;71:1172-1175. [PubMed] [DOI]|
|260.||Boissonnat P, El Bekkali Y, Salles G, Dumortier J, Roussoulieres A, Sebbag L, Gare J, Robin J, Ninet J, Bastien O. Regression of gastric lymphoma of mucosa associated with lymphoid tissue (MALT) following cardiac transplantation. J Heart Lung Transplant. 2002;21:1044-1045. [PubMed] [DOI]|
|261.||Montalban C, Manzanal A, Boixeda D, Redondo C, Alvarez I, Calleja JL, Bellas C. Helicobacter pylori eradication for the treatment of low-grade gastric MALT lymphoma: follow-up together with sequential molecular studies. Ann Oncol. 1997;8 Suppl 2:37-39. [PubMed] [DOI]|
|262.||Wündisch T, Mösch C, Neubauer A, Stolte M. Helicobacter pylori eradication in gastric mucosa-associated lymphoid tissue lymphoma: Results of a 196-patient series. Leuk Lymphoma. 2006;47:2110-2114. [PubMed] [DOI]|
|263.||Gupta V, Eden AJ, Mills MJ. Helicobacter pylori and autoimmune neutropenia. Clin Lab Haematol. 2002;24:183-185. [PubMed] [DOI]|
|264.||Papadaki HA, Pontikoglou C, Stavroulaki E, Minadakis G, Eliopoulos DA, Pyrovolaki K, Skordilis P, Eliopoulos GD. High prevalence of Helicobacter pylori infection and monoclonal gammopathy of undetermined significance in patients with chronic idiopathic neutropenia. Ann Hematol. 2005;84:317-320. [PubMed] [DOI]|
|265.||Papadaki HA, Pontikoglou C, Eliopoulos DG, Pyrovolaki K, Spyridaki R, Eliopoulos GD. Helicobacter pylori infection is probably the cause of chronic idiopathic neutropenia (CIN)-associated splenomegaly. Am J Hematol. 2006;81:142-144. [PubMed] [DOI]|
|266.||Lim W, Crowther MA, Eikelboom JW. Management of antiphospholipid antibody syndrome: a systematic review. JAMA. 2006;295:1050-1057. [PubMed] [DOI]|
|267.||Cicconi V, Carloni E, Franceschi F, Nocente R, Silveri NG, Manna R, Servidei S, Bentivoglio AR, Gasbarrini A, Gasbarrini G. Disappearance of antiphospholipid antibodies syndrome after Helicobacter pylori eradication. Am J Med. 2001;111:163-164. [PubMed] [DOI]|
|268.||Stasi R, Stipa E, Masi M, Oliva F, Sciarra A, Perrotti A, Olivieri M, Zaccari G, Gandolfo GM, Galli M. Prevalence and clinical significance of elevated antiphospholipid antibodies in patients with idiopathic thrombocytopenic purpura. Blood. 1994;84:4203-4208. [PubMed]|
|269.||Lipp E, von Felten A, Sax H, Müller D, Berchtold P. Antibodies against platelet glycoproteins and antiphospholipid antibodies in autoimmune thrombocytopenia. Eur J Haematol. 1998;60:283-288. [PubMed] [DOI]|
|270.||Macchi L, Rispal P, Clofent-Sanchez G, Pellegrin JL, Nurden P, Leng B, Nurden AT. Anti-platelet antibodies in patients with systemic lupus erythematosus and the primary antiphospholipid antibody syndrome: their relationship with the observed thrombocytopenia. Br J Haematol. 1997;98:336-341. [PubMed] [DOI]|
|271.||Costen MT, Parkin BT, Davison CR, Crick MP. Central serous chorioretinopathy and antiphospholipid antibodies--results of a pilot study. Eye (Lond). 2004;18:938. [PubMed] [DOI]|
|272.||Cotticelli L, Borrelli M, D’Alessio AC, Menzione M, Villani A, Piccolo G, Montella F, Iovene MR, Romano M. Central serous chorioretinopathy and Helicobacter pylori. Eur J Ophthalmol. 2006;16:274-278. [PubMed]|
|273.||International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003;121:749-757. [PubMed] [DOI]|
|274.||Osler W, McRae T. Diseases of the stomach. The principles and practice of medicine. New York: Appleton 1920; 425.|
|275.||Twomey JJ, Laughter AH, Villanueva ND, Kao YS, Lidsky MD, Jordan PH. Gastric secretory and serologic studies on patients with neoplastic and immunologic disorders. Arch Intern Med. 1971;128:746-749. [PubMed] [DOI]|
|276.||Doberauer C, Sanner B, Henning B. Multiple myeloma involving the stomach with vitamin B12 deficiency. Eur J Gastroenterol Hepatol. 1999;11:205-207. [PubMed] [DOI]|
|277.||Chanarin I. The megaloblastic aenemias. 2nd ed. Oxford: Blackell Scientific Pubications 1979; .|
|278.||Elsborg L, Mosbech J. Pernicious anaemia as a risk factor in gastric cancer. Acta Med Scand. 1979;206:315-318. [PubMed] [DOI]|
|279.||Borch K. Epidemiologic, clinicopathologic, and economic aspects of gastroscopic screening of patients with pernicious anemia. Scand J Gastroenterol. 1986;21:21-30. [PubMed] [DOI]|
|280.||Hsing AW, Hansson LE, McLaughlin JK, Nyren O, Blot WJ, Ekbom A, Fraumeni JF. Pernicious anemia and subsequent cancer. A population-based cohort study. Cancer. 1993;71:745-750. [PubMed]|
|281.||Carmel R. Megaloblastic anemias: disorders of impaired DNA synthesis. Wintrobe’s Clinical Hema-tology. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins 2004; 1367-1395.|
|282.||Goyal A, Langer JC, Zutter M, Swanson P, Kraus MD, Bartlett N, Shackelford GD, Longtine JA, Perlmutter DH. Primary gastric plasmacytoma: a rare cause of hypertrophic gastritis in an adolescent. J Pediatr Gastroenterol Nutr. 1999;29:424-430. [PubMed] [DOI]|
|283.||Ahmad A, Govil Y, Frank BB. Gastric mucosa-associated lymphoid tissue lymphoma. Am J Gastroenterol. 2003;98:975-986. [PubMed] [DOI]|
|284.||Gonzalez Cueto D, Bruno S, Bustos Fernandez LM, Narbaitz M. [Gastric solitary plasmacytoma associated with +Helicobacter pylori infection]. Acta Gastroenterol Latinoam. 1999;29:119-123. [PubMed]|
|285.||Kato K, Sugitani M, Nagata T, Nishinarita S, Kawamura F, Takahashi Y, Ishii Y, Kawamura Y, Komuro S, Yanai M. A case of gastric plasmacytoma associated with Helicobacter pylori infection: improvement of abnormal endoscopic and EUS findings after H. pylori eradication. Gastrointest Endosc. 2001;53:352-355. [PubMed]|
|286.||Papadaki HA, Skordilis P, Minadakis G, Roussomoustakaki M, Katrinakis G, Psyllaki M, Tzardi M, Kouroumalis E, Eliopoulos GD. Complete regression of primary gastric plasmacytoma following Helicobacter pylori eradication. Ann Hematol. 2003;82:589-592. [PubMed] [DOI]|
|287.||Tursi A, Modeo ME. Monoclonal gammopathy of undetermined significance predisposing to Helicobacter pylori-related gastric mucosa-associated lymphoid tissue lymphoma. J Clin Gastroenterol. 2002;34:147-149. [PubMed] [DOI]|
|288.||Braggio E, Fonseca R. Genomic abnormalities of Waldenström macroglobulinemia and related low-grade B-cell lymphomas. Clin Lymphoma Myeloma Leuk. 2013;13:198-201. [PubMed] [DOI]|
|289.||Feingold ML, Goldstein MJ, Lieberman PH. Multiple myeloma involving the stomach. Report of a case with gastroscopic observations. Gastrointest Endosc. 1969;16:107-110. [PubMed]|
|290.||Kyle RA, Pierre RV, Bayrd ED. Multiple myeloma and acute myelomonocytic leukemia. N Engl J Med. 1970;283:1121-1125. [PubMed] [DOI]|
|291.||Law IP, Blom J. Second malignancies in patients with multiple myeloma. Oncology. 1977;34:20-24. [PubMed] [DOI]|
|292.||Bergsagel DE, Bailey AJ, Langley GR, MacDonald RN, White DF, Miller AB. The chemotherapy on plasma-cell myeloma and the incidence of acute leukemia. N Engl J Med. 1979;301:743-748. [PubMed] [DOI]|
|293.||Nelson RS. Tumores malignos del estómago distintos del carcinoma. Gastroenterología Henry Bockus. 3rd ed. Barcelona, España: Salvat Editores 1980; 1058-1078.|
|294.||Brouet JC, Fermand JP, Laurent G, Grange MJ, Chevalier A, Jacquillat C, Seligmann M. The association of chronic lymphocytic leukaemia and multiple myeloma: a study of eleven patients. Br J Haematol. 1985;59:55-66. [PubMed] [DOI]|
|295.||Kaufmann H, Ackermann J, Nösslinger T, Krömer E, Zojer N, Schreiber S, Urbauer E, Heinz R, Ludwig H, Huber H. Absence of clonal chromosomal relationship between concomitant B-CLL and multiple myeloma--a report on two cases. Ann Hematol. 2001;80:474-478. [PubMed] [DOI]|
|296.||Wöhrer S, Isaacson PG, Raderer M. Complete regression of primary gastric plasmacytoma following Helicobacter pylori eradication. Ann Hematol. 2004;83:666. [PubMed] [DOI]|
|297.||Wöhrer S, Raderer M, Streubel B, Chott A, Drach J. Concomitant occurrence of MALT lymphoma and multiple myeloma. Ann Hematol. 2004;83:600-603. [PubMed] [DOI]|
|298.||Malik AA, Ganti AK, Potti A, Levitt R, Hanley JF. Role of Helicobacter pylori infection in the incidence and clinical course of monoclonal gammopathy of undetermined significance. Am J Gastroenterol. 2002;97:1371-1374. [PubMed] [DOI]|
|299.||Wolkersdörfer GW, Haase M, Morgner A, Baretton G, Miehlke S. Monoclonal gammopathy of undetermined significance and Russell body formation in Helicobacter pylori gastritis. Helicobacter. 2006;11:506-510. [PubMed] [DOI]|
|300.||Rajkumar SV, Kyle RA, Plevak MF, Murray JA, Therneau TM. Helicobacter pylori infection and monoclonal gammopathy of undetermined significance. Br J Haematol. 2002;119:706-708. [PubMed] [DOI]|
|301.||Gok F, Ugur Y, Ozen S, Dagdeviren A. Pathogenesis-related adhesion molecules in Henoch-Schonlein vasculitis. Rheumatol Int. 2008;28:313-316. [PubMed] [DOI]|
|302.||Reinauer S, Megahed M, Goerz G, Ruzicka T, Borchard F, Susanto F, Reinauer H. Schönlein-Henoch purpura associated with gastric Helicobacter pylori infection. J Am Acad Dermatol. 1995;33:876-879. [PubMed] [DOI]|
|303.||Cecchi R, Torelli E. Schönlein-Henoch purpura in association with duodenal ulcer and gastric Helicobacter pylori infection. J Dermatol. 1998;25:482-484. [PubMed]|
|304.||Novák J, Szekanecz Z, Sebesi J, Takáts A, Demeter P, Bene L, Sipka S, Csiki Z. Elevated levels of anti-Helicobacter pylori antibodies in Henoch-Schönlein purpura. Autoimmunity. 2003;36:307-311. [PubMed] [DOI]|
|305.||Fu KI, Yagi S, Mashimo Y, Sugitani K, Imamaki K, Yanagisawa M, Maekawa S, Morimoto Y, Fujimori T. Regression of Helicobacter pylori-negative duodenal ulcers complicated by Schonlein-Henoch purpura with H. pylori eradication therapy: the first report. Dig Dis Sci. 2005;50:381-384. [PubMed] [DOI]|
|306.||Mytinger JR, Patterson JW, Thibault ES, Webb J, Saulsbury FT. Henoch-Schönlein purpura associated with Helicobacter pylori infection in a child. Pediatr Dermatol. 2008;25:630-632. [PubMed] [DOI]|
|307.||Grivceva-Panovska V, Grivceva Stardelova K, Serafimoski V. Henoch-Schönlein purpura in an adult patient: extragastric, cutaneous manifestation of helicobacter pylori infection. Prilozi. 2008;29:291-301. [PubMed]|
|308.||Hoshino C. Adult onset Schönlein-Henoch purpura associated with Helicobacter pylori infection. Intern Med. 2009;48:847-851. [PubMed] [DOI]|
|309.||Mozrzymas R, d’Amore ES, Montini G, Guariso G. Schönlein-Henoch vasculitis and chronic Helicobacter pylori associated gastritis and duodenal ulcer: a case report. Pediatr Med Chir. 1997;19:467-468. [PubMed]|
|310.||Shin JI, Koh H, Lee JS. Henoch-Schönlein purpura associated with helicobacter pylori infection: the pathogenic roles of IgA, C3, and cryoglobulins? Pediatr Dermatol. 2009;26:768-769. [PubMed] [DOI]|
|311.||Lehtinen M, Ogmundsdottir HM, Bloigu A, Hakulinen T, Hemminki E, Gudnadottir M, Kjartansdottir A, Paavonen J, Pukkala E, Tulinius H. Associations between three types of maternal bacterial infection and risk of leukemia in the offspring. Am J Epidemiol. 2005;162:662-667. [PubMed] [DOI]|
|312.||Diamantidis MD, Ioannidou-Papagiannaki E, Kountouras J, Mandala E, Tsapournas G, Frida-Michailidou I, Klonizakis P, Zavos C, Haralambidou-Vranitsa S, Vlachaki E. High prevalence of Helicobacter pylori infection in Greek patients with myelodysplastic syndromes. Acta Haematol. 2010;124:141-149. [PubMed] [DOI]|
|313.||Kawamata T, Tojo A. Helicobacter pylori-induced thrombocytosis clinically indistinguishable from essential thrombocythemia. Leuk Lymphoma. 2012;53:1423-1424. [PubMed] [DOI]|
|314.||Fioredda F, Haupt R, Castagnola E, Barabino A, Micalizzi C, Dini G, Dufour C. Helicobacter pylori-associated large gastric ulcer during treatment for childhood leukemia. J Pediatr Hematol Oncol. 2002;24:759-762. [PubMed] [DOI]|
|315.||Dolatkhah R, Khoshbaten M, Asvadi Kermani I, Reza Bonyadi M, Ghojazadeh M, Sanaat Z, Asvadi Kermani T, Dolatkhah N. Upper gastrointestinal bleedings in patients with hereditary coagulation disorders in Northwest of Iran: prevalence of Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 2011;23:1172-1177. [PubMed] [DOI]|
|316.||Schulman S, Rehnberg AS, Hein M, Hegedus O, Lindmarker P, Hellström PM. Helicobacter pylori causes gastrointestinal hemorrhage in patients with congenital bleeding disorders. Thromb Haemost. 2003;89:741-746. [PubMed]|
|317.||Braden B, Wenke A, Karich HJ, Dietrich CF, Scharrer I, Caspary WF, Lembcke B. Risk of gastrointestinal bleeding associated with Helicobacter pylori infection in patients with hemophilia or von Willebrand’s syndrome. Helicobacter. 1998;3:184-187. [PubMed] [DOI]|
|318.||Tincani E, Bertoni G, Silingardi M, Ghirarduzzi A, Bedogni G, Iori I. Helicobacter pylori, a frequent and potentially dangerous guest in the gastroduodenal mucosa of anticoagulated patients. Am J Med. 2000;108:165-167. [PubMed] [DOI]|
|319.||Beswick EJ, Suarez G, Reyes VE. H pylori and host interactions that influence pathogenesis. World J Gastroenterol. 2006;12:5599-5605. [PubMed]|
|320.||Carmel R. Megaloblastic anemias: disorders of impaired DNA synthesis. Wintrobe’s Clinical Hematology. 13 ed. Philadelphia, PA: Lippincott Williams & Wilkins 2013; 927-953.|
|321.||Karpatkin S. Autoimmune (idiopathic) thrombocytopenic purpura. Lancet. 1997;349:1531-1536. [PubMed] [DOI]|
|322.||Shiu MH, Karas M, Nisce L, Lee BJ, Filippa DA, Lieberman PH. Management of primary gastric lymphoma. Ann Surg. 1982;195:196-202. [PubMed] [DOI]|