Hematologic manifestations of Helicobacter pylori infection

Table 1 Hematological manifestation of Helicobacter pylori infection

Recognized as extragastric manifestation

Iron deficiency[19-28]

Vitamin B12 (cobalamina) deficiency[25,27]

Immune thrombocytopenia[19,21-28]

Gastric MALT lymphoma[19-37]

Unrecognized as extragastric manifestation

Autoimmune neutropenia[263-265]

Antiphospholipid syndrome[267]

Plasma cell dyscrasias[284-286]

Schöenlein-Henoch purpura[302-310]

Other hematologic manifestation (childhood leukemia[311], myelo dysplastic syndrome[312], thrombocytosis[313])

MALT: Mucosa-associated lymphoid tissue.

Table 2 Association between immune thrombocytopenia and Helicobacter pylori infection in adults n (%)

Ref.	Year	Country	Patients with ITP	H. pylori-infected ITP patients	Treated patients	H. pylori-eradicated patients	Patients with platelet response
Gasbarrini et al[154]	1998	Italy	18	11 (61.1)	11	8 (72.7)	8 (100)
Emilia et al[155]	2001	Italy	30	13 (43.3)	13	12 (92.3)	6 (50.0)
Emilia et al[156]	2002	Italy	7	3 (42.9)	3	3 (100)	2 (66.7)
Veneri et al[157]	2002	Italy	35	25 (71.4)	16	15 (93.8)	11 (73.3)
Veneri et al[158]	2005	Italy	43	43 (100)	43	41 (95.3)	20 (48.8)
Stasi et al[159]	2005	Italy	137	64 (46.7)	52	52 (100)	17 (32.7)
Suvajdzic et al[162]	2006	Serbia	54	39 (72.2)	30	23 (76.7)	6 (26.1)
Sayan[161]	2006	Turkey	34	20 (58.8)	20	18 (90.0)	8 (44.0)
Emilia et al[160]	2007	Italy	75	38 (50.7)	38	34 (89.5)	23 (67.6)
Scandellari et al[204]	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[163]	2002	Japan	40	25 (62.5)	19	19 (100)	12 (63.2)
Kohda et al[164]	2003	Japan	51	31 (60.8)	26	24 (92.3)	14 (58.3)
Ando et al[165]	2003	Japan	61	50 (82.0)	29	27 (93.1)	13 (48.1)
Hashino et al[166]	2003	Japan	22	14 (63.6)	14	13 (92.9)	5 (38.5)
Hino et al[167]	2003	Japan	30	21 (70.0)	21	18 (85.7)	10 (55.6)
Kato et al[168]	2004	Japan	20	20 (100)	20	17 (85.0)	11 (64.7)
Ando et al[169]	2004	Japan	20	17 (85.0)	17	15 (88.2)	10 (66.7)
Nomura et al[170]	2004	Japan	42	28 (66.7)	28	28 (100)	15 (53.6)
Sato et al[171]	2004	Japan	53	39 (73.6)	32	27 (84.4)	15 (55.6)
Takahashi et al[172]	2004	Japan	20	15 (75.0)	15	13 (86.7)	7 (53.8)
Fujimura et al[173]	2005	Japan	435	300 (69.0)	228	161 (70.6)	101 (62.7)
Inaba et al[174]	2005	Japan	35	25 (71.4)	25	25 (100)	11 (44.0)
Tsutsumi[175]	2005	Japan	25	17 (68.0)	9	9 (100)	6 (66.7)
Suzuki et al[176]	2005	Japan	36	25 (69.4)	13	11 (84.6)	6 (54.5)
Asahi et al[177]	2006	Japan	37	26 (70.3)	26	26 (100)	16 (61.5)
Ishiyama et al[178]	2006	Japan	14	14 (100)	14	14 (100)	8 (57.1)
Satake et al[179]	2007	Japan	38	26 (68.4)	26	23 (88.5)	13 (56.5)
Kodama et al[180]	2007	Japan	116	67 (57.8)	52	44 (84.6)	27 (61.4)
Kong et al[186]	2008	China	31	31 (100)	31	31 (100)	23 (74.2)
Rostami et al[188]	2008	Iran	129	79 (61.2)	71	62 (87.3)	30 (48.4)
Asahi et al[181]	2008	Japan	34	23 (67.6)	23	23 (100)	14 (60.9)
Suzuki et al[182]	2008	Japan	36	36 (100)	36	31 (86.1)	20 (64.5)
Wu et al[187]	2009	Chine	31	31 (100)	31	31 (100)	21 (67.7)
Tsumoto et al[183]	2009	Japan	30	21 (70.0)	21	20 (95.2)	10 (50.0)
Tag et al[190]	2010	South Korea	25	23 (92.0)	23	23 (100)	11 (47.8)
Sato et al[184]	2011	Japan	31	31 (100)	31	31 (100)	18 (58.1)
Kikuchi et al[185]	2011	Japan	31	19 (61.3)	19	19 (100)	10 (52.6)
Payandeh et al[189]	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[191]	2007	Colombia	32	29 (90.6)	29	26 (89.7)	21 (80.8)
Jackson et al[192]	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)

H. pylori: Helicobacter pylori; ITP: Immune thrombocytopenic purpura.

Table 3 Association between immune thrombocytopenia and Helicobacter pylori infection in children n (%)

Ref.	Year	Country	Patients with ITP	H. pylori-infected ITP patients	Treated patients	H. pylori-eradicated patients	Patients with platelet response
Rajantie et al[200]	2003	Finland	17	9 (52.9)	9	9 (100)	5 (55.6)
Neefjes et al[201]	2007	Netherlands	47	3 (6.4)	3	3 (100)	3 (100)
Ferrara et al[202]	2009	Italy	24	8 (33.3)	8	8 (100)	8 (100)
Russo et al[203]	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[197]	2003	Taiwan	22	9 (40.9)	9	9 (100)	5 (55.6)
Hayashi et al[198]	2005	Japan	10	2 (20.0)	2	1 (50.0)	1 (100)
Hamidieh et al[199]	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)

H. pylori: Helicobacter pylori; ITP: Immune thrombocytopenic purpura.

Table 4 Paradigm changes in the management of hematologic diseases related to Helicobacter pylori infection and its medical and social impact

Disease	Accepted paradigm	New paradigm	Medical and social impact
Iron deficiency1	The management of ID is palliative and is based on iron supplementation[38], but it often does not treat the immediate cause of ID[41]	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[38]. It also reduces the prevalence of H. pylori infection and associated diseases such as gastric cancer[4], and peptic acid disease[3]
Vitamin B12 deficiency2	Vitamin B12 deficiency management is palliative and is based on the supplementation of vitamin[38], but often it does not treat the underlying cause of deficiency of vitamin B12[320]	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[131] associated with chronic disease[38]. These include the closely related gastric cancer and diverse diseases such as Alzheimer's disease[108,109], dementia[110,111], depression[112], cerebral stroke[113,114] pulmonary embolism[115,116], acute myocardial infarction and coronary heart disease[117]. 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[38] and non-curative and palliative treatment[131]. 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[322]	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[38], with non-curative and palliative treatment[322]. This change transforms a neoplastic disease with difficult and expensive management into an infectious disease with an excellent prognosis and low treatment cost[323]

¹With or without anemia;

²Cobalamine;

³Previously called idiopathic thrombocytopenic purpura and autoimmune thrombocytopenic purpura[138]. H. pylori: Helicobacter pylori; ITP: Immune thrombocytopenic purpura; MALT: Mucosa-associated lymphoid tissue.