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Iglay K, Aldridge ML, Calcinai M, Wolford E, Ashrani AA. The global epidemiology of acquired factor X deficiency. Hematology 2025; 30:2476254. [PMID: 40151020 DOI: 10.1080/16078454.2025.2476254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 03/03/2025] [Indexed: 03/29/2025] Open
Abstract
OBJECTIVES To summarize available data and contribute to a broader understanding of the global incidence and prevalence of acquired factor X deficiency. METHODS A comprehensive review of English-language publications from PubMed and Embase was conducted. The majority of publications on acquired factor X deficiency were associated with light-chain (AL) amyloidosis. Therefore, this review is structured to assess publications reporting on (1) acquired factor X deficiency associated with AL amyloidosis or (2) acquired factor X deficiency associated with other causes. RESULTS The literature includes case reports, case-series, and limited population-based reports of the epidemiology of acquired factor X deficiency. Though no definitive global incidence or prevalence estimates for AL-amyloidosis-associated acquired factor X deficiency were identified, the finding that roughly 6-14% of patients with AL amyloidosis have factor X activity levels below 45-50% of normal highlights the rarity of acquired factor X deficiency associated with AL-amyloidosis. Indeed, AL amyloidosis itself is a rare disorder with an estimated annual incidence of ∼10 cases per million population. Only case reports were available to inform the epidemiology of acquired factor X deficiency not associated with AL amyloidosis. We identified 35 cases from 29 papers published from around the globe. At least 25 of those patients experienced a bleeding event, with factor X activity levels ranging from <1% to 39%. CONCLUSION More population-based data are needed to understand the epidemiology of acquired factor X deficiency; however, the limited data seem to indicate this condition is quite rare. The variation across papers in thresholds used to define deficiency highlights the need for a standardized definition to better inform drug development, resource allocation, and regulatory decision-making.
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Affiliation(s)
- Kristy Iglay
- Real-world Evidence and Patient Outcomes, CERobs Consulting, LLC, Wrightsville Beach, NC, USA
| | - Molly L Aldridge
- Real-world Evidence and Patient Outcomes, CERobs Consulting, LLC, Wrightsville Beach, NC, USA
| | | | - Eric Wolford
- Clinical Development, Kedrion Biopharma, Inc., Durham, NC, USA
| | - Aneel A Ashrani
- Division of Hematology, Department of Internal Medicine, Mayo Clinic-Rochester, Rochester, MI, USA
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Muchtar E, Grogan M, Aus dem Siepen F, Waddington-Cruz M, Misumi Y, Carroll AS, Clarke JO, Sanchorawala V, Milani P, Caccialanza R, Da Prat V, Pruthi R, Quintana LF, Bridoux F. Supportive care for systemic amyloidosis: International Society of Amyloidosis (ISA) expert panel guidelines. Amyloid 2025; 32:93-116. [PMID: 39985185 DOI: 10.1080/13506129.2025.2463678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Revised: 01/25/2025] [Accepted: 02/02/2025] [Indexed: 02/24/2025]
Abstract
Systemic amyloidosis refers to a group of protein misfolding disorders resulting in organ deposition with amyloid, leading to organ dysfunction, ultimately resulting in organ failure and death if not successfully treated. Treatment is type-specific and aimed at the underlying source of the misfolded protein. In the past decades, treatments have become increasingly available across the various amyloidosis types with improved response rates and longer survival. Supportive care measures are an integral part of care for patients with systemic amyloidosis to improve symptom burden and quality of life, reduce healthcare costs, and potentially prolong survival while type-directed therapy takes effect. In these guidelines, we provide supportive care recommendations across eight areas of interest in systemic amyloidosis: cardiology, nephrology, peripheral neuropathy, central nervous system involvement, autonomic neuropathy, gastroenterology, coagulopathy and bleeding, nutrition and hematology. These guidelines were developed on behalf of the International Society of Amyloidosis (ISA) by experts in the above fields and provide the best available evidence and expertise for supportive care in these rare disorders.
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Affiliation(s)
- Eli Muchtar
- Division of Hematology, Mayo Clinic, Rochester, MN, USA
| | - Martha Grogan
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA
| | - Fabian Aus dem Siepen
- Department of Cardiology, Angiology and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany
| | - Marcia Waddington-Cruz
- National Amyloidosis Referral Center, CEPARM, University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Yohei Misumi
- Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Antonia S Carroll
- Faculty of Medicine and Health, Brain and Mind Centre, Translational Research Collective University of Sydney, Sydney, Australia
- Department of Neurology, Royal Prince Alfred Hospital, Sydney, Australia
- Department of Neurology and Neurophysiology, St. Vincent's Amyloidosis Centre, St. Vincent's Hospital, Sydney, Australia
| | - John O Clarke
- Division of Gastroenterology and Hepatology, Stanford University, Redwood City, CA, USA
| | - Vaishali Sanchorawala
- Amyloidosis Center, Boston University Chobanian and Avedisian School of Medicine, Boston Medical Center, Boston, MA, USA
| | - Paolo Milani
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
- Amyloidosis Research and Treatment Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo Pavia, Pavia, Italy
| | - Riccardo Caccialanza
- Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Valentina Da Prat
- Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Rajiv Pruthi
- Division of Hematology, Mayo Clinic, Rochester, MN, USA
| | - Luis F Quintana
- Amyloidosis and Myeloma Unit, Nephrology Department, National Reference Center on Complex Glomerular Disease (CSUR), Hospital Clínic de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Frank Bridoux
- Department of Nephrology, Centre Hospitalier Universitaire, National Reference Center for AL amyloidosis, MGCS and MGRS, Université de Poitiers, Poitiers, France
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3
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Hughes MS, Lentzsch S. Primary systemic amyloidosis: A brief overview. Presse Med 2025; 54:104267. [PMID: 39672504 DOI: 10.1016/j.lpm.2024.104267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 11/14/2024] [Indexed: 12/15/2024] Open
Abstract
Primary systemic amyloidosis, or light chain (AL) amyloidosis, is a rare lymphoproliferative disorder in which aberrant light-chain immunoglobulins secreted into the bloodstream aggregate into fibrils and deposit into tissues, causing widespread organ damage and, if not treated, death. This review provides a comprehensive summary of the pathophysiology and manifestations of AL amyloidosis; standard-of-care diagnostic approach; typical treatment regimens; and areas of active investigation.
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Affiliation(s)
- Michael Sang Hughes
- Department of Hematology/Oncology, Columbia University Irving Medical Center, 161 Fort Washington Avenue, 6GN-435, New York, NY 10032, United States of America.
| | - Suzanne Lentzsch
- Department of Hematology/Oncology, Columbia University Irving Medical Center, 161 Fort Washington Avenue, 6GN-435, New York, NY 10032, United States of America
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4
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Jeffrey S, Hamilton C, Ames PRJ. Acquired factor V and factor X Deficiency coexisting with acquired dysfibrinogenaemia in a patient with light chain myeloma. Blood Coagul Fibrinolysis 2024; 35:139-140. [PMID: 38358896 DOI: 10.1097/mbc.0000000000001280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2024]
Abstract
An elderly woman with light chain myeloma presented with prolonged epistaxis and extensive cutaneous haematomas: her kappa/lambda ratio was high at 395, her coagulation screen, thrombin and reptilase times were abnormal, her FV and FX were in the low range in the absence of specific inhibitors, her Clauss fibrinogen was low at 0.95 g/l but antigenic FNG was 1.58 g/l. The patient denied treatment and died of progressive renal failure. We wish to describe the unusual association of FX and FV deficiency co-existing with an acquired dysfibrinogenaemia.
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Affiliation(s)
| | | | - Paul R J Ames
- Dumfries & Galloway Royal Infirmary, Dumfries, UK
- Immune Response & Vascular Disease Unit, Universidade NOVA de Lisboa, Lisboa, Portugal
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Danesin N, Scapinello G, Del Prete D, Naso E, Berno T, Visentin A, Bonaldi L, Martines A, Bertorelle R, Vianello F, Gurrieri C, Zambello R, Castellani C, Fedrigo M, Rizzo S, Angelini A, Trentin L, Piazza F. When Waldenström macroglobulinemia hits the kidney: Description of a case series and management of a "rare in rare" scenario. Cancer Rep (Hoboken) 2024; 7:e2062. [PMID: 38662353 PMCID: PMC11044914 DOI: 10.1002/cnr2.2062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 02/29/2024] [Accepted: 03/09/2024] [Indexed: 04/26/2024] Open
Abstract
BACKGROUND Renal injury related to Waldenström macroglobulinemia (WM) occurs in approximately 3% of patients. Kidney biopsy is crucial to discriminate between distinct histopathological entities such as glomerular (amyloidotic and non-amyloidotic), tubulo-interstitial and non-paraprotein mediated renal damage. In this context, disease characterization, management, relationship between renal, and hematological response have been poorly explored. We collected clinical, genetic and laboratory data of seven cases of biopsy-proven renal involvement by WM managed at our academic center and focused on three cases we judged paradigmatic discussing their histopathological patterns, clinical features, and therapeutic options. CASE In this illustrative case series, we confirm that serum creatinine levels and 24 h proteinuria are parameters that when altered should prompt the clinical suspicion of WM-related renal involvement, even if at present there are not precise cut-off levels recommending the execution of a renal biopsy. In our series AL Amyloidosis (n = 3/7) and tubulo-interstitial infiltration by lymphoma cells (n = 3/7) were the two more represented entities. BTKi did not seem to improve renal function (Case 1), while bortezomib-based regimens demonstrated a beneficial activity on the hematological and organ response, even when used as second-line therapy after chemoimmunotherapy (Case 3) and also with coexistence of anti-MAG neuropathy (Case 2). In case of poor response to bortezomib, standard chemoimmunotherapy (CIT), such as rituximab-bendamustine, represents an effective option (Case 1, 6, and 7). In our series, CIT generates durable responses more frequently in cases with amyloidogenic renal damage (Case 1, 5, and 7). CONCLUSION In this illustrative case series, we confirm that serum creatinine levels and 24 h proteinuria are parameters that when altered should prompt the clinical suspicion of WM-related renal involvement, even if at present there are not precise cut-off levels recommending the execution of a renal biopsy. Studies with higher numerosity are needed to better clarify the pathological and clinical features of renal involvement during WM and to determine the potential benefit of different therapeutic regimens according to the histopathological subtypes.
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Affiliation(s)
- Nicolò Danesin
- Hematology Unit, Department of MedicineUniversity of PadovaPadovaItaly
| | - Greta Scapinello
- Hematology Unit, Department of MedicineUniversity of PadovaPadovaItaly
| | - Dorella Del Prete
- Nephrology, Dialysis and Transplantation Unit, Department of MedicineUniversity of PadovaPadovaItaly
| | - Elena Naso
- Nephrology, Dialysis and Transplantation Unit, Department of MedicineUniversity of PadovaPadovaItaly
| | - Tamara Berno
- Hematology Unit, Department of MedicineUniversity of PadovaPadovaItaly
| | - Andrea Visentin
- Hematology Unit, Department of MedicineUniversity of PadovaPadovaItaly
| | - Laura Bonaldi
- Immunology and Molecular Oncology Diagnostic Unit, Veneto Institute of OncologyIOV‐IRCCSPadovaItaly
| | - Annalisa Martines
- Immunology and Molecular Oncology Diagnostic Unit, Veneto Institute of OncologyIOV‐IRCCSPadovaItaly
| | - Roberta Bertorelle
- Immunology and Molecular Oncology Diagnostic Unit, Veneto Institute of OncologyIOV‐IRCCSPadovaItaly
| | - Fabrizio Vianello
- Hematology Unit, Department of MedicineUniversity of PadovaPadovaItaly
- Veneto Institute of Molecular MedicineFondazione per la Ricerca Biomedica AvanzataPadovaItaly
| | - Carmela Gurrieri
- Hematology Unit, Department of MedicineUniversity of PadovaPadovaItaly
| | - Renato Zambello
- Hematology Unit, Department of MedicineUniversity of PadovaPadovaItaly
- Veneto Institute of Molecular MedicineFondazione per la Ricerca Biomedica AvanzataPadovaItaly
| | - Chiara Castellani
- Cardiovascular Pathology Unit, Department of Cardiac, Thoracic and Vascular Sciences and Public HealthUniversity of PadovaPadovaItaly
| | - Marny Fedrigo
- Cardiovascular Pathology Unit, Department of Cardiac, Thoracic and Vascular Sciences and Public HealthUniversity of PadovaPadovaItaly
| | - Stefania Rizzo
- Cardiovascular Pathology Unit, Department of Cardiac, Thoracic and Vascular Sciences and Public HealthUniversity of PadovaPadovaItaly
| | - Annalisa Angelini
- Cardiovascular Pathology Unit, Department of Cardiac, Thoracic and Vascular Sciences and Public HealthUniversity of PadovaPadovaItaly
| | - Livio Trentin
- Hematology Unit, Department of MedicineUniversity of PadovaPadovaItaly
| | - Francesco Piazza
- Hematology Unit, Department of MedicineUniversity of PadovaPadovaItaly
- Veneto Institute of Molecular MedicineFondazione per la Ricerca Biomedica AvanzataPadovaItaly
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6
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Ehrlich MI, Hughes MS, Labadie BW, Siegelin MD, D’Ovidio F, Bijou R, Lentzsch S, Arcasoy SM. Lung Transplantation for Pulmonary AL Amyloidosis. Transplant Direct 2024; 10:e1577. [PMID: 38380351 PMCID: PMC10876228 DOI: 10.1097/txd.0000000000001577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 11/08/2023] [Accepted: 11/18/2023] [Indexed: 02/22/2024] Open
Affiliation(s)
- Matthew I. Ehrlich
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY
| | - Michael S. Hughes
- Department of Hematology/Oncology, Columbia University College of Physicians and Surgeons, New York, NY
| | - Brian W. Labadie
- Department of Hematology/Oncology, Columbia University College of Physicians and Surgeons, New York, NY
| | - Markus D. Siegelin
- Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY
| | - Frank D’Ovidio
- Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY
- Center for Advanced Lung Disease and Transplantation, New York-Presbyterian Hospital, New York, NY
| | - Rachel Bijou
- Department of Cardiology, Columbia University College of Physicians and Surgeons, New York, NY
| | - Suzanne Lentzsch
- Department of Hematology/Oncology, Columbia University College of Physicians and Surgeons, New York, NY
| | - Selim M. Arcasoy
- Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY
- Center for Advanced Lung Disease and Transplantation, New York-Presbyterian Hospital, New York, NY
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7
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Zhang X, Tang F, Gao YY, Song DZ, Liang J. Hepatomegaly and jaundice as the presenting symptoms of systemic light-chain amyloidosis: A case report. World J Gastrointest Oncol 2024; 16:550-556. [PMID: 38425387 PMCID: PMC10900159 DOI: 10.4251/wjgo.v16.i2.550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Revised: 12/11/2023] [Accepted: 12/26/2023] [Indexed: 02/02/2024] Open
Abstract
BACKGROUND Light chain (AL) amyloidosis is a plasma cell dyscrasia characterized by the pathologic production and extracellular tissue deposition of fibrillar proteins derived from immunoglobulin AL fragments secreted by a clone of plasma cells, which leads to progressive dysfunction of the affected organs. The two most commonly affected organs are the heart and kidneys, and liver is rarely the dominant affected organ with only 3.9% of cases, making them prone to misdiagnosis and missed diagnosis. CASE SUMMARY A 65-year-old woman was admitted with a 3-mo history of progressive jaundice and marked hepatomegaly. Initially, based on enhanced computed tomography scan and angiography, Budd-Chiari syndrome was considered and balloon dilatation of significant hepatic vein stenoses was performed. However, additional diagnostic procedures, including liver biopsy and bone marrow-examination, revealed immunoglobulin kapa AL amyloidosis with extensive liver involvement and hepatic vascular compression. The disease course was progressive and fatal, and the patient eventually died 5 mo after initial presentation of symptoms. CONCLUSION AL amyloidosis with isolated liver involvement is very rare, and can be easily misdiagnosed as a vascular disease.
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Affiliation(s)
- Xu Zhang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin 300170, China
| | - Fei Tang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin 300170, China
| | - Yan-Ying Gao
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - De-Zhao Song
- Department of Interventional Radiology, The Third Central Hospital of Tianjin, Tianjin 300170, China
| | - Jing Liang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin 300170, China
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8
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Rekhtina IG, Khyshova VA, Zozulya NI, Dvirnyk VN, Mendeleyeva LP. [Hemostasis disorders in patients with systemic AL-amyloidosis]. TERAPEVT ARKH 2023; 95:746-750. [PMID: 38158916 DOI: 10.26442/00403660.2023.09.20237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 07/21/2021] [Indexed: 01/03/2024]
Abstract
AIM To analyze the frequency and nature of hemorrhagic and thrombotic complications in patients with systemic AL-amyloidosis and compare with laboratory changes in the hemostasis system. MATERIALS AND METHODS The prospective study included 40 patients with newly diagnosed AL-amyloidosis. To detect amyloid, all patients underwent bone marrow trephine biopsy and duodenal biopsy, and 28 (70%) patients underwent biopsy of the affected organ. Before the start of therapy, all patients were determined the platelet count, activated partial thromboplastin time, thrombin time, fibrinogen concentration, time of XIIa-dependent fibrinolysis, antithrombin III, D-dimer, activity of blood coagulation factors VIII, X and vWF. The statistical part of the study was carried out using the IBM SPSS Statistics 2017 system software (SPSS, Chicago, IL, USA). RESULTS In 20 (50%) patients, hemorrhages on the skin and mucous membranes were diagnosed as vascular purpura. Before the start of therapy, 7 (17.5%) patients had thrombosis, including leg vein thrombosis (5 patients), ischemic stroke (2 patients). There was a direct correlation between thrombotic complications and cutaneous hemorrhagic syndrome (p=0.007). In 15 (75%) cases, cutaneous hemorrhagic syndrome was accompanied by hypercoagulable shifts in the hemostasis system. Of the 20 patients with cutaneous hemorrhagic syndrome, 19 (95%) patients had kidney damage, including 15 patients with nephrotic syndrome. Hematoma type of bleeding, as well as heavy bleeding was not observed, including after a biopsy of the internal organs. According to the totality of hemostasis indicators, hypercoagulation syndrome was more often observed (in 23; 56% of patients). Hypocoagulation was diagnosed only in 2 (5%) patients with liver damage, 16 (39%) patients had normocoagulation. CONCLUSION Cutaneous hemorrhagic syndrome is the most common clinical manifestation of disorders in the hemostasis system in patients with AL-amyloidosis. The relationship of hemorrhages on the skin with nephrotic syndrome has been established, which may indicate a single pathogenetic mechanism. Cutaneous hemorrhagic syndrome is associated with hypercoagulable shifts in hemostasis and a high risk of thrombotic complications.
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Affiliation(s)
| | | | - N I Zozulya
- National Medical Research Center for Hematology
| | - V N Dvirnyk
- National Medical Research Center for Hematology
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9
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Furlan A, Sartori F, Gherlinzoni F. Acquired Isolated Factor VII Deficiency in Plasma Cell Dyscrasias: A Brief Presentation of Two Plasma-Cell-Leukemia-Related Cases and Review of Literature. J Clin Med 2023; 12:5837. [PMID: 37762778 PMCID: PMC10531634 DOI: 10.3390/jcm12185837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Revised: 09/04/2023] [Accepted: 09/06/2023] [Indexed: 09/29/2023] Open
Abstract
Acquired isolated factor VII (FVII) deficiency is a rare but important discovery in patients with plasma cell disorders with significant therapeutic and prognostic implications. The present analysis and review of cases reported in the literature is intended to highlight disease-related characteristics associated with this rare clotting defect, clinical manifestations and outcome, and potential underlying mechanisms, and to provide guidance on how to manage these patients in terms of prophylactic and therapeutic measures. The discovery of acquired FVII deficiency in a patient with multiple myeloma (MM) or monoclonal gammopathy of uncertain significance (MGUS) should prompt an evaluation for AL amyloidosis, particularly for amyloid hepatosplenic involvement, whenever not previously documented. Acquired FVII deficiency in patients with MM and AL amyloidosis is frequently associated with severe bleeding diathesis, also related to a number of concomitant predisposing factors, adversely affecting the outcome. The prompt institution of a rapidly acting therapy is crucial to prevent severe bleeding complications and positively impact outcome. Recombinant activated factor VII (rVIIa) may represent a useful supportive care measure, both in treating active bleeding and in the peri-procedural setting. However, further clinical experience is needed to optimize the therapeutic management of this rare disorder.
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Affiliation(s)
- Anna Furlan
- Hematology Unit, Azienda ULSS2 Marca Trevigiana, 31100 Treviso, Italy; (F.S.); (F.G.)
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10
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Kietaibl S, Ahmed A, Afshari A, Albaladejo P, Aldecoa C, Barauskas G, De Robertis E, Faraoni D, Filipescu DC, Fries D, Godier A, Haas T, Jacob M, Lancé MD, Llau JV, Meier J, Molnar Z, Mora L, Rahe-Meyer N, Samama CM, Scarlatescu E, Schlimp C, Wikkelsø AJ, Zacharowski K. Management of severe peri-operative bleeding: Guidelines from the European Society of Anaesthesiology and Intensive Care: Second update 2022. Eur J Anaesthesiol 2023; 40:226-304. [PMID: 36855941 DOI: 10.1097/eja.0000000000001803] [Citation(s) in RCA: 129] [Impact Index Per Article: 64.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2023]
Abstract
BACKGROUND Management of peri-operative bleeding is complex and involves multiple assessment tools and strategies to ensure optimal patient care with the goal of reducing morbidity and mortality. These updated guidelines from the European Society of Anaesthesiology and Intensive Care (ESAIC) aim to provide an evidence-based set of recommendations for healthcare professionals to help ensure improved clinical management. DESIGN A systematic literature search from 2015 to 2021 of several electronic databases was performed without language restrictions. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to assess the methodological quality of the included studies and to formulate recommendations. A Delphi methodology was used to prepare a clinical practice guideline. RESULTS These searches identified 137 999 articles. All articles were assessed, and the existing 2017 guidelines were revised to incorporate new evidence. Sixteen recommendations derived from the systematic literature search, and four clinical guidances retained from previous ESAIC guidelines were formulated. Using the Delphi process on 253 sentences of guidance, strong consensus (>90% agreement) was achieved in 97% and consensus (75 to 90% agreement) in 3%. DISCUSSION Peri-operative bleeding management encompasses the patient's journey from the pre-operative state through the postoperative period. Along this journey, many features of the patient's pre-operative coagulation status, underlying comorbidities, general health and the procedures that they are undergoing need to be taken into account. Due to the many important aspects in peri-operative nontrauma bleeding management, guidance as to how best approach and treat each individual patient are key. Understanding which therapeutic approaches are most valuable at each timepoint can only enhance patient care, ensuring the best outcomes by reducing blood loss and, therefore, overall morbidity and mortality. CONCLUSION All healthcare professionals involved in the management of patients at risk for surgical bleeding should be aware of the current therapeutic options and approaches that are available to them. These guidelines aim to provide specific guidance for bleeding management in a variety of clinical situations.
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Affiliation(s)
- Sibylle Kietaibl
- From the Department of Anaesthesiology & Intensive Care, Evangelical Hospital Vienna and Sigmund Freud Private University Vienna, Austria (SK), Department of Anaesthesia and Critical Care, University Hospitals of Leicester NHS Trust (AAh), Department of Cardiovascular Sciences, University of Leicester, UK (AAh), Department of Paediatric and Obstetric Anaesthesia, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (AAf), Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark (AAf), Department of Anaesthesiology & Critical Care, CNRS/TIMC-IMAG UMR 5525/Themas, Grenoble-Alpes University Hospital, Grenoble, France (PA), Department of Anaesthesiology & Intensive Care, Hospital Universitario Rio Hortega, Valladolid, Spain (CA), Department of Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania (GB), Division of Anaesthesia, Analgesia, and Intensive Care - Department of Medicine and Surgery, University of Perugia, Italy (EDR), Department of Anesthesiology, Perioperative and Pain Medicine, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA (DFa), University of Medicine and Pharmacy Carol Davila, Department of Anaesthesiology & Intensive Care, Emergency Institute for Cardiovascular Disease, Bucharest, Romania (DCF), Department of Anaesthesia and Critical Care Medicine, Medical University Innsbruck, Innsbruck, Austria (DFr), Department of Anaesthesiology & Critical Care, APHP, Université Paris Cité, Paris, France (AG), Department of Anesthesiology, University of Florida, College of Medicine, Gainesville, Florida, USA (TH), Department of Anaesthesiology, Intensive Care and Pain Medicine, St.-Elisabeth-Hospital Straubing, Straubing, Germany (MJ), Department of Anaesthesiology, Medical College East Africa, The Aga Khan University, Nairobi, Kenya (MDL), Department of Anaesthesiology & Post-Surgical Intensive Care, University Hospital Doctor Peset, Valencia, Spain (JVL), Department of Anaesthesiology & Intensive Care, Johannes Kepler University, Linz, Austria (JM), Department of Anesthesiology & Intensive Care, Semmelweis University, Budapest, Hungary (ZM), Department of Anaesthesiology & Post-Surgical Intensive Care, University Trauma Hospital Vall d'Hebron, Barcelona, Spain (LM), Department of Anaesthesiology & Intensive Care, Franziskus Hospital, Bielefeld, Germany (NRM), Department of Anaesthesia, Intensive Care and Perioperative Medicine, GHU AP-HP. Centre - Université Paris Cité - Cochin Hospital, Paris, France (CMS), Department of Anaesthesiology and Intensive Care, Fundeni Clinical Institute, Bucharest and University of Medicine and Pharmacy Carol Davila, Bucharest, Romania (ES), Department of Anaesthesiology and Intensive Care Medicine, AUVA Trauma Centre Linz and Ludwig Boltzmann-Institute for Traumatology, The Research Centre in Co-operation with AUVA, Vienna, Austria (CS), Department of Anaesthesia and Intensive Care Medicine, Zealand University Hospital, Roskilde, Denmark (AW) and Department of Anaesthesiology, Intensive Care Medicine & Pain Therapy, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany (KZ)
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11
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Pardos-Gea J, Cortina V, Marques-Soares JR, Martínez F, Gironella M. Severe bleeding diathesis as onset of light-chain amyloidosis: combined excessive fibrinolysis and acquired von Willebrand disease in a young patient. Blood Coagul Fibrinolysis 2023; 34:79-81. [PMID: 36165074 DOI: 10.1097/mbc.0000000000001163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Our report shows a case of primary light-chain amyloidosis in a young patient that reflects the potential severity of bleeding diathesis associated with this plasma cell dyscrasia and the difficulty of diagnosis when only hemorrhagic manifestations are present at the onset of disease. The patient presented with recurrent and severe muscular bleeding secondary to associated acquired von Willebrand disease and fibrinolysis dysfunction. Treatment with bortezomib-cyclophosphamide and sequential hematopoietic stem cell transplantation solved coagulation alterations. On the basis of our case, we review previous reports and discuss the potential mechanism of dysfunction of coagulation in light-chain amyloidosis.
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Affiliation(s)
| | - Vicente Cortina
- Department of Hematology and Vall d'Hebrón Institute of Oncology (VHIO), Vall d'Hebrón University Hospital, Barcelona, Spain
| | | | - Fernanda Martínez
- Department of Hematology and Vall d'Hebrón Institute of Oncology (VHIO), Vall d'Hebrón University Hospital, Barcelona, Spain
| | - Merche Gironella
- Department of Hematology and Vall d'Hebrón Institute of Oncology (VHIO), Vall d'Hebrón University Hospital, Barcelona, Spain
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Gao YJ, Shen KN, Chang L, Feng J, Mao YY, Zhang L, Cao XX, Zhou DB, Li J. Prevalence, clinical characteristics and treatment outcome of factor X deficiency in a consecutive cohort of primary light-chain amyloidosis. Leuk Res 2022; 120:106917. [PMID: 35849875 DOI: 10.1016/j.leukres.2022.106917] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 06/16/2022] [Accepted: 07/03/2022] [Indexed: 12/27/2022]
Abstract
Factor X (FX) deficiency is prevalent in light-chain (AL) amyloidosis but its clinical significance was not investigated deeply. We conducted a retrospective analysis of a consecutive cohort with 207 primary AL amyloidosis patients. FX deficiency was present in 129 patients (62.3%). Those with FX deficiency had higher dFLC (299.6 mg/L vs. 102.3 mg/L, P < 0.001), higher cardiac troponin I (0.05 μg/L vs. 0.02 μg/L, P < 0.001) and N-terminal pro-brain natriuretic peptide (3115 ng/L vs. 392 ng/L, P < 0.001), and more patients with bone marrow plasma cells > 10% (18.0% vs. 4.3%, P = 0.008). The prevalence of FX deficiency increased with the Mayo 2004 stage. FX-deficient patients exhibited inferior overall survival (P < 0.001) and progression-free survival (P < 0.001) than others. Fifty-five patients with FX deficiency received retesting of FX activity after anti-plasma cell therapy. The median variation in FX activity was + 6.8% (range, -24.5% ~ +73.4%). Better improvement of FX activity was observed in patients with complete hematologic response (+18.2% vs. +4.0%, P = 0.036) and at least one organ response (+14.4% vs. +3.4%, P = 0.024). FX deficiency is associated with a heavier disease burden and poorer survival in primary AL amyloidosis. Improvement of FX activity tends to appear in patients with better hematologic and organ responses after chemotherapy.
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Affiliation(s)
- Ya-Juan Gao
- Department of Hematology, Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Kai-Ni Shen
- Department of Hematology, Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Long Chang
- Department of Hematology, Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Feng
- Department of Hematology, Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yue-Ying Mao
- Department of Hematology, Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lu Zhang
- Department of Hematology, Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xin-Xin Cao
- Department of Hematology, Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dao-Bin Zhou
- Department of Hematology, Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jian Li
- Department of Hematology, Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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13
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Oghina S, Delbarre MA, Poullot E, Belhadj K, Fanen P, Damy T. [Cardiac amyloidosis: State of art in 2022]. Rev Med Interne 2022; 43:537-544. [PMID: 35870985 DOI: 10.1016/j.revmed.2022.04.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 04/17/2022] [Accepted: 04/30/2022] [Indexed: 10/17/2022]
Abstract
The 3 main types of cardiac amyloidosis are linked to two protein precursors: AL amyloidosis secondary to free light chain deposits in the context of monoclonal gammopathy (mainly of undetermined significance or myeloma) and transthyretin amyloidosis (ATTR), comprising wild-type transthyretin amyloidosis (ATTRwt for wild type) and hereditary transthyretin amyloidosis (ATTRv for variant). These diseases are underdiagnosed and highly prevalent in common cardiac phenotypes in recent studies (heart failure with preserved ejection fraction, severe aortic stenosis, hypertrophic cardiomyopathy). Myocardial amyloid infiltration affects all cardiac structures and clinically promotes predominantly heart failure, conductive disorders and cardioembolic events. The search for extracardiac signs makes it possible to arouse diagnostic suspicion. Electrocardiogram, echocardiography and cardiac MRI can suspect cardiac amyloidosis. The diagnostic confirmation follows a simple algorithm including a systematic search for monoclonal gammapathy and a disphosphonate scintigraphy. Histological proof is necessary in case of AL or ATTR amyloidosis with concomitant monoclonal gammopathy in order to initiate specific treatment. Due to the late disease onset in ATTRv, genetic testing must be routine in all cases of ATTR. These diseases are no longer perceived as incurable since recent therapeutic innovations. A better knowledge of the disease is more than ever necessary.
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Affiliation(s)
- S Oghina
- Service de cardiologie, Centre Hospitalier Universitaire Henri-Mondor, AP-HP (Assistance Publique-Hôpitaux de Paris), 1, rue Gustave-Eiffel, 94010 Créteil, France; Centre de référence national des amyloses cardiaques et réseau amylose Mondor, Filière Cardiogen, Centre Hospitalier Universitaire Henri-Mondor, AP-HP (Assistance Publique-Hôpitaux de Paris), 1, rue Gustave-Eiffel, 94010 Créteil, France.
| | - M A Delbarre
- Service de cardiologie, Centre Hospitalier Universitaire Henri-Mondor, AP-HP (Assistance Publique-Hôpitaux de Paris), 1, rue Gustave-Eiffel, 94010 Créteil, France; Centre de référence national des amyloses cardiaques et réseau amylose Mondor, Filière Cardiogen, Centre Hospitalier Universitaire Henri-Mondor, AP-HP (Assistance Publique-Hôpitaux de Paris), 1, rue Gustave-Eiffel, 94010 Créteil, France
| | - E Poullot
- Centre de référence national des amyloses cardiaques et réseau amylose Mondor, Filière Cardiogen, Centre Hospitalier Universitaire Henri-Mondor, AP-HP (Assistance Publique-Hôpitaux de Paris), 1, rue Gustave-Eiffel, 94010 Créteil, France; Service d'anatomo-pathologie, Centre Hospitalier Universitaire Henri-Mondor, AP-HP (Assistance Publique-Hôpitaux de Paris), 1, rue Gustave-Eiffel, 94010 Créteil, France
| | - K Belhadj
- Centre de référence national des amyloses cardiaques et réseau amylose Mondor, Filière Cardiogen, Centre Hospitalier Universitaire Henri-Mondor, AP-HP (Assistance Publique-Hôpitaux de Paris), 1, rue Gustave-Eiffel, 94010 Créteil, France; Service d'hématologie lymphoïde, Centre Hospitalier Universitaire Henri-Mondor, AP-HP (Assistance Publique-Hôpitaux de Paris), 1, rue Gustave-Eiffel, 94010 Créteil, France
| | - P Fanen
- Centre de référence national des amyloses cardiaques et réseau amylose Mondor, Filière Cardiogen, Centre Hospitalier Universitaire Henri-Mondor, AP-HP (Assistance Publique-Hôpitaux de Paris), 1, rue Gustave-Eiffel, 94010 Créteil, France; Service de génétique, Centre Hospitalier Universitaire Henri-Mondor, AP-HP (Assistance Publique-Hôpitaux de Paris), 1, rue Gustave-Eiffel, 94010 Créteil, France; Centre Hospitalier Universitaire Henri-Mondor, AP-HP (Assistance Publique-Hôpitaux de Paris), FHU SENEC, 1, rue Gustave-Eiffel, 94010 Créteil, France
| | - T Damy
- Service de cardiologie, Centre Hospitalier Universitaire Henri-Mondor, AP-HP (Assistance Publique-Hôpitaux de Paris), 1, rue Gustave-Eiffel, 94010 Créteil, France; Centre de référence national des amyloses cardiaques et réseau amylose Mondor, Filière Cardiogen, Centre Hospitalier Universitaire Henri-Mondor, AP-HP (Assistance Publique-Hôpitaux de Paris), 1, rue Gustave-Eiffel, 94010 Créteil, France; Centre Hospitalier Universitaire Henri-Mondor, AP-HP (Assistance Publique-Hôpitaux de Paris), FHU SENEC, 1, rue Gustave-Eiffel, 94010 Créteil, France
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Abstract
The treatment of patients with systemic light chain (AL) amyloidosis is a challenge to hematologists. Despite its generally small size, the underlying clone causes a rapidly progressing, often devastating multiorgan dysfunction through the toxic light chains that form amyloid deposits. Clinical manifestations are deceitful and too often recognized at an irreversible stage. However, hematologists are in the unique position to diagnose AL amyloidosis at a pre-symptomatic stage checking biomarkers of amyloid organ involvement in patients with monoclonal gammopathies at higher risk to develop the disease. Adequate technology and expertise are needed for a prompt and correct diagnosis, particularly for ruling out non-AL amyloidoses that are now also treatable. Therapy should be carefully tailored based on severity of organ involvement and clonal characteristics, and early and continual monitoring of response is critical. Three recent randomized clinical trials moved AL amyloidosis to evidence-based era. Above all, the daratumumab-bortezomib combination is a new standard-of-care for newly diagnosed patients inducing rapid and deep responses that translate into high rates of organ response. The availability of new effective drugs allows to better personalize the therapy, reduce toxicity, and improve outcomes. Patients should be treated within clinical trials whenever possible.
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Simms LN, Suarez LSK, Deeb K, Proenza J. The 13-year bleed: Exuberant amyloid angiopathies, angiodysplasias, and acquired coagulopathies of the gut. SAGE Open Med Case Rep 2021; 9:2050313X211040018. [PMID: 34484792 PMCID: PMC8414616 DOI: 10.1177/2050313x211040018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 07/29/2021] [Indexed: 11/17/2022] Open
Abstract
Amyloidosis is a disorder characterized by extracellular deposits of proteins that are
prone to aggregate and form insoluble fibrils. Amyloid deposits limited to a single organ
or tissue without the involvement of any other site in the body is uncommon. We report a
75-year-old man with previously treated non-Hodgkin’s lymphoma who presented with
recurrent gastrointestinal hemorrhage. Histopathology showed amyloid deposition within
vascular malformations. His bleeding continued with the cause rooted in the fundamental
building blocks—clotting factors. We discuss the interplay of the pathophysiology of
lymphoma, amyloidosis, and factor X deficiency in a patient with preexisting
angiodysplasias leading to refractory gastrointestinal bleeding. To our knowledge, there
are only 3 reported cases of concomitant amyloidosis and angiodysplasia in the colon, and
none involving the small bowel.
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Affiliation(s)
- Larnelle N Simms
- Internal Medicine Resident, University of Miami Palm Beach Regional GME Consortium, Atlantis, FL, USA
| | - Laura Suzanne K Suarez
- Internal Medicine Resident, University of Miami Palm Beach Regional GME Consortium, Atlantis, FL, USA
| | - Khaled Deeb
- Department of Internal Medicine, West Palm Beach Veterans Affairs Medical Center, West Palm Beach, FL, USA
| | - Jose Proenza
- Department of Gastroenterology, West Palm Beach Veterans Affairs Medical Center, West Palm Beach, FL, USA
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