PDF icon Download PDF
Semin Thromb Hemost
DOI: 10.1055/a-2669-7739
Review Article

Transfusion-Dependent Thalassemia and Venous Thromboembolism Management: Position Statement from the Steering Committees of Hemostasis and Erythrocyte and Hemoglobinopathies Study Groups—Hellenic Society of Haematology

Vasiliki Danilatou 
1   School of Medicine, European University Cyprus, Nicosia, Cyprus
2   Research Department, Eunomia Limited, Dublin, Ireland
,
Emmanouil Papadakis
3   Ob/Gyn Hematology Clinic – Thrombosis and Hemostasis Clinic, Genesis Hospital, Thessaloniki, Greece
,
Elias Kyriakou
4   Department of Laboratory Hematology, Clinical Hemostasis and Blood Transfusion Services, “Attikon” University Hospital, Athens, Greece
,
Efrosyni Nomikou
5   Blood Bank, Hemophilia Unit and Thrombosis Disorders Department, Hippocrateio General Hospital of Athens, Athens, Greece
,
Sophia Delicou
6   Thalassemia and Sickle Cell Unit, Expertise Center of Hemoglobinopathies and Their Complications, Hippokrateio General Hospital, Athens, Greece
,
Fotios Girtovitis
7   Blood Center, AHEPA University General Hospital of Thessaloniki, Thessaloniki, Greece
› Author Affiliations
› Further Information
   Permissions and Reprints
Preview

Abstract

Venous thromboembolism is often underestimated in transfusion-dependent thalassemia (TDT) patients, as arterial thrombotic events are more commonly observed. Although therapeutic advancements have transformed this disease from a once-fatal childhood disease into a manageable chronic condition, some treatments may contribute to an increased risk of thrombosis. Additionally, the prolonged life expectancy of these patients further contributes to the overall thrombotic risk. Patients with thalassemia major present multiple challenges when considering anticoagulation therapy. The decision-making process is complicated by a delicate balance between thrombotic risk—driven by disease-related and treatment-associated factors—and potential bleeding tendencies, particularly in the presence of comorbid conditions such as liver dysfunction, hypersplenism, or thrombocytopenia. Therefore, ongoing assessment of both thrombotic and bleeding risk and the implementation of appropriate preventive strategies are essential to optimize patient outcomes. This document presents a consensus statement from the Steering Committee of the Hemostasis Working Group of the Hellenic Society of Hematology, offering guidance on thromboprophylaxis and anticoagulation management in adult TDT patients.

Keywords

transfusion-dependent thalassemia - thalassemia major - venous thromboembolism - thromboprophylaxis - anticoagulation


Publication History

Received: 05 June 2025

Accepted: 28 July 2025

Accepted Manuscript online:
29 July 2025

Article published online:
22 August 2025

© 2025. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Farmakis D. Management of Transfusion Dependent Thalassemia (TDT). A Short Guide. 2nd ed.. Thalassemia International Federation; 2022. . Accessed February 13, 2025 at: https://thalassaemia.org.cy/wp-content/uploads/2022/08/TDT-GUIDE-2022-FOR-web.pdf
    Search in Google Scholar
  • 2 Cappellini MD. Coagulation in the pathophysiology of hemolytic anemias. Hematology (Am Soc Hematol Educ Program) 2007; 2007 (01) 74-78
    Search in Google Scholar
  • 3 World Health Organization. Regional desk review of haemoglobinopathies with an emphasis on thalassaemia and accessibility and availability of safe blood and blood products as per these patients' requirement in South-East Asia under Universal Health Coverage. 2021 . Accessed August 4, 2025 at: https://www.who.int/publications/i/item/9789290228516
    Search in Google Scholar
  • 4 Kattamis A, Forni GL, Aydinok Y, Viprakasit V. Changing patterns in the epidemiology of -thalassemia. Eur J Haematol 2020; 105 (06) 692-703
    Search in Google Scholar
  • 5 Sleiman J, Tarhini A, Bou-Fakhredin R, Saliba AN, Cappellini MD, Taher AT. Non-transfusion-dependent thalassemia: an update on complications and management. Int J Mol Sci 2018; 19 (01) 182
    Search in Google Scholar
  • 6 Michaeli J, Mittelman M, Grisaru D, Rachmilewitz EA. Thromboembolic complications in beta thalassemia major. Acta Haematol 1992; 87 (1-2): 71-74
    Search in Google Scholar
  • 7 Gillis S, Cappellini MD, Goldfarb A, Ciceri L, Fiorelli G, Rachmilewitz EA. Pulmonary thromboembolism in thalassemia intermedia patients. Haematologica 1999; 84 (10) 959-960
    Search in Google Scholar
  • 8 Hong J, Ahn SY, Lee YJ. et al.; Korean Society of Hematology Thrombosis and Hemostasis Working Party. Updated recommendations for the treatment of venous thromboembolism. Blood Res 2021; 56 (01) 6-16
    Search in Google Scholar
  • 9 Konstantinides SV, Meyer G, Becattini C. et al.; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; 41 (04) 543-603
    Search in Google Scholar
  • 10 Stevens SM, Woller SC, Baumann Kreuziger L. et al. Executive summary. Chest 2021; 160 (06) 2247-2259
    Search in Google Scholar
  • 11 Ortel TL, Neumann I, Ageno W. et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv 2020; 4 (19) 4693-4738
    Search in Google Scholar
  • 12 Cappellini MD, Motta I, Musallam KM, Taher AT. Redefining thalassemia as a hypercoagulable state. Ann N Y Acad Sci 2010; 1202 (01) 231-236
    Search in Google Scholar
  • 13 Taher AT, Musallam KM, Inati A. The hypercoagulable state in thalassemia intermedia. Hemoglobin 2009; 33 (Suppl. 01) S160-S169
    Search in Google Scholar
  • 14 Borenstain-Ben Yashar V, Barenholz Y, Hy-Am E, Rachmilewitz EA, Eldor A. Phosphatidylserine in the outer leaflet of red blood cells from β-thalassemia patients may explain the chronic hypercoagulable state and thrombotic episodes. Am J Hematol 1993; 44 (01) 63-65
    Search in Google Scholar
  • 15 Kyriakou DS, Alexandrakis MG, Kyriakou ES. et al. Activated peripheral blood and endothelial cells in thalassemia patients. Ann Hematol 2001; 80 (10) 577-583
    Search in Google Scholar
  • 16 Youssry I, Soliman N, Ghamrawy M. et al. Circulating microparticles and the risk of thromboembolic events in Egyptian beta thalassemia patients. Ann Hematol 2017; 96 (04) 597-603
    Search in Google Scholar
  • 17 Vasilopoulou M, Stafylidis C, Politou M. The thrombotic spectrum of B-thalassemia. Thromb Update 2022; 7: 100102
    Search in Google Scholar
  • 18 Abosdera MM, Almasry AE, Abdel-Moneim ES. Coagulation defects in thalassemic patients. Pediatr Neonatol 2017; 58 (05) 421-424
    Search in Google Scholar
  • 19 Franchini M, Targher G, Montagnana M, Lippi G. Iron and thrombosis. Ann Hematol 2008; 87 (03) 167-173
    Search in Google Scholar
  • 20 Kalamara TV, Dodos K, Vlachaki E. Splenectomy is significantly associated with thrombosis but not with pulmonary hypertension in patients with transfusion-dependent thalassemia: a meta-analysis of observational studies. Front Med (Lausanne) 2023; 10: 1259785
    Search in Google Scholar
  • 21 Taher AT, Musallam KM, Karimi M. et al. Splenectomy and thrombosis: the case of thalassemia intermedia. J Thromb Haemost 2010; 8 (10) 2152-2158
    Search in Google Scholar
  • 22 Kyriakaki S, Pyrovolaki K, Klironomos E, Sfyridaki K. PB2397 Thromboembolic events in thalassemia: A 20-year experience of a Greek thalassemia center. HemaSphere 2019; 3 (S1): 1066
    Search in Google Scholar
  • 23 Winslow ER, Brunt LM, Drebin JA, Soper NJ, Klingensmith ME. Portal vein thrombosis after splenectomy. Am J Surg 2002; 184 (06) 631-635 , discussion 635–636
    Search in Google Scholar
  • 24 Crary SE, Buchanan GR. Vascular complications after splenectomy for hematologic disorders. Blood 2009; 114 (14) 2861-2868
    Search in Google Scholar
  • 25 Sirachainan N, Wijarn P, Chuansumrit A, Kadegasem P, Wongwerawattanakoon P, Soisamrong A. Aspirin resistance in children and young adults with splenectomized thalassemia diseases. Thromb Res 2015; 135 (05) 916-922
    Search in Google Scholar
  • 26 O'Driscoll A, Mackie IJ, Porter JB, Machin SJ. Low plasma heparin cofactor II levels in thalassaemia syndromes are corrected by chronic blood transfusion. Br J Haematol 1995; 90 (01) 65-70
    Search in Google Scholar
  • 27 Eldor A, Rachmilewitz EA. The hypercoagulable state in thalassemia. Blood 2002; 99 (01) 36-43
    Search in Google Scholar
  • 28 Moratelli S, De Sanctis V, Gemmati D. et al. Thrombotic risk in thalassemic patients. J Pediatr Endocrinol Metab 1998; 11 (Suppl. 03) 915-921
    Search in Google Scholar
  • 29 Sherief LM, Abd El-Salam SM, Kamal NM. et al. Nutritional biomarkers in children and adolescents with Beta-thalassemia-major: An Egyptian center experience. BioMed Res Int 2014; 2014: 261761
    Search in Google Scholar
  • 30 Cappellini MD, Musallam KM, Marcon A, Taher AT. Coagulopathy in Beta-thalassemia: current understanding and future perspectives. Mediterr J Hematol Infect Dis 2009; 1 (01) e2009029
    Search in Google Scholar
  • 31 Barrano B, Bertrand G, Isaja T, Curreri R, Musumeci S. Plasma homocysteine is not involved in the thrombotic risk of beta-thalassemia major patients. Acta Haematol 2000; 104 (2-3): 148-150
    Search in Google Scholar
  • 32 Mustafa NY, Marouf R, Al-Humood S, Al-Fadhli SM, Mojiminiyi O. Hypercoagulable state and methylenetetrahydrofolate reductase (MTHFR) C677T mutation in patients with beta-thalassemia major in Kuwait. Acta Haematol 2010; 123 (01) 37-42
    Search in Google Scholar
  • 33 Rahimi Z, Ghaderi M, Nagel RL, Muniz A. Prevalence of thrombotic risk factors among β-thalassemia patients from Western Iran. J Thromb Thrombolysis 2008; 26 (03) 229-233
    Search in Google Scholar
  • 34 Nigam N, Singh PK, Agrawal M, Nigam S, Gupta H, Saxena S. MTHFR C677T, prothrombin G20210A, and Factor V Leiden (G1691A) polymorphism and beta-thalassemia risk: a meta-analysis. Cureus 2020; 12 (09) e10743
    Search in Google Scholar
  • 35 Kashef S, Karimi M, Amirghofran Z. et al. Antiphospholipid antibodies and hepatitis C virus infection in Iranian thalassemia major patients. Int J Lab Hematol 2008; 30 (01) 11-16
    Search in Google Scholar
  • 36 Chinsuwan J, Klaihmon P, Kadegasem P. et al. High prevalence of antiphospholipid antibodies in children with non-transfusion dependent thalassemia and possible correlations with microparticles. Mediterr J Hematol Infect Dis 2020; 12 (01) e2020071
    Search in Google Scholar
  • 37 Lin SY, Chang YL, Yeh HC, Lin CL, Kao CH. Blood transfusion and risk of venous thromboembolism: A population-based cohort study. Thromb Haemost 2020; 120 (01) 156-167 W
    Search in Google Scholar
  • 38 Tantiworawit A, Dumnil S, Osataphan N. et al. The pros and cons of splenectomy in transfusion dependent thalassemia patient. Blood 2018; 132 (Suppl. 01) 4901
    Search in Google Scholar
  • 39 Taher A, Isma'eel H, Mehio G. et al. Prevalence of thromboembolic events among 8,860 patients with thalassaemia major and intermedia in the Mediterranean area and Iran. Thromb Haemost 2006; 96 (04) 488-491
    Search in Google Scholar
  • 40 Cappellini MD, Taher AT. The use of luspatercept for thalassemia in adults. Blood Adv 2021; 5 (01) 326-333
    Search in Google Scholar
  • 41 Srisukh S, Ongphiphadhanakul B, Bunnag P. Hypogonadism in thalassemia major patients. J Clin Transl Endocrinol 2016; 5: 42-45
    Search in Google Scholar
  • 42 Henke PK, Kahn SR, Pannucci CJ. et al.; American Heart Association Advocacy Coordinating Committee. Call to action to prevent venous thromboembolism in hospitalized patients: a policy statement from the American Heart Association. Circulation 2020; 141 (24) e914-e931
    Search in Google Scholar
  • 43 Yuan S, Bruzelius M, Håkansson N, Åkesson A, Larsson SC. Lifestyle factors and venous thromboembolism in two cohort studies. Thromb Res 2021; 202: 119-124
    Search in Google Scholar
  • 44 Fung EB, Xu Y, Kwiatkowski JL. et al.; Thalassemia Clinical Research Network. Relationship between chronic transfusion therapy and body composition in subjects with thalassemia. J Pediatr 2010; 157 (04) 641-647 , 647.e1–647.e2
    Search in Google Scholar
  • 45 Taher AT, Cappellini MD, Musallam KM. Development of a thalassemia-related thrombosis risk scoring system. Am J Hematol 2019; 94 (08) E207-E209
    Search in Google Scholar
  • 46 Cronin M, Dengler N, Krauss ES. et al. Completion of the updated Caprini Risk Assessment Model (2013 Version). Clin Appl Thromb Hemost 2019; 25: 1076029619838052
    Search in Google Scholar
  • 47 Spyropoulos AC, Anderson Jr FA, FitzGerald G. et al.; IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest 2011; 140 (03) 706-714
    Search in Google Scholar
  • 48 Gibson CM, Spyropoulos AC, Cohen AT. et al. The IMPROVEDD VTE Risk Score: Incorporation of D-Dimer into the IMPROVE Score to Improve Venous Thromboembolism Risk Stratification. TH Open 2017; 1 (01) e56-e65
    Search in Google Scholar
  • 49 Häfliger E, Kopp B, Darbellay Farhoumand P. et al. Risk assessment models for venous thromboembolism in medical inpatients. JAMA Netw Open 2024; 7 (05) e249980
    Search in Google Scholar
  • 50 Hartmann J, Hermelin D, Levy JH. Viscoelastic testing: an illustrated review of technology and clinical applications. Res Pract Thromb Haemost 2022; 7 (01) 100031
    Search in Google Scholar
  • 51 Harahsheh Y, Ho KM. Use of viscoelastic tests to predict clinical thromboembolic events: A systematic review and meta-analysis. Eur J Haematol 2018; 100 (02) 113-123
    Search in Google Scholar
  • 52 Shastry S, Mohan G, Pa P, Mundkur S, Kurien A, Ahammad J. Role of thromboelastogram in monitoring the activation of the coagulation pathway and assessing the associated risk factors for hypercoagulable state in transfusion dependent thalassemia patients. Transfus Apher Sci 2023; 62 (02) 103583
    Search in Google Scholar
  • 53 Gowda RY, Gudi JG, Mandolikar RY, Srevatsa K, Kangle RP, Jali SM. A laboratory approach consideration for thrombotic risk assessment in transfusion-dependent beta-thalassemia major utilizing complete blood count cell population data and basic screening hemostatic parameters. J Sci Soc 2024; 51 (03) 388-392
    Search in Google Scholar
  • 54 Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJGM, Lip GYH. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138 (05) 1093-1100
    Search in Google Scholar
  • 55 Aessopos A, Farmakis D, Loukopoulos D. Elastic tissue abnormalities resembling pseudoxanthoma elasticum in β thalassemia and the sickling syndromes. Blood 2002; 99 (01) 30-35
    Search in Google Scholar
  • 56 Srevatsa K, Kangle RP, Jali SM, Resident J, Author C. Role of prothrombin time international normalized ratio and activated partial thromboplastin time in beta thalassemia major: A cross sectional study. Indian J Pathol Oncol 2019; 6 (02) 237-241
    Search in Google Scholar
  • 57 Theodoridou S, Economou M, Vyzantiadis TA. et al. Laboratory investigation of platelet function in patients with thalassaemia. Acta Haematol 2014; 132 (01) 45-48
    Search in Google Scholar
  • 58 Papadakis E, Brenner B. Thrombosis in pregnant women with hemolytic anemia. Semin Thromb Hemost 2023; 49 (04) 364-370
    Search in Google Scholar
  • 59 Anderson S, Perram J, Nelson A, Matthews S, Gou M, Ho PJ. Pregnancy and assisted reproductive technology use in Australian female transfusion-dependent haemoglobinopathy patients: a 20-year retrospective analysis. Intern Med J 2024; 54 (02) 290-294
    Search in Google Scholar
  • 60 Royal College of Obstetrician and Gynecologists. Management of Beta Thalassaemia in Pregnancy. Green-Top Guideline No. 66. 2014
    Search in Google Scholar
  • 61 De Sanctis V, Soliman AT, Elsedfy H. et al. Review recommendations on management of adult female thalassemia patients with hypogonadism based on literature review and experience of ICET-A Network specialists. Mediterr J Hematol Infect Dis 2017; 9 (01) e2017001
    Search in Google Scholar
  • 62 Trenor III CC, Chung RJ, Michelson AD. et al. Hormonal contraception and thrombotic risk: a multidisciplinary approach. Pediatrics 2011; 127 (02) 347-357
    Search in Google Scholar
  • 63 Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2019; 364: k4810
    Search in Google Scholar
  • 64 Bruce D, Atoyebi W, Drasar E. on behalf of Wessex and Thames Valley Haemoglobinopathy Network. Surgery in adults with thalassaemia [Internet]. Version 1.1. August 2022. Authorised by Noemi Roy. Oxford, UK: Wessex & Thames Valley Haemoglobinopathy Network. Available at: https://nssg.oxford?haematology.org.uk/red-cell/documents/acute-management-thalassaemia/S56-surgery-in-adults-with-thalassaemia.pdf
  • 65 Taher AT, Cappellini MD. How I Treat. Sickle Cell Disease and Thalassemia. How I manage medical complications of β-thalassemia in adults. American Society of Haematology; 2018. Vol. 132. 1781-1791 . Accessed August 4, 2025 at: http://ashpublications.org/blood/article-pdf/132/17/1781/1468099/blood818187.pdf
    Search in Google Scholar
  • 66 Alexakis N, Dardamanis D, Albanopoulos K. et al. Incidence, risk factors, and outcome of portal vein thrombosis after laparoscopic-assisted splenectomy in β-thalassemia patients: a prospective exploratory study. J Laparoendosc Adv Surg Tech A 2013; 23 (02) 123-128
    Search in Google Scholar
  • 67 Poparn H, Kittikalayawong Y, Techavichit P. et al. The incidence and methods for detecting aspirin resistance in pediatric patients. Pediatric Health Med Ther 2024; 15: 333-338
    Search in Google Scholar
  • 68 Kaokunakorn T, Ruchutrakool T, Suwanawiboon B. et al. Comparison of the efficacy between 81 mg bid of aspirin and 162 mg od of aspirin in splenectomized thalassemic patients with aspirin resistance. Blood 2023; 142 (Suppl. 01) 5247-5247
    Search in Google Scholar
  • 69 Longo F, Motta I, Pinto V. et al. Treating thalassemia patients with luspatercept: an expert opinion based on current evidence. J Clin Med 2023; 12 (07) 2584
    Search in Google Scholar
  • 70 Raso S, Antonella M, Spasiano A. et al. P1467: The employment of direct oral anticoagulants in patients affected by thalassemia: A multicenter analysis from the extension-myocardial iron overload in Thalassemia Network (E-MIOT). HemaSphere 2023; 7 (S3): e581019c
    Search in Google Scholar
  • 71 Farmakis D, Porter J, Taher A, Domenica Cappellini M, Angastiniotis M, Eleftheriou A. 2021 Thalassaemia International Federation Guidelines for the Management of Transfusion-dependent Thalassemia. HemaSphere 2022; 6 (08) e732
    Search in Google Scholar
  • 72 Saposnik G, Bushnell C, Coutinho JM. et al.; American Heart Association Stroke Council; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; Council on Cardiovascular and Stroke Nursing; and Council on Hypertension. Diagnosis and management of cerebral venous thrombosis: a scientific statement from the American Heart Association. Stroke 2024; 55 (03) e77-e90
    Search in Google Scholar
  • 73 Riva N, Ageno W. Direct oral anticoagulants for unusual-site venous thromboembolism. Res Pract Thromb Haemost 2021; 5 (02) 265-277
    Search in Google Scholar
  • 74 Mulder FI, Bosch FTM, Young AM. et al. Direct oral anticoagulants for cancer-associated venous thromboembolism: a systematic review and meta-analysis. Blood 2020; 136 (12) 1433-1441
    Search in Google Scholar
  • 75 Ribic C, Crowther M. Thrombosis and anticoagulation in the setting of renal or liver disease. Hematology (Am Soc Hematol Educ Program) 2016; 2016 (01) 188-195
    Search in Google Scholar