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DOI: 10.1055/a-2510-6301
Anemia and Prognosis in Patients with Acute Venous Thromboembolism
Funding The SWITCO65+ project was funded by the Swiss National Science Foundation (grant no. 33CSCO-122659/139470).

Abstract
Background Studies found an association between anemia and overall mortality and major bleeding (MB) in patients with acute venous thromboembolism (VTE), but whether anemia is causally related to death, bleeding, or recurrent VTE is uncertain.
Objectives To explore the association between anemia at baseline and short-/long-term clinical outcomes in a prospective cohort of 928 patients with acute VTE.
Methods We defined anemia as a hemoglobin <13 g/dL for men/< 12 g/dL for women. The primary outcome was overall mortality, secondary outcomes were MB and recurrent VTE at 3 months (short term) and over the entire follow-up (long term). An independent committee determined the cause of death. We examined the association between anemia and clinical outcomes using multivariable regression, adjusting for confounders, periods of anticoagulation, and the competing risk of death if appropriate.
Results Overall, 42% of patients had anemia. After a median follow-up of 30 months, 21.4% died, 13.8% experienced MB, and 12.4% had recurrent VTE. Anemia was associated with long-term overall mortality (adjusted HR 1.46, 95%CI 1.06–2.02) but not with short-term mortality, MB, or recurrent VTE. Per 1 g/dL increase in hemoglobin, long-term mortality risk decreased by 8%. Anemic patients were more likely to die from left ventricular failure than non-anemic patients (9.8% versus 1.3%).
Conclusion Anemic patients with VTE carried a higher long-term mortality risk than those without anemia, possibly due to an excess in mortality from left ventricular failure. The lack of an independent relationship between anemia and bleeding indicated that anemia might have confounding rather than causal effects.
Authors' Contribution
Guarantor of the content of the manuscript including data and analysis: E. H. Study concept and design: E.H., D.A. Data acquisition: D.A., M.M., M.R. Statistical analysis: O.S. Manuscript writing: E. Hofmann, D.A. Revision of the manuscript: E.H., O.S., M.M., N.R., T.T., M.R., D.A. All authors approved the final manuscript.
Publikationsverlauf
Eingereicht: 22. Oktober 2024
Angenommen: 06. Januar 2025
Artikel online veröffentlicht:
27. Januar 2025
© 2025. Thieme. All rights reserved.
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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References
- 1 Nutritional anaemias. Report of a WHO scientific group. World Health Organ Tech Rep Ser 1968; 405: 5-37
- 2 Donzé J, Labarère J, Méan M, Jiménez D, Aujesky D. Prognostic importance of anaemia in patients with acute pulmonary embolism. Thromb Haemost 2011; 106 (02) 289-295
- 3 Kuperman A, López-Reyes R, Bosco LJ. et al; RIETE Investigators. Anemia and bleeding in patients receiving anticoagulant therapy for venous thromboembolism. J Thromb Thrombolysis 2018; 45 (03) 360-368
- 4 Goto S, Turpie AGG, Farjat AE. et al; GARFIELD-VTE investigators. The influence of anemia on clinical outcomes in venous thromboembolism: results from GARFIELD-VTE. Thromb Res 2021; 203: 155-162
- 5 Yamashita Y, Morimoto T, Amano H. et al; COMMAND VTE Registry Investigators. Influence of baseline anemia on long-term clinical outcomes in patients with venous thromboembolism: from the COMMAND VTE registry. J Thromb Thrombolysis 2019; 47 (03) 444-453
- 6 Chopard R, Piazza G, Falvo N. et al. An original risk score to predict early major bleeding in acute pulmonary embolism: the syncope, anemia, renal dysfunction (PE-SARD) bleeding score. Chest 2021; 160 (05) 1832-1843
- 7 Jiménez D, Escobar C, Martí D. et al. Association of anaemia and mortality in patients with acute pulmonary embolism. Thromb Haemost 2009; 102 (01) 153-158
- 8 Chow W, Wong C, Lau JK, Chow V, Kritharides L, Ng ACC. Impact of persistent anaemia on mortality in patients hospitalised with acute pulmonary embolism: an Australian retrospective observational study. BMJ Open 2019; 9 (04) e027112
- 9 Obradovic S, Dzudovic B, Subotic B. et al. Association of blood leukocytes and hemoglobin with hospital mortality in acute pulmonary embolism. J Clin Med 2023; 12 (19) 6269
- 10 Justyna A, Dzikowska-Diduch O, Pacho S. et al. Decreased haemoglobin level measured at admission predicts long term mortality after the first episode of acute pulmonary embolism. J Clin Med 2022; 11 (23) 7100
- 11 Gaboreau Y, Zenatti N, Vermorel C, Imbert P, Bosson JL, Pernod G. Anemia and bleeding in patients receiving anticoagulant therapy for venous thromboembolism: comment. J Thromb Thrombolysis 2018; 46 (01) 84-87
- 12 Sandén P, Renlund H, Svensson PJ, Själander A. Bleeding complications in venous thrombosis patients on well-managed warfarin. J Thromb Thrombolysis 2016; 41 (02) 351-358
- 13 Ruíz-Giménez N, Suárez C, González R. et al; RIETE Investigators, Findings from the RIETE Registry. Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Thromb Haemost 2008; 100 (01) 26-31
- 14 Nieto JA, Solano R, Ruiz-Ribó MD. et al; Riete Investigators. Fatal bleeding in patients receiving anticoagulant therapy for venous thromboembolism: findings from the RIETE registry. J Thromb Haemost 2010; 8 (06) 1216-1222
- 15 Anand IS, Chandrashekhar Y, Ferrari R, Poole-Wilson PA, Harris PC. Pathogenesis of oedema in chronic severe anaemia: studies of body water and sodium, renal function, haemodynamic variables, and plasma hormones. Br Heart J 1993; 70 (04) 357-362
- 16 Antwi-Baffour S, Kyeremeh R, Annison L. Severity of anaemia has corresponding effects on coagulation parameters of sickle cell disease patients. Diseases 2019; 7 (04) 59
- 17 Zenati N, Gaboreau Y, Provencher CB, Albaladejo P, Bosson JL, Pernod G. Anaemia as an independent key risk factor for major haemorrhage in patients treated with vitamin K antagonists: results of the SCORE prospective cohort. Thromb Res 2017; 151: 83-88
- 18 McQuilten ZK, Thao LTP, Pasricha SR. et al. Effect of low-dose aspirin versus placebo on incidence of anemia in the elderly: a secondary analysis of the aspirin in reducing events in the elderly trial. Ann Intern Med 2023; 176 (07) 913-921 Erratum in: Ann Intern Med. 2023 Sep; 176(9):1288
- 19 Méan M, Righini M, Jaeger K. et al. The Swiss cohort of elderly patients with venous thromboembolism (SWITCO65+): rationale and methodology. J Thromb Thrombolysis 2013; 36 (04) 475-483
- 20 Ganz DA, Bao Y, Shekelle PG, Rubenstein LZ. Will my patient fall?. JAMA 2007; 297 (01) 77-86
- 21 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
- 22 Rosendaal FR, Cannegieter SC, van der Meer FJ, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69 (03) 236-239
- 23 Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94 (446) 496-509
- 24 Solomon A, Blum A, Peleg A, Lev EI, Leshem-Lev D, Hasin Y. Endothelial progenitor cells are suppressed in anemic patients with acute coronary syndrome. Am J Med 2012; 125 (06) 604-611
- 25 Schmidt-Lucke C, Rössig L, Fichtlscherer S. et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 2005; 111 (22) 2981-2987
- 26 Wang P, Zheng L, Yan S. et al. Understanding the role of red blood cells in venous thromboembolism: a comprehensive review. Am J Med Sci 2024; 367 (05) 296-303
- 27 Messi M, Beneyto Afonso C, Stalder O. et al. Long-term clinical outcomes in older patients with acute venous thromboembolism who have renal impairment. Thromb Res 2022; 218: 64-71
- 28 Spirk D, Husmann M, Hayoz D. et al. Predictors of in-hospital mortality in elderly patients with acute venous thrombo-embolism: the SWIss Venous ThromboEmbolism Registry (SWIVTER). Eur Heart J 2012; 33 (07) 921-926
- 29 Faller N, Limacher A, Méan M. et al. Predictors and causes of long-term mortality in elderly patients with acute venous thromboembolism: a prospective cohort study. Am J Med 2017; 130 (02) 198-206
- 30 Lange N, Méan M, Stalder O. et al. Anticoagulation quality and clinical outcomes in multimorbid elderly patients with acute venous thromboembolism. Thromb Res 2019; 177: 10-16
- 31 Kuijer PM, Hutten BA, Prins MH, Büller HR. Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism. Arch Intern Med 1999; 159 (05) 457-460
- 32 Seiler E, Limacher A, Méan M. et al. Derivation and validation of a novel bleeding risk score for elderly patients with venous thromboembolism on extended anticoagulation. Thromb Haemost 2017; 117 (10) ). Epub ahead of print.
- 33 Prandoni P, Noventa F, Ghirarduzzi A. et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 2007; 92 (02) 199-205
- 34 Heit JA, Lahr BD, Ashrani AA, Petterson TM, Bailey KR. Predictors of venous thromboembolism recurrence, adjusted for treatments and interim exposures: a population-based case-cohort study. Thromb Res 2015; 136 (02) 298-307
- 35 Hansson PO, Sörbo J, Eriksson H. Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors. Arch Intern Med 2000; 160 (06) 769-774
- 36 Rubin DB. Multiple Imputation for Nonresponse in Surveys. Vol. 81. John Wiley & Sons; 2004
- 37 Groenveld HF, Januzzi JL, Damman K. et al. Anemia and mortality in heart failure patients a systematic review and meta-analysis. J Am Coll Cardiol 2008; 52 (10) 818-827
- 38 van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 2014; 124 (12) 1968-1975