Thromb Haemost 2013; 109(01): 79-84
DOI: 10.1160/TH12-05-0361
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

The influence of thrombophilia on the long-term survival of patients with a history of venous thromboembolism

Sylvia Reitter-Pfoertner
1   Division of Haematology and Haemostaseology, Department of Medicine I, Medical University Vienna, Austria
,
Thomas Waldhoer
2   Center for Public Health, Department of Epidemiology, Medical University Vienna, Austria
,
Michaela Mayerhofer
1   Division of Haematology and Haemostaseology, Department of Medicine I, Medical University Vienna, Austria
,
Ernst Eigenbauer
3   Section of Medical Information Management und Imaging, Center for Medical Statistics, Infomatics and Intelligent Systems, Medical University Vienna, Austria
,
Cihan Ay
1   Division of Haematology and Haemostaseology, Department of Medicine I, Medical University Vienna, Austria
,
Christine Mannhalter
4   Department of Laboratory Medicine, Medical University of Vienna, Austria
,
Paul Alexander Kyrle
1   Division of Haematology and Haemostaseology, Department of Medicine I, Medical University Vienna, Austria
,
Ingrid Pabinger
1   Division of Haematology and Haemostaseology, Department of Medicine I, Medical University Vienna, Austria
› Author Affiliations
Further Information

Publication History

Received: 31 May 2012

Accepted after major revision: 18 October 2012

Publication Date:
25 November 2017 (online)

Summary

Data on the long-term survival following venous thromboembolism (VTE) are rare,and the influence of thrombophilia has not been evaluated thus far. Our aim was to assess thrombophilia-parameters as predictors for long-term survival of patients with VTE. Overall, 1,905 outpatients (99 with antithrombin-, protein C or protein S deficiency, 517 with factor V Leiden, 381 with elevated factor VIII and 160 with elevated homocysteine levels, of these 202 had a combination and 961 had none of these risk factors) were included in the study between September 1, 1994 and December 31, 2007. Retrospective survival analysis showed that a total of 78 patients (4.1%) had died during the analysis period, among those four of definite or possible pulmonary embolism and four of bleeding. In multivariable analysis including age and sex an association with increased mortality was found for hyperhomocysteinemia (hazard ratio 2.0 [1.1.-3.5]) whereas this was not the case for all other investigated parameters. We conclude that the classical hereditary thrombophilia risk factors did not have an impact on the long-term survival of patients with a history of VTE. Thus our study supports the current concept that thrombophilia should not be a determinant for decision on long term anticoagulation. However, hyperhomocysteinaemia, known as a risk factor for recurrent VTE and arterial disease, might impact survival.

 
  • References

  • 1 Naess IA, Christiansen SC, Romundstad P. et al. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost 2007; 05: 692-699. DOI:10.1111/j.1538-7836.2007.02450.x.
  • 2 Heit JA, Silverstein MD, Mohr DN. et al. Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based, cohort study. Arch Intern Med 1999; 159: 445-453. DOI:10.1001/archinte.159.5.445.
  • 3 Anderson Jr FA, Wheeler HB, Goldberg RJ. et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 1991; 151: 933-938. DOI:10.1001/archinte.1991.00400050081016.
  • 4 Schulman S, Lindmarker P, Holmstrom M. et al. Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months. J Thromb Haemost 2006; 04: 734-742. DOI:10.1111/j.1538-7836.2006.01795.x.
  • 5 Garcia-Fuster MJ, Forner MJ, Fernandez C. et al. Long-term prospective study of recurrent venous thromboembolism in patients younger than 50 years. Pathophysiol Haemost Thromb 2005; 34: 6-12. DOI:10.1159/000088541.
  • 6 Prandoni P, Lensing AW, Cogo A. et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996; 125: 1-7.
  • 7 Reitter SE, Waldhoer T, Mayerhofer M. et al. Long-term survival of patients with a history of venous thromboembolism. Ann Hematol 2011; 90: 585-94. DOI:10.1007/s00277-011-1160-0.
  • 8 Thaler E, Lechner K. Antithrombin III deficiency and thromboembolism. Clin Haematol 1981; 10: 369-390.
  • 9 Dahlback B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-1008. DOI:10.1073/pnas.90.3.1004.
  • 10 Griffin JH, Evatt B, Zimmerman TS. et al. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370-1373. DOI:10.1172/JCI110385.
  • 11 Schwarz HP, Fischer M, Hopmeier P. et al. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64: 1297-1300.
  • 12 Koster T, Blann AD, Briet E. et al. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152-155. DOI:10.1016/S0140-6736(95)90166-3.
  • 13 den Heijer M, Koster T, Blom HJ. et al. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med 1996; 334: 759-762. DOI:10.1056/NEJM199603213341203.
  • 14 Kyrle PA, Minar E, Bialonczyk C. et al. The risk of recurrent venous thromboembolism in men and women. N Engl J Med 2004; 350: 2558-2563. DOI:10.1056/NEJMoa032959.
  • 15 Eichinger S, Kyrle PA. Duration of anticoagulation after initial idiopathic venous thrombosis--the swinging pendulum: risk assessment to predict recurrence. J Thromb Haemost 2009; 07 (Suppl. 01) 291-295. DOI:10.1111/j.1538-7836.2009.03383.x.
  • 16 Christiansen SC, Cannegieter SC, Koster T. et al. Thrombophilia, clinical factors, and recurrent venous thrombotic events. J Am Med Assoc 2005; 293: 2352-2361. DOI:10.1001/jama.293.19.2352.
  • 17 Rosendaal FR, Heijboer H. Mortality related to thrombosis in congenital antithrombin III deficiency. Lancet 1991; 337: 1545. DOI:10.1016/0140-6736(91)93234-Z.
  • 18 van Boven HH, Olds RJ, Thein SL. et al. Hereditary antithrombin deficiency: heterogeneity of the molecular basis and mortality in Dutch families. Blood 1994; 84: 4209-4213.
  • 19 Allaart CF, Rosendaal FR, Noteboom WM. et al. Survival in families with hereditary protein C deficiency, 1820 to 1993. Br Med J 1995; 311: 910-913. DOI:10.1136/bmj.311.7010.910.
  • 20 Hille ET, Westendorp RG, Vandenbroucke JP. et al. Mortality and causes of death in families with the factor V Leiden mutation (resistance to activated protein C). Blood 1997; 89: 1963-1967.
  • 21 Pabinger I, Vossen CY, Lang J. et al. Mortality and Inherited Thrombophilia: results from the European Prospective Cohort on Thrombophilia (EPCOT). J Thromb Haemost 2012; 10: 217-222. DOI:10.1111/j.1538-7836.2011.04573.x.
  • 22 Kovar FM, Marsik CL, Joukhadar C. et al. Coagulation factor VIII levels are associated with long-term survival - interactions with gender in a large hospital-based cohort. Wien Klin Wochenschr 2010; 122: 334-340. DOI:10.1007/s00508-010-1386-1.
  • 23 Statistics Austria.. www.statistik.at/web_en 2010.
  • 24 Pabinger I, Grafenhofer H, Kaider A. et al. Preeclampsia and fetal loss in women with a history of venous thromboembolism. Arterioscler Thromb Vasc Biol 2001; 21: 874-879. DOI:10.1161/01.ATV.21.5.874.
  • 25 Kyrle PA, Minar E, Hirschl M. et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000; 343: 457-462. DOI:10.1056/NEJM200008173430702.
  • 26 Kaplan EL MP. Nonparametric-estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457-481. DOI:10.1080/01621459.1958.10501452.
  • 27 Flinterman LE, van Hylckama Vlieg A, Cannegieter SC. et al. Long-term survival in a large cohort of patients with venous thrombosis: incidence and predictors. PLoS Med 2012; 09: e1001155. DOI:10.1371/journal.pmed.1001155.
  • 28 Bots ML, Launer LJ, Lindemans J. et al. Homocysteine and short-term risk of myocardial infarction and stroke in the elderly: the Rotterdam Study. Arch Intern Med 1999; 159: 38-44. DOI:10.1001/archinte.159.1.38.
  • 29 Kearon C, Akl EA, Comerota AJ. et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e419S-e494S. DOI:10.1378/chest.11-2301.