Download PDF
Thromb Haemost 2022; 122(06): 1017-1026
DOI: 10.1055/s-0041-1740184
Stroke, Systemic or Venous Thromboembolism

Do Patients with a Family or Personal History of Venous Thromboembolism have an Increased Risk of Recurrence?

Jonas Florin
1   Department of General Internal Medicine, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland
,
Odile Stalder
2   CTU Bern, University of Bern, Bern, Switzerland
,
Christine Baumgartner
1   Department of General Internal Medicine, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland
,
Marie Méan
3   Service of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland
,
Nicolas Rodondi
1   Department of General Internal Medicine, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland
4   Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
,
Drahomir Aujesky
1   Department of General Internal Medicine, Bern University Hospital (Inselspital), University of Bern, Bern, Switzerland
› Author Affiliations Funding This study was funded by Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (33CSCO-122659/139470).
› Further Information
Also available at
    Permissions and Reprints

Abstract

Background A family (FH) and personal history (PH) of venous thromboembolism (VTE) are commonly evaluated risk factors for recurrence. We examined the association between FH/PH of VTE and the risk of recurrence and whether a stronger history status (i.e., both FH/PH vs. no FH/PH) carries an increased recurrence risk.

Methods We prospectively followed 813 patients aged ≥ 65 years with acute VTE from 9 Swiss hospitals. We classified patients into four groups: no FH/PH, FH only, PH only, and both FH/PH. The primary outcome was recurrent VTE during the full observation period. We examined the association between FH/PH status and the time to VTE recurrence using competing risk regression, adjusting for confounders and periods of anticoagulation.

Results Of 813 patients with VTE, 59% had no FH/PH, 11% a FH only, 24% a PH only, and 7% had both a FH and PH of VTE. Overall, 105 patients had recurrent VTE during the full observation period. After adjustment, patients with a FH only (subhazard ratio [SHR] 0.8, 95% confidence interval [CI] 0.4–1.7), PH only (SHR 1.5, 95% CI 0.9–2.5), and both FH/PH (SHR 1.4, 95% CI 0.6–3.1) did not have an increased risk of recurrent VTE compared with those without FH/PH. When we considered the period after the completion of initial anticoagulation only, the results were similar.

Conclusion Our findings indicate that in patients with acute VTE, a FH and/or PH of VTE does not convey an increased risk of recurrent VTE. In particular, we did not find a “dose–effect” relationship between FH/PH status and VTE recurrence.

Keywords

family history - personal history - venous thromboembolism


Publication History

Received: 19 July 2021

Accepted: 10 October 2021

Article published online:
28 December 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 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
    CrossrefPubMedSearch in Google Scholar
  • 2 Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR. Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA 2005; 293 (19) 2352-2361
    CrossrefPubMedSearch in Google Scholar
  • 3 Kyrle PA, Minar E, Bialonczyk C, Hirschl M, Weltermann A, Eichinger S. The risk of recurrent venous thromboembolism in men and women. N Engl J Med 2004; 350 (25) 2558-2563
    CrossrefPubMedSearch in Google Scholar
  • 4 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
    CrossrefPubMedSearch in Google Scholar
  • 5 Zöller B, Li X, Ohlsson H, Ji J, Sundquist J, Sundquist K. Family history of venous thromboembolism as a risk factor and genetic research tool. Thromb Haemost 2015; 114 (05) 890-900
    PubMedSearch in Google Scholar
  • 6 Baglin T. Using the laboratory to predict recurrent venous thrombosis. Int J Lab Hematol 2011; 33 (04) 333-342
    CrossrefPubMedSearch in Google Scholar
  • 7 Zöller B, Li X, Sundquist J, Sundquist K. Age- and gender-specific familial risks for venous thromboembolism: a nationwide epidemiological study based on hospitalizations in Sweden. Circulation 2011; 124 (09) 1012-1020
    CrossrefPubMedSearch in Google Scholar
  • 8 Zöller B, Ohlsson H, Sundquist J, Sundquist K. Family history of venous thromboembolism (VTE) and risk of recurrent hospitalization for VTE: a nationwide family study in Sweden. J Thromb Haemost 2014; 12 (03) 306-312
    CrossrefPubMedSearch in Google Scholar
  • 9 Sundquist K, Sundquist J, Svensson PJ, Zöller B, Memon AA. Role of family history of venous thromboembolism and thrombophilia as predictors of recurrence: a prospective follow-up study. J Thromb Haemost 2015; 13 (12) 2180-2186
    CrossrefPubMedSearch in Google Scholar
  • 10 de Moreuil C, Le Mao R, Le Moigne E. et al. Long-term recurrence risk after a first venous thromboembolism in men and women under 50 years old: a French prospective cohort. Eur J Intern Med 2021; 84: 24-31
    CrossrefPubMedSearch in Google Scholar
  • 11 Hron G, Eichinger S, Weltermann A. et al. Family history for venous thromboembolism and the risk for recurrence. Am J Med 2006; 119 (01) 50-53
    CrossrefPubMedSearch in Google Scholar
  • 12 Mello TB, Orsi FL, Montalvao SA, Ozelo MC, de Paula EV, Annichinno-Bizzachi JM. Long-term prospective study of recurrent venous thromboembolism in a Hispanic population. Blood Coagul Fibrinolysis 2010; 21 (07) 660-665
    CrossrefPubMedSearch in Google Scholar
  • 13 Gauthier K, Kovacs MJ, Wells PS, Le Gal G, Rodger M. REVERSE investigators. Family history of venous thromboembolism (VTE) as a predictor for recurrent VTE in unprovoked VTE patients. J Thromb Haemost 2013; 11 (01) 200-203
    CrossrefPubMedSearch in Google Scholar
  • 14 Anderson Jr FA, Spencer FA. Risk factors for venous thromboembolism. Circulation 2003; 107 (23, Suppl 1): I9-I16
    PubMedSearch in Google Scholar
  • 15 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
  • 16 Nemeth B, Lijfering WM, Nelissen RGHH. et al. Risk and risk factors associated with recurrent venous thromboembolism following surgery in patients with history of venous thromboembolism. JAMA Netw Open 2019; 2 (05) e193690
    CrossrefPubMedSearch in Google Scholar
  • 17 Barbar S, Noventa F, Rossetto V. et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 2010; 8 (11) 2450-2457
    CrossrefPubMedSearch in Google Scholar
  • 18 Kapoor S, Opneja A, Gollamudi J, Nayak LV. Prior history of venous thromboembolism is a significant risk factor for recurrence of thrombosis after cancer diagnosis. Paper presented at: 62nd Annual Meeting and Exposition of American Society of Hematology; December 6, 2020; Virtual Conference
    PubMed
  • 19 Pabinger I, Grafenhofer H, Kaider A. et al. Risk of pregnancy-associated recurrent venous thromboembolism in women with a history of venous thrombosis. J Thromb Haemost 2005; 3 (05) 949-954
    CrossrefPubMedSearch in Google Scholar
  • 20 Le Gal G, Righini M, Roy PM. et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med 2006; 144 (03) 165-171
    Search in Google Scholar
  • 21 Wells PS, Anderson DR, Rodger M. et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003; 349 (13) 1227-1235
    Search in Google Scholar
  • 22 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
    CrossrefPubMedSearch in Google Scholar
  • 23 Le Gal G, Righini M, Sanchez O. et al. A positive compression ultrasonography of the lower limb veins is highly predictive of pulmonary embolism on computed tomography in suspected patients. Thromb Haemost 2006; 95 (06) 963-966
    Thieme ConnectPubMedSearch in Google Scholar
  • 24 Büller HR, Davidson BL, Decousus H. et al; Matisse Investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med 2003; 349 (18) 1695-1702
    CrossrefPubMedSearch in Google Scholar
  • 25 Dauzat M, Laroche JP, Deklunder G. et al. Diagnosis of acute lower limb deep venous thrombosis with ultrasound: trends and controversies. J Clin Ultrasound 1997; 25 (07) 343-358
    CrossrefPubMedSearch in Google Scholar
  • 26 Fraser DG, Moody AR, Morgan PS, Martel AL, Davidson I. Diagnosis of lower-limb deep venous thrombosis: a prospective blinded study of magnetic resonance direct thrombus imaging. Ann Intern Med 2002; 136 (02) 89-98
    CrossrefPubMedSearch in Google Scholar
  • 27 Fraser DG, Moody AR, Davidson IR, Martel AL, Morgan PS. Deep venous thrombosis: diagnosis by using venous enhanced subtracted peak arterial MR venography versus conventional venography. Radiology 2003; 226 (03) 812-820
    CrossrefPubMedSearch in Google Scholar
  • 28 Enden T, Sandvik L, Kløw NE. et al. Catheter-directed Venous Thrombolysis in acute iliofemoral vein thrombosis–the CaVenT study: rationale and design of a multicenter, randomized, controlled, clinical trial (NCT00251771). Am Heart J 2007; 154 (05) 808-814
    CrossrefPubMedSearch in Google Scholar
  • 29 Kearon C, Ginsberg JS, Hirsh J. The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Ann Intern Med 1998; 129 (12) 1044-1049
    CrossrefPubMedSearch in Google Scholar
  • 30 Righini M, Paris S, Le Gal G, Laroche JP, Perrier A, Bounameaux H. Clinical relevance of distal deep vein thrombosis. Review of literature data. Thromb Haemost 2006; 95 (01) 56-64
    Thieme ConnectPubMedSearch in Google Scholar
  • 31 Heit JA, Mohr DN, Silverstein MD, Petterson TM, O'Fallon WM, Melton III LJ. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 2000; 160 (06) 761-768
    CrossrefPubMedSearch in Google Scholar
  • 32 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
    CrossrefPubMedSearch in Google Scholar
  • 33 Méan M, Limacher A, Stalder O. et al. Do factor V Leiden and prothrombin G20210A mutations predict recurrent venous thromboembolism in older patients?. Am J Med 2017; 130 (10) 1220.e17-1220.e22
    CrossrefPubMedSearch in Google Scholar
  • 34 Méan M, Aujesky D, Lämmle B, Gerschheimer C, Trelle S, Angelillo-Scherrer A. Design and establishment of a biobank in a multicenter prospective cohort study of elderly patients with venous thromboembolism (SWITCO65+). J Thromb Thrombolysis 2013; 36 (04) 484-491
    CrossrefPubMedSearch in Google Scholar
  • 35 Büller HR, Gent M, Gallus AS, Ginsberg J, Prins MH, Baildon R. Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997; 337 (10) 657-662
    CrossrefPubMedSearch in Google Scholar
  • 36 Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94 (446) 496-509
    Search in Google Scholar
  • 37 Novacek G, Weltermann A, Sobala A. et al. Inflammatory bowel disease is a risk factor for recurrent venous thromboembolism. Gastroenterology 2010; 139 (03) 779-787
    CrossrefPubMedSearch in Google Scholar
  • 38 Gupta R, Ammari Z, Dasa O. et al. Long-term mortality after massive, submassive, and low-risk pulmonary embolism. Vasc Med 2020; 25 (02) 141-149
    CrossrefPubMedSearch in Google Scholar
  • 39 Naess IA, Christiansen SC, Romundstad P, Cannegieter SC, Rosendaal FR, Hammerstrøm J. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost 2007; 5 (04) 692-699
    CrossrefPubMedSearch in Google Scholar
  • 40 Spencer FA, Gore JM, Lessard D. et al. Venous thromboembolism in the elderly. A community-based perspective. Thromb Haemost 2008; 100 (05) 780-788
    Thieme ConnectPubMedSearch in Google Scholar
  • 41 Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial. Lancet 1960; 1 (7138): 1309-1312
    CrossrefPubMedSearch in Google Scholar
  • 42 Rubin D. Multiple imputation for nonresponse in surveys. Stat Pap (Berl) 1990; 31 (01) 180-180
    CrossrefPubMedSearch in Google Scholar
  • 43 Kearon C. Natural history of venous thromboembolism. Circulation 2003; 107 (23, Suppl 1): I22-I30
    CrossrefPubMedSearch in Google Scholar
  • 44 Murin S, Romano PS, White RH. Comparison of outcomes after hospitalization for deep venous thrombosis or pulmonary embolism. Thromb Haemost 2002; 88 (03) 407-414
    Thieme ConnectPubMedSearch in Google Scholar
  • 45 Samama MM. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study. Arch Intern Med 2000; 160 (22) 3415-3420
    CrossrefPubMedSearch in Google Scholar
  • 46 Eriksson H, Lundström T, Wåhlander K, Clason SB, Schulman S. THRIVE III Investigators. Prognostic factors for recurrence of venous thromboembolism (VTE) or bleeding during long-term secondary prevention of VTE with ximelagatran. Thromb Haemost 2005; 94 (03) 522-527
    PubMedSearch in Google Scholar
  • 47 Engbers MJ, van Hylckama Vlieg A, Rosendaal FR. Venous thrombosis in the elderly: incidence, risk factors and risk groups. J Thromb Haemost 2010; 8 (10) 2105-2112
    CrossrefPubMedSearch in Google Scholar
  • 48 Kearon C, Akl EA, Ornelas J. et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149 (02) 315-352
    CrossrefPubMedSearch in Google Scholar
  • 49 Baglin T, Luddington R, Brown K, Baglin C. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet 2003; 362 (9383): 523-526
    CrossrefPubMedSearch in Google Scholar
  • 50 Prins MH, Lensing AWA, Prandoni P. et al. Risk of recurrent venous thromboembolism according to baseline risk factor profiles. Blood Adv 2018; 2 (07) 788-796
    CrossrefPubMedSearch in Google Scholar
  • 51 Mulatu A, Melaku T, Chelkeba L. Deep venous thrombosis recurrence and its predictors at selected tertiary hospitals in Ethiopia: a prospective cohort study. Clin Appl Thromb Hemost 2020; 26: 1076029620941077
    CrossrefPubMedSearch in Google Scholar
  • 52 Iorio A, Kearon C, Filippucci E. et al. Risk of recurrence after a first episode of symptomatic venous thromboembolism provoked by a transient risk factor: a systematic review. Arch Intern Med 2010; 170 (19) 1710-1716
    CrossrefPubMedSearch in Google Scholar
  • 53 Ridker PM, Goldhaber SZ, Danielson E. et al; PREVENT Investigators. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003; 348 (15) 1425-1434
    CrossrefPubMedSearch in Google Scholar