Venous thromboembolism and bleeding in a community setting

 

 Buy Article Permissions and Reprints

Summary

Bleeding is the most frequent complication of antithrombotic therapy for venous thromboembolism (VTE). However, little attention has been paid to the impact of bleeding after VTE in the community setting. The purpose of this investigation was to describe the incidence rate of bleeding after VTE, to characterize patients most at risk for bleeding, and to assess the impact of bleeding on rates of recurrent VTE and all-cause mortality. The medical records of residents of the Worcester (MA, USA) metropolitan area diagnosed with ICD-9 codes consistent with potential VTE during 1999, 2001, and 2003 were individually validated and reviewed by trained data abstracters. Clinical characteristics, acute treatment, and outcomes (including VTE recurrence rates, bleeding rates, and mortality) over follow-up (up to 3 years maximum) were evaluated. Bleeding occurred in 228 (12%) of 1,897 patients with VTE during our follow-up. Of these, 115 (58.8%) had evidence of early bleeding occurring within 30 days of VTE diagnosis. Patient characteristics associated with bleeding included impaired renal function and recent trauma. Other than a history of prior VTE, the occurrence of bleeding was the strongest predictor of recurrent VTE (hazard ratio [HR] 2.18; 95% confidence interval [CI] 1.54–3.09) and was also a predictor of total mortality (HR 1.97; 95%CI 1.57–2.47). The occur-rence of bleeding following VTE is associated with an increased risk of recurrent VTE and mortality. Future study of antithrombotic strategies for VTE should be informed by this finding. Advances that result in decreased bleeding rates may paradoxically decrease the risk of VTE recurrence.

• References

• 1 Fiessinger JN. et al. Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis. A randomized trial. J Am Med Assoc 2005; 293: 681-689.
  CrossrefPubMedGoogle Scholar
• 2 Buller HR. et al. for the Matisse Investigators. Fondaparinox or enoxaparin for the initial treatment of symptomatic deep vein thrombosis. A randomized trial. Ann Intern Med 2004; 140: 867-873.
  CrossrefPubMedGoogle Scholar
• 3 Kearon C. et al. Comparison of low-intensity warfarin therapy with conventional intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349: 631-639.
  CrossrefPubMedGoogle Scholar
• 4 Eikelboom JW. et al. Adverse impact of bleeding on prognosis in patients with acute coronary syndromes. Circulation 2006; 114: 774-782.
  CrossrefPubMedGoogle Scholar
• 5 Rao SV. et al. Impact of bleeding severity on clinical outcomes among patients with acute coronary syndromes. Am J Cardiol 2005; 96: 1200-1206.
  CrossrefPubMedGoogle Scholar
• 6 Spencer FA. et al, for the GRACE Investigators. Does comorbidity account for the excess mortality in patients with major bleeding in acute myocardial infarction. Circulation 2007; 116: 2793-2801.
  CrossrefPubMedGoogle Scholar
• 7 Spencer FA. et al. The Worcester Venous Thromboembolism Study: A population-based study of the clinical epidemiology of venous thromboembolism. J Gen Intern Med 2006; 21: 722-727.
  CrossrefPubMedGoogle Scholar
• 8 Spencer FA. et al. Outcomes after deep vein thrombosis and pulmonary embolism in the community: The Worcester Venous Thromboembolism Study. Arch Intern Med 2008; 168: 425-430.
  CrossrefPubMedGoogle Scholar
• 9 Silverstein MD. et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism. A 25-year population-based study. Arch Intern Med 1998; 158: 585-593.
  CrossrefPubMedGoogle Scholar
• 10 Grambsch PM, Therneau TM. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika 81: 515-526.
  PubMedGoogle Scholar
• 11 Palaretti G. et al. Thrombotic events during oral anticoagulant treatement : results of the inception-cohort, prospective, collaborative ISCOAT study : iS-COAT study group (Italian Study on Complications of Oral Anticoagulant Therapy). Thrombo Haemost 1997; 78: 1438-1443.
  PubMedGoogle Scholar
• 12 Abdelhafiz AH, Wheeldon NM. Results of an open-label prospective study of anticoagulant therapy for atrial fibrillation in an outpatient anticoagulation clinic. Clin Ther 2004; 26: 1470-1478.
  CrossrefPubMedGoogle Scholar
• 13 Beyth RJ. et al. Prospective evaluation of an index for predicting risk of major bleeding in outpatients treated with warfarin. Am J Med 1998; 105: 91-99.
  CrossrefPubMedGoogle Scholar
• 14 Gitter MJ. et al. Bleeding and thromboembolism during anticoagulant therapy: a population based study in Rochester, Minnesota. Mayo Clin Proc 1995; 70: 725-733.
  CrossrefPubMedGoogle Scholar
• 15 Steffensen FH. et al. Major haemorrhagic complications during oral anticoagulant therapy in a Danish population-based cohort. J Intern Med 1997; 242: 497-503.
  CrossrefPubMedGoogle Scholar
• 16 Willey VJ. et al. Management patterns and outcomes of patients with venous thromboembolism in the usual community practice setting. Clin Ther 2004; 26: 1149-1159.
  CrossrefPubMedGoogle Scholar
• 17 Pengo V. et al. for the ISCOAT Study Group. (Italian Study on Complications of Oral Anticoagulant Therapy). Oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and risk of bleeding: a multicenter inception cohort study. Thromb Haemost 2001; 85: 418-422.
  Article in Thieme ConnectPubMedGoogle Scholar
• 18 Hylek E, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994; 120: 897-802.
  CrossrefPubMedGoogle Scholar
• 19 White RH. et al. Major bleeding after hospitalization for deep vein thrombosis. Am J Med 1999; 107: 414-424.
  CrossrefPubMedGoogle Scholar
• 20 Prandoni P. et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100: 3484-3488.
  CrossrefPubMedGoogle Scholar
• 21 Iorio A. et al. Low-molecular-weight heparin for the long-term treatment of symptomatic venous thromboembolism: meta-analysis of the randomized comparisons with oral anticoagulants. J Thromb Haemost 2003; 01: 1906-1913.
  CrossrefPubMedGoogle Scholar
• 22 van Dongen CJJ. et al. Cochrane Peripheral Vascular Diseases Group. Fixed dose subcutaneous low-molecular-weight heparin versus adjusted dose unfractionated heparin for venous thromboembolism (update in Cochrane Database Syst Rev. 2008). Cochrane Database of Systematic Reviews 1, 2008.
  PubMedGoogle Scholar
• 23 Lee AYY. et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349: 146-153.
  CrossrefPubMedGoogle Scholar
• 24 LaPointe NM. et al. Enoxaparin dosing and associated risk of in-hospital bleeding and death in patients with non-ST-segment elevation acute coronary syndromes. Arch Intern Med 2007; 167: 1539-1544.
  CrossrefPubMedGoogle Scholar
• 25 Rao SV. et al. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. J Am Med Assoc 2004; 292: 555-562.
  CrossrefPubMedGoogle Scholar
• 26 Sabatine MS. et al. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation 2005; 111: 2042-2049.
  CrossrefPubMedGoogle Scholar
• 27 Yusuf S. et al. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med 2006; 354: 1464-1476.
  CrossrefPubMedGoogle Scholar