Cancer patients requiring interruption of long-term warfarin because of surgery or chemotherapy induced thrombocytopenia: the use of fixed sub-therapeutic doses of low-molecular weight heparin

Am J Hematol. 2012 Apr;87(4):388-91. doi: 10.1002/ajh.23122. Epub 2012 Feb 28.

Abstract

No data are available regarding the management of cancer patients requiring interruption of long-term vitamin-K antagonist (VKA) therapy. For this purpose, we tested the efficacy and safety of fixed doses of low-molecular weight heparin (LMWH) in substitution of VKA because of invasive procedures or chemotherapy-induced thrombocytopenia. In cancer patients on VKA, therapy was discontinued 5 ± 1 days before surgery or chemotherapy. Heparin was given at prophylactic dosage in patients at low risk and at fixed subtherapeutic doses (3,800 or 4,000 UI anti-FXa, b.i.d.) in those at high-risk for thrombosis. LMWH was reinitiated 12 hr after surgery and VKA the day after. In patients receiving chemotherapy, LMWH was reinitiated 12/24 hr after obtaining a stable platelet count ≥ 30,000 mmc(3) and VKA after a stable platelet count ≥ 50,000 mmc(3) . Thromboembolism and major bleeding events were recorded from the time of VKA suspension to 30 ± 2 days postprocedure or until the next chemotherapy. Overall, 156 patients (56.4% at low risk and 43.5% at high risk for thrombosis) were enrolled; 34.6% underwent major surgery, 40.4% nonmajor surgery, and 25% chemotherapy. Thrombotic events occurred in five patients [3.2%, 95% confidence interval (CI): 1.41-7.27], four belonging to the high-risk and one to the low-risk group. Major bleeding occurred in five patients (3.2%, 95 CI: 1.41-7.27), all belonging to the high-risk group (three during major surgery and two during chemotherapy). In conclusion, LMWH given at fixed subtherapeutic is a feasible and relatively safe approach for bridging therapy in cancer patients on long-term VKA.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Atrial Fibrillation / complications
  • Female
  • Heart Valve Prosthesis / adverse effects
  • Hemorrhage / chemically induced
  • Heparin, Low-Molecular-Weight / administration & dosage*
  • Heparin, Low-Molecular-Weight / adverse effects
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Neoplasms / blood*
  • Neoplasms / complications
  • Neoplasms / drug therapy
  • Neoplasms / surgery
  • Postoperative Complications / drug therapy
  • Postoperative Complications / prevention & control*
  • Prospective Studies
  • Risk
  • Thrombocytopenia / chemically induced
  • Thromboembolism / epidemiology
  • Thromboembolism / etiology
  • Thromboembolism / prevention & control*
  • Thrombophilia / drug therapy*
  • Thrombophilia / etiology
  • Warfarin / adverse effects
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • Antineoplastic Agents
  • Heparin, Low-Molecular-Weight
  • Warfarin