Comparison of Subcutaneous Unfractionated Heparin with a Low Molecular Weight Heparin (Fragmin®) in Patients with Venous Thromboembolism and Contraindications to Coumarin

Abstract

SummaryIntravenous heparin followed by oral anticoagulant therapy (e. g. with coumarin) is still the most widely used treatment for deep venous thromboembolism. Self-administered subcutaneous injections of heparin have been thought of as a promising alternative to coumarin, but the high doses required for ongoing prophylaxis have raised concerns about the possible development of bone disease. Certainly, long-term heparin therapy has been reported to cause osteoporosis in both laboratory animals and humans.This study aimed to compare the efficacy and safety of unfractionated (UF) heparin with that of a low molecular weight heparin (Fragmin®, Kabi Pharmacia) in the prevention of recurrent deep venous thrombosis (DVT) and pulmonary embolism (PE) in a consecutive series of patients with contraindications to coumarin therapy. The patients comprised 40 men and 40 women, aged between 19 and 92 years (mean age, 68 years). They had all previously been diagnosed as having acute DVT and had been treated with conventional doses of heparin while in hospital. All patients had at least one of the following conditions: recent blood loss (either spontaneous or during admission while receiving heparin therapy); active gastroduodenal ulcer disease; psychological or physical inability or unwillingness to understand and accept the need for regular laboratory monitoring during coumarin treatment; chronic alcoholism; dementia; pregnancy; recent neurosurgery, and pericardial effusion; or were over 80 years of age. They were randomly allocated to receive either UF heparin, 10,000 IU s.c. b.d., or Fragmin®, 5000 IU anti-Factor Xa s. c. b. d., for a period of 3-6 months.Two patients taking UF heparin were readmitted to hospital 2 and 3 months after discharge, owing to symptomatic, scintigraphically proven recurrent PE. No patients receiving Fragmin® had recurrent PE. There were 10 reports of minor bleeding: six in patients receiving UF heparin and four in patients on Fragmin®. Furthermore, there were seven cases of spinal fracture: six in patients on UF heparin, and one in a patient taking Fragmin®.We conclude that fixed doses of both UFH and Fragmin® appear to be quite effective and safe for use in patients with a high risk of bleeding. In our experience, however, UF heparin is associated with an unacceptably high incidence of spinal fracture.