Self-Managed Long-Term Low-Molecular-Weight Heparin Therapy Compared with Usual-Care Anticoagulation for the Treatment of Patients with Proximal Venous Thrombosis: Harm Associated with Thrombocytopenia.

Context: A substantial clinical need exists for an alternate to vitamin-K-antagonists for treating deep-vein thrombosis in many patients. Long-term low-molecular-weight heparin, body-weight adjusted, avoids anticoagulant monitoring and may be associated with less harm due to thrombocytopenia.

Objective: Considerable evidence suggests that reporting of harms-related data* from randomized clinical trials needs improvement. In accordance with CONSORT* we present a harm analysis regarding thrombocytopenia.

Design: Randomized clinical trial using objective outcome measures.

Setting: 30 centres across Canada.

Participants: Acute symptomatic proximal-vein thrombosis patients.

Intervention: Therapeutic tinzaparin subcutaneously once-daily, or intravenous unfractionated heparin/oral vitamin-K-antagonist therapy for 3 months.

Main Outcome Measures: Benefit was assessed by assessing the frequency of symptomatic objectively documented recurrent venous thromboembolism and harm by objectively documented hemorrhagic complications and the outcome of thrombocytopenia.

Results: Benefit and bleeding harm are reported elsewhere. Long-term low-molecular-weight heparin treatment was at least as effective but associated with less harm due to bleeding than usual care. Thrombocytopenia occurred in 21 of 369 (5.7%) patients receiving tinzaparin versus 9 of 368 (2.4%) patients receiving usual care (absolute difference 3.3). Six of 9 patients with thrombocytopenia receiving usual care died (66.7 percent, 95 percent confidence interval 29.9 to 92.5) versus 4 of 21 with thrombocytopenia receiving low-molecular-weight heparin (19 percent, 95 percent confidence interval 5.4 to 41.9 percent) (absolute difference 47.6 percent, 95 percent confidence interval 82.7 to 12.5 percent, p=0.03). Recurrent venous thromboembolism occurred infrequently in patients with thrombocytopenia.

Conclusion: Our findings suggest that harm associated with thrombocytopenia in patients receiving intravenous unfractionated heparin versus low-molecular-weight heparin favors low-molecular-weight heparin use. Further evaluation in rigorous trials is required.