Without anticoagulation prophylaxis, deep venous thrombosis occurs in up to 30 percent of patients after abdominal surgery and in 40 to 70 percent of patients after major orthopedic surgery on the lower limbs. Ardeparin sodium, a low-molecular-weight heparin, and danaparoid sodium, a heparinoid, have received approval from the U.S. Food and Drug Administration for use in the prevention of deep venous thrombosis. Danaparoid is approved in the United States only for use in patients who have had hip replacement, and ardeparin is approved only for use in those who have had knee replacement. Consultants for the Medical Letter on Drugs and Therapeutics reviewed the evidence for the use of these two agents.

Low-molecular-weight heparins are produced by depolymerizing standard heparin. These heparins inactivate factor Xa and thrombin (factor IIa). They are more bioavailable than standard heparin after subcutaneous injection and have a longer half-life, resulting in the need for fewer doses per day. The plasma heparin concentrations are more predictable, permitting use of fixed dosages without routine monitoring of heparin activity.

Danaparoid sodium is a mixture of heparan sulfate, dermatan sulfate and chondroitin sulfate derived from porcine intestinal mucosa. It has a higher anti-Xa:anti-IIa ratio and a longer half-life than low-molecular-weight heparins. It can be given in fixed weight-adjusted doses once or twice daily and generally does not require laboratory monitoring. Few controlled trials of danaparoid have been published. One randomized controlled trial found that deep venous thrombosis occurred after hip replacement in 17 percent of the patients treated with danaparoid and in 32 percent of the patients treated with heparin and dihydroergotamine. One patient in each group developed pulmonary embolus.

Results of a double-blind randomized trial comparing ardeparin with placebo in patients undergoing knee surgery demonstrated that deep vein thrombosis occurred in 30 percent of the patients taking ardeparin and in 59 percent of the patients receiving placebo, a significant difference. Rates of major bleeding events were similar in both groups. Another study demonstrated that bleeding was more common with use of ardeparin. The incidence of bleeding complications with low-molecular-weight heparins or danaparoid appears to be similar to the rates with standard heparin. Heparin-induced thrombocytopenia may occur with any of these agents but appears to be less common with low-molecular-weight heparin and has not been reported with short-term use of danaparoid. Although the low-molecular-weight heparins are approved only for use in specific procedures, many experts believe that they could be used interchangeably for any of these major surgeries.

The Medical Letter consultants conclude that ardeparin and danaparoid appear to be slightly more effective than warfarin or standard heparin but have a similar incidence of bleeding complications and a lower incidence of thrombocytopenia. Unlike standard heparin, they can be given once or twice a day in fixed weight-adjusted dosages and do not usually require laboratory monitoring.