Patients with the antiphospholipid antibody syndrome and a history of thrombosis have a high rate of recurrent thrombosis (in the range of 50% to 70%) if they are not given prolonged warfarin therapy. High-intensity warfarin therapy, to an international normalized ratio (INR) of 3.0 to 3.5, had been advocated for these patients. This recommendation was based primarily on a retrospective analysis, however, and two prospective clinical trials have now demonstrated that most of these patients can be adequately treated with conventional levels of anticoagulation (i.e., an INR of 2.0 to 3.0).¹ On the other hand, there are clearly some patients with antiphospholipid antibody syndrome who experience recurrent thrombosis with conventional anticoagulation and hence require a higher level of treatment.

The key to management of Trousseau syndrome is diagnosis and treatment of the underlying tumor. Unfortunately, tumors often present explosively in patients with Trousseau syndrome and may not respond to the usual therapies. In a prospective study, cancer patients had an approximately threefold increase in the rate of recurrent thrombosis and a twofold increase in the rate of major bleeding during warfarin treatment of deep vein thrombosis (DVT). These complications occurred mostly during the first few months of anticoagulation and did not reflect underanticoagulation or overanticoagulation but correlated with the extent and severity of the underlying cancer.¹ The likely explanation for the increased thrombosis recurrence in these patients is relative warfarin resistance, whereas the increased bleeding may be related to bleeding at the primary tumor site. A prospective trial found that the risk of recurrent venous thromboembolism was 50% lower in cancer patients who received long-term treatment with the low-molecular-weight heparin dalteparin than in those who received oral anticoagulation; there was no significant difference in the risk of major bleeding.² If a patient is receiving chemotherapy for the underlying cancer, an exacerbation of the disseminated intravascular coagulation associated with tumor lysis should be anticipated. An increase in the dose of heparin may be required.

Persistent elevation of D-dimer levels may help identify patients who are more likely to have recurrent venous thrombosis. In a prospective study, D-dimer levels that remained elevated 1 month after the discontinuance of warfarin were associated with a higher recurrence risk (approximately threefold to eightfold higher), whereas normal D-dimer levels had a high negative predictive value for recurrence.¹ Thus, patients with elevated D-dimer levels merit more vigilant monitoring and consideration of long-term anticoagulation.

The optimal intensity and duration of warfarin treatment in DVT have been the subject of many large clinical trials over the past decade. As regards the intensity of oral anticoagulation, an INR of 2 to 3 has proved optimal, with a low rate of thrombosis recurrence and a rate of major bleeding of about 3% a year. In comparison, treatment to an INR of 1.5 to 1.9 is less effective in reducing recurrent thrombosis (al though it is better than placebo) and provides no significant reduction in bleeding risk.^1,2