The hypercoagulable state. Who, how, and when to test and treat.

Patients with a family history of thrombosis, early-onset or recurring thrombosis, thrombosis at unusual sites, or warfarin-induced skin necrosis should be investigated for a possible underlying inherited hypercoagulable disorder. These include AT-III deficiency, protein C and S deficiencies, and APC resistance. Many patients should also be evaluated for the antiphospholipid syndrome, an acquired disorder. Functional assays are more useful than immunologic assays for diagnosing AT-III deficiency, protein C and S deficiencies, and APC resistance. A molecular probe is now available for the abnormal factor V most often responsible for APC resistance. Testing for the antiphospholipid syndrome involves assays for the lupus anticoagulant and anticardiolipin antibodies. AT-III and protein C concentrates are now available for short-term therapy. Long-term prophylactic administration of warfarin may have to be considered for some symptomatic patients with proven abnormalities, especially after more than one thrombotic event. While the management of asymptomatic persons remains controversial, the use of prophylactic anticoagulation should be anticipated for trauma, surgery, pregnancy, or other high-risk situations.