Laboratory screening of thrombophilia. Evaluation of the diagnostic efficacy of a global test to detect congenital deficiencies of the protein C anticoagulant pathway

Clinical laboratories are at present confronted with increasing demands for thrombophilia work-up, which may seriously overwhelm their capacity. Recently methods able to investigate the protein C anticoagulant pathway globally have been proposed In this study we investigated the reliability of one such method for its ability to detect patients with known defects of the pathway by testing plasmas from patients with the FVQ(506) mutation, with congenital protein C, protein S or antithrombin deficiencies, and patients with previous history of thrombosis, but no identifiable defects. The results show that the new global test fulfils the requirements for congenital protein C deficiency and activated protein C resistance associated with the FVQ(506) mutation, which account for more than half of the congenital defects found in thrombophilia. However, congenital protein S deficiency very often remains undetected by this test. Improvement of sensitivity toward this component of the protein C anticoagulant pathway would enroll the global test as a suitable candidate to explore the pathway. Since antithrombin, which also remains undetected by this test, is an additional important risk factor for venous thrombosis, devoting time and effort to developing global tests able to detect defects in both the antithrombin and protein C pathways is warranted. Blood Coag Fibrinol 9:485-489 (C) 1998 Lippincott Williams & Wilkins.