Screening for identified and unidentified protein C pathway defects by the Agkistrodon contortrix venom test in consecutive patients

To determine the real performance of the Agkistrodon contortrix venom (ACV) screening test for protein C (PC) pathway defects, we studied 400 consecutive patients referred for the study of personal venous thrombosis or for family study. All 82 patients with factor V Arg 506 Gin (FVR506Q) (n = 82), 6 patients with activated PC resistance without FV P506Q, 17 patients with PC deficiencies, and 9 patients with combined defects were identified by an abnormal ACV result Three of 6 protein S deficiencies overlapped the normal range. Among the 280 patients without a PC pathway defect, 63 of 193 with thrombosis and 18 of 87 asymptomatic subjects (relatives of patients with thrombosis) had an abnormal ACV result. A significant linear inverse relationship was observed between the ACV results and factor VIII. However 31 of 63 patients (49%) with thrombosis and 15 of 18 (83%) asymptomatic subjects with an abnormal ACV had a normal factor Vm level. This test, with a 100% negative predictive value, is reliable for screening for PC deficiencies and for FV R506Q and can be used safely as an exclusion test. Moreover the test may be useful to indicate in the PC pathway, unidentified risk factors for venous thrombosis.