CLINICAL-FEATURES OF THROMBOPHILIA IN FAMILIES WITH GENE DEFECTS IN PROTEIN-C OR PROTEIN-S COMBINED WITH FACTOR-V-LEIDEN

Twenty-nine clinically well-characterized, symptomatic index patients, 15 with protein C and 14 with protein S deficiency, in whom the genet ic defect had been identified, were investigated for the presence of f actor V Leiden. In six of 15 (40%) propositi with protein C and four o f 14 (29%) with protein S deficiency, factor V Leiden was present. The age at first thrombosis was significantly lower (P < 0.001) in the te n propositi with a combined genetic defect (mean age 18.4 +/- 6.6 year s) than in those with a single defect (mean age 32.6 +/- 10.4 years). Spontaneous occurrence, recurrence and site of thrombosis were similar in propositi with the single and the combined defect. Family studies led to the identification of a combined defect in 18 individuals from 11 families (11 propositi and 29 relatives), seven subjects had no abn ormality, and in 15 a single defect was found. In individuals with a c ombined defect, thrombosis-free survival time was significantly shorte r than in individuals with a single defect, even after exclusion of in dex patients. None of the seven individuals without genetic abnormalit y had experienced thrombosis. Our findings indicate a higher risk for development of thrombosis in individuals with a combined defect compar ed with those with a single defect. (C) 1998 Rapid Science Ltd.