THE CLINICAL EXPRESSION OF HEREDITARY PROTEIN-C AND PROTEIN-S DEFICIENCY - A RELATION TO CLINICAL THROMBOTIC RISK-FACTORS AND TO LEVELS OF PROTEIN-C AND PROTEIN-S

We investigated 103 first-degree relatives of 13 unrelated protein C o r protein S deficient patients to assess the role of additional thromb otic risk factors and of protein C and protein S levels in the clinica l expression of hereditary protein C and protein S deficiency. Fifty-s even relatives were protein C (37) or protein S deficient (20). Thromb oembolic events occurred in 30% of protein C deficient and in 35% of p rotein S deficient persons, compared with 3% and 0% in their normal co ntrols respectively (P < 0.05). In protein C deficient persons, the me dian thromboembolic event-free survival was 55 years, while in protein S deficiency this interval was 33 years (P = 0.047). In the protein C deficient group 64% of the initial events occurred spontaneously, as did 71% in the protein S deficient group. Recurrent thromboembolic eve nts were more often associated with concomitant risk factors than the initial events: 64% and 50% in persons with protein C or protein S def iciency respectively. These findings suggest a substantial role for th ese risk factors in triggering thromboembolic events in deficient pers ons. Protein C antigen and protein S antigen levels were similar in sy mptomatic and asymptomatic deficient persons. Total, but not free, pro tein S antigen levels were significantly higher in symptomatic protein C deficient persons, as were protein C antigen and activity levels in symptomatic protein S deficient ones. The clinical implication of thi s finding is not yet clear.