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 or protein S deficient patients to assess the role of additional thrombotic risk factors and of protein C and protein S levels in the clinical expression of hereditary protein C and protein S deficiency. Fifty-seven relatives were protein C (37) or protein S deficient (20). Thromboembolic events occurred in 30% of protein C deficient and in 35% of protein S deficient persons, compared with 3% and 0% in their normal controls respectively (P < 0.05). In protein C deficient persons, the median 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 events were more often associated with concomitant risk factors than the initial events: 64% and 50% in persons with protein C or protein S deficiency respectively. These findings suggest a substantial role for these risk factors in triggering thromboembolic events in deficient persons. Protein C antigen and protein S antigen levels were similar in symptomatic and asymptomatic deficient persons. Total, but not free, protein 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 this finding is not yet clear.
Henkens
C M
CM
Division of Haemostasis, Thrombosis and Rheology, University Hospital, Groningen, The Netherlands.
van der Meer
J
J
Hillege
J L
JL
van der Schaaf
W
W
Bom
V J
VJ
Halie
M R
MR
D000293:Adolescent; D000328:Adult; D001778:Blood Coagulation Disorders / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000378:metabolism; D020151:Protein C Deficiency; D017293:Protein S / Q000378:metabolism; D018455:Protein S Deficiency; D012307:Risk Factors; D013923:Thromboembolism / Q000097:blood / Q000235:genetics*
D011486:Protein C; D017293:Protein S