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Background: Protein S is an important regulatory protein of the coagulation cascade. The risk for venous thrombosis associated with protein S deficiency has been uncertain because all previous risk estimates used phenotypic evaluation alone, which can be ambiguous. Objective: To quantitate the risk for thrombosis associated with a characterized protein S gene mutation that causes a Gly295 [right arrow] Val substitution and protein S deficiency. Design: Retrospective study of a single extended family. Setting: University hospital referral center. Participants: A 122-member protein S-deficient family, in which 44 members had a recently characterized gene defect. Measurements: Comprehensive history of thrombosis, history of exposure to acquired risk factors for thrombosis, levels of total and free protein S antigen, and genotype for the mutation causing the Gly295 [right arrow] Val substitution. Results: Kaplan-Meier analysis of thrombosis-free survival showed that the probability of remaining free of thrombosis at 30 years of age is 0.5 (95% Cl, 0.33 to 0.66) for carriers of the Gly295-Val mutation compared with 0.97 (Cl, 0.93 to 1.0) for normal family members (P [is less than] 0.001). In a multivariate Cox regression model that included smoking and obesity, the mutation was a strong independent risk factor for thrombosis (hazard ratio, 11.5 [Cl, 4.33 to 30.6]; P [is less than] 0.001). For free (but not total) protein S antigen levels, the distributions of persons with and persons without the mutation did not overlap. Conclusions: Protein S deficiency, as defined by the presence of a causative gene mutation or a reduced level of free protein S antigen, is a strong independent risk factor for venous thrombosis in a clinically affected family., Persons deficient for protein S due to a genetic mutation appear to be at greater risk for developing deep venous blood clots. Protein S helps regulate the anticoagulation process. Deep venous blood clot risk was analyzed in 122 members of a family that had 44 individuals with the protein S defect. Those carrying the mutation were 11.5 times more likely to develop a deep venous blood clot compared to those not carrying the mutation, even after controlling for weight and smoking history. Protein S blood levels were a distinguishing factor between those with the defect and those without the defect.

Women who develop severe preeclampsia early in pregnancy may have certain blood abnormalities that predispose them to this condition. Detection of these abnormalities may have implications for prenatal care and for future pregnancies. Preeclampsia is a complication of pregnancy that includes high blood pressure and protein in the urine. Researchers performed blood tests 10 weeks after delivery on 101 patients who had severe preeclampsia early in their pregnancies. Thirty-nine patients had hypertension even when they were not pregnant, and a history of hypertension is an important risk factor for severe preeclampsia. Protein S deficiency, activated protein C resistance, high levels of homocysteine, and anticardiolipin antibodies were associated with severe early-onset preeclampsia.