Survival in families with hereditary protein C deficiency, 1820 to 1993

OBJECTIVES —To establish the survival of individuals heterozygous for hereditary protein C deficiency, who have an increased risk ofvenous thrombotic events, and to compare it with the survival of the general population. DESIGN —Retrospective study in pedigrees of23 families with hereditary protein C deficiency for period 1820 and 1993. SETTING —23 completed family trees of 24 probandsfrom various parts of the Netherlands with symptoms of protein C deficiency. SUBJECTS —All 736 members of the 23 families with a50% or 100% probability of being (or having been) heterozygous for the genetic defect on the basis of DNA analysis or their place inthe pedigrees, following mendelian rules. MAIN OUTCOME MEASURES —Observed mortality compared with the mortality of thegeneral Dutch population; the standardised mortality ratio was calculated by dividing the observed mortality by the expected mortality. RESULTS —No excess mortality was found in the 206 proved heterozygous individuals and “obligatory transmitters” (those who havedefinitely passed on the deficiency) (standardised mortality ratio 0.95 (95% confidence interval 0.5 to 1.2)) or in the 530 familymembers with a 50% genetic probability of heterozygosity (1.10 (0.9 to 1.3)). CONCLUSION —Heterozygous individuals withhereditary protein C deficiency type I have normal survival compared with the general population. Prophylactic anticoagulant treatmentmay prevent thrombotic events in heterozygous individuals but may not be expected to improve their survival.