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

Department of Haematology, Haemostasis and Thrombosis Research Centre, University Hospital, Building 1, C2-R, PO Box9600, 2300 RC Leiden, Netherlands

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.

Key messages
* Individuals heterozygous for hereditary protein C deficiency have an increased risk of venous thrombotic events, including pulmonary embolism
* Anticoagulant prophylaxis may prevent such events, reducing morbidity
* Whether anticoagulant prophylaxis will also reduce mortality is not known
* This study shows that mortality is no higher in heterozygous individuals than in the general population
* Anticoagulant prophylaxis should not therefore be expected to improve the survival of heterozygous individuals

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