Increased risk of venous thrombosis in carriers of hereditary protein C deficiency defect.
The relevance of heterozygosity for hereditary protein C deficiency as a risk factor for venous thrombosis has been disputed because heterozygotes without symptoms have been identified among blood donors and relatives of homozygotes. As a result, clinicians do not know whether to offer prophylaxis or not. We have compared thrombosis-free survival in 161 heterozygous and normal members of the families of 24 heterozygotes for protein C deficiency referred from several centres in the Netherlands and with a history of symptoms. We studied the influence of heterozygosity and of putative additional risk factors on the occurrence of thrombotic events noted when a medical history was taken. Protein C activities were measured but a diagnosis of heterozygosity was based on the presence of the specific mutation in one of the protein C genes identified in the proband of the family. We found a significant difference in the thrombosis-free survival of the 77 heterozygotes and 84 normals: by age 45, 50% of heterozygotes and 10% of normal relatives can be expected to have had a manifestation of venous thromboembolism. The presence of such a mutation was clearly associated with an increased risk of venous thrombotic events. Thrombotic events occurred more often in years in which the patient had been immobile for more than a week or had had surgery. Other putative risk factors showed no significant effect in the incidence of thrombotic events. About 50% of all first episodes and 65% of recurrences of venous thromboembolism in the heterozygotes were spontaneous--ie, there was no predisposing event such as surgery or pregnancy. There was no increased risk for arterial occlusions in heterozygotes. We conclude that members of the family of a symptomatic heterozygote proband who are heterozygous for the mutation in the protein C gene have an increased risk of venous thrombotic events compared with their normal family members. For such individuals prophylactic anticoagulation should be considered; the decision will need to be taken on an individual basis.
Allaart
C F
CF
Department of Hematology, University Hospital Leiden, Netherlands.
Poort
S R
SR
Rosendaal
F R
FR
Reitsma
P H
PH
Bertina
R M
RM
Briët
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000235:genetics; D020151:Protein C Deficiency; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis; D013924:Thrombophlebitis / Q000453:epidemiology* / Q000235:genetics
D011486:Protein C