The Clinical Spectrum of Protein C Deficiency in a Large New England Kindred

Abstract

A family with a high incidence of venous thromboembolism over six generations has been investigated. Medical histories have been obtained on 136 of the 368 members of the kindred which allowed assignment of individuals into positive, equivocal, or negative categories with respect to their thrombotic manifestations. Protein C levels were determined by antigenic assay. Patients with protein C levels less than 66% of normal (mean, minus 2 SD) were classified as having protein C deficiency.The mean age of onset of thrombotic manifestations in the 10 protein C deficient patients with a positive history was 33.8 ± 16.4 years while the mean age of the deficient group with a negative history was 22.0 ± 10.9 years. We conclude that there exists a striking association between thromboembolic disease and protein C deficiency within this large New England kindred.

Paediatric thrombo-embolism: the influence of non-genetic factors and the role of activated protein C resistance and protein C deficiency

“…In another preliminary report on 28 children, 7 (25%) had APC resistance [21]. Our single centre study of 37 children with thrombosis clearly confirms APC resistance and protein C deficiency [5,18] as significant genetic risk factors, although the magnitude of this effect was much less marked. APC resistance was found in only 5 (13.5%) and protein C deficiency in 2 (5.5%) patients.…”

“…Genetic risk factors for thrombo-embolism in children include deficiency of the anticoagulatory proteins C, S, antithrombin, heparin-cofactor II and 2-macroglobulin, the carbohydrate deficient glycoproteins (CDG) syndrome, hyperhomocysteinaemia, dysfibrinogenaemia, dysplasminogenaemia and hyperlipoproteinaemia [1,4,5,[8][9][10][11][12]16]. However, such traits can only be identified in 5%-10% of children with thrombosis [6].…”

Thrombophilias—Practical Implications and Testing Caveats

“…Similar to deficiency of antithrombin and protein S, protein C deficiency is a risk factor for mainly venous thromboembolism [14,15]. A few cases of arterial thromboembolism have been reported in patients with protein C deficiency.…”

Genetic polymorphisms associated with carotid artery intima-media thickness and coronary artery calcification in women of the Kronos Early Estrogen Prevention Study

“…Mutations may occur in several pathways: 1) components of the anticoagulant pathway, 2) mutations that down-or upregulate the procoagulant pathway, 3) mutations that downregulate fibrinolysis, and 4) mutations of the immunological pathway (69). However, isolated impairment of one of these pathways is insufficient to cause thrombosis (10,28,59). Thus, in the setting of changes in hormonal status (estrogen-deplete or -replete), interactions among pathways linking hemostasis to cardiovascular risk represent complex genetic phenomena.…”