Hereditary Protein C Deficiency

Abstract

Hereditary protein C deficiency, which is inherited as an autosomal-dominant trait, predisposes to venous thrombotic disease. Heterozygotes are at risk for superficial thrombophlebitis, deep venous thrombosis and/or pulmonary embolism, which may occur without apparent cause at a young age. Other manifestations are cerebral venous thrombosis and mesenteric vein thrombosis. In severe, often homozygous, protein C deficiency, a purpura fulminans syndrome may occur shortly after birth, resulting in death due to extensive thrombosis, if it is not adequately treated. The thrombotic manifestations in heterzygotes are effectively prevented by coumarin therapy. However, in the initial phase of oral anticoagulant therapy, the patients have an increased risk for the development of coumarin-induced haemorrhagic skin necrosis. The purpura fulminans syndrome can be treated with either replacement therapy or with coumarin therapy. Heparin appears to be ineffective in the prevention of both the purpura fulminans syndrome and the coumarin-induced skin necrosis.

Hereditary thrombophilia: identification of nonsense and missense mutations in the protein C gene.

“…Protein C deficiency represents a major cause of thrombotic disease (3,(20)(21)(22)(23)(24) through the malfunction of an antithrombotic regulatory system including protein C, protein S, and an endothelial cell cofactor, thrombomodulin (24). However, the molecular basis of protein C deficiency is still almost completely unknown.…”

“…Hereditary thrombophilia, an autosomal dominant disease with a prevalence of 1 in 7500, is characterized by recurrent venous thrombosis in heterozygotes and neonatal purpura fulminans in homozygotes, due to a deficiency of any of three antithrombotic proteins, i.e., antithrombin III (1), protein S (2), or protein C (3). Protein C is a precursor of a plasma serine protease (4)(5)(6), exerting its anticoagulant activity through inactivation of factors Va and VIIIa, as well as stimulation of fibrinolysis (3).…”

“…Protein C is a precursor of a plasma serine protease (4)(5)(6), exerting its anticoagulant activity through inactivation of factors Va and VIIIa, as well as stimulation of fibrinolysis (3). Its cDNA (7)(8)(9) and gene (10,11) have been cloned and sequenced, and the gene has been mapped on chromosome 2 (12).…”

Genetics of Antiphospholipid Syndrome

“…Protein C deficiency has been implicated in adverse pregnancy outcomes such as deep venous thrombosis (DVT), preeclampsia, intrauterine growth restriction, and recurrent pregnancy loss (Greer, 2003). Family studies from the Netherlands and the US have shown that family members who are PC deficient are at an 8-10 fold increased risk of venous thrombosis, and, by age 40, 50% or more will have experienced a thrombotic event (Bovill et al, 1989); (Broekmans, 1985). The initial episode of venous thromboembolism in patients with protein C deficiency is apparently spontaneous in approximately 70 % of cases.…”

Perioperative management of a patient with purpura fulminans syndrome due to protein C deficiency

“…2 , 4 Patients with heterozygous protein C deficiency are at risk for superficial thrombophlebitis, deep venous thrombosis and pulmonary embolism, which may occur without apparent cause at a young age. 7,8 Patients with homozygous protein C deficiency present shortly after birth with life-threatening neonatal thrombosis, hemorrhagic necrosis due to vascular thrombosis, retinal hemorrhage and purpura fulminans. The site of mutation in this patient was found recently.…”