ProCMD : 3D Protein C Mutations Database


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The protein C system and coagulation disorders

All the known coagulation disorders that affect the protein C system cause a reduced activity or effect of the APC system. The disorders can be divided into two categories: reduced activity due to protein deficiency and reduced effect due to APC resistance. APC disorders are known to increase the risk of thrombophylia, especially deep vein thrombosis.

Protein C deficiency

Two types of protein C deficiency exist. The predominant type I deficiency is characterised by a reduction in the biological activity as well as the antigen level of protein C, whereas the level of protein C antigen is normal but the biological activity is reduced in the type II deficiency. The relative risk of deep vein thrombosis with protein C deficiency is approximately 7.0 compared with normal controls. Studies suggested that protein C deficiency alone is a relatively low risk factor, and that the risk of thrombosis is considerably increased only if other genetic or acquired risk factor are present. Homozygous protein C deficiency is a rare condition and is associated with severe, often fatal thrombosis in the neonatal period.

APC resistance

APC resistance is the most common genetic defect that predisposes to thrombosis, and the most common mutation causing APC resistance is the factor VLeiden (in 90% of all cases). The prevalence of factor VLeiden in patient with deep venous thrombosis is approximately 40-50%, resulting in a relative risk factor of 7.0. In factor VLeiden the Arg 506 is mutated into a Gln, making it impossible for APC to cleavage at this site. In addition, cleavage at Arg 506 of intact factor V is necessary to convert it into the anticoagulant cofactor Vac that participates in the inactivation of factor VIIIa by APC.

References:
Activated protein C resistance and myocardial infarction.
Laffan M. A.
Heart
Vol. 80 (4), pp. 319-321, 1998

Thrombophilia: disorders predisposing to venous thromboembolism.
Pineo G. F., Hull R. D.
Clin. Haematol.
Vol. 11 (3), pp. 525-540, 1998


The protein C anticoagulant system: inherited defects as basis for venous thrombosis
Dahlback B.
Thromb. Res.
Vol. 77 (1), pp. 1-43, 1995