Protein c deficiency (hereditary)D68.5

A protein C disorder was first described in 1981 by Griffin et al.

Heterozygous or homozygous mutation of the protein C gene with a deficiency or lack of protein C. Protein C is a vitamin K-dependent protease that is produced in the liver.

Together with a coenzyme, protein S, the protein C/protein S system is activated via the thrombin-thrombomodulin complex in a negative feedback reaction and inhibits the activated factors V and VIII (Va, VIIIa) by proteolytic cleavage. Thus, the protein C/protein S system plays a key role in the inhibition of hemostasis, because with this action it controls the activation of factor X to Xa and thus of prothrombin to thrombin.

A distinction is made between a heterozygous and a homozygous form in congenital protein C deficiency. Over 160 mutations of the protein C gene have been described. Most mutations are missense mutations that lead to the exchange of individual amino acids and thus to a type I defect.

In the analysis of protein C and protein S defects, a distinction is made between protein concentration and protein activity.

• Type I: In the case of such a deficiency, both the concentration and the activity are reduced due to a synthesis disorder.
• Type II: In this case the protein concentration is within the normal range. The biological activity is clearly reduced.

Hereditary deficiencies are distinguished between the homozygous and heterozygous form. In the homozygous form, the protein C activity is below 1%. Clinically, this already impresses the newborn with a purpura fulminans that is incompatible with life.
In the heterozygous form, the disease is predominantly type I, i.e. a reduction in protein concentration. The protein C activity is 50% of the norm.

The incidence of protein C deficiency is 1.3% of the population. In patients with recurrent phlebothromboses, protein C deficiency can be detected in 5-8%.

1. HA Neumann (2014) The coagulation system. ABW-Wissenschaftsverlag GmbH Berlin S. 217ff.