Protein C deficiency
|Protein C deficiency|
|Classification and external resources|
Protein C deficiency is a rare genetic trait that predisposes to thrombotic disease. It was first described in 1981. The disease belongs to a group of genetic disorders known as thrombophilias. The prevalence of protein C deficiency has been estimated to about 0.2% to 0.5% of the general population. Protein C deficiency is associated with an increased incidence of venous thromboembolism (relative risk 8-10), whereas no association with arterial thrombotic disease has been found.
The main function of protein C is its anticoagulant property as an inhibitor of coagulation factors V and VIII. A deficiency results in a loss of the normal cleaving of Factors Va and VIIIa. There are two main types of protein C mutations that lead to protein C deficiency:
- Type I: Quantitative defects of protein C (low production or short protein half life)
- Type II: Qualitative defects, in which interaction with other molecules is abnormal. Defects in interaction with thrombomodulin, phospholipids, factors V/VIII and others have been described.
The majority of people with protein C deficiency lack only one of the functioning genes, and are therefore heterozygous. Before 1999, only sixteen cases of homozygous protein C deficiency had been described (two abnormal copies of the gene, leading to absence of functioning protein C in the bloodstream). This may manifest itself as purpura fulminans in the newborn.
Protein C is vitamin K-dependent. Patients with Protein C deficiency are at an increased risk of developing skin necrosis while on warfarin. Protein C has a short half life (6hrs) compared with other vitamin K-dependent factors and therefore is rapidly depleted with warfarin initiation, resulting in a transient hypercoagulable state.
Primary prophylaxis with low-molecular weight heparin, heparin, or warfarin is often considered in known familial cases. Anticoagulant prophylaxis is given to all who develop a venous clot regardless of underlying cause.
Studies have demonstrated an increased risk of recurrent venous thromboembolic events in patients with protein C deficiency. Therefore, long-term anticoagulation therapy with warfarin may be considered in these patients.
Homozygous protein C defect constitutes a potentially life-threatening disease, and warrants the use of supplemental protein C concentrates.
- Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C (1981). "Deficiency of protein C in congenital thrombotic disease". J. Clin. Invest. 68 (5): 1370–3. doi:10.1172/JCI110385. PMC 370934. PMID 6895379.
- Khan S, Dickerman JD (2006). "Hereditary thrombophilia". Thromb J 4 (1): 15. doi:10.1186/1477-9560-4-15. PMC 1592479. PMID 16968541.
- Goldenberg NA, Manco-Johnson MJ. Protein C deficiency. Haemophilia. 2008 Nov;14(6):1214-21
- Pediatr Transplant. 2009 Mar;13(2):251-4. Epub 2008 May 11. Long-term survival of a child with homozygous protein C deficiency successfully treated with living donor liver transplantation.