Because activated protein C degrades coagulation factors Va and VIIIa, deficiency of protein C predisposes to venous thrombosis.
(See also Overview of Thrombotic Disorders.)
Protein C is a vitamin K–dependent protein, as are coagulation factors II (prothrombin), VII, IX, and X and proteins S and Z. Because activated protein C (APC) degrades factors Va and VIIIa, APC is a natural plasma anticoagulant. Decreased protein C due to a genetic or an acquired abnormality predisposes to venous thrombosis (1).
Heterozygous deficiency of plasma protein C has a prevalence of 0.2 to 0.5% (2); in family studies of symptomatic probands, the life-time risk of venous thromboembolism (VTE) is high. Also, the risk of recurrent VTE is high (3). It is important to recognize that outcomes observed in family studies may not be generalizable to all patients with protein C deficiency.
Homozygous deficiency or doubly heterozygous deficiency causes neonatal purpura fulminans, ie, a severe neonatal type of disseminated intravascular coagulation (DIC), which manifests with ecchymoses and extensive venous and arterial thromboses, usually on the first day of life.
Acquired decreases in protein C occur in patients with liver disease or disseminated intravascular coagulation (DIC)
Diagnosis is based on antigenic and functional plasma assays of protein C.
General references
1. Dinarvand P, Moser KA. Protein C Deficiency. Arch Pathol Lab Med 2019;143(10):1281-1285. doi:10.5858/arpa.2017-0403-RS
2. Tait RC, Walker ID, Reitsma PH, et al. Prevalence of protein C deficiency in the healthy population. Thromb Haemost 1995;73(1):87-93.
3. Lijfering WM, Brouwer JL, Veeger NJ, et al. Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives. Blood 2009;113(21):5314-5322. doi:10.1182/blood-2008-10-184879
Treatment of Protein C Deficiency
Anticoagulation
warfarin loading doses. Instead, once patients are therapeutically anticoagulated with a parenteral agent, warfarin should be started at the estimated maintenance dose (eg, 5 mg daily) and parenteral anticoagulation should continue for at least 5 days and until the INR is ≥ 2.
warfarin for prevention of venous thromboembolism in patients with protein C deficiency.
