[MIM 612 304]

Autosomal recessive transmission (sometimes dominant) of a mutation of the PROC gene (2q13-q14).

Protein C is a vitamin K-dependent anticoagulant synthesized in the liver. It is present in the plasma in its inactivated form and is converted to its activated form in case of activation of the coagulation (binding of thrombin to thrombomodulin): in presence of   cofactor, protein S, calcium and phospholipids. It is then able to inhibit factors Va and VIIIa.

Two types are distinguished:

-        type I (75-80 %): the antigen and the activity are reduced

-        type II: the activity alone is reduced. On distinguishes subtype IIAM (24 %) where the active site of the protein is abnormal and subtype IIAC (0,5-1 %) where the catalytic site is intact.

The protein C deficiency can be:

-        congenital homozygous or compound heterozygous: 1 / 160 000 - 360,000 births.
Neonatal manifestations: formation of intravascular thrombi with cutaneous (purpura fulminans, bruises, blisters and cutaneous gangrene) and central (kidneys, brain, eyes) lesions

-        congenital heterozygous (protein C level is about 50 % of normal): 1/200-300; generally asymptomatic until adulthood  (deep venous thromboses) but children may suffer from thrombotic accidents.

-        acquired: in case of sepsis, DIC, liver failure, anti-vitamin K or L-asparaginase treatments; this should be kept in mind in presence of a thrombotic accident in a child.

The protein C level varies according to ethnic origin and age:

-        newborn: about 35 %

-        1 to 5 years of age: about 65 %

-        6 to 10 years of age: about 70 %

Some drugs may cause a moderate increase of protein C and thus conceal a deficiency: androgens, estroprogestational drugs.

In the same way, dabigatran and rivaroxaban may distort the plasmatic dosage of protein C.

Anesthetic implications:

give fresh frozen plasma (10-20 mL/kg) or, better, human protein C (60-80 IU/kg).

References : 

-        Stenberg TL, Bailey MK, Lazarchick J, Brahen NH. 
Protein C deficiency as a cause of pulmonary embolism in the perioperative period. 
Anesthesiology 1991; 74: 364-6.

Updated: May 2019