Recessive carriers may have variable expressivity. This is a genotype with recommended actions if clinically confirmed. In brief:
- Thrombophilia due to protein C deficiency (PROC) is characterized by reduced or absent coagulation activity.
- Partial PROC deficiency (heterozygous forms) can lead to an increased risk of venous thromboembolism (VTE), commonly a deep vein thrombosis (DVT; i.e. a blood clot) of the lower limbs with or without pulmonary embolism (PE; a clot lodged in the lungs). Cerebral venous thrombosis (CVT) may occur as well.
- Heterozygotes usually have no symptoms until adulthood. VTE events are mainly provoked by factors such as surgery, pregnancy, immobilization, or exogenous hormone use. Antithrombotic prophylaxis might be be effective in reducing stroke risk.
- Women with PROC deficiency are at an increased risk of VTE during pregnancy, with an estimated VTE risk of 0.1-0.8% per pregnancy without a prior VTE and 4-17% with a prior VTE.
- Perioperative VTE prophylaxis is recommended for patients with PROC deficiency during and after gynecological surgery
- Based on the increased risk of VTE, all pregnant women with an inherited thrombophilia should be referred to a local expert and undergo individualized risk assessment which may modify pregnancy management decisions; see detailed recommendations in the full ClinGen document (URL below).
- Thrombophilic disorders (including PROC deficiency) are contraindications for the use of estrogen containing prescription drugs approved for the prevention of postmenopausal osteoporosis.
- Patients with severe PROC deficiency (homozygous or compound heterozygous forms with undetectable PROC levels) typically manifest several hours to days after birth and may develop purpura fulminans, a life-threatening condition involving severe clotting throughout the body and causing necrosis of tissues.
The full ClinGen Actionability report about thrombophilia due to protein C deficiency (PROC) can be found here.
Genetic counseling may be available to you through your health-care network. In the US, genetic counselors may be found via this webpage of the National Society of Genetic Counselors.