RISK FACTORS
β’ Oral contraceptives, pregnancy, and the use of hormone replacement therapy (HRT) increase the risk of
venous thrombosis in patients with protein C deficiency
β’ Patients with protein C defi ciency and another prothrombotic state such as factor V Leiden have increased rates of thrombosis
β’ Patients heterozygous for protein C deficiency who are begun on warfarin without concomitant heparin can
develop warfarin-induced skin necrosis because the half life of other vitamin K-dependent clotting factors,
prothrombin, factor IX and factor X, are much longer than protein C (4-8 hours). These patients develop
extremely low levels of protein C and develop necrosis of the skin over central areas of the body such as the
breast, abdomen, buttocks and genitalia.
GENERAL MEASURES
β’ Routine anticoagulation for aymptomatic patients with protein C deficiency is not recommended
β’ Anticoagulation is recommended for patients with protein C deficiency and a first thrombosis
β’ The role of family screening for protein C deficiency is unclear since most patients with this mutation do
not have thrombosis. Screening should be considered for woman considering using oral contraceptives or
pregnancy with a family history of protein C deficiency.
DRUG(S) OF CHOICE
. Low molecular weight heparin (LMWH)
. Enoxaparin (Lovenox) 1 mg/kg SQ bid. Alternatively, 1.5 mg/kg SQ per day. Initially for at least 5 days or
until INR is 2-3 at which time it can be stopped
. Tinzaparin (Innohep) 175 anti-Xa IU/kg SQ q/day
. Dalteparin (Fragmin) 200 IU/kg q/day
. Oral anticoagulant - warfarin (Coumadin) 5 mg po q/day initially and maintained on warfarin with an INR of 2-3 for at least 6 months
Contraindications:
. Active bleeding precludes anticoagulation; risk of bleeding is a relative contraindication to long-term
anticoagulation
. Warfarin is contraindicated in patients with a prior history of warfarin-induced skin necrosis
Precautions:
. Observe patient for signs of embolization, further thrombosis, or bleeding
. Avoid IM injections
. Periodically check stool and urine for occult blood, monitor complete blood counts including platelets
. Heparin - thrombocytopenia and/or paradoxical thrombosis with thrombocytopenia
. Warfarin - necrotic skin lesions (typically breasts, thighs and buttocks)
. LMWH - adjust dose in renal insufficiency
ALTERNATIVE DRUGS Heparin 80 mg/kg IV bolus followed by 18 mg/kg/hr. Adjust dose depending on PTT.
PATIENT MONITORING Warfarin requires periodic (monthly after initial stabilization) monitoring of the INR
PREVENTION/AVOIDANCE Patients with protein C deficiency without thrombosis do not require prophylactic treatment
POSSIBLE COMPLICATIONS Recurrent thrombosis (requires indefinite anticoagulation)
EXPECTED COURSE/PROGNOSIS
β’ When compared to normal individuals, persons with protein C deficiency have normal life spans
β’ By age 45, half of the people heterozygous for protein C deficiency will have venous thrombosis that is spontaneous half of the time