RISK FACTORS
β’ Oral contraceptives, pregnancy, and the use of hormone replacement therapy (HRT) increase the risk of
venous thrombosis in patients with protein S deficiency
β’ Patients with protein S deficiency and another prothrombotic state such as factor V Leiden or the prothrombin 20210 mutation have increased rates of thrombosis
β’ Patients heterozygous for protein S defi ciency who are begun on warfarin without concomitant heparin can
develop warfarin-induced skin necrosis because the half life of prothrombin, another vitamin K-dependent
clotting factors, is much longer than protein S (42 hours). These patients develop extremely low levels of
protein S relative to prothrombin 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 asymptomatic patients with protein S deficiency is not recommended
β’ Patients with protein S deficiency and a first thrombosis should be anticoagulated
β’ The role of family screening for protein S 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 factor protein S 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 adjusted to INR of 2-3. Patients should be maintained on warfarin 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 S deficiency without thrombosis do not require
prophylactic treatment
POSSIBLE COMPLICATIONS Recurrent thrombosis (requires indefi nite anticoagulation). Recurrence rate is 3.5% per year.
EXPECTED COURSE/PROGNOSIS
β’ The odds ratio of thrombosis in a patient with protein S deficiency is relatively low. However, families with
protein S deficiency have high rates of venous thromboembolism in protein S defi cient people as compared
with unaffected family members.
β’ Smoking and obesity increase the thrombotic risk in protein S deficient patients