Name
ANTITHROMBIN DEFICIENCY
DESCRIPTION
DETAIL
CAUSES: * GENETIC -------------------------------------------------------------------------- DIFFERENTIAL DIAGNOSIS β’ Factor V Leiden β’ Protein C deficiency β’ Protein S defi ciency β’ Dysfi brinogenemia β’ Dysplasminogenemia β’ Homocysteinemia β’ Prothrombin 20210 mutation β’ Elevated factor VIII levelsβ’ Antithrombin levels in the presence of heparin β’ Antithrombin activity assays
TYPENOTES
Drugs that may alter lab results:Heparin & asparaginase can lower antithrombin levels Disorders that may alter lab results:Liver disease, DIC, nephritic syndrome and preeclampsia reduce antithrombin levels β’ Ac thrombosis can lower antithrombin LRISK FACTORS β’ Oral contraceptives, pregnancy, and the use of hormone replacement therapy (HRT) increase the risk of venous thrombosis in patients with antithrombin deficiency β’ Patients with antithrombin defi ciency and another prothrombotic state such as factor V Leiden or the prothrombin 20210 mutation have increased rates of thrombosis GENERAL MEASURES β’ Routine anticoagulation for asymptomatic patients with antithrombin deficiency is not recommended β’ Patients with antithrombin deficiency and a first thrombosis should be anticoagulated initially with unfractionated heparin followed by oral anticoagulation with warfarin β’ The role of family screening for antithrombin deficiency is unclear since most patients with this mutation do not have thrombosis. Screening should be considered for women considering using oral contraceptives or pregnancy with a family history of factor protein S deficiency. DRUG(S) OF CHOICE β’ Warfarin can be initiated at 5 mg daily . Recurrent thrombosis requires indefi nite anticoagulation. β’ Heparin initial bolus of 80 U/kg followed by infusion of 18 U/kg/hr. Frequent monitoring of the PTT is important as nearly half of patients deficient in antithrombin require more than 40,000 U of heparin daily to adequately prolong the PTT. Once the INR is 2-3, heparin can be stopped after 5 total days of therapy. β’ Oral anticoagulant following the initial administration of heparin. Warfarin (Coumadin) 5 mg po q/day 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 PRECAUTIONS: β’ Observe patient for signs of embolization, further thrombosis, or bleeding β’ Avoid IM injections β’ Periodically check stool and urine for occult blood, monitor complete blood counts including platelets β’ Heparin - thrombocytopenia and/or paradoxical thrombosis with thrombocytopenia PATIENT MONITORING: Warfarin requires periodic (monthly after initial stabilization) monitoring of the INR PREVENTION/AVOIDANCE Patients with antithrombin defi ciency without thrombosis do not require prophylactic treatment POSSIBLE COMPLICATIONS: Recurrent thrombosis (requires indefi nite anticoagulation) EXPECTED COURSE/PROGNOSIS: The odds ratio of thrombosis in a patient with antithrombin deficiency is much higher than in other thrombophilic conditions. The recurrence rate is similarly high. There is no difference in clinical severity between patients with Type I defects and those with type II mutations involving the thrombin binding site.
RELATED DISEASE
Not Available Disease
DISEASE
INVESTIGATION
BLEEDING TIME, CLOTTING TIME, COMPLETE BLOOD COUNT