Name
FACTOR V LEIDEN
DESCRIPTION
DETAIL
CAUSES : Point mutation causing substitution of arginine for glycine in residue 506 of factor V gene rendering it less susceptible to inactivation by activated protein C. Activated protein C is generated when protein C binds to its endothelial receptor, thrombomodulin. Activated protein C and its cofactor, protein S, lead to inactivation of factors V and VIII. Factor V Leiden is the most common cause of resistance to activated protein C. -------------------------------------------------------------------------- DIFFERENTIAL DIAGNOSIS β’ Protein C deficiency β’ Protein S deficiency β’ Antithrombin deficiency β’ Other causes of activated protein C resistance (e.g., antiphospholipid antibodies) β’ Dysfibrinogenemia β’ Dysplasminogenemia β’ Homocysteinemia β’ Prothrombin 20210 mutation β’ Elevated factor VIII levelsβ’ Factor V Leiden Mutation Analysis SPECIAL TESTS β’ DNA-based test for factor V mutation β’ Plasma-based coagulation assay using factor V deficient plasma to which patient plasma is added along with purified activated protein C. The relative prolongation of the activated partial thromboplastin time (aPTT) is used to assay for the defect. IMAGING : Magnetic resonance angiography (MRA), venography, arteriography to detect thrombosis
TYPENOTES
RISK FACTORS: Oral contraceptives increase the risk of thrombosis. he risk is halved when the patient uses a desogestrel-containing OC. Hormone replacement therapy (HRT) and selective estrogen receptor modulators (SERM) both increase the riskGENERAL MEASURES : β’ Patients with factor V Leiden and a fi rst thrombosis should be anticoagulated initially with heparin or low molecular weight heparin followed by oral anticoagulation with warfarin. Patients should be maintained on warfarin with an INR of 2 to 3 for at least 6 months. Recurrent thrombosis requires indefi nite anticoagulation. PATIENT EDUCATION : β’ Patients should be educated about use of oral anticoagulant therapy if taking such β’ Avoid NSAIDs while on warfarin β’ The role of family screening is unclear since most patients with this mutation do not have thrombosis. In a patient with a family history of Factor V Leiden, consider screening during pregnancy or if considering oral contraceptive use. DRUG(S) OF CHOICE : . Low molecular weight heparin (LMWH) . Enoxaparin (Lovenox) 1mg/kg SC bid 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 SC qd . Dalteparin (Fragmin) 200 IU/kg SC qd . Oral anticoagulant . Warfarin (Coumadin) 5 mg qd initially and adjusted to an INR of 2-3 PRECAITIONS: β’ Observe patient for signs of embolization, further thrombosis or bleeding β’ Avoid IM injections. Periodically check stool and urine for occult blood, monitor complete blood counts including platelets. β’ Heparin - thrombocytopenia and/or paradoxical thrombosis with thrombocytopenia β’ Warfarin - necrotic skin lesions (typically breasts, thighs, buttocks) β’ LMWH - adjust dosage in renal insufficiency ALTERNATIVE DRUGS : β’ Heparin 80 mg/kg IV bolus followed by 18 mcg/kg/hr. Adjust dose depending on aPTT. PATIENT MONITORING : β’ Warfarin use requires periodic (approximately monthly after initial stabilization) INR measurements with a goal of 2-3 PREVENTION/AVOIDANCE : β’ Patients with factor V Leiden without thrombosis do not require prophylactic treatment POSSIBLE COMPLICATIONS : β’ Venous or arterial thrombosis β’ Bleeding in anticoagulated patients EXPECTED COURSE/PROGNOSIS : Most patients heterozygous for factor V Leiden do not have thrombosis. Homozygotes have about a 50% incidence of thrombosis. Recurrence rates after a first thrombosis are not clear with some investigators finding rates as high as 5% and others fi nding rates similar to the general population. Despite the increased risk for thrombosis, factor V Leiden does not increase overall mortality.
RELATED DISEASE
Not Available Disease
DISEASE
INVESTIGATION
COMPLETE BLOOD COUNT, MR ANGIOGRAPHY, COAGULATION PROFILE, COLOR DOPPLER