Anticoagulation and DVT

Anticoagulation in Deep Vein Thrombosis(According to American College of Chest Physician guidelines)Jibran MohsinResident, Surgical Unit ISIMS/Services Hospital, LahoreRationaleAnticoagulant therapy remains the mainstay of medical therapy for DVT because it(s)

Is noninvasive, Treats most patients (approximately 90%) with no immediate demonstrable physical sequelae of DVT,Has low risk of complications, and outcome data demonstrate an improvement in morbidity and mortality.Ideal Anticoagulant DrugPrevent pathologic thrombosisLimiting reperfusion injuryi.e. preservation of extrinsic pathway (Tissue Factor-VIIa initial phase)

Allow physiologic thrombosisLimiting bleeding(normal response to vascular injury)i.e. attenuation of secondary intrinsic pathway propagation phaseTILL NOWNO SUCH DRUG EXIST..All anticoagulant drugs have increased bleeding risk as their principle toxicityOPTIONSInitial short-term anticoagulationLong-term anticoagulation

Conventional HeparinUnfractionated heparin-UFH (IV)

Fixed-dose UFH (SC)

LMWH (SC)

Warfarin (oral)New (NO Monitoring required)Factor Xa inhibitorFondaparinux (SC)

Factor Xa inhibitors Rivaroxaban (oral)Apixaban (oral)Direct thrombin inhibitorsDabigatran (oral)Indirect Thrombin Inhibitors

Antithrombin(AT): endogenous anticoagulant; inactivates IIa(thrombin), IXa, Xa, XIa and XIIa6HeparinHeterogeneous mixture of sulfated mucopolysaccharides

Cofactor for AT-protease interaction without being consumed

Mechanism of Action

Also inhibits activation of factor VIII

Inactivatesinhibits conversion Low Dosefactor Xa prothrombin to thrombin

High Dosefactors IX, X, XI, and XII and thrombin fibrinogen to fibrinEtymologyIn 1916, McLean, a second-year medical student atJohns Hopkins University, working under the guidance of Howell investigate procoagulant preparations, isolated a fat-soluble phosphatide anticoagulant in canine liver tissue

hence its name (heparor "" is Greek for "liver")similar to word HEPATIC

HeparinOnset: IV (immediate); SC (20-30 min)

Metabolized in the liver (partial) and reticuloendothelial system (partial)

Half-life: 60-90 min average (longer at higher doses)

Excretion: UrineHeparinStorageStore heparin solutions at room temperature; do not freezeDo not use if discolored/precipitatesAutoclavable

IV PreparationRecommended infusion concentration25,000 units in 500 mL D5W 50 units/mL premixed infusion solution

IV AdministrationIV injection may be given undiluted or diluted in 50-100 mL NS or D5WInfusion: Dilute in NS, D5W, or other compatible fluidContinuous IV therapy is preferred intermittent IV therapy produces a higher incidence of bleeding abnormalitiesInvert IV bag at least 6 times to ensure mixing and prevent pooling of medicationUse constant-rate IV infusion pump

ParameterUnfractionated Heparin (UFH)Low Molecular Weight Heparin (LMWH)Molecular Weight5000 30,000150 kg)Anti Xa units- 4 hours after dose(therapeutic level 0.5-1 unit/mL ------ BD dosing)(therapeutic level 1.5 units/mL-----OD dosing)*Use of PTT for heparin monitoring is problematicNo standardization scheme for PTT as for PT i.e. INR (range 1.6 -6 times control PTT)Prolonged baseline PTT due to factor deficiency or inhibitors or lupus coagulant

** IV heparin treatment of choice in end stage renal diseaseDosageUFHTherapeuticIVLoading DoseInfusion dose80 units/kg18 units/kg/hr5000 units1300 units/hrS/CLoading DoseMaintenance Dose250 units/kg250 units/kg q12hr17,500 units250 units/kg q12hrProphylactic(S/C)5000 units SC q8-12hr, OR7500 units SC q12hrProphylacticTherapeuticEnoxaparin(s/c)30 mg twice daily OR40 mg once daily1 mg/kg twice daily1.5 mg/kg once dailyDalteparin(s/c)5000 units once daily200 units/kg once daily*Start Heparin/LMWH within the first 24 hours of diagnosis, reducing the incidence of recurrent VTE during the first 3 months from 25% to 5%ToxicityBleeding (major side effect)More in elderly female and renal failure

Anaphylaxis/Allergy to heparin of animal origin

Reversible alopecia

Osteoporosis and spontaneous fracture (long-term, high-dose use)

Clear postprandial lipemiaActivation of lipoprotein lipase

Mineralocorticoid deficiency

Increased ALT/AST

Local effects: Pain, local irritation, erythema, injection site ulcer.

New thrombus/thrombocytopenia while patient on heparin therapy..suspect HITHeparin Induced Thrombocytopenia(with or without thrombosis)

immune-mediated reaction resulting from irreversible aggregation of plateletsSystemic hypercoagulable state1-4 % (10-30 % medscape) cases treated with UFH for min 7 daysSurgical patients>pediatrics>pregnancy(rare)Bovine UFH >Procine UFH > LMWHVenous(more common) and arterial thrombosisIncreased risk in presence of indwelling catheter/prosthetic cardiac valve

Monitoringfrequent platelet count

TREATMENTStop heparin(if platelets