Presentation on theme: "Parenteral Anticoagulant"— Presentation transcript:
1 Parenteral Anticoagulant BY : Maha khalidSupervisor : Pro Dr Seham Hafez
2 Parenteral Anticoagulant UFH & LMWH allconsist of highMW molecules thatAre highly ionized (they don'tabsorbed from GIT they mustgiven byIV infusion ordeep SC injection.( never IM )LMWHUFHFondaparinux
3 Objective of anticoagulation To prevent death & recurrent event with acceptable rate of bleeding complications.Considering the high mortality rate (30 %) in untreated patient with suspected PE anticoagulant treatment should be consider while a waiting definitive diagnostic confirmation.
4 Goals of anticoagulation therapy 1-The efficacy of heparin therapy depends on achieving a critical therapeutic level of heparin within the first 24 hours of treatment. The critical therapeutic level of heparin is 1.5 times the baseline control value or the upper limit of normal range of the activated partial thromboplastin time (aPTT).This level of anticoagulation is expected to correspond to a heparin blood level of U/mL by the protamine sulfate titration assay and by the antifactor X assay.
5 UFH Vs LMWH1-Standard heparin is comprised of an unfractionated heterogeneous mixture of polysaccharide chains with mean molecular weights ranging from to daltons.2-LMWHs are formed by depolymerization of unfractionated heparin side chains, producing “smaller” heparin fragments, with mean molecular weights ranging from 1000 daltons to daltons.
7 UFH Vs LMWH1- Both types of heparin inactivate factor Xa by interacting with antithrombin (AT)2- unfractionated heparin (UFH) is able to inactivate factor IIa through formation of a tertiary complex.3- UFH inactivates factors IIa and Xa and affects the apTT (activated partial thromboplastin time )4-LMWH inhibits factor Xa and minimally affects factor IIa; thus activated partial thromboplastin time is not used to measure its anticoagulant activity
11 Anticoagulant Properties of UFH 1-Inhibits the thrombin-mediatedconversion of fibrinogen to fibrin3-Inhibits activation of fibrinstabilizing enzyme2-Inhibits the aggregationof platelets by thrombin4-Inhibits activated factors XII, XI, IX, X and II
12 When unfractionated heparin is used, the aPTT should not be checked until 6 h after the initial heparin bolus because an extremely high or low value during this time should not provoke any action.Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis
14 can give once or at the most UFH Vs LMWHLMWH have potential desirable PKthan heparin, they excreted renally &have longer half lives1-Heparin half life is 1 hrsbut it shorter in patientwith PE Itexcreted byboth hepatic & renal waysit would take 5 hrs( five half livesto reach steady state, a loading dose isrequired to reducedthe timeto achieve adequateanticoagulationhave morepredictable doseresponse than UFH.,theycan give once or at the mosttwice daily in fixed dose.
15 UFH Vs LMWH Hemorrhage Heparin LMWH risk commoner in of hemorrhage mayproducefewerhemorrhagiccomplication &monitoringofeffect isnotroutinelyrequiredLMWHriskof hemorrhageisincreasedin thosegivenheparin byIntermittentintravenousbolusrather thanbycontinuousadministration.Heparincommoner inpatientswith sever heartor liver disease,renal disease, general debility& womenaged over60 years.The risk ofhemorrhageis increasedin thosewith prolongedclotting timesHemorrhageMoreless
16 LMWH Heparin HIT Thrombocytopenia LMWH are less likely to produce thrombocytopenia this complication only in :Patient only previoulsly developed thrombocytopenia after UFH .HeparinHITLMWHThrombocytopenia
17 Heparin induced thrombocytopenia “ HIT “ the second type occureafter 6 daysof FIRSTtreatment orhours to 2-3 dayswith re-exposure.the first occursafter 3-5 daysafter initiateof treatmentoften result in muchmore reduction inplateletscount & increased riskof thromboembolism .doesnot result incomplication
18 HIT ( Mechanism )HIT is the most common drug-induced thrombocytopenia in adults, complicating 1-4% of full-dose exposures to standard heparin. Unlike other thrombocytopenias, HIT carries a high thrombotic morbidity (30-50%) and mortality (10-15%) because it is a syndrome of platelet activation. Heparin forms a complex with platelet factor 4 (PF4) which is released from platelets by platelet activation. Antibody directed against the heparin-PF4 complex binds via its Fab region. The antibody-heparin-PF4 immune complex binds to the Fc receptor on the surface of the platelet leading to activation of the platelet.
21 Complications of HIT 1-•Deep vein thrombosis• 2-Pulmonary embolism• 3-Myocardial infarction•4-Occlusion of limb arteries (possibly resulting in amputation)•5-Cerebrovascular accidents (stroke )6-Skin necrosis•7-End-organ damage (e.g., adrenal, bowel, spleen, gallbladder or hepatic infarction; renal failure)•8-Death
22 Treatment of HIT : C/I must be stopped should be AVOIDED 1-ALL heparin (lines, flushes, heparin-coated catheters, LMWH )should be AVOIDEDPlatelet transfusion(transfusion may precipitate thrombosis)warfarin in the acute phase of HIT(its use may precipitate venous gangrene and thrombosis).C/I
23 highly specific direct in order to prevent further [1-lepirudin (rDNA)for injectionhighly specific directinhibitor of thrombinindicated as ananticoagulantfor prophylaxisor treatment ofthrombosis inpatients with HITand associatedthromboembolicdiseasein order to prevent furthercomplications.Treatment of HIT :2-Argatroban is asynthetic directthrombin inhibitorindicated as ananticoagulantfor prophylaxisor treatmentof thrombosis inpatients with HIT
24 For how long UFH &LMWH should be used ? 1-Heparin used in immediate stages of venousthrombosis & PE until the effect of warfarinbecome apparent .In the past it has been continued for 7-10 daysbut recent evidence indicate that 3-5 days of therapy maybe sufficient in many instances :this will reduce the risk of HIT which normally occurred after 6 days.2- LMWH are used for similar length but they are give SC without loading dose & without routinely monitoring.
25 Enoxaparin Only LMWH approved by FDA for both treatment and prophylaxis of DVT and PE.DoseAdult :DVT/PE: 1 mg/kg SC q12h or 1.5 mg/kg SC qd Prophylaxis of DVT: 30 mg SC q12h Prophylaxis in abdominal surgery: 40 mg SC qd,first dose given 2 h prior to surgery PediatricDVT/PE: 1 mg/kg SC q 12hInteractions:Platelet inhibitors or oral anticoagulants (eg, dipyridamole, salicylates, aspirin, NSAIDs,sulfinpyrazone, ticlopidine) may increase risk of bleeding
26 Enoxaparin(Con”d) Pregnancy contraindicationDocumented hypersensitivity; major bleeding; thrombocytopeniaPregnancyB - Usually safe but benefits must outweigh the risksPrecautionsIf thromboembolic event occurs despite LMWH prophylaxis,discontinue drug and initiate alternate therapy; elevation ofhepatic transaminases may occur but is reversible;HIT may occur; 1 mg protamine sulfatereverses effect of approximately 1 mg enoxaparinif significant bleeding complications develop
27 When LMWH will need dose adjustment : in patient with renal failuredose adjustment according toanti-Xa level.If crcl less than 30ml/minheparin is preferredAlso patientat high risk ofbleedingheparin shouldbe considering asit effectis easy toreversed.very thin or veryobese patientdoseadjustmentAccordingto factor Xapregnancy.
28 FONDAPARINUXSynthetic anticoagulant that works by inhibiting factor Xaa key component involved in blood clotting. Provideshighly predictable response.Bioavailability is 100%. Has a rapid onset of action anda half-life of h,allowing for sustainedantithrombotic activity over 24-h periodDoes not affect prothrombin time or activated partialThromboplastin time, nor does it affect platelet functionDose : 2.5 mg SC qd
29 administration of platelet inhibitors, DRUG INTERACTIONS:None reported; increased risk of bleeding possiblewith concurrentadministration of platelet inhibitors,oral anticoagulants, or thrombolytic agentsContraindicationDocumented hypersensitivity; seriously impaired kidney functionor in patientswho weigh <110 lb; patients given spinal anesthesiaor spinal puncturePregnancyC - Safety for use duringpregnancy has not been established.PrecautionsWhen spinal anesthesia or spinal punctureused, may develop blood clot in spine, which can result in long-term or permanent paralysis
31 Several meta-analyses have indicated that: 1-LMWHis associatedwith lessbleedingand fewerepisodes ofheparin-InducedthrombocytopeniaThanUFH2-patientsreceivingLMWH reporteda higher qualityoflife in terms ofphysical andsocialfunctionand senseof well-being.3- Treatment of DVTwith LMWHwas morecost-effectivethan therapy withUFHbecausethe length ofThe hospitalstay was reduced by 60to 70 percent withoutan increase in the costof home health care
32 But Two recent studies of patients with DVT : To compare the effect of LMWH given on an outpatient basis SC twice daily with that of UFH given by continuous IV infusion in the No significant different was hospital found in rates of recurrent venous thromboembolism, hemorrhagic complications, development of thrombocytopenia or mortality. LMWH were as safe and effective as UFH and most patients were managed at home immediately after diagnosis or a brief hospitalization.