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Heparin in CRRTBenan Bayrakci, 2014

McLean2. Year medical studentFound a powerfull anticoagulant in dog liver and published in 1916 in dr hovells lab.2

Antitrombin 3Inactive Thrombin (IIa)V, VIII, XIII, FibrinogenInactive Factor XaCommon PathwayInactive Factor IXa, XIIaContact activation PathwayAntitrombin 3Antitrombin 3Heparin Binds to Antithrombin III and Speeds up its action by a 1000-foldAlsoReleases Tissue factor pathway inhibitor form endothelium Binds to platelets and inhibits platelet aggregation

UFH is made up of heparin molecules of varied sizes (530 kDa). Larger fragments: Anti-IIa activity and are cleared rapidly (measured by APTT) Smaller fragments: Inhibit Xa (normal APTT because of its delayed clearance)

Warkentin, 2003Acctually it is much complicated!Not sure if anybody really undrstand the whole mechanism6

Warkentin, 2003

Acctually it is much complicated!Not sure if anybody really undrstand the whole mechanism7ProtocolsHeparin infusion prior to filter Bolus with 10-30 units/kgInfuse heparin at 5-20 units/kg/hrPost filter ACT measurement Adjust post filter ACT 180-200 secsInterval of checking is local standard and varies from 1-4 hr increments

8Anticoagulant effectFilter efficacyCircuit lifeComplicationsMonitoring Efficacy of UFH for prolonging filter life is proportional to the APTT and not to the heparin doseAPTT is maintained between 3445 seconds, or an APTT of 1.52.0 times normalMost commonly used anticoagulant worldwide for CRRT Widely available Simple to monitor InexpensiveFamiliar to physicians Easy to administerReversible with protamineAdvantagesUnpredictable and complex pharmacokinetics resulting in dosing variabilityHeparin-induced thrombocytopeniaHeparin resistance because of low patient antithrombin levelsRisks of hemorrhage (bleeding episodes: 1050%, mortality 15%) DisadvantagesAnticoagulant effects are restricted to the circuit, lower risk of bleedingDifficulty in estimating the amount of protamine required Initial ratio of 100 between prefilter heparin (in units) and postfilter protamine (in mg)Subsequent adjustment according to APTTRequires measurement of both circuit and patient APTTThe heparinprotamine complex is taken up by the reticuloendothelial system and broken down, then heparin and protamine are released back into the circulationProtocols are cumbersome and difficult to standardize Protamine infusion is associated with hypotension, anaphylaxis, cardiac depression, leukopenia, and thrombocytopeniaRegional Unfractionated HeparinProtamineHave higher anti-XaPharmacokinetics is more predictable because of less plasma protein bindingMore reliable anticoagulant responseLower incidence of HITReversal with protamine is less effectiveDalteparin, enoxaprin, and nadroparin have been studied in CRRTExcreted renally, their effects are prolonged in renal failureSpecial coagulation assays are required to monitor anti-Xa activityLow Molecular Weight Heparins

Longer filter survival times, and lower cost, bleeding complications not increased Determination of anti-Xa levels aiming at 0.250.35 IU/ml is recommended

174 patientsNo significant difference in survival up to day 30 There were more metabolic disturbanceswith citrate anticoagulationRegional anticoagulation with citrate does not eliminate any need for heparin since, many other indications for systemic anticoagulation may emerge during therapyCitrate anticoagulation has distinct advantages with regard to haemofilter patency and the risk of HIT and bleeding

For patients who are at low risk of bleeding and do not have other contraindications to heparin such as HIT, consider using UFHFor patients who are at high risk for bleeding and who do not have liver failure, consider using regional citrate anticoagulationNeither citrate nor heparin anticoagulation should be regarded as a therapeutic standard, since there is no advantage of one of these substances with regard to patient mortality.17Optimal anti-thrombotic activity Minimal bleeding complicationsNegligible systemic effectsInexpensiveHave a short half-lifeCan be easily reversedMonitoring methods should be simple and availableThe ideal anticoagulant should provide

f you do have tell us

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Heparin was used to be manufactured in factories from porcine intestine or bovine lung Ok lets dont use it anymore!

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