Heparin LMWH Thrombin

8/14/2019 Heparin LMWH Thrombin

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Interventional Lecture Series

Thrombin/LMWH/Heparin


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Heparin and LMWH


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Given Vial ~ 2/3molecules arebiologically inert

To be biologicallyactive needs 5

repititions of thepentasaccharide ->this unit binds theantithrombin

No direct affinity tothrombin but inhibitsformation of thrombin


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Major Minor

Procoagulant


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Heparin bindstoAntithrombincausing aconformational

change w/amplifies itsanti-Xa activity

To inactivatethrombin,heparin mustsimultaneouslybind to AT andThrombin thereforemolecule lengthis important

Only exert effecton antithrombinand inhibit Xawithout action onthrombin


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Antithrombin Serine Protease Inhibitor

Large size does not penetrate clot well

Responsible for anticoagulant effect of all heparins (UFH, LMWH, Pentasaccarides)

Inhibits Xa

Affinity for Xa is increased 2000x by pentasaccaride sequence of heparin

Congenital and Acquired deficiencies Liver disease Nephrotic syndrome Continuous heparin therapy (50-60% decrease)


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Guidelines

For patients not receiving IIb/IIIa 70-100U/Kg bolus, check ACT after 5 minutes Achieve Target ACT 250-300 Hemotec Achieve Target ACT 300-350 Hemochron ACT< 250 addtl 2K-5K bolus

For patients receiving IIb/IIIa 50-70U/Kg bolus, check ACT after 5 minutes Achieve Target ACT 200


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Early Trials

Overall improved clinical outcomes with increased minor bleeding complications


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UFH according tocurrent guidelineswith ACTmonitoring


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Guidelines Dosing of Lovenox depends on the last SQ dose given

(After administration of 2 SQ doses!!) Last SQ dose 8hrs or less -> no addtl dosing SQ 8-12 hours -> 0.3mg/kg IV Greater than 12 hours -> 0.75 to 1mg/kg IV or SQ can be given

Xa Level (reasonable if Weight >150Kg) 0.8 to 1.8 IU/ml is recommended

Renal Dosing CrCl 30-60ml/kg 0.75 mg/kg SQ bid CrCl


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Pentasaccarides


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Fondaparinux / Arixtra

After 2.5mg dose therapeutic level achievedafter 2.5 hours !!!Oasis dosing and PE dosing are different

Therefore Dr. Kern prescribes the wrong dose all thetime

Renal Clearance 50% less renal clearance for CrCL 30ml/min

life 17-21 hours


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Direct Thrombin Inhibitors in

PCI


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Early Angioplasty Trials

HAT (Hirudin)

No significantlong termbenefit for Hirudindespitesomewhatlower cardiacevent rates


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Bivalirudin Trial


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Contemporary PCI - Cachet


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Contemporary PCI - Cachet


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Contemporary PCI REPLACE-1


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Contemporary PCI

Main limitation of previous studies is rather small overall size.

Setup for REPLACE -2: 6,000 patient,large clinical trial on the use and effects of bivalirudin in a contemporary PCI andstenting.


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Replace - 2


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Replace - 2 Claim made by

study thatbivalirudin issuperior toheparin

Claim madebased onEpistent/Espritdata publishedearlier

NOrandomizedarm for heparinalone in thisstudy


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Bleeding major driver of bivalirudin benefit


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Major bleeding correlates with death


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Acuity Trial


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ACUITY Trial


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ACUITY Trial


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ACUITY Trial


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ACUITY Trial


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ACUITY Trial The hypothesis of this

randomization indicate thatcompared to a routineupstream use of a IIb/IIIainhibitor in all patients withACS, withholding the upfronttherapy with IIb/IIIa for adeferred administration in thecath lab only to those patientsundergoing PCI with result in: similar 30-day rates of death,

MI, or unplannedrevascularization for ischemia reduced bleeding, or major

bleeding complication improved cost effectiveness


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ACUITY Trial


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ACUITY Trial


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H i I d d


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Heparin InducedThrombocytopenia

HIT II Platelet drop >50% or 150K Usually seen 5 days after start of heparin Unexplained thrombosis (increases risk 40x)

50% risk of thrombosis @ 30 days Presence of Anti-Heparin PS4 complex, (NAP-2 receptor) Occurs with Heparin, Lovenox (no report of arixtra even though antibodies to PS4

have been discovered in patients) Qualitative and functional assay

Differentiate from type I HIT 15% of patients receiving heparin transient decrease in platelet count (down to 50% normal) without any further

symptoms secondary to platelet sequesteration. Platelet counts recover even if heparin continues to be administered. Platelet counts rarely fall below 100,000. Type I HIT is not due to an auto-immune disorder (as Type II is).


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Therapeutic Options

LMWH high cross-reactivity Warfarin initially can induce skin necrosis ASA is inadequate Options remain:

Lepirudin (limited by significant anaphylaxis if agent is used more than

once) Argatroban Bivalirudin

Treatment should be continued for at least 4weeks Coumadin may be added after Plateletcounts recovered to >150K


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Questions

Thank you for your attention andparticipation

Documents

Heparin LMWH Thrombin