Anticoagulants (STEMI/NSTEMI/UA) Flashcards
Anticoagulants for ACS
A and B levels
--class I recommendations in ACS: UFH and Enox = level A Fondaparinux and bivalirudin = level B (if pt as HIT etc)
Anticoagulants considerations
Refers to the inhibition of thrombin and/or other proteins in clotting cascade
when managing pts who require antiplatelet and anticoag combos:
–supratherapeutic INRs can be reduced with Vit K or FFP
–Warfarin is usually withheld until INR = 2 for new starts
Heparin MOA
Binds thrombin (factor II) and prevents conversion of fibrinogen to fibrin
- IXa, Xa, Fibrin
- requires ATIII as cofactor***
Antiplatelet and anicoagulant properties (not thrombolytic, only prevents further thrombin formation)
- HMWH –less bound to thrombin
- LMWH—favors Xa
Heparin Metabolism
Immediate onset with infusion
Therapeutic concentration is 0.2-0.4 via protamine titration with aPTT of 1.5-2.5x control
Half life 1.5 hrs
Transported to reticuloendothelial system, phagocytized as elimination **
Na and Ca heparin are bioequivalent
Heparin CI/Precautions
Monitor platelets frequently/daily
CI:
Bleeding(active/uncontrolled)
Inability to monitor aPTT or heparin concentrations
TCP
Precaution:
Allergic and hypersensitivy reports are increasing
Baxter single use, multi use, and lock-flush heparins implicated, recalled for hypotension and CV collapse
Baxter heparins-no bolus, slowest rates, close monitoring
Keep antihistamines and steroids close at hand
Heparin SE
Bleeding (especially pts with renal failure and elderly women)
HIT (4% of pts getting UFH x7days—surgical pts at higest risk)
LMWH lower risk
Heparin Considerations
Sulfated mucopoly-saccharide of variable molecular wt
(LMWH favor Xa, HMWF unspecific; electronegative charge facilitates protein binding including the intrinsic coagulation pathway)
Endogenous heparin found in mast cells (treat sources: pig intestine and cow lung)
Bleeding, death, hypotension, anaphylaxis, hypersensitivity rxn related to batches of heparin processed in china for Baxter
USP now has standardized heparin units
LMWH names
Enoxaparin
Dalteparin
Tinzaparin
LMWH MOA
As a whole: they have variable anti Xa activity, variable antithrombotic effects
LMWH consideraions
Similarities: more consistent and predictable then heparin
Simplified dosing and monitoring ☺
May result in more bleeding in renal pts ☹
LMWH resistance is not clear
Enoxaparin MOA
Similar/better efficacy and advantages over heparin (binding specificity, 10x greater anti Xa activity, less factor II activity, 1 or 2x/day, linear, consistent bioavailability, consistent anticoagulation
Enoxaparin Metabolism
Peak anti Xa activity within 3-5 hrs
RENAL elimination via glomerular filtration
- anti Xa activity increase with GFR 30-50
- AUC increases 65% with GFR 8 hrs single dose
Enoxaparin CI/Precautions
CI: -active major bleeding -Heparin or LMWH sensitivity or allergy -antiplatelet antibody to enoxaparin or heparin Precautions: -use of antiplatelets or anticoags -indwelling cath/recent surgery -active/recent minor hemorrhage -low body wt
Dalteparin MOA
NSTE-ACS with ASA +/- PCI and clopidogrel
Dalteparin Metabolism
Peak anti Xa activity in 2-4 hrs
Increases with higher doses
Half life 3-5 hrs with preserved renal function
-4-8 hr on dialysis
Dalteparin CI
CI:
- Previous dalteparin hypersensitivity
- Active major bleeding
precautions: - active ulcer, hemorrhage, bleeding diathesis
- recent surgery, trauma
- concomitant antiplatelet therapy
- previous hit
- hx of hemorrhagic stroke
- renal impairment
Fondaparinux Indications
- STEMI pts receiving fibrinolytics
- NSTEMI PCI
- Conservative tx
- Pts at risk for bleeding
Fondaparinux CI
CI:
CrCl
Fondaparinux SE
Monitor signs/sx of Bleeding
Hb
HCT
PLTS
Direct Thrombin Inhibitor is
Bivalirudin
MOA Bivalirudin
20 AA synthetic direct thrombin inhibitor
-analogue to natureal 65 AA thrombin inhibitor (derived from hirudo medicinalis leech)
- binds catalytic site on thrombin and temporarily prevents soluble and clot bound thrombin interactions:
- -platelet activation
- -fibrinogen cleavage
- -thrombin amplification and propagation
Slowly reversible as bivalirudin is cleaved off complex**
Rapid and dose related prolongation of aPTT
- Inhibits factor Xa
- Activates protein C
- Focused/less systemic anticoagulation
- Avoids platelet activation associated with UFH
Bivalirudin Metabolsim
Dose dependent and rapid prolongation of aPTT within first 2 minutes
Peak effect 2 hrs
Proteolytic cleavage in blood plasma
70% renal cleaance in 2 hrs GREAT FOR PROCEDURES!!
Mod to severe renal impairment reduces clearance by 20%, failure 80% (this is a trend)
Half life depends on GFR:
>30 22-34 min
Bilalirudin CI
CI:
Active bleeding
Previous bivalirudin hypersensitivity
Bilalvirudin Precautions
Precautions:
- brachytherapy using bivalirudin > thrombus
- bleeding risk factors
- elderly
- RENAL IMPAIRMENT