Anticoagulants (STEMI/NSTEMI/UA)

Question 1

Anticoagulants for ACS

A and B levels

Answer 1

--class I recommendations in ACS:
UFH and Enox = level A
Fondaparinux and bivalirudin = level B (if pt as HIT etc)

Question 2

Anticoagulants considerations

Answer 2

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

Question 3

Heparin MOA

Answer 3

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

Question 4

Heparin Metabolism

Answer 4

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

Question 5

Heparin CI/Precautions

Answer 5

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

Question 6

Heparin SE

Answer 6

Bleeding (especially pts with renal failure and elderly women)

HIT (4% of pts getting UFH x7days—surgical pts at higest risk)
LMWH lower risk

Question 7

Heparin Considerations

Answer 7

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

Question 8

LMWH names

Answer 8

Enoxaparin
Dalteparin
Tinzaparin

Question 9

LMWH MOA

Answer 9

As a whole: they have variable anti Xa activity, variable antithrombotic effects

Question 10

LMWH consideraions

Answer 10

Similarities: more consistent and predictable then heparin
Simplified dosing and monitoring ☺
May result in more bleeding in renal pts ☹
LMWH resistance is not clear

Question 11

Enoxaparin MOA

Answer 11

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

Question 12

Enoxaparin Metabolism

Answer 12

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

Question 13

Enoxaparin CI/Precautions

Answer 13

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

Question 14

Dalteparin MOA

Answer 14

NSTE-ACS with ASA +/- PCI and clopidogrel

Question 15

Dalteparin Metabolism

Answer 15

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

Question 16

Dalteparin CI

Answer 16

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

Question 17

Fondaparinux Indications

Answer 17

• STEMI pts receiving fibrinolytics
• NSTEMI PCI
• Conservative tx
• Pts at risk for bleeding

Question 18

Fondaparinux CI

Answer 18

CI:

CrCl

Question 19

Fondaparinux SE

Answer 19

Monitor signs/sx of Bleeding
Hb
HCT
PLTS

Question 20

Direct Thrombin Inhibitor is

Answer 20

Bivalirudin

Question 21

MOA Bivalirudin

Answer 21

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

Question 22

Bivalirudin Metabolsim

Answer 22

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

Question 23

Bilalirudin CI

Answer 23

CI:
Active bleeding
Previous bivalirudin hypersensitivity

Question 24

Bilalvirudin Precautions

Answer 24

Precautions:

• brachytherapy using bivalirudin > thrombus
• bleeding risk factors
• elderly
• RENAL IMPAIRMENT