Download GPIIb - IIIa - ICU education

DR.AMENA FATIMA
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A CASCADE OF REACTIONS INVOLVED IN
CONVERSION OF SOLUBLE FIBRRINOGEN
TO INSOLUBLE FIBRIN.
COLLAGEN
THROMBIN
ADP
Aggregation
GpIIb/IIIa
GpIIb/IIIa
GpIIb/IIIa
Adrenaline
Platelet
Adhesion
vWF
Endothelium
Exposed Collagen
Targets for anti-platelet therapy
ADP receptor
antagonists
Clopidogrel
Phosphodiesterase
inhibitors
dipyridamole
ADP
receptor
Signalling
Fibrinogen Receptor
Antagonists
THROMBIN
receptor
COX-1
TXA2
- IIIa
Aspirin
AA
pathways
GPIIb
Thrombin
inhibitors
II
NSAIDs
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Factor i – fibrinogen
Factor ii – prothrombin
Factor iii – tissue thrombo plastin
Factor iv – calcium
Factor v – labile factor (pro accelerin)
Factor vii – pro covertin; stable factor
Factor viii – Anti heamophilic factor ‘A’
Factor ix – Anti heamophilic factor ‘B’ or christamas factor
Factor x – stuart prover factor
Factor xi – plasma thromboplastin antecedent
Factor xii – hagemann factor
Factor xiii – fibrin stabilizing factor
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Factor xiv- pre kallikrein
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Factor xv – HMWK(high mol. Wt. kininogen
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Factor xvi – vWF vonwillibrand factor
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Factor xvii – Anti thrombin iii
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Factor viii – heparin factor ii
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Factor xix – protien ‘c’
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Factor xx – protien ‘s’
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categories
 vit k antagonist
 Heparin- 1.UFH
2.LMWH
 ANTI-PLATELET AGENTS
 NOVEL ANTICOAGULANTS
 ANTI-FIBRINOLYTICS
 ACQUIRED INHIBITORS OF COAGULATION.
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DIRECT THROMBIN INHIBITORSdabigatran,argatroban,lepirudin
Indirect thrombin inhibitors-1.heparinenoxaparin,UFH,LMWH. 2.fondaparinux
VITK EPOXIDE REDUCTASE INHIBITORSwarfarin.
Direct Xa inhibitors-rivaroxaban,apixaban.
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Drug-warfarin
MOA- inhibition of vit k dependant clotting
factors(ii,vii,ix,x)
Uses-stroke prevention,atrial fibrillation,pts
with artificial heart
valve,DVT,PE,antiphospholipidsyndrome,rarel
y in MI.
Tests-PT (INR)
Reversal -1.stop warfarin temporarily
.2. inj. Vit.k (new factors synthesis)
3.prothrombin complex
concentrate(factor ii.vii,ix,x,proteinc &s)
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1. FONDAPARINUX
2.HEPARIN
UFH
DRUGS: Heparin
MOA- via blocking factor Xa and thrombin.
TEST:APTT.
REVERSAL: protamine sulphate(1mg for 100u of
heparin given in previous 2-3 hrs) slow i.v
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For patients starting IV UFH, we suggest that
the initial bolus and the initial rate of the
continuous infusion be weight adjusted (bolus
80 units/kg followed by 18 units/kg per h for
VTE; bolus 70 units/kg followed by 15
units/kg per h for cardiac or stroke patients) or
use of a fixed dose (bolus 5,000 units followed
by 1,000 units/h) rather than alternative
regimens (Grade 2C).
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Immune reaction to heparin,witin 5-14 days of therapy.
Moderate thrombocytopenia,
No bleeding
Prothrombotic state due to platelet aggregation causing
devastating arterial,microvascular or venous thrombosis.
TESTS:heparin-platelet factor 4antibodies,serotonin release
assay or whole blood aggregometry.
Management:use of lmwh,less duration.
Reversal:stop the drug,start alternative anti coagulants
DANAPAROID or THROMBIN INHIBITOR SUCH AS
LEPIRUDIN OR ARGATROBAN.
For patients receiving heparin in whom
clinicians consider the risk of HIT to be > 1%,
we suggest that platelet count monitoring be
performed every 2 or 3 days from day 4 to day
1For patients receiving heparin in whom
clinicians consider the risk of HIT to be > 1%,
we suggest that platelet count monitoring be
performed every 2 or 3 days from day 4 to day
14 (or until heparin is stopped, whichever
occurs first) (Grade 2C).
4 (or until heparin is stopped, whichever
occurs first) (Grade 2C).
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For patients receiving heparin in whom
clinicians consider the risk of HIT to be > 1%,
we suggest that platelet count monitoring be
performed every 2 or 3 days from day 4 to day
14 (or until heparin is stopped, whichever
occurs first) (Grade 2C).
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DRUGS: Enoxaparin,daltiparin,tinzaparin.
MOA:blocks factor Xa
TEST: Usually no monitoring ,anti-Xa assay.
REVERSAL:difficult, partially reversed by
protamine (1mg for 1mg enoxaparin)
Therapeutic Dose of LMWH in Patients With
Decreased Renal Function
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Therapeutice dose:1mg/kg 12 hrly;
1.5mg/kg 24 hrly
For patients receiving therapeutic LMWH who
have severe renal insufficiency (calculated
creatinine clearance < 30 mL/min), we suggest
a reduction of the dose rather than using
standard doses (Grade 2C).
30 mg S.C /24hours
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Drugs:dabigatran,argatoban,lepirudin,bivalirudin.
MOA:blocks thrombin.
TEST:not specific,normal APTT suggest no abn in
hemostasis.
REVERSAL:withdrawl of
medication.,identification of bleeding source and
control of bleeding via surgical or radiological
means.,fluid replacement and maintainence of
good urine output.
Drug dose improvement for dabigatran in renal
failre since renally excreated.
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Drug dose improvement for dabigatran in
renal failre since renally excreated.
Reversal:oral activated charcoal within 2 hrs of
dabigatran,hemodialysis/hemo[erfusion.
Use of prothrombin complex conc or rFviia is
controversial for bleeding control with
dabigatran.
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Drugs:rivaroxaban,apixaban
MOA:blocks Xa
TEST:normal PT suggest preserved hemostasis
Reversal:not specific. Cessation of
drug,supportive care.
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COX INHIBITORS: Aspirin
GLYCOPROTEIN IIb/iiia INHIBITORS:
abciximab, eptifibatide, tirofiban
ADP INHIBITORS: Clopidogrel.
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Drug:aspirin
MOA:Blocks cycloxygenase to convert
arachadonic acid into thromboxane
(irreversible)
Reversal: platelet transfusion
TEST:Platelet function test
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Drugs:clopidogrel,ticagrelor,abciximab,tirofiba
n
MOA:binds to platelet receptors P2Y12 which
are ADP binding receptor,thus supresses ADP
mediated activation of GP Iia/IIIb for platelet
aggregation
TEST:platelet function test
Management:platelet transfusion if major
bleeding.desmopressin,rFVIIa .
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Drugs:tranexamic acid,EACA(epsilon amino
caproic acid.
MOA:these are lysine analogue,competitively
binds to lysine binding sites on plasminogen
molecule hence inhibits fibrinolysis.
Uses:major bleeding ,(even with anti
coagulants)
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Auto anti bodies against factor VIII,IX,V,VWF
REVERSAL:rFVIIa,PCCs,FEIBA(factor eight
inhibitor bypassing
activity),steroids,cyclophosphamide.,pkasmap
heresis,immunoadsorption.
Thank
you