1. ANTI-COAGULANT IN ICU
DR.AMENA FATIMA

2. COAGULATION
A CASCADE OF REACTIONS INVOLVED IN CONVERSION OF SOLUBLE FIBRRINOGEN TO INSOLUBLE FIBRIN.

3. Platelet plug formation :

4. Platelet Activation Pathways
ADP
Adrenaline
COLLAGEN
THROMBIN
ADP
GpIIb/IIIa
Aggregation
GpIIb/IIIa
Aggregation
GpIIb/IIIa
Aggregation
GpIIb/IIIa
Adhesion
Platelet
Multiple pathways are responsible for platelet activation.
Platelets adhere to damaged blood vessels via cell surface adhesion molecules and their membrane receptors such as glycoprotein Ib/IX (GP Ib/IX), the ligand for von Willebrand factor (VWF), which in turn can activated platelets and cause conformational changes.
Further, other activators including thrombin, adrenaline, ADP, and collagen can also activate platelets. When activation occurs, the glycoprotein IIb/IIIa membrane receptor (GP IIb/IIIa) is exposed. This receptor forms bridges using fibrinogen resulting in aggregation.
Platelet activation also exposes a phospholipid surface (meeting place) upon which coagulation proteins carry out their reactions. The sequential activation of these coagulation factors ultimately leads to the formation of fibrin, which is a critical component in stabilizing the hemostatic plug.
Thrombin when generated, plays a pivotal role in hemostasis, via both fibrin conversion and platelet activation.
GpIb
Adrenaline
Adhesion
vWF
Exposed Collagen
Endothelium

5. Targets for anti-platelet therapy ADP receptor Aspirin -
Thrombin
inhibitors
ADP
ADP receptor antagonists
Clopidogrel II
receptor
THROMBIN
receptor
COX-1
Aspirin
Phosphodiesterase inhibitors
dipyridamole
Signalling AA
NSAIDs
pathways
TXA2
GPIIb -
IIIa
Fibrinogen Receptor
Antagonists
Fibrinogen

7. Coagulation cascade

8. 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

9. Factor xiv- pre kallikrein
Factor xv – HMWK(high mol. Wt. kininogen
Factor xvi – vWF vonwillibrand factor
Factor xvii – Anti thrombin iii
Factor viii – heparin factor ii
Factor xix – protien ‘c’
Factor xx – protien ‘s’

12. ANTI-THROMBOTIC AGENTS
categories
vit k antagonist
Heparin- 1.UFH LMWH
ANTI-PLATELET AGENTS
NOVEL ANTICOAGULANTS
ANTI-FIBRINOLYTICS
ACQUIRED INHIBITORS OF COAGULATION.

13. ANTI COAGULANTS
DIRECT THROMBIN INHIBITORS-dabigatran,argatroban,lepirudin
Indirect thrombin inhibitors-1.heparin-enoxaparin,UFH,LMWH. 2.fondaparinux
VITK EPOXIDE REDUCTASE INHIBITORS-warfarin.
Direct Xa inhibitors-rivaroxaban,apixaban.

14. Vit k antagonist 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,rarely in MI.
Tests-PT (INR)

15. Reversal -1.stop warfarin temporarily
.2. inj. Vit.k (new factors synthesis)
3.prothrombin complex concentrate(factor ii.vii,ix,x,proteinc &s) .

16. INDIRECT THROMBIN INHIBITORS
1. FONDAPARINUX 2.HEPARIN

17. 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

18. dosage
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).

19. HIT(heparin induce thrombocytopenia)
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.

20. 4T SCORE FOR HITS
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).

21. 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).

22. LWMH 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)

23. Therapeutic Dose of LMWH in Patients With Decreased Renal Function
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

24. DIRECT THROMBIN INHIBITORS
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.

25. Dabigatran
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.

26. DIRECT XaINHIBITORS Drugs:rivaroxaban,apixaban MOA:blocks Xa
TEST:normal PT suggest preserved hemostasis
Reversal:not specific. Cessation of drug,supportive care.

27. Antiplatelet agents COX INHIBITORS: Aspirin
GLYCOPROTEIN IIb/iiia INHIBITORS: abciximab, eptifibatide, tirofiban
ADP INHIBITORS: Clopidogrel.

28. Cox inhibitor Drug:aspirin
MOA:Blocks cycloxygenase to convert arachadonic acid into thromboxane (irreversible)
Reversal: platelet transfusion
TEST:Platelet function test

29. GP IIa/IIIb or ADP INHIBITORS
Drugs:clopidogrel,ticagrelor,abciximab,tirofiban
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 .

30. ANTI-FIBRINOLYTICS
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)

31. Acquired inhibitors of coagulation
Auto anti bodies against factor VIII,IX,V,VWF
REVERSAL:rFVIIa,PCCs,FEIBA(factor eight inhibitor bypassing activity),steroids,cyclophosphamide.,pkasmapheresis,immunoadsorption.

32. Thank you
Thank you