coagulation pathway

1. DR.M.ANEEQUE
aneeque86@gmail.com
Department of Anesthesiology SICU and
Pain Management
Civil Hospital Karachi

2. Coagulation is a major haemostatic
function responsible for prevention and
termination of bleeding following injury.
It is balanced by fibrinolytic system.

3. MECHANISM OF BLOOD
COAGULATION
The blood coagulation takes place in three
steps.
i. Formation of prothombin activator in
response to rupture or damage to the blood
vessels.
ii. Conversion of prothombin activator to
thombin.
iii. The thrombin act as an enzyme to convert
fibrinogen to fibrin thread that mesh
platelates, Blood cells and plasma to form the
clots.

4. Coagulation system is divided into two
pathways
Extrinsic Pathway:
Which begins after trauma to vascular
wall and surrounding tissue.
Intrinsic Pathway:
Which begins in blood itself

8. FIBRINOLYSIS
If coagulation is continue and un controlled
then spontaneous clot formation results
pathological state
The process of fibrinolysis results
breakdown of clot.
In this tissue injury -> release of
plasminogen -> plasmin which bind to
fibrin and form fibrin degradation producet

9. Prothrombin time (PT)
Test of Extrinsive pathway
Measure Vitamin K dependent factor activity
(factor II, VII, IX and X)
Normal value 12-14 seconds
International normalize ratio (INR)
Standardized PT reporting
Normal value 0.8-1.2 seconds
Most sensitive to alteration in factor VII levels.
Prolonged decrease of normal factor VII activity.

10. ACTIVATED PARTIAL PROTHROMBIN
(APTT)
Test for intrinsic common pathway
Depends activity of all coagulation factor except
factor VII, XIII
Normal value 25-35 seconds
Prolonged only if coagulation factor reduced to
<30% of normal

11. ACTIVATED CLOTTING TIME (ACT)
Monitor heparin anti-coagulant in the
cardiac vascular surgery.
Normal value 90-120 seconds.

12. THROMBIN CLOTTING TIME (TCT)
1. Reflect abnormalities in fibrinogen ->
fibrin.
2. Prolonged by heparin, low fibrinogen
thrombin inhibitor.

13. BLEEDING TIME (BT)
Monitor platelet function
Non-specific indicator of platelet function.
Unreliable
No evidence as a predictor of risk of hemorrhage
Useful indicator of efficacy of anti-platelet therapy.
Insensitive to mild platelet defect.

14. Lab Test Component Measured Normal Value
Bleeding Time Platelet Function,
Vascular integrity
3-10 minutes
PT I, II, V, VII, IX & X 12-14 seconds
APTT I,II,V,VIII,IX,X,XI &XII
except VII & XIII
24-35 seconds
Thrombin Time I & II 12-20 seconds

15. COAGULATION DISORDER
Congenital Disorder:
Disorder of clotting may not present until
challenged by trauma, surgery in adult life.
Acquired Disorder:
Is due to lack of synthesis of coagulation
factor.
Increased loss due to DIC, Massive Blood
Loss.
A family history of hemophilia A, B sex linked
recessive, Von willbrand disease

16. In severe hemophilia A (factor VIII) bleeding occurs
spontaneously.
In mild hemophilia A (factor VIII) bleeding occurs
only after trauma.
Medical problem such as liver disease,
malabsorption (Vitamin K Deficiency) infection,
malignancy, DIC, auto-immune disease,
systemic lupus erythematous, rheumatoid
arthritis as well as medication aspirin, NSAIDS.

17. Disorder Platelet Count PT/INR APTT TT Fibrinogen Others
Hemophilia A Normal
Normal
Increase
Normal
Normal Decrease VIII
Hemophilia B
Normal Normal
Increase
Normal
Normal
Decrease IX
Vonwillebrand
disease
Normal Normal
Increase
Normal
Normal
Decrease VIII,
VWF, Increase
bleeding time
Liver Disease
Normal
Increase Increase
Normal
Normal Decrease V
Vitamin K
deficiency
Normal Increase
Increase
Normal
Normal
Decrease II,
VII, IX & X
Massive
Transfusion
Decrease
Increase
Increase
Normal Normal /
Decrease
Normal FDP
(Fibrinogen de-
gradation
product)
Heparin
Normal Normal
Increase
Increase
Normal
Increase ANT
Xa
Warfarin
Normal Increase
Increase
Normal
Normal
Decrease II,
VII, IX & X

18. Haemostatic Process
Effected
Class of Drug Specific Drug
Platelet plug formation Anti Platelet drug NSAID,Clopidogrel
Coagulation cascade IV anticoagulant
oral anticoagulant
Heparin
Warferin
Fibrinolysis Fibrinolytic agent Streptokinase , urokinase
DRUGS EFFECTING COAGULATION

19. Prostaglandin
synthesis
ADP binding
GPIIb/IIIa receptor
Antiplatelet drug targets

20. Aspirin
inhibits cyclo-oxygenase
 thromboxane A2 synthesis
inhibits both COX 1 and COX 2
irreversibly
Should stop 7 days prior to
surgery

22. COX-1 vs COX-2 inhibitors

23. • GI ulceration
• Haemorrhage
• Bronchospasm
• Interstitial nephritis, papillary
necrosis, proteinuria, renal failure
• Reye’s syndrome in children
Adverse effects

24. Alternative to aspirin
First choice for aspirin intolerance
Clopidogrel
Block activation of platelets by
reducing ADP activation of Gp IIb /
IIIa receptor complex
Should stop 5 days prior to surgery

25. Heparin
Glycoaminoglycan containing a mixture of sulfated
muco-polysaccharides of various sizes
- Un-fractionated (5000-30000 Da)
- Low molecular weight (LMWH) (1000-10000
Da)

26. Heparin
- enhances the action of Antithrombin III (AT-III) (plasma
protease inhibitor) 1000 fold ↑ activity
- antithrombin III inhibits clotting factor proteases,
Thrombin (IIa), IXa, Xa, XIa and XIIa, by forming stable complexes
- heparin binds to AT-III and causes a conformational change
thereby activating AT-III
LMWH
- predominantly inhibit factor Xa
Mechanism of Action

28. Increased bleeding
- antidote (protamine sulfate)
Heparin induced thrombocytopaenia
Osteoporosis with long term high-dose
administration 3-6mths
Inhibit aldosterone synthesis
Adverse effects

29. Unpredictable pharmacokinetics
Requires regular monitoring
Infusion
Higher incidence of HITs
Rebound ischaemia
Unfractionated heparin

30. Eg Enoxaparin; Tinzaparin
More predictable pharmacokinetics
Lower incidence of heparin-associated thrombocytopenia
Ease of administration s/c injection
No need for monitoring
Possible improvement in outcomes of acute coronary
syndromes
Low Mol Weight Heparins

31. Highly plasma protein bound
Metabolised by liver
Substrate of CYP450 enzymes
Excreted in urine and stool
Warfarin
Should stop 2-4 days prior to surgery

32. Block the Vitamin K-dependent glutamate carboxylation
of precursor clotting
factors II, VII, IX and X
Also inhibits Proteins C & S
8-12 hour delay in action because of T1/2 of clotting
factors in plasma
recovery needs synthesis of new clotting factors
action is reversed with vitamin K
Mechanism of action

34. Bleeding
Contraindicated in pregnancy
- teratogenic effects, crosses placenta risk
foetal haemorrhage
Warfarin induced skin necrosis
- paradoxical local thrombosis
- increased in patients with protein C or S
deficiency
"Purple toes syndrome," cholesterol
microembolization
Hepatic dysfunction
Adverse effects

35. Derived from bacterial protein
Cleaves Plasminogen
Low fibrin specificity
Cheap
Streptokinase
Fibrinolytics

36. Intrinsic compound
Isolated from urine or renal cell
cultures
Cleaves plasminogen
Urokinase