Hemostasis is the process of stopping blood loss from damaged vessels and occurs in three main steps: primary hemostasis involving platelet plug formation, secondary hemostasis involving the coagulation cascade, and fibrinolysis to restore blood flow. The coagulation cascade consists of three steps to stabilize and reinforce the platelet plug through conversion of prothrombin to thrombin and fibrinogen to fibrin. Various laboratory tests can monitor components of hemostasis, while common drugs like aspirin, clopidogrel, heparin, and warfarin can affect different parts of the hemostatic process. Careful monitoring and reversal of anticoagulants is important around surgery.

1. By : Dr Karrar Adil

2. Definition
is the process that stops blood loss from a
damaged vessel.

3. Purpose Of Hemostasis
 Ensure that coagulation mechanisms
are :
 Activated when there is an injury .
 Not unnecessarily activated .
 Restore tissue blood flow after repair of
injury (fibrinolysis).

4. Steps of Hemostasis
3 main steps :
1. Primary hemostasis : local vasoconstriction
and platelet plug formation (within 5 minutes )
2. secondary hemostasis : Coagulation cascade
(within hours).
3. Fibrinolysis (within days).

5. Platelet Plug Formation :
Vascular injury
Endothelial damage and collagen exposure
Platelets activation by Von Willebrand factor
Release contents of cytoplasmic granules :
 adenosine diphosphate (ADP): accelerates
platelet aggregation/activation.
 thromboxane (Tx A2): vasoconstriction and
increase ADP release from platelets.

7. Coagulation cascade
 To stabilize and reinforce the weak
platelet plug.
 3 steps :
1. Formation of prothrombin activator.
2. Conversion of prothrombin into
thrombin.
3. Conversion of fibrinogen to fibrin.

9. Coagulation Cascade

10. Fibrinolysis
 Plasminogen → plasmin → Lysis of clot
 Activators of plasminogen :
1. Endogenous substances : Tissue
plasminogen activator (tPA) (released
from endothelium) .
2. Exogenous substances: streptokinase,
urokinase, & tPA .

11. Abnormally activated (primary) fibrinolysis
may appear after :
 Burns
 Prostatic and neurosurgery
 Cardiopulmonary bypass (CPB)
 After streptokinase or urokinase therapy.

12. Virchow's triad
(thrombogenesis)

13. What prevent coagulation in
normal tissue ?
 Normal blood flow
 Prostacyclin (PGI2) (vasodilator & inhibit
platelet aggregation)
 Antithrombin III (inhibit all factors except
VII)
 Protein C & S (inhibit factor V & VIII)
 Tissue factor pathway inhibitor (TFI)

14. Hemostatic Balance
Procoagulant Anticoagulant
Plasminogen activator inhibitor Protein s and protein c
Antiplasmin Tissue factor pathway inhibitor
(TFI)
Tissue factor Fibrinolytic System
Clotting Factors Antithrombin III

16. Laboratory Monitoring
LABORATORY
TEST
COMPONENTS
MEASURED
NORMAL
VALUES
Bleeding time  platelet function
 vascular integrity
3 - 10 mins
PT I, II, V, VII, IX, X 12 - 14 secs
PTT I, II, V, VIII, IX, X, XI,
XII
24 - 35 secs
Thrombin time I, II 12 - 20 secs

17. Prothrombin Time (PT)
 Test of extrinsic and common pathways
activity
 Measures vitamin K - dependent factors
activity(factors II, VII, IX, X)
 Normal values: 12-14 seconds
 Most sensitive to alteration in F VII
levels
 55 % ↓ of normal F VII activity →
Prolonged PT

18. International Normalized Ratio
(INR)
 Standardizes PT reporting
 Normal values: 0.8 -1.2
 Recommended therapeutic: 2-3

19. Activated Partial Prothrombin
Time (aPTT)
 Test for intrinsic and common pathways
 Dependent on activity of all coagulation
factors, except VII and XIII
 Normal values: 25 -35 seconds
 Monitors heparin Rx & screen for hemophilia
 Prolonged only if coagulation factors reduced
to < 30 % of normal.

20. Bleeding time
 Monitors platelet function
 Not very reliable
 Variable from each institution
 No evidence as
• A predictor of risk of hemorrhage
• Useful indicator of efficacy of antiplatelet
therapy

21. Drugs affecting Hemostasis
HEMOSTATIC
PROCESS
AFFECTED
CLASS OF
DRUGS
SPECIFIC
DRUGS
platelet plug
formation inhibition
antiplatelet drugs reversible: NSAID
irreversible: ASA
coagulation cascade IV anticoagulants
oral anticoagulants
standard and LMW
heparins
warfarin
fibrinolysis fibrinolytic agents Streptokinase
Urokinase
t-PA

22. ASPIRIN
 Complete & irreversible block of platelet
 (50 -150mg/d)
 Ability to aggregate restore in 4-5 days
of stopping aspirin
 Recommended time for discontinuation
before surgery → 7-10 days

23. Clopidogrel
 Platelet adenosine diphosphate receptor
antagonist.
 irreversible platelet inhibition
 Loading dose 300mg then 75 mg/day
 Recommended time for discontinuation before
surgery → 7-10 days

24. Unfractionated Heparin
Mode of action :
Binds and ↑ anti - thrombin III (AT III) activity
to 1,000 fold →binds & inactivates factors IIa
and factor Xa
Degree of inhibition: F Xa = IIa
 high risk of bleeding during & after surgery
 stop at least 6 hrs before surgery
 restarted ~ 12 hrs postop. if needed with close monitoring
 immediate reversal: protamine sulfate .

25. Low molecular weight heparin
 Enhances AT-III interaction with Factor IIa &
Factor Xa
 Less anti -IIa than standard heparin
 Degree of inhibition: F Xa > IIa
 Gold standard for surgical Thrombo-
prophylaxis .
 prophylactic regimen : Start 12-48 hr after
surgery (in NORTH AMERICA ).

26. Warfarin
 inhibits synthesis of vitamin k dependent
factors II,VII, IX, X and protein C & S by
prevention of gamma carboxylation of
these factors.
 By competing vit K on its binding site on
hepatocytes where carboxylation
occurs.

27. Reversal:
 Stopping medication and waiting for ~4 days
for PT normalization
 Vitamin K PO or IV (1-2mg)
 Immediate: FFP (1-2 units) (dose is 5-8
mL/kg), rFVIIa, prothrombin complex
concentrate.
check PT prior to surgery

28. THANK YOU ..