1. Hemostasis Hemostasis depends on the integrity of Blood vessels
Platelets
Coagulation factors

2. STEPS IN HEMOSTASIS
Transient arteriolar vasoconstriction due to reflex neurogenic mechanism and secretion of endothelin.
Formation of primary platelet plug due to adhesion of platelets to collagen and traces of thrombin.
Conversion into permanent plug supported by fibrin clot formed by activation of the coagulation cascade.
Lysis of fibrin and confinement of clot to the site of injury.

3. Intrinsic Pathway XII XIIa Extrinsic Pathway XI XIa VIIa TF VII IX IXa
HMWK
Prekallikerin
Surface
XII
XIIa
Extrinsic Pathway XI
XIa
VIIa TF
VII IX
IXa
VIIIa X Xa Va
Prothrombin
Thrombin
Fibrinogen
Fibrin
XIIIa
Cross linked fibrin

4. Prothrombin Time XIIa XII XI XIa VIIa TF VII XI IXa VIIIa X Xa Va
HMWK
Prekallikerin
Surface
XIIa
XII XI
XIa
VIIa TF
VII XI
IXa
VIIIa X Xa Va
Prothrombin
Thrombin
Fibrinogen
Fibrin
XIIIa
Cross linked fibrin

5. Partial Thromboplastin Time
HMWK
Prekallikerin
Surface
XIIa
XII XI
XIa
VIIa TF
VII XI
IXa
VIIIa X Xa Va
Prothrombin
Thrombin
Fibrinogen
Fibrin
XIIIa
Cross linked fibrin

6. Antithrombin III AT III XIIa XII XI XIa VIIa TF VII XI IXa VIIIa X Xa
HMWK
Prekallikerin
Surface
XIIa
XII XI
XIa
VIIa TF
VII XI
IXa
VIIIa X Xa Va
Prothrombin
Thrombin
AT III
Fibrinogen
Fibrin
XIIIa
Cross linked fibrin

7. Protein C Protein C XIIa XII VIIa TF VII XI XIa XI VIIIa X Xa Va
HMWK
Prekallikerin
Surface
Protein C
XIIa
XII
VIIa TF
VII XI
XIa XI
IXa
VIIIa X Xa Va
Prothrombin
Thrombin
Fibrinogen
Fibrin
XIIIa
Cross linked fibrin

8. ANTITHROMBOTIC FUNCTION OF NORMAL ENDOTHELIUM
Separation of blood from subendothelium that activates platelets and initiates blood coagulation
Release of PGI2 that diminishes platelet response to activating stimuli
Binding sites for anticoagulants
Thrombomodulin binds thrombin altering its enzymatic activity with activation of protein C.
Antithrombin III binding sites

9. PROTHROMBOTIC ROLE OF ENDOTHELIUM
Production of von Willebrand factor.
Synthesis of TF (induced by TNF, IL-1).
Binding of IXa and Xa on their surfaces.

10. Dual Role of Endothelium
Production of VWF
Synthesis of TF
Binding of IXa and Xa
Separation of blood from subendothelium
Release of PGI2
Binding sites for:
Thrombomodulin
Antithrombin III
INHIBITION OF
CLOTTING
INDUCTION OF
CLOTTING

11. Virchow’s Triad Thrombosis Endothelial Injury Hypercoagulability
Abnormal Bl. Flow
Hypercoagulability

12. Endothelial injury Important in heart and arterial thrombosis
Caused by
Hemodynamic stresses
Homocystinuria and hypercholesterolemia
Cigarette smoking
Inflammatory conditions
Results in
Platelet interaction with subendothelial collagen
Release of tissue factor

13. Alteration in Blood Flow
Turbulence in heart and arteries lead to endothelial injury
Stasis is the major cause of venous thrombosis
Stasis and turbulence lead to
Disruption of laminar flow causing platelets endothelial contact
Prevent dilution of activated factors
Decrease inflow of coagulation factor inhibitors
Help activate endothelial cells leading to thrombosis and leukocyte adhesion

14. Hypercoagulability Genetic Causes Acquired Causes Factor V mutation
Antithrombin III deficiency
Protein C deficiency
Protein S deficiency
Defects in fibrinolysis
Acquired Causes
Bed rest and immobilization
Myocardial infarction
Tissue damage (surgery, accidents, burns)
Cancer
Artificial valves
Antiphospholippid syndrome
Polycythemia
Sickle cell disease
Oral contraceptives and hyperestrogenemia

15. Arterial thrombi
Endothelial damage
Against bl. flow
Prominent
Gray
Yes
Heart; coronary, cerebral, aorta
Venous thrombi
Stasis
With bl. blow
Less prominent
Red
Yes
Lower limb veins
Etiology
Growth
Lines of Zahn
Color
Occlusive
Location