Hemostasis and blood clotting disorders

1. Dr. Fahad Abdulwahab Jameel
MSc. FKBMS (Hematopathology)
Hemostasis
Lecture 1

2. Haemostasis
 Is the physiological arrest of hemorrhage at sites of vascular leakage.
 There are mainly 5 systems which interact together to ensure
hemostasis, namely :
 1. Vascular factors.
 2. Platelets.
 3. Coagulation system.
 4. Natural Coagulation inhibitors.
 5. Fibrinolytic system.

3. RESPONSE TO VASCULAR INJURY
Vessel
Leakage
Constriction
Platelet
Plug
Fibrin
reinforced
Platelet
Plug
Secondary
hemostasis
Remodelling
& Fibrinolysis
Return
to normal
Primary hemostasis

4. Endothelial
Cells Role
 First and foremost barrier between blood
and subendothelium.
 Its basic function as a non-thrombogenic
permeability barrier.
 Synthesis of a number of factors some
with clot promoting, others with
anticoagulant roles.

5. Vessel wall
components
that are
hemostatically
active :
 Subendothelium :
 vWF.
 Collagen.
 Fibrinogen (fibrin)
 TF.
 Media :
 Collagen.
 Adventitia :
 Collagen.
 TF.

6. Platelets

8. Platelet
function
 Adhesion
 Shape change and spreading
 Aggregation
 Secretion

9. Platelets
Adhesion
 Initial step after breach in endothelium
through of Adhesive proteins :

10. Ultrastructural
Shape Changes
In platelets

11. Aggregation
of Platelets
 Cross-linking of platelets through binding
of fibrinogen or other bivalent or
multivalent ligands like vWF to GP
IIb/IIIa on Adjacent cells.

12. Secretion of
Platelets :
 There are three types of granules in
Platelets which are released or secreted:
1. Dense bodies ( gamma granules):
 containing ADP, ATP, Calcium and 5-HT.

13. Secretion of
Platelets :
2.. α-granules :
Contain a huge number of proteins including :
a. Platelet specific proteins :
b. Adhesive proteins.
c. Multimerin.
d. Coagulation factors
e. Mutagenic factors.
f. Vascular endothelial Growth factor.
g. Transforming Growth factor –β.

14. Dense tub sys.
ADP,ATP, 5HT,Ca+2
vWF, PF4, PDGF,
thrombospondin,fibrinogen
FV,VIII, PS, PAI-1

15. conformational change in GPIIb/IIIa receptors
shape change and spreading
aggregation
secretion and release of agonists
further aggregation.
Subendothelial exposure
Activation of Platelets
Exposure of –Ve
charged PL
Coagulation
promoted
Platelets Adhesion

16. Coagulation pathways-Old version
vWF

17. Natural Coagulation pathway inhibitors
Factor
I
Fibrin
VIIIa
Va
Act. Plat.
Activated Protein C
Activated Protein C
Antithrombin
TFPI

18. The
Fibrinolytic
system
 Basic physiological role of this system is to
ensure that no excess fibrin is deposited or
if an excess is deposited, it is rapidly
removed. Moreover, the fibrin mesh formed
is removed as part of the remodelling.
FIBRIN ORCHESTRATES ITS OWN
DESTRUCTION

19. The Components of the Fibrinolytic
system
Plasminogen and Plasmin
Plasminogen activators
Endogenous (tissue or Plasma derived)
Exogenous (bacterial or venom derived)
Inhibitors of plasmin
Inhibitors of Plasminogen activators.

20.  Basic Screening tests for Haemostasis :
 1. Platelets count (Normal range 150 000 – 450 000/cmm) : a
reduced platelets count is associated with increased liability to
bleeding.
 2. Bleeding time (NR 2 – 10 minutes) : is prolonged if there is
reduced platelets count or function, or if there is a vascular defect.
 3. Prothrombin Time (PT) : this is a test which tests the extrinsic
and the common pathway of the coagulation .
 4. Activated Partial Thromboplastine Time (APTT): This test is used
to test for intrinsic and the common pathway.
 5. Thrombin time : this tests the last step in the coagulation
pathway i.e. the conversion of Fibrinogen (factor I) to fibrin.

21. Activated Partial
Thromboplastin Time

22. Prothrombin Time

23. T.T.
Thrombin Time