1. Platelets (Thrombocytes)
Platelets are produced by the bone marrow. They are not whole cells, but are fragments of extraordinarily large bone marrow-bound megakaryocytes.
The hormone THROMBOPOIETIN (produced by liver) increases the # of megakaryocytes in the bone marrow, stimulating them to produce more platelets
* Cell fragments bound to megakaryocytes
* “Bud Off” and are released into the blood

2. In Bone Marrow

3. Thrombocyte Development

4. Thrombocytes Shape: Minute round or oval discs (2-4 ) non-nucleated
Number: – /mm3
Life span: 8-12 days, removed by tissue macrophage as spleen so, the number increases after spleenectomy.

5. Platelet structure 1- Surface coat: mucopolysaccharide
2- Plasma membrane: is formed of 3 layers and invaginates inside to form open membrane system and contain phospholipids. This membrane is the basis structure of platelet factor 3 (PF3)
3- Beneath the membrane there are:
a- Microfilaments b- Microtubules

6. 4- Granules : 3 types of granules
- Dense granules contain (ADP) serotonin and calcium.
- Specific (Alpha) granules contain platelet growth factor, beta thromboglobulin, fibrinogen, clotting factors as V, XIII, platelet factor 4 (PF4) which is heparin antagonist factor.
- Dense tubular system contains calcium and may be site of synthesis of prostaglandin and thromboxane A2
5-mitochondria, glycogen & lysosomes which contain hydrolytic enzymes

7. Platelet structure

8. Von Willebrand factor (vWF)
An adhesive protein formed by the vascular endothelial cells and secreted in the plasma.
It is formed by megakaryocytes and stored in the platelets.
Blood clotting factor VIII circulated in plasma bound to vWF

9. Hemostasis
It is the stoppage of bleeding in case of small vascular injury.
It depends on:
the vascular wall, platelets and the clotting factors

10. [I] Vascular factor (local vascular spasm)
Causes
a- Direct effect of serotonin and thromboxane A2 released from platelets  V.C.
b- Injury of endothelium   endothelial derived relaxing substance  V.C.
c- Pain  nervous V.C. reflex

11. [II] Formation of platelet plug
1) Platelet adhesion:
Following blood vessel injury, platelets adhere to the exposed subendothelial collagen.
Adhesion depends on
a. A surface membrane glycoportein
b. Von-Willebrand factor

12. 3) Platelet aggregation
2) Platelets release:
a- Release of platelets contents such as ADP, serotonin, VWF, fibrinogen and platelet factor
b- Platelets enzymes form thromboxane A2
 release of platelets contents .
3) Platelet aggregation
Released ADP and thromboxaneA2 platelet aggregation  further release  more aggregation and so on.

13. Activated platelets adhere to other activated platelets.
This is mediated by adhesive receptors on the platelet surface that bind to vWF and fibrinogen.
Thus, fibrinogen forms a bridge between activated platelets  plug formation

14. Platelet Activation Pathways
ADP
Adrenaline
COLLAGEN
THROMBIN
ADP
GpIIb/IIIa
Aggregation
GpIIb/IIIa
Aggregation
GpIIb/IIIa
Aggregation
GpIIb/IIIa
Adhesion
Platelet
GpIb
Adrenaline
Adhesion
vWF
Exposed Collagen
Endothelium

16. 4) Platelet plug
At first, the plug is loose then becomes firm and tight (by contraction of contractile proteins and by fibrin threads).
The normal endothelial cells around the injury release prostacyclin.
Prostacyclin causes limitation of the plug to site of the injury by inhibition of platelet aggregation.

17. Importance of the plug A- It stops blood loss from small vessels
B- It closes the minute ruptures of very small vessels, which occur hundreds of times daily
C- The chemicals released from the platelets help other mechanisms of hemostasis:
- Serotonin and thromboxane A2 V.C.
- platelet factor 3 and clotting factors (factor V and fibrinogen and factor XIII) help clotting
release thrombasthenin & ATP  clot retraction
- Release of platelet growth factor  repair of the damaged vessels.

18. Steps of formation of platelets plug

19. [III] Blood coagulation
It needs the following clotting factors
I (Fibrinogen)
II (prothrombin)
III (thromboplastin)
tissue factor
IV (Calcium)
V (Labile factor)
VII (stable factor)
IX (christmas factor)
VIII (anti-haemophilia globulin)
X (Stuart prower factor)
XI (plasma thromboplastin antecadent)
XII (Hageman factor)
XIII (fibrin stabilizing factor)
Platelet factor-3 (phospholipid)
vWF
High molecular weight kininogen and prekallikrein.

20. The clotting factors are formed in
The liver
Some clotting factors require vit.K in their
synthesis from the liver (factor II,VII,XI and X)
Megakaryocytes
Share in formation of fibrinogen, Factor V, XIII and vWF.
Macrophages
Share in synthesis of factors V, VII, IX and X.
Endothelial cells
form vWF

21. Mechanism of blood coagulation (Coagulation cascade)
(1) Intrinsic pathway
by surface activator
Collagen of injured blood vessel
(inside the body)
(2) Extrinsic pathway
by tissue factor
(thromboplastin) from
tissue damage

22. Steps of blood clotting
A- Extrinsic pathway:
extrinsic because it depends on external factors from the tissue
“tissue thromboplastin” (lipoprotein mixture)

23. Activation of the Blood Clotting Cascade via Tissue Factor
Extrinsic pathway
Activation of the Blood Clotting Cascade via Tissue Factor

24. B- Intrinsic pathway:
1- When the blood comes in contact with subendothelial collagen in injured blood vessel.
2- Also, subendothelial collagen activate the platelet to release platelets phospholipids

25. Intrinsic pathway Xa Sub-endothelial collagen XII XIIa XI XIa IX IXa X
Prekallikrein IX
IXa
VIII
VIIIa X Xa Va V
XIII
Prothrombin
Thrombin
XIIIa
Fibrinogen
Fibrin
(soluble)
Fibrin (insoluble)

26. Intrinsic Pathway Extrinsic Pathway Blood Vessel Injury (collagen)
Tissue Injury
Tissue Factor
XII
XIIa
Thromboplastin XI
XIa IX
IXa
VIIa
VII X Xa X
Thrombin
Prothrombin
Fribrin monomer
Fibrinogen
Fibrin polymer
XIII

28. Interaction between the extrinsic and intrinsic mechanisms
1- Both pathways begins at the same time but the extrinsic mechanism takes seconds whereas the extrinsic mechanism takes 2-10 minutes.
2- The intrinsic mechanism clots the blood in the injured vessel, whereas the extrinsic mechanism clots the blood that escapes into the tissue
3- Both pathways are complementary as factor VIIa activate IX also XIIa, X1, Xa and thrombin activate VII