2. PLATELETS
(PLT) Thrombocytes

3. Platelets
Thrombocytes are
Fragments of megakaryocytes

4. Hematopoiesis

5. Platelets – cont. Steps: Stem cell Site of formation: Bone marrow
Megakaryoblast
Megakaryocyte
Platelets

6. Platelets Formation (Thrombopoiesis)
Regulation of thrombopoiesis by
Thrombombopoietin

7. Regulation of Thrombopoiesis
Thrombopoietin regulates the differentiation of megakaryocytes and platelets, It is a hormone released by the liver and kidney.

8. Regulation of Thrombopoiesis cont..
Thrombopoietin is bound to the surface of platelets by the mpl receptor (CD 110) and destroyed, thereby reducing megakaryocyte exposure to the hormone.

9. Regulation of Thrombopoiesis cont..
Therefore, the rising and dropping platelet concentrations regulate the Thrombopoietin levels. Low platelets lead a higher degree of Thrombopoietin level and therefore higher exposure to the undifferentiated bone marrow cells, leading to differentiation into megakaryocytes and further maturation of these cells. On the contrary, high platelet concentrations lead to the reversal of these physiologic mechanisms

10. Platelets Platelets are non-nucleated, small, round or oval discs.
They are formed in the bone marrow by fragmentation of the cytoplasm of giant cells called “Megakaryocytes”.
Platelet count normally = 150, ,000/µl. 10

11. Function of Platelets
Plays a role in Hemostasis = prevention of blood loss.
Whenever a vessel is severed or ruptured, Hemostasis is achieved by several mechanisms;
Vascular spasm.
Formation of a platelet plug.
Formation of a blood clot as a result of blood coagulation.

12. Begins with Platelet activation
Platelet Functions
Begins with Platelet activation

13. Platelet Activation Adhesion Shape change Aggregation Release
Clot Retraction

14. Platelet function
Adhesion
Aggregation
TxA2
ADP
Secretion

16. Platelet Adhesion
Platelets stick to exposed collagen underlying damaged endothelial cells in vessel wall

17. Platelet Release Reaction
Platelets activated by adhesion
Extend projections to make contact with each other
Release Thromboxin A2, Serotonin & ADP activating other platelets
Serotonin & Thromboxin A2 are vasoconstrictors decreasing blood flow through the injured vessel. ADP causes stickiness

18. Platelet Aggregation
Activated platelets stick together and activate new platelets to form a mass called a Platelet Plug
Plug reinforced by fibrin threads formed during clotting process

19. Platelet
Adhesion
Endothelium
2. Shape change
3. Aggregation

20. Resting platelet
Activated platelet

21. Platelet shape change and Aggregation

22. Platelet Aggregation

23. Platelet Plug Formation
Blood vessel injury.
Platelets come in contact with damaged blood vessel.
They become activated and adhere to the injured area.
This will activate even more platelets to come to the injured area resulting in platelet plug formation.

24. Platelet haemostatic plug formation

25. Platelet Plug formation Cont.
The platelet plug is a loose plug that is usually successful in blocking the blood loss if the vascular opening is small.
Then, during the process of blood coagulation, the stronger fibrin threads are formed that will strengthen the platelet plug.

26. Platelet Plug
Aggregation of platelets at the site of injury to stop bleeding
Exposed collagen attracts platelets
Activated platelets release of platelet ADP & TXA2   the stickiness of platelets   Platelets aggregation  plugging of the cut vessel
Intact endothelium secret prostacyclin  inhibit aggregation

27. Activated Platelets Secrete: 5HT  vasoconstriction
Platelet phospholipid (PF3)  clot formation
Thromboxane A2 (TXA2) is a prostaglandin formed from arachidonic acid
Function:
vasoconstriction
Platelet aggregation
(TXA2 inhibited by aspirin)

28. Blood coagulation Initiation on blood coagulation occurs by two ways:
The extrinsic pathway: initiated by trauma to blood vessel.
The intrinsic pathway: initiated in the blood itself.

29. Clotting Factors

30. EXTRINSIC MECHNANISM FOR INITIATING CLOTTING

31. INTRINSIC MECHNANISM FOR INITIATING CLOTTING

33. ROLE OF THROMBIN IN HEMOSTASIS

34. ACTION OF THROMBIN ON FIBRONOGEN TO FORM FIBRIN

35. Blood trauma or contact with collagen
The Intrinsic Pathway
Blood trauma or contact with collagen
The Extrinsic Pathway
Tissue trauma
F XII
F XIIa
HMW Kininogen
Prekallikrein
Tissue factor (TF)
FXI
FXIa
Ca++
FVIIa
FVII
F IX
F IXa
Ca++
FVIII
PLTs
Ca++
F X
F Xa
Blood clot FV
PLTs, Ca++
Prothrombin
Thrombin
FINAL COMMON PATHWAY
Fibrinogen
Fibrin

36. Bleeding Disorders Excessive bleeding can result from;
Platelet defects: deficiency in number (thrombocytopenia) or defect in function.
Deficiency in coagulation factors (e.g. hemophilia).
Vitamin K deficiency.

37. Bleeding Disorders Cont…
Hemophilia:
↑ bleeding tendency.
X-linked disease.
Affects males.
85% due to FVIII deficiency (hemophilia A), and 15% due to FIX deficiency (hemophilia B).
Vitamin K deficiency & liver disease:
Almost all coagulation factors are synthesized in the liver.
Prothrombin, FVII, FIX, & FX require vitamin K for their synthesis.

38. Blood trauma or contact with collagen
The Intrinsic Pathway
Blood trauma or contact with collagen
The Extrinsic Pathway
Tissue trauma
F XII
F XIIa
HMW Kininogen
Prekallikrein
Tissue factor (TF)
FXI
FXIa
Ca++
FVIIa
FVII
F IX
F IXa
Ca++
FVIII
PLTs
Ca++
Blood clot
Hemophilia
F X
F Xa FV
PLTs, Ca++
Prothrombin
Thrombin
Fibrinogen
Fibrin

39. Anticoagulants Heparin Warfarin Liver, lungs, mast cells, basophils
Direct antithrombin
Prevent the conversion of Prothrombin to Thrombin
Injection only
6-8 hours
Warfarin
Almost all coagulation factors are synthesized in the liver.
Suppresses the synthesis of Prothrombin, FVII, FIX, & FX vitamin K dependent factors
Orally
48 hours

40. Thank you for listening