1. HMIM BLOCK 224
PLATELET AND
HEMOSTASIS
Dr. Zahoor
Lecture - 6

2. Objectives Define hemostasis Platelet production and function
Describe platelet aggregation
Describe blood coagulation pathways
Describe the mechanism of fibrinolysis and repair
Summarize some common hemostatic disorders

3. Platelets
Platelets are cell fragments Formed in bone marrow from megakaryocytes
Platelet lack nuclei
Normal count ,000 /mm3
Platelet diameter 2-4 m
Life span 8-12 days
Stored in spleen (30%)

4. Platelets Active cytoplasm Cytoplasm has Actin + myosin
Enzyme synthesis + storage of calcium
Synthesis of prostaglandins
Dense granules containing ADP, Thromboxine II, serotonin
Liver produces hormone thrombopoietin which increases the
number of platelets

5. Platelets Membrane - coat of glycoproteins adhesion to injured area
- phospholipids activation of intrinsic pathway of coagulation
- adenylate cyclase cAMP activate other platelets

6. Hemopoiesis

7. DEVELOPMENT OF PLATELET

8. Hemostasis Hemostasis refers to the stoppage of bleeding
Actions that limit or prevent blood loss include:
1. Blood vessel spasm
2. Platelet plug formation
3. Blood coagulation

9. Hemostasis

10. Coagulation Factors
Liver and Endothelial cell

11. 1. Blood Vessel Spasm 1. Blood vessel spasm
Triggered by pain receptors (vasoconstrictor release from nerve ending)
Damaged endothelium releases endothelin that constrict the vessels
Smooth muscle in blood vessel contracts
Platelet release serotonin( vasoconstrictor)

12. 2. Stages of platelet plug formation
Platelet adhesion
Platelet activation
ADP
Thromboxane formation (TXA2)
Both cause platelet aggregation
Platelet aggregation leads to platelet plug

13. Platelet Plug Formation

14. 3. Blood Coagulation 3. Blood coagulation
A blood clot forms via series of reactions
Blood coagulation mechanism are
1. Intrinsic pathway
2. Extrinsic pathway

15. Clotting Cascade
Series of steps involving 12 plasma clotting factors that lead to final conversion of fibrinogen into a stabilized fibrin mesh
Intrinsic pathway
Involves 7 separate steps
Starts when factor XII (Hageman factor) is activated by coming into contact with exposed collagen in injured vessel or foreign surface such as glass test tube

16. Blood Coagulation
See Intrinsic Pathway

17. Clotting Cascade Extrinsic pathway Requires only 4 steps
Requires contact with tissue factors external to the blood
Tissue thromboplastin – Factot III released from traumatized tissue directly activates factor X
Factor III and factor VII are required

18. Blood Coagulation
See Extrinsic Pathway

19. Clot Pathways
Intrinsic and Extrinsic

20. Clot under microscope

21. SUMMARY

22. what are the factors that prevent blood clotting in healthy
person ?

23. Factors that prevent a blood coagulation in healthy person
The smooth lining of blood vessels discourages the accumulation of platelets and clotting factors
Endothelium releases many factors that act as anti thrombotic and anticoagulant
Intact endothelium releases
Prostacyclin(PGI2)-
ADP dephosphatase
Inhibits platelet aggregation

24. Factors that prevent a blood coagulation in healthy person
Plasmin – plasma protein produced by liver, is present in blood in an inactive form plasminogen
tPA – Tissue plasminogen activator from tissue converts plasminogen to plasmin which causes degradation of fibrin
Applied – tPA genetically engineered is used in myocardial infarction to dissolve thrombus in coronary artery

25. Factors that prevent a blood coagulation in healthy person
Heparin sulphate – bind and activate antithrombin III.
Antithrombin III inactivate thrombin.
Some cells such as basophils and mast cells secrete heparin (an anticoagulant)

26. Fate of Blood Clots
After a blood clot forms it retracts and pulls the edges of a broken blood vessel together while squeezing the fluid serum from the clot
Platelet-derived growth factor stimulates smooth muscle cells and fibroblasts to repair damaged blood vessel walls
Plasmin digests the blood clots

27. Important A thrombus is an abnormal blood clot inside the blood vessel
An embolus is a blood clot moving through the blood vessels

29. Clinical Application

30. Abnormal Blood Clotting
Thrombus
Abnormal intravasculaar clot attached to a vessel wall
Emboli
Freely floating clots
Factors that can cause thromboembolism
Roughened vessel surfaces associated with atherosclerosis
Imbalances in the clotting-anticlotting systems
Slow-moving blood

31. Coagulation Defects I. Hepatic failure
almost all clotting factors are made in the liver
II. Vitamin K deficiency
required for II (prothrombin), VII, IX, and X
III. Hemophilia
Factor VIII (hemophilia A 1/10,000),
IV. Factor IX (hemophilia B 1/100,000)

32. Bleeding Disorder - Thrombocytopenia
Thrombocytopenia (decrease platelet)
There is bleeding in small capillaries and blood vessels, mucosa, skin
ITP Idiopathic thrombocytopenic purpura - autoimmune (common)
PURPURIC SPOTS ON SKIN : minute hemorrhages in subcutaneous tissue
Thrombocytopenic Purpura

33. Hemophilia
It is an X-linked disorder resulting from a deficiency in factor VIII
Hemophilia A is classic hemophilia (a disease referring to the inability to clot blood).
Individuals with deficiencies in factor VIII suffer
Joint and muscle hemorrhage,
Easy bruising and
Prolonged bleeding occurs from wounds.
Treatment of hemophilia A is accomplished by infusion of factor VIII concentrates prepared from either human plasma or by recombinant DNA technology.

34. HEMOPHILIA It’s a X linked recessive disease Females are carriers
Male suffer from disease.

35. Hemophilia B
Hemophilia B results from deficiencies in factor IX.

36. Thank you