1. asilmi HEMOSTASIS Ahmad Shihada Silmi Faculty of Sciences IUG Med. Tech. Dep. Room # B326

2. asilmi HEMOSTASIS An overview of Haemostatic Mechanism, Platelet structure and function, Define the term hemostasis, coagulation, fibrinolysis, and hemorrhage. List the major and minor systems involved in maintaining hemostasis. List the major and minor systems involved in maintaining hemostasis. Describe the events that take place in primary hemostasis.

3. asilmi HEMOSTASIS List the function of the vascular system. Describe the major functions of the endothelium. Name the three structural zones of platelets.

4. asilmi HEMOSTASIS OBJECTINES Describe the composition and functions of the peripheral zone, the sol-gel zone, and the organelle zone. Explain the role of platelets in the haemostatic process. List steps in platelet plug formation List steps in platelet plug formation Name essential elements for the process of platelet adhesion.

5. asilmi HEMOSTASIS OBJECTINES Describe the process of platelet aggregation. Describe the events take place in secondary hemostasis. Describe the events take place in secondary hemostasis. Name the product responsible for stabilization of the haemostatic plug. Name the product responsible for stabilization of the haemostatic plug. List characteristics for the contact coagulation proteins. List characteristics for the contact coagulation proteins. List characteristics for the prothrombin proteins. List characteristics for the prothrombin proteins.

6. asilmi HEMOSTASIS OBJECTINES Interaction of the Fibrinolytic, Coagulation Systems and Related Pathology. Name the component of the coagulation and fibrinolytic system. List plasminogen activators and negative feedback clotting mechanisms.

7. asilmi HEMOSTASIS OBJECTINES Describe plasmin’s action in forming the intermediate degradation product, D dimer. Name the primary inhibitor of the fibrinolytic system. Describe the physiologic interactions of the proteolytic system.

8. asilmi HEMOSTASIS OBJECTIVES Acquired coagulation disorders Objectives Following this conference, the student will be able to Explain the classification of acquired disorder of haemostasis such as: Hepatic disease, vitamin K deficiency, renal disease, haeorrhagic disease of the newborn, overdosage with anticoagulant, massive transfusion syndrome. Explain the action of oral anticoagulants

9. asilmi HEMOSTASIS OBJECTINES Acquired coagulation disorders Objectives Name the most common laboratory test used to monitor oral anticoagulant therapy List mechanisms and clinical conditions associated with DIC. Define the three generalized clinical states of DIC with regard to the typical Laboratory abnormalities associated with each state. Describe the use of laboratory tests to distinguish primary fibrnolysis from DIC. Identify therapies for treatment of DIC

10. asilmi HEMOSTASIS OBJECTIVES Quantitative and Qualitative Vascular and Platelet Disorders. Both Congenital and Acquired. Congenital Disorder of platelet Function 1- Bernard Soulier Syndrome (BSs). 2- Glanzmann’s thrombasthenia

11. asilmi HEMOSTASIS Objectives. Definition of Hemostasis Haemostatic components Concepts of Normal Hemostasis Role of Coagulation in Hemostasis Primary and Secondary Role of Blood Vessels in Hemostasis Role of Blood Vessels in Hemostasis Coagulation Proteins Coagulation Proteins Factor Nomenclature Factor Nomenclature Coagulation Groups Coagulation Groups Phospholipids Contribution to Coagulation. Phospholipids Contribution to Coagulation.

12. asilmi Vessel wall, Blood flow & Coagulation Substances

13. asilmi In Case if there is an Endothelial Injury ( Bleeding must be prevented at site of injury)

14. asilmi Flow must be Maintained

15. asilmi HEMOSTASIS Definition Hemostasis: drives from the Greek meaning “The stoppage of blood flow”. There are three haemostatic components: 1- The extra-vascular (The tissues surrounding blood vessels) involved in Hemostasis when local vessel is injured. It plays a part in Hemostasis by providing back-pressure on the injured vessel through swelling and trapping of escaped blood.

16. asilmi HEMOSTASIS The three haemostatic components 2- The vascular (The blood vessels through which blood flow) it depends on the size, amount, of smooth muscle within their walls and integrity of the endothelial cell lining. 3- The intra-vascular (The platelets and plasma proteins that circulate within the blood vessels). These components are involved in Coagulation (clot or thrombus formation) or Fibrinolysis (clot or thrombus dissolution).

17. asilmi

18. HEMOSTASIS Concepts of Normal Hemostasis Under normal conditions, the formation and dissolution of thrombi is maintained in a delicate balance. (fig ).

19. asilmi Without this balance, the individual may experience either excessive bleeding (poor clot formation or excessive Fibrinolysis) Vaso-occlusion (uncontrolled formation of thrombin in vascular system, occluding vessels and depriving organs of blood).

20. asilmi HEMOSTASIS There are certain conditions associated with excessive bleeding are referred to as: Hypo-coagulable states. Such as, Hemophilia or deficiency in one of the plasma coagulation proteins such as factors VIII. Acquired conditions such as DIC, Liver and Kidney diseases. In addition to Coagulation promotion, vessel injury initiates Fibrinolysis through endothelial cell release of tissue Plasminogen activators (tPAS). This is to ensure that excessive coagulation does not occur.

21. asilmi HEMOSTASIS Role of Coagulation in Hemostasis Coagulation: Is the process where by on vessel injury, Plasma protein, Tissue factors and Calcium interact on the surface of the platelets to form a Fibrin clot. Platelets provide a surface for the coagulation reaction, and interact with fibrin to form a stable platelet fibrin clot.

22. asilmi HEMOSTASIS Tissue factors (except Ca and Tissue Thromboplastin) normally circulate in the plasma as inactive proteins. On activation some factors form enzymatic proteins known as Seiren Proteases that activate other specific factors in the coagulation sequence. Other conditions are related to uncontrolled thrombosis are called Hyper-coagulable state. This is related to an appropriate formation of thrombi in the vascular vessels that occlude normal blood flow.

23. asilmi HEMOSTASIS Hemostasis can be divided into two stages: Primary and Secondary. Primary and Secondary. Primary hemostasis includes the platelet and vascular response to vessel injury. Secondary hemostasis includes the coagulation factors response to such injury. Together, platelets, vessels, and coagulation factors combine to stop bleeding and allow for vessel repair through formation of a stable fibrin-platelet plug at the site of injury.

24. asilmi HEMOSTASIS Role of Blood Vessels in Hemostasis Blood flows through the vascular system to and from all parts of the body. The vascular system consists of capillaries, arteries, and veins. Blood normally carried within vessels whose physical capabilities include Contraction (narrowing) and Dilation, which are controlled by the smooth muscle of the vessel media.

25. asilmi HEMOSTASIS Vasoconstriction and Vasodilatation provide the means for control blood flow rate and blood pressure. Substances released from the endothelial cells and sub- endothelial smooth muscles also contribute to normal blood flow and prevent abnormal formation of clot.

26. asilmi

39. Summary of Important Vascular Function asilmi

40. 40 Vascular Endothelium Function Prostacyclin Thromboxane A 2 ELAMs, ICAMs von Willebrand factor Vasodilation, inhibition of platelet aggregation From platelets, constrict muscular arteries Cytokines induce synthesis to promote leukocyte adhesion Promote platelet-collagen adhesion to exposed sub- endothelium

41. 41 Vascular Endothelium Function Tissue factor pathway inhibitor Thrombomodulin Tissue plasminogen activator Heparan sulfate proteoglycans Tissue factor Anticoagulant- Inhibits coagulation extrinsic pathway Anticoagulant- Inhibits coagulation by activating protein C system Anticoagulant- Inhibits coagulation by activating fibrinolysis Anticoagulant- Inhibits coagulation by activating antithrombin Procoagulant- Inflammatory cytokines (IL-1, TNF) induce expression

42. asilmi