1. Hemostasis & blood coagulation Dr. Wasif Haq

2. Hemostasis Hemostasis: prevention of blood loss. Is hemostasis same as homeostasis?

3. Why doesn’t blood clot in body? Smooth endothelium surface. Glycocalyx Thrombomodulin binding with Thrombin and activation of Protein C inactivating factor 5 and factor 8.

4. Hemostasis steps Vascular spasm Platelet plug formation Blood clot formation & fibrous tissue enclosure of blood clot.

5. Hemostasis Primary Hemostasis: Vascular contraction, platelet adhesion & formation of a soft aggregate plug. Short lived. Secondary Hemostasis: Activation of clotting factors. Stabilizes the clot.

6. Step 1.Vascular spasm Vessel wall contraction Contraction related to severity of trauma. Result of A) Nervous reflex (pain and other impulses from endothelium and adjacent tissue), B) Local myogenic spasm(major contributor) C) Humoral factors(from platelets Thromboxane A2 & Prostaglandins)

7. Step 1.Vascular spasm

8. Platelets Also called as Thrombocytes. Fragments of Megakaryocytes. No nuclei. Normal count 150,000-300,000 per micro liter.

9. Platelet structure Surface coating ‘Glycoprotein’ prevents platelet binding but stimulation in trauma and injury. Platelet wall also releases Phospolipids which has rolein extrinsic and intrinsic pathway of clotting.

10. Contents of Platelets Contractile proteins e.g. Actin,Myosin & Thrombosthenin. Endoplasmic reticulum & Golgi apparayus remanants- enzyme syntheisis and Ca++ storage. Mitochondria-ATP & ADP formation. Enzymes-Prostaglandin synthesis. Fibrin stabilizing factor-Strengthening the clot Growth factor- Vessel wall cells growth for repairing damaged vessel wall.

11. Step 2.Platelet Plug Platelet swelling upon contact with injured vessel. Release of sticky granuels helping to adhere to injured collagen and protein ‘von Willebrand factor.’ Activativation of adjacent proteins by A.D.P. & Thromboxane A2 Platelet plug stabilized by fibrin threads.

12. Step 2.Platelet Plug

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15. Step 3.Blood clot Traumatized vessel wall,adherent proteins and platelets release substances to activate clotting proteins. 3-6minutes plugging of small injuries followed by clot retraction in next 20-60mins. Clot can be covered completely by fibrous tissue or dissolved by plasmin protein.

16. Step 3.Blood clot

17. Mechanism of blood coagulation Reactions in blood Formation of activated substances (Prothrombin activator) Prothrombin Thrombin Fibrinogen Fibrin Calcium and Platelets

18. Thrombin & Fibrinogen Thrombin acts on Fibrinogen forming Fibrin monomers which polymerize to form Fibrin. Fibrin stabilizing factor released from platelets which is activated by Thrombin,helps to stabilize clot. Thrombin once activated starts a vicious cycle,activating Fibrinogen and other clotting factors.

19. Thrombin & Fibrinogen

20. Coagulation pathways Intrinsic Pathway: By blood itself. Proceeds slowly. Extrinsic Pathway: Trauma to vessel wall & surrounding tissue Rapid activation. Ca++ essential as helps in thrombin activation and formation of fibrin fibers from fibrinogen monomers.

21. Diseases and disorders Thrombus: Abnormal clot in blood vessel, static. Embolus: Freely flowing clot, mobile. Hemophilia: Bleeding disease caused by factor 8 deficiency. Treatment: injection of factor 8. Thrombocytopenia: very low quantity of plateets. Two types Thrombocytoenia purpura & Idiopathic thrombocytopenia.

22. Anticoagulants For body: Heparin-action lasts for 1.5-4 hours Coumarin(Warfarin) action lasts for 1-3 days after therapy cessation. For lab use: citrates and oxalates.

23. Lab tests Bleeding time:1-6 minutes. Depends upon depth of wound and degree of hyperemia. Clotting time: 2-6minutes by Capillary tube method. Prothrombin time: indication of total quantity of Prothrombin in blood. 12 seconds.

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