قناة سنة ثانية بشري (دفعة 53)

Clot Retraction & Repair • Occurs within 30–60 minutes. • Due to actin & myosin in platelets. • PDGF: Stimulates fibroblasts & smooth muscle repair. • Endothelial growth factor: Restores vessel lining. Fibrinolysis • Breakdown of fibrin after healing (starts ~2 days). • Prevents vessel blockage. • Plasminogen → plasmin: • Digests fibrin & fibrinogen → FDPs. • FDPs inhibit thrombin & cause vasodilation. Plasminogen Activators: • t-PA & u-PA (from endothelium) • Thrombin • Factor XII • Lysosomal enzymes Plasminogen Inhibitors: • PAI-1 & PAI-2 • Antiplasmin Protein C & S System • Activated Protein C → inactivates Factors V & VIII. • Protein S → cofactor. • Activated on thrombomodulin. • Also inhibits PAI (enhancing fibrinolysis).

Clotting Factors • Most synthesized in liver. • Vitamin K needed for factors II, VII, IX, X (1972). • Many steps require Ca²⁺ and platelet phospholipids. Extrinsic Pathway • Trigger: Release of tissue factor (Factor III). • Factor VII → VIIa. • Tissue factor + VIIa + Ca²⁺ activate Factor X → Xa. • Xa + V → prothrombin activator. Intrinsic Pathway • Trigger: Activation of Factor XII → XIIa (contact with collagen or foreign surface). • Requires HMWK & prekallikrein. • Leads to activation of Factor X. Common Pathway • Xa + V + phospholipids → prothrombin activator. • Prothrombin → thrombin. • Thrombin + Ca²⁺ → fibrinogen → fibrin. • Factor XIII + Ca²⁺ → cross-linking → stable clot.

Stages of Hemostasis • Vasoconstriction • Platelet plug formation • Blood coagulation (clotting) 1. Vascular Spasm • Local vasoconstriction of injured vessels. • Triggered by: • Myogenic spasm (trauma) • Pain reflexes • Release of vasoconstrictors: thromboxane A2 & serotonin 2. Platelet Plug Formation Steps: • Platelet adhesion • Platelet activation • Platelet aggregation Changes in platelets: • Become irregular with filopodia. • Increased surface area. • Increased ability to bind to each other. Mechanisms: • Adhesion: Platelets bind exposed collagen using vWF. • Activation: Phospholipase A2 activates; granules release ADP, serotonin, Ca²⁺, TXA2. • Aggregation: Released factors activate nearby platelets → forming the plug. 3. Blood Coagulation (Clotting) • Formation of fibrin network over platelet plug. • Involves intrinsic & extrinsic pathways. • Cascade converts proenzymes → active enzymes. Final steps: • Formation of prothrombin activator • Prothrombin → thrombin • Thrombin → fibrinogen to fibrin

Overall Learning Goals • Understand the normal process of hemostasis. • Know the role of platelets in hemostasis. • Recognize the nomenclature of clotting factors. • Understand the clotting cascade. • Identify common hemostatic disorders. • Know medications used in treatment of hemostatic disorders. ⸻ Important Definitions • Hemostasis: Normal process to stop bleeding. • Thrombosis: Pathologic clot formation. • Hemorrhage: Bleeding. • Coagulopathy: Defect in coagulation causing abnormal bleeding. • Thrombocytopenia: Low platelet count. • Thrombocytosis: High platelet count.

🟡 5 . Hemostasis and blood Coagulation : ⬇️⬇️⬇️⬇️

هذا شيت ال platelet كمل ي شباب ♥️.

6. Platelet Abnormalities 1. Thrombocytopenia • Low platelet count → ↑ bleeding risk 2. Thrombasthenia • Platelet count normal • Defective function → impaired adhesion or aggregation

5. Role of Aspirin in Inhibiting Clot Formation • TXA₂ and prostacyclin are made from membrane phospholipids • Aspirin inhibits COX enzyme (Cyclo-oxygenase) • COX inhibition → ↓ TXA₂ → ↓ platelet aggregation • Platelets cannot synthesize new COX (no nucleus) → Effect lasts 10 days (platelet lifespan) • Long-term aspirin → ↑ bleeding time and ↓ clot formation

4. Thrombopoiesis • Platelet production from megakaryocytes • Stimulated by Thrombopoietin (TPO) • Platelets have no nucleus → formed by cytoplasmic fragmentation • Life span = 10 days