1. Blood Week 7 Dr. Walid Daoud A. Professor

2. Anemia ____________________________ Anemia is decrease in O2 carrying capacity of blood due to: 1- Decreased number of RBCs:. Less than 4.5 million/mm 3 in males.. Less than 4.5 million/mm 3 in males.. Less than 3.9 million/mm 3 in females.. Less than 3.9 million/mm 3 in females. 2- Decreased Hb content of blood:. Less than 13.5 g/dl in males.. Less than 13.5 g/dl in males.. Less than 11.5 g/dl in females.. Less than 11.5 g/dl in females.

3. Classification & Causes of Anemia _____________________________ According to size of RBCs & Hb content: I-Normocytic Normochromic Anemia: Both size of RBCs & Hb content are normal but RBCs number is decreased. Both size of RBCs & Hb content are normal but RBCs number is decreased. Causes: Causes: -Acute blood loss (Hemorrhagic anemia). -Acute blood loss (Hemorrhagic anemia). -Bone marrow depression (Aplastic anemia). -Bone marrow depression (Aplastic anemia). -Breakdown of RBCs (Hemolytic anemia). -Breakdown of RBCs (Hemolytic anemia).

4. Classification & Causes of Anemia ____________________________ II-Microcytic Hypochromic Anemia or Iron Deficiency Anemia: Both size of RBCs and Hb contents are less than normal. Both size of RBCs and Hb contents are less than normal. Causes: Causes: -Decreased iron intake in diet. -Decreased iron intake in diet. -Failure of iron absorption. -Failure of iron absorption. -Chronic blood loss. -Chronic blood loss.

5. Classification & Causes of Anemia _____________________________ III-Macrocytic Hyperchromic Anemia or Megaloblastic Anemia: Both size of RBCs and Hb content are more than normal. Both size of RBCs and Hb content are more than normal. Causes: Causes: -Vitamin B 12 deficiency. -Vitamin B 12 deficiency. -Folic acid deficiency. -Folic acid deficiency.

6. Platelets or Thrombocytes ____________________________ Non-nucleated, granulated bodies, 2-4 µm in diameter. Normal platelet count: 150,000-450,000/mm 3 Decreased platelet count (Thrombocytopenia). Increased platelet count (Thrombocytosis).

7. Formation of Platelets ____________________________ Pluripotential stem cell in bone marrow ↓ interleukin ↓ interleukinCFU-M ↓ GM-CSF ↓ GM-CSFMegakaryocyte ↓ thrombopoietin ↓ thrombopoietinPlatelets CFU-M = Colony forming unit-megakayocyte. CFU-M = Colony forming unit-megakayocyte. GM-CSF=Granulocye-monocyte colony stimulating factor. GM-CSF=Granulocye-monocyte colony stimulating factor.

8. Structure of Platelets ___________________________ A. Platelet membrane. B. Platelet cytoplasm: 1- Beneath membrane: microtubules & ptn. 2- Intracellular organelles: 3- Glycogen granules. 4- Enzymes for synthesis of prostaglandins. 5- Granules:. Dense granules.. Dense granules.. Alpha granules.. Alpha granules.

9. Hemostasis ___________________________ It means stoppage of bleeding from an injured blood vessel. Hemostatic process consists of: I- Local vasoconstriction of injured blood vessel. II- Temporary hemostatic plug formation. III-Blood clot formation.

10. Hemostasis ___________________________ I- Local vasoconstriction: 1- Nervous reflex. 1- Nervous reflex. Initiated by pain sensation. Initiated by pain sensation. 2- Local myogenic contraction. 2- Local myogenic contraction. Due to direct damage of blood vessels. Due to direct damage of blood vessels. 3- Chemical substances. 3- Chemical substances. Serotonin and thromboxane A 2 liberated Serotonin and thromboxane A 2 liberated from platelets cause vasoconstriction. from platelets cause vasoconstriction.

11. Hemostasis ___________________________ II- Temporary Hemostatic Plug Formation: 1- Platelet adhesion. 1- Platelet adhesion. 2- Platelet activation. 2- Platelet activation. 3- Release reaction. 3- Release reaction. 4- Platelet aggregation. 4- Platelet aggregation. 5- Platelet procoagulant activity. 5- Platelet procoagulant activity. 6- Platelet fusion. 6- Platelet fusion.

12. Hemostasis ___________________________ III- Blood Coagulation (Blood Clotting): Properties of Blood Coagulation Factors: Properties of Blood Coagulation Factors: ContactProthrombinFibrinogenGroup XI, XII Stable Not consum II, VII, IX, X Stable Only II is consumed I,V,VIII,XIII All in liver V and VIII lose their activity All are consumed FactorsSynthesisStorage Consumption by clotting

13. Hemostasis ___________________________ The clotting mechanism: The loose platelet plug changes to blood clot: 1-Fibrinogen forms a loose then tight fibrin clot catalyzed by factor XIII and Ca 2+. 2-Thrombin converts fibrinogen to fibrin. 3-Active factor X converts prothrombin to thrombin. 4-Factor X is activated by either extrinsic or intrinsic pathways.

14. Hemostasis ___________________________ A. Intrinsic Pathway: In vivo (in plasma) or in vitro (glass of tube). - Activation of factor XII by HMW kininogen and kallikrein in plasma. - XIIa activates factor XI. - XIa activates factor IX. - IXa forms a complex with VIIIa & activates factor X in presence of phospholipids (PF3) and Ca 2+.

15. Hemostasis ___________________________ B- Extrinsic Pathway: Initiated only in vivo by tissue thromboplastin (TPL, factor III); they are group of tissue phospholipoprotein released from damaged vascular and connective tissues. - TPL activates factor VII. - VIIa directly activates factor X in presence of Ca 2+ TPL and phospholipids (PL) and indirectly through activation of factor IX.

16. Hemostasis ___________________________ Common Part in Both Pathways: - Xa converts prothrombin to thrombin. - Thrombin transforms soluble fibrin to insoluble fibrin. - Thrombin in presence of Ca 2+ activates factor XIII which stabilizes fibrin clot. - Contraction of actin, myosin and thrombosthenin of platelets causes clot retraction and squeezes serum out.

17. Hemostasis ___________________________ Important notes: - Extrinsic pathway is very rapid (15 sec.) while intrinsic pathway is slow (1-6 min.). - Injury of a blood vessel will trigger both the intrinsic system by exposed collagen and extrinsic system by tissue thromboplastin. - In test tube, clotting occurs only by intrinsic system by glass or addition of collagen. - In intravenous thrombosis, clotting occurs via intrinsic system by exposure of clotting factors to subendothelial collagen.

18. Anticoagulant Mechanisms ____________________________ Limiting reactions: prevent blood clotting in healthy blood vessels and breakdown any clots already formed. A.General:1- Smooth vascular endothelium. 2- Rapid flow of blood. 2- Rapid flow of blood. 3- Heparin. 3- Heparin. B.Specific:1- Thromboxane A 2 & Prostacyclin. 2- Antithrombin III. 2- Antithrombin III. 3- Fibrinolytic system. 3- Fibrinolytic system.

19. The Fibrinolytic System ____________________________ Thrombomodulin binds thrombin to form thrombomodulin-thrombin system which activate protein C which causes: -Inactivation of factor Va and VIIIa. -Inactivation of inhibitor of tissue plasminogen activator (t-PA), ↑ formation of plasmin. Plasmin (fibrinolysin) is an enzyme formed from plasminogen. It lyses fibrin & fibrinogen forming fibrin-degradation products (FDP) which inhibits thrombin.

20. Anticoagulants ____________________________ Substances used to prevent blood clotting. Substances used to prevent blood clotting. A- In vitro anticoagulants: in a test tube: 1-Removal of Ca 2+ : 1-Removal of Ca 2+ :. Oxalates: precipitates Ca 2+.. Oxalates: precipitates Ca 2+.. Citrates: binds Ca 2+ by deionizing them. Citrates: binds Ca 2+ by deionizing them 2-Silicon: prevents activation of factor XII. 2-Silicon: prevents activation of factor XII. 3-Heparin. 3-Heparin.

21. Anticoagulants ____________________________ B- In vivo anticoagulants: inside the body: DicumarolHeparin Plant Competitive inhibition of vitamin K in liver, ↓ factors II, VII, IX, X. Only in vivo. SlowLongOral Vitamin K Mast cell & basophil Facilitates action of thrombin. In vivo and vitro RapidShort I.V. and I.M. Protamine sulphate OriginAction Site of action OnsetDurationRouteAntidote

22. Abnormalities of Hemostasis ____________________________ 1-Thrombocytopenic purpura: S.C. hemorrhage - ↓ Platelets count below 50,000 / mm 3. - Bleeding time is prolonged.. 2-Vitamin K deficiency: due to: -Decreased formation: absent intestinal flora. -Decreased absorption: bile duct obstruction. 3-Hemophilia: congenital sex-linked disease -Hemophilia A: absence factor VIII. -Hemophilia B: absence factor IX. -Hemophilia C: absence factor XI.