Chapter 36 Hemostasis and Blood Coagulation Hemostasis Coagulation

  • Slides: 25
Download presentation
Chapter 36: Hemostasis and Blood Coagulation

Chapter 36: Hemostasis and Blood Coagulation

Hemostasis, Coagulation 1. Vascular Spasm 2. Platelet plug 3. Formation of clot

Hemostasis, Coagulation 1. Vascular Spasm 2. Platelet plug 3. Formation of clot

Clot Formation

Clot Formation

Platelets Formed in bone marrow, 150 -350, 000 /µl Sequestered in spleen (30%) 2

Platelets Formed in bone marrow, 150 -350, 000 /µl Sequestered in spleen (30%) 2 -4 m in diameter, life span 8 -12 days, no nucleus Active cytoplasm actin + myosin enzyme synthesis + storage of calcium synthesis of prostaglandins dense granules containing ADP and ATP a-granules (fibrinogen, PDGF, v. WF, fibronectin) fibrin stabilizing factor

Platelets Membrane Receptors: thrombin, ADP, epi, serotonin Adhesion proteins: v. WF, fibronectin, collagen, fibrinogen

Platelets Membrane Receptors: thrombin, ADP, epi, serotonin Adhesion proteins: v. WF, fibronectin, collagen, fibrinogen coat of glycoproteins adhesion to injured areas phospholipids activation of intrinsic pathway adenylate cyclase c. AMP activate other platelets

Activators of platelets • Collagen and microfibrillar proteins • ADP released from damaged RBCs

Activators of platelets • Collagen and microfibrillar proteins • ADP released from damaged RBCs and activated platelets • Thromboxane from activated platelets • Platelet activating factor from basophils • Epinephrine (stress) • Thrombin

Platelets Vessel injury or atherosclerotic plaque rupture subendothelial protein layer exposed platelets bind to

Platelets Vessel injury or atherosclerotic plaque rupture subendothelial protein layer exposed platelets bind to subendothelial v. WF, and collagen via surface glycoproteins. platelets swell release platelet agonists from granules generate thrombin activation of new platelets crosslinking of platelet aggregate by surface glycoprotein contractile elements pull fibrin threads

Platelets Leukotrienes (chemoattractants) Thromboxane (release more granules) Release of thrombospondin (stabilizes platelet-fibrin) Release of

Platelets Leukotrienes (chemoattractants) Thromboxane (release more granules) Release of thrombospondin (stabilizes platelet-fibrin) Release of PDGF (stimulates smooth muscle proliferation) Release of ADP (attracts more platelets)

Platelet inhibition

Platelet inhibition

Formation of a Clot Intrinsic TF (Tissue factor) Surface Contact XII-----XIIa Extrinsic XI-----XIa IX-----IXa

Formation of a Clot Intrinsic TF (Tissue factor) Surface Contact XII-----XIIa Extrinsic XI-----XIa IX-----IXa TF-VIIa TF VII Tissue Damage X------Xa------X XIII Prothrombin Thrombin Fibrinogen Common Fibrin XIIIa Stable Fibrin

Fibrin • Polymerization catalyzed by Factor XIIIa • XIIIa crosslinks fibronectin • Fibronectin promotes

Fibrin • Polymerization catalyzed by Factor XIIIa • XIIIa crosslinks fibronectin • Fibronectin promotes in growth fibroblasts • XIIIa crosslinks a 2 -antiplasmin • a 2 -antiplasmin protects from plasmin

Blood Coagulation 1. Formation of prothrombin activator in response to blood damage or vessel

Blood Coagulation 1. Formation of prothrombin activator in response to blood damage or vessel rupture

Blood Coagulation 2. Conversion of prothrombin into thrombin prothrombin (factor II) --- formed in

Blood Coagulation 2. Conversion of prothrombin into thrombin prothrombin (factor II) --- formed in the liver Split in two thrombin --- proteolytic enzyme a) acts on fibrinogen b) stimulates fibrin stabilizing factor c) acts on prothrombin + clotting factors (positive feedback)

Blood Coagulation 3. Conversion of fibrinogen into fibrin threads fibrinogen (factor I) --- formed

Blood Coagulation 3. Conversion of fibrinogen into fibrin threads fibrinogen (factor I) --- formed in the liver a) fibrin is split into fibrin monomers b) automatic polymerization into long fibrin threads (weak) c. ) fibrin stabilization (strong bonds requires Factor XIII) 30 -60 clot retracts, platelets required

Formation of Prothrombin Activator I. Extrinsic pathway tissue trauma tissue thromboplastin (+VII) Rapid and

Formation of Prothrombin Activator I. Extrinsic pathway tissue trauma tissue thromboplastin (+VII) Rapid and explosive in nature (15 seconds) X activation II. Intrinsic pathway blood trauma, contact with collagen or activated platelets XII XI IX (+VIII) X activation slower (2 -6 minutes) many components (cascade) Common pathway Xa combined with V and platelet phospholipids (PF 3) + Ca++ prothrombin activator: prothrombin fibrinogen

Extrinsic Pathway

Extrinsic Pathway

Intrinsic Pathway

Intrinsic Pathway

Intravascular Anticoagulants I. Endothelial Cells smooth surface + glycocalyx II. Antithrombin action of FIBRIN

Intravascular Anticoagulants I. Endothelial Cells smooth surface + glycocalyx II. Antithrombin action of FIBRIN (absorbs thrombin) III. Antithrombin III (alpha-globulin, combines with heparin) antithrombin destroys thrombin IV. Heparin: conjugated polysaccharide, negative charge little action unless combined with antithrombin III increased affinity of antithrombin III

Fibrinolytic System Plasminogen = circulating globulin Plasmin = proteolytic enzyme, similar to trypsin digest

Fibrinolytic System Plasminogen = circulating globulin Plasmin = proteolytic enzyme, similar to trypsin digest fibrin threads, fibrinogen, and other clotting factors Significance: removal of tiny little clots Plasminogen activators: Tissue Plasminogen Activator (TPA), urokinase, streptokinase Plasminogen inhibitors: plasminogen activator inhibitor (PAI-1) inhibits TPA Alpha 2 -antiplasmin blocks binding plasminogen to fibrin

Coagulation Defects I. Vitamin C deficiency lack of stable collagen (elderly, alcoholics) II. Hepatic

Coagulation Defects I. Vitamin C deficiency lack of stable collagen (elderly, alcoholics) II. Hepatic failure almost all clotting factors are made in the liver III. Vitamin K deficiency required for II (prothrombin), VII, IX, and X fat malabsorption due to lack of bile secretion IV. Hemophilia Factor VIII (hemophilia A 1/10, 000), Factor IX (hemophilia B 1/100, 000) chromosome X

Coagulation Defects V. Thrombocytopenia bleeding small capillaries and blood vessels mucosal, skin low number

Coagulation Defects V. Thrombocytopenia bleeding small capillaries and blood vessels mucosal, skin low number of platelets ITP- autoimmune (common) VI. Disseminated Intravascular Clotting abnormal bleeding and clot formation critically ill patients coagulation and clot lysis in uncontrolled manner due to massive tissue damage depletion of clotting factors

In Vivo Coagulation Thromboembolic conditions venous thrombosis, pulmonary embolism artificial heart valves, by-pass surgery

In Vivo Coagulation Thromboembolic conditions venous thrombosis, pulmonary embolism artificial heart valves, by-pass surgery long-term bed immobilization HEPARIN — immediate anticoagulation for overdose stop infusion 3 -4 hrs, protamine counteracts heparin COUMARINS — compete Vitamin K, 2 -4 days to act reverse with FFP and Vitamin K

In Vitro Coagulation HEPARIN — hemodialysis heart-lung machine CALCIUM CHELATORS bind calcium which is

In Vitro Coagulation HEPARIN — hemodialysis heart-lung machine CALCIUM CHELATORS bind calcium which is required for clotting

Blood Coagulation Tests Platelet count 150 -300, 000/ µl thrombocytopenia - aplastic anemia, autoimmune

Blood Coagulation Tests Platelet count 150 -300, 000/ µl thrombocytopenia - aplastic anemia, autoimmune platelet function - myeloproliferative, uremia, drugs (aspirin, antibiotics), von Willebrand Disease Bleeding Time time for skin wound to stop bleeding <6 minutes, test of platelets

Tests of Clotting Pathway Intrinsic XII XI IX Extrinsic VIII PT a. PTT Activated

Tests of Clotting Pathway Intrinsic XII XI IX Extrinsic VIII PT a. PTT Activated Partial Thromboplastin Time X Prothrombin Time V Prothrombin (II) Thrombin