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Define hemostasis
ID 3 parts of hemostasis triangle
- The balance between clotting and bleeding
- Platelet aggregation, blood vessel wall, blood coagulation
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4 steps floowing loss of vascular integrity
- Vascular contriction
- Platelet activation
- Formation of fibrin clot
- Clot lysis/would healing
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What secretes Thromboxane?
What is its role?
- Platelets secrete TXA2
- Activates additional platelets
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What is the role of fibrinogen?
stimulates platelet clumping
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Define:
1. White thrombus
2. Red thrombus
- 1. platelet plug of only platelets
- 2. plug also includes RBCs
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What is the role of fibrin?
Forms clot/mesh to stabilize platelet plug
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What is the role of plasmin?
Dissolution of the clot
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What is the role of thrombopoietin?
- Stimulates maturation of megakaryocytes
- Produced when platelet levels drop
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Name and describe the 3 granules of a platelet
- Dense granules - contain serotonin (vasoconstrictor), Ca, ADP, ATP
- Alpha granules - contain fibrinogen, vWF and growth factors
- Lambda granules - lysosomes
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How are platelet granule contents released?
Granules fuse with Canaliculi (channels) in platelet membrane
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What mediates adhesion of platelets to exposed collagen?
- vWF (von Willebrand factor)
- bridges glycoprotein of platelet to collagen
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What is the end result of platelet signal transduction?
- G-protein CRs initiate cascade that increases Ca in cell, stimulating Phospholipase A2 (PLA2) release
- Stimulates increase TXA2 release
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Which stimulates/inhibits platelet activity:
Thromboxane
Prostaglandin
- Thromboxane - stimulates (from platelet)
- Prostaglandin - inhibits (from vessel wall)
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Define the instrinsic coagulation pathway, ID its factors, and its goal
- Formation of clot without tissue injury (all components in plamsa)
- XII, XI, IX, VIII, X
- X --> Xa converts prothrombin to thrombin, which converts fibrinogen to fibrin
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Define the extrinsic coagulation pathway, ID its factors and its goal
- Clot formation in response to tissue injury
- Tissue factor, VII, X
- X --> Xa converts prothrombin to thrombin, which converts fibrinogen to fibrin
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What inhibits the extrinsic pathway?
Tissue Factor Inhibitor
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Describe thrombin negative feedback
- Thrombin combines with thrombomodulin
- Converts C to Ca, which degrades factors Va and VIIIa
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Describe dissolution of fibrin clots
- Plasminogen converted to plasmin by Tissue plasminogen activator and urokinase
- Digests fibrin
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Hemophilia A:
a. cause
b. treament
- a. deficiency in factor VIII
- b. infusion of factor VIII
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Hemophilia B:
a. cause
b. treatment
- a. deficiency in factor IX
- b. infusion of factor IX
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Describe the cause of fibrinogen disorders
- deficiencies of factor XIII
- no cross-linking of fibrin
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What is von Willebrand Disease?
- Inherited deficiency in vWF
- Defective platelet adhesion
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How does heparin act as an anticoagulant?
Activates antithrombin III, which inhibits proteases of the coagulation cascade
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How does coumadin act as an anticoagulant?
- Inhibits vit k dependent reactions in thrombin function
- Delayed maximum effect (days)
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What is the function of aspirin and its mechanism?
- Inhibitor of platelet activation
- Reduces TXA2 production
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