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37 Cards in this Set
- Front
- Back
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What are the 3 important haemstatic mechanisms?
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1) Maintain blood in a fluid state while circulating within the vascular system
2) Arrests bleeding at the site of injury by formation of hemostatic plug 3) Ensure the removal of the hemostatic plug when healing is complete A delicate balance between procoagulation and anticoagulation mechanisms |
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What are the 3 main components of procoagulation haemostasis in the body?
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1) Blood vessels
2) Platelets 3) Clotting factors |
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What are the 5 main components of haemostasis (pro and anticoagulant)?
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1) Blood vessels
2) Platelets 3) Clotting factors 4) Coagulation inhibitors 5) Fibrinolysis |
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What is the normal range of platelet counts in the body?
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150 - 400 x 10^9/L
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What is the normal lifespan of a platelet?
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7-10 days
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How long does it take for a megakaryocyte to form from a stem cell?
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~10 days
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What does sequestration mean?
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Normally, 1/3 of the platelets are trapped in the spleen but if splenomegaly occurs, then 90% can be trapped in the spleen.
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Where are platelets produced?
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In the BM. They are made by fragmentation from megakaryoctye.
1 megakaryocyte = up to 4000 platelets |
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What is the major regulator of platelet production?
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Thrombopoeitin - it increases the production and maturation rate of megakaryocytes.
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Describe the stages in platelet production in the BM?
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Hematopoietic stem cell ->
Myeloid progenitor cell -> Megakaryoblast -> Megakaryocyte -> Platelet |
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How long does it take for platelets to be formed in the BM?
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10 days
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What is endomitosis?
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DNA replication in the absence of nuclear of cytoplasmic division.
Increases cytoplasmic volume as the nuber of nuclear lobes increase in multiples of two (2-124) |
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How can you differentiate between new and old platelets?
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New platelets will be bigger then old platelets.
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How are platelets (dying) removed from the body?
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50% by the spleen
33% by the liver 17% by the BM and LN |
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Why is the external coat of the platelet so important?
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It contains a glycoprotein coat which has many receptors which are necessary for platelet adhesion and aggregation.
The glycoprotein coat contains phospholipids which are required to initiate coagulation factors (intrinsic pathway). |
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What types of granules are found in the platelet and what do they contain?
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Alpha Granules - growth factors (platelet derived growth factor, insulin-like growth factor) and clotting proteins (fibrinogen, fibronectin, vWF).
Dense Granules = ADP/ATP, Ca+2, serotonin, histamine, epinephrine) |
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What are some special morphological features of platelets?
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They have no nucleus
They have invaginated membranes to increase SA for coagulation factor absorption. |
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What is the primary function of platelets?
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Formation of the initial haemostatic plug at site of vascular injury.
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What are the 3 steps in platelet formation of the plug?
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1) Adhesion to vessel wall
2) Secretion of granules 3) Aggregation |
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How does the shape of platelets change once they become activated?
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From a discoid shape to a spherical shape with pseudopods
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What steps are involved in platelet aggregation?
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1) GpIbIX binding to vWF activates the GpIIbIIIa receptors, exposing fibrinogen binding sites.
2) Fibrinogen binds the GpIIbIIIa receptors and binds the platelets to each other (aggregates). 3) ADP and TXA2 recruit more platelets (intrinsic feedback loop) |
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What does Gp IIbIX bind in the platelet plug? What about GpIIb/IIIa?
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GpIIbIX binds the platelet to vWF which is bound to the exposed vessel wall.
GpIIbIIIa binds the platelet to fibrinogen, which connect to another platelet. |
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How do platelets adhere to the vessel wall?
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Receptors (GpIaIIa) halt platelet flow by binding to the collagen of the exposed vessel wall.
Subendothelial microfibrils bind vWF which then binds GpIbIX on the platelets |
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What is TXA2's role in platelet plug formation?
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The exposed collagen in the vessel wall stimulates prostaglandin synthesis via the arachadonic pathway -> TXA2
TXA2 raises Ca+2 and causes degranulation of the platelet TXA2 also, causes vasconstriction to decrease flow and increase platelet contact. TXA2 (with ADP) recruit other platelets to the site of injury for aggregation |
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What two coagulation factors require platelet phospholipids?
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Xa and IIa
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How do the platelets help to localize the clot?
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The phospholipid layer and the fibrinogen connecting the platelets help to localize the clotting factors to the sight of the injury.
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What components make up primary hemostasis?
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1) Blood vessel and vasoconstriction
2) von Wilderbrand factor (vWF) 3) platelets |
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What component(s) make up secondary hemostasis?
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Coagulation factors / cascade - addition of fibrin
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In general, what are the initial steps involved in platelet plug formation?
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1) Blood vessel wall gets damaged, exposing collagen
2) vWF in the plasma uncoils and binds to the unexposed endothelial collagen and gets cleaved by metalloproteases 3) Blood vessel constricts 4) vWF binds collagen, platelets bind vWF and together they form the platelet plug |
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Where is vWF synthesized?
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Endothelial cells and megakaryoctyes
It is stored in Weiberl-Palade bodies in endothelial cells and alpha-granules in platelets |
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What are the two major components involved in platelet positive feedback loops?
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ADP
TXA2 |
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How is coagulation initiated during a vessel injury?
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Membrane bound tissue factor (TF) which becomes exposed by vascular injury, interacts with plasma factor VII (extrinsic pathway).
TF-VIIa can activate factors IX and X to from a small amount of factor IIa (thrombin). IIa can then activate factor V and VIII to get the intrinsic pathway going to amplify the clotting response. |
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What coagulation factors are vitamin K dependent?
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II, VII, IX and X
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What coagulation factors are involved in the intrinsic pathway?
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XII -> XI -> IX -> X
Factor VIII acts on factor IX to activate factor X. |
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What does the common pathway of coagulation consist of?
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BE FAMILIAR WITH THE CLOTTING CASCADE
Xa converts prothrombin (II) to thrombin (IIa) Thrombin converts fibrinogen to fibrin monomer. Hydrogen bonding forms a fibrin polymer which is crosslinked (via factor XIIIa) to stabilize the clot |
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What role does proteins C & S have in coagulation?
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Proteins C & S are vitamin K dependent inhibitors of coagulation factors V and VIII.
Thrombin (IIa) binds to endothelial cell surface receptor thrombomodulin which activates protein C. Protein C destroys factors V and VIII, and is enhance by protein S. |
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Following vascular injury, what initiates the clotting cascade?
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VIIa, TF, Phosphoplipids and Ca+2
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