Hemostasis Flashcards
What is the main goal of hemostasis?
To stop blood loss
What are two main problems with hemostasis that does not work appropriately?
Too much hemostasis=thrombus
Too little hemostasis = hemorrhage
What is primary hemostasis? What is secondary hemostasis?
Primary hemostasis is the formation of a platelet plug over a wound; secondary is the formation of a fibrin clot
What is the first brief episode that occurs before primary hemostasis?
A damaged vessel will normally undergo vasoconstriction
What is the first stage of primary hemostasis and what happens at that stage?
Adhesion
Von Willebrand factor is released by the endothelium and targets platelets for attachment to the site of injury
What are the functions of Von WIllebrand factor?
- bind to the platelet receptor
- bind to collagen
- bind and stabilize factor VIII
What is the second stage of primary hemostasis and what happens at that stage?
Aggregation
1) more platelets are recruited to the site of injury. In the process they undergo a conformation change from smooth to spiny to increase surface area
2) fibrinogen binds to glycoprotein IIb-IIIa
What causes the change in platelet shape at the second state of primary hemostasis?
Increased ADP receptors
What is the third stage of primary hemostasis and what happens at that stage?
Secretion
Platelet granules are secreted out of the open canalicular system
What are the consequences of granule secretion by the platelets?
vasoconstriction (serotonin),
modulation of growth of the vessel walls (platelet-derived growth factor) and
cell adhesion and fluid phase coagulation (clotting factors).
What is the fourth stage of primary hemostasis and what happens at that stage?
Activation
Phospholipase A2 cleaves arachadonic acid from the phospholipid layer which ultimately becomes thromboxane A2
How do the cell membranes of activated platelets differ from resting platelets?
Activated platelets express their phosphatidylserine on their outer leaflets
How do platelets support clot retraction?
Platelets have a small actin-myosin contractile apparatus that will contract and draw fibrin strands together into a mesh
What two factors inhibit platelet aggregation?
Nitric oxide and prostacyclins
What is Factor I in the clotting cascade? What is its role in the cascade?
Fibrinogen–adhesive protein, forms clot
What is Factor II in the clotting cascade? What is its role in the cascade?
Prothrombin–main enzyme of coagulation
What is Factor III in the clotting cascade? What is its role in the cascade?
Tissue factor–initiator of coagulation
What is Factor IV in the clotting cascade? What is its role in the cascade?
Calcium–a cofactor in many reactions
What is Factor V in the clotting cascade? What is its role in the cascade?
Labile factor—Cofactor for conversion of prothrombin to thrombin (also activates factor X)
What is Factor VII in the clotting cascade? What is its role in the cascade?
Proconvertin–activates coagulation cascade
What is Factor VIII in the clotting cascade? What is its role in the cascade?
anti-hemophilic factor—cofactor to activate factor X
What is Factor IX in the clotting cascade? What is its role in the cascade?
Christimas factor—activates factor X
What is Factor X in the clotting cascade? What is its role in the cascade?
Stuart-Prower factor–activation of prothrombin to thrombin
What is Factor XI in the clotting cascade? What is its role in the cascade?
plasma prothrombin antecedent–activates factor IX
What is Factor XII in the clotting cascade? What is its role in the cascade?
Hageman factors—activator of PTT in intrinsic testing
What is Factor XIII in the clotting cascade? What is its role in the cascade?
fibrin stabilizing factor—cross links fibrin clot
What are the two main functions of thrombin?
Clipping fibrinopeptides from fibrinogen to give fibrin monomer
Activating Factor XIII
What are the first steps in the clotting process up to the initial thrombin production?
1) Tissue factor activates and binds factor VII
2) Complex activates factors IX and X
3) Initially activated Factor Xa makes a small amount of thrombin and then is shut off
What does the initial thrombin product activate?
1) Factor V
2) Factor VIII
3) Factor XI
4) Protein C
What do factor V and factor VIII promote? What do those products promote?
V and VIII promote Factor X
These promote the production of more thrombin
What are the means by which the coagulation cascade is measure in a laboratory?
Intrinsic pathway–>Partial thromboplastin
Extrinsic pathway–>Prothrombin time
Where are the clotting factors produced?
Most are made in the liver, but Factor VIII is made in endothelial cells of the liver; Von Willebrand factor is made in endothelial cells and megakaryocytes
Which factors and proteins are dependent on Vitamin K?
II, VII, IX, X and Protein C and S
How does Vitamin K work chemically?
It acts as a cofactor to add a second carboxyl group to glutamic acid–this allows calcium to bind in the activation process
What are five main functions of thrombin?
- cleavage of fibrinogen to fibrin
- activation of other clotting factors (V,VIII, XI, XIII)
- activation of platelets
- activation of endothelial cells
- binds thrombomodulin and activates protein C
What are the three main means of stopping a clot?
1) decreasing blood flow to a site
2) Hepatic clearance of activated cofactors
3) Plasma inhibitors
What are the three main plasma inhibitors and how do they function?
Antithrombin–inactivates thrombin by direct binding
Protein C—Shuts off Factor Va and VIIIa
Protein S promotes fibrinolysis
What is Factor V Leiden?
Protein C for some reason loses specificity for factor Va and increases the risk of a clot
How is fibrinolysis promoted?
Tissue plasminogen activator made by the restored endothelium converts plasminogen to plasmin which breaks fibrin into D-dimers
What are roles of the endothelium in the clotting cascade?
1) Promotes coagulation by aligning coagulation factors and exposure of tissue factor
2) Synthesizes and stores von WIllebrand factor, tissue plasminogen activator, and plasminogen activator inhibitor
3) Supports antithrombin inactivation of thrombin
4) Inhibits platelet adherence by making prostacyclins and NO
