Intro to Hemostasis Flashcards
Hemostasis:
the ability of the body to stop bleeding from a damaged blood vessel when it occurs and to eventually repair the defect in the vessel wall so that normal blood flow to and from the involved area can be maintained
Different components involved in the hemostatic process
- The coagulation cascade
- The anticoagulation regulatory pathways
- The fibrinolytic system, which breaks down formed clots
- The endothelial cell lining of blood vessels, which prevents clots in the resting state and promotes clot formation following injury
- Platelets
which coagulation factors are serine proteases?
- Factor II
- Factor VII
- Factor IX
- Factor X
- Factor XI
- Factor XII
- Prekallikrein
which coagulation factors are cofactors?
- Factor III
- Factor V
- Factor VIII
- Factor HMWK
Components of the intrinsic tenase:
Factors VIII and IX
Components of the extrinsic tenase:
Factors III and VII
Components of the prothrombinase:
Factors V and X
Explain the role of vitamin K in coagulation
Vitamin K is required for generation of Gla residues, so deficiency results in non-functional protein
list the factors that are vitamin K dependent
Vitamin K dependent factors (all contain a “gla” domain): factors II, VII, IX, and X, along with the anticoagulant protein C. Protein S is also vitamin K dependent, though it functions in coagulation as a cofactor for protein C and not as a serine protease.
Describe how fibrinogen is converted to fibrin by thrombin, leading to an insoluble fibrin network
- fibrin is composed of three globules (central = E and outer = Ds)
- when activated, thrombin cleaves off 2 small peptides (fibrinopeptides A and B), and the release of A leads to exposure of a site on E that aligns non-covalently with a complementary D site
- the release of B allos for aggregation of growing fibrils
- Factor XIIIa covalently crosslinks adjacent D domains –> stabilization and strength
2 main functions of von Willebrand factor in coagulation
- platelet adhesion and aggreagation
- serves as a carrier protein for factor VIII in the plasma.
- –It is stored in Weibel-Palade bodies in endothelial cells and in α-granules of platelets, but in the circulating plasma, it binds to and protects factor VIII, significantly prolonging its half-life (12 hrs vs 2 hrs).
Complications of VWF deficiency
Patients with severe deficiency of VWF have low levels of circulating factor VIII, leading to a bleeding disorder similar to classical hemophilia A (factor VIII deficiency). They have a coexistent platelet function defect, leading to a very severe bleeding problem.
List the components of the intrinsic and extrinsic pathways
Intrinsic: XII, XI, IX, X,
Extrinsic: VII
Common: X, V, prothrombin, XIII, fibrinogen
initiation phase
- vascular disruption -> exposure of plasma ato TF
- TF binds to VIIa in the presence of Ca++
- TF-VIIa complex can bind factor X –> Xa and IX –> IXa
- at the same time generates more VIIa
- Xa slowly activates Va –> small amounts of prothrombinase complex –> small amounts of thrombin
amplification phase
- on the surface of platelets
- initial procoagulant signal is amplified –> small amounts of of thrombin are generated on TF-bearing cells
- Thrombin activates: V –> Va and VIII –> VIIIa which bind to the platelet surface
- Xa forms prothrominase complex with Va, changing small amounts of prothrombin –> thrombin
