01 Biology Of Hemostasis Flashcards
Four major physiologic events in hemostasis?
Vascular constriction
Platelet plug formation
Fibrin formation
Fibrinolysis
What is the initial response to vessel injury?
Vasoconstriction
Substances that promote vasoconstriction?
Thromboxane A2 (TXA2)
Endothelin
Serotonin (5-HT)
Bradykinin and Fibrinopeptides
Normal circulating number of platelets?
150,000-400,000
Lifespan of platelets?
7-10 days
What happens in primary hemostasis?
Injury to the intimate layer in the vascular wall exposes subendothelial collagen to which platelets adhere.
Von Willebrand factor (vWF), a protein in the subendothelium, binds to glycoproteins I/IX/V on the platelet membrane.
Following adhesion, platelets initiate a release reaction that recruits other platelets to seal the disrupted vessel.
What is the final event in primary hemostasis?
Following adhesion, platelets initiate a release reaction that recruits other platelets from the circulating blood to seal the disrupted vessel.
Principal mediators in platelet aggregation?
Adenosine diphosphate
Serotonin
Can hemostasis occur in heparinized patients?
Yes.
Platelet aggregation is reversible and is not associated with secretion. Heparin does not interfere with this reaction, hence hemostasis can occur in the heparinized patient.
Origin of thromboxane A2 (TXA2)?
Arachidonic acid released from the platelet membranes is converted by cyclooxygenase to prostaglandin G2 (PGG2) and then to prostaglandin H2 (PGH2).
This in turn is converted to TXA2.
Effects of TXA2?
Thromboxane A2 has potent vasoconstriction and platelet aggregation effects.
Arachidonic acid may also be shuttled to adjacent endothelial cells and converted to prostacyclin (PGI2). Actions of PGI2?
PGI2 is a vasodilator and acts to inhibit platelet aggregation.
How is platelets cyclooxygenase affected by medications?
Platelet cyclooxygenase is irreversibly inhibited by aspirin and reversible blocked by NSAIDs.
But it is not affected by COX-2 inhibitors.
In the second wave of platelet aggregation, a release reaction occurs in which several substances (ADP, Ca2+, serotonin, TXA2, alpha-granule proteins) are discharged.
What is the required cofactor for this process?
Fibrinogen, which acts as a bridge for the GP IIb/IIIa receptor on the activated platelets.
The release reaction results in compaction of the platelets into a plug. This is IRREVERSIBLE.
Thrombospondin is a protein secreted by the alpha-granules. What is its role in the second wave of platelet aggregation?
It stabilizes fibrinogen binding to the activated platelet surface and strengthens platelet-platelet interactions.
Which substances inhibit the second wave of platelet aggregation?
Aspirin
NSAIDs
Cyclic adenosine mono phosphate (cAMP)
Nitric oxide (NO)
The intrinsic pathway begins with?
The activation of factor XII, which subsequently activates factor XI, IX, and VIII.
Why is the intrinsic pathway called as such?
In this pathway, each of the primary factors is “intrinsic” to the circulating plasma, whereby no surface is required to initiate the process.
What initiates the extrinsic pathway?
Tissue factor (TF) is released or exposed on the endothelial surface, binding to circulating factor VII, facilitating its activation to VIIa.
The common pathway begins with?
The activation of factor X to Xa (in the presence of VIIIa).
Subsequently, Xa (with the help of factor Va) converts factor II (prothrombin) to thrombin, and then factor I (fibrinogen) to fibrin.
When does clot formation occur?
Clot formation occurs after fibrin monomers are cross-linked to polymers with the assistance of factor XIII.
An elevated activated partial thromboplastin time (aPTT) is associated with which arm of the cascade?
Intrinsic arm (II,IX, X, XI, XII)
An elevated prothrombin time (PT) is associated with which arm of the cascade?
Extrinsic arm (II, VII, X)
Vitamin K deficiency or warfarin use affects which factors?
Factors II, VII, IX, X (27910)
