01 Biology Of Hemostasis

Question 1

Four major physiologic events in hemostasis?

Answer 1

Vascular constriction
Platelet plug formation
Fibrin formation
Fibrinolysis

Question 2

What is the initial response to vessel injury?

Answer 2

Vasoconstriction

Question 3

Substances that promote vasoconstriction?

Answer 3

Thromboxane A2 (TXA2)
Endothelin
Serotonin (5-HT)
Bradykinin and Fibrinopeptides

Question 4

Normal circulating number of platelets?

Answer 4

150,000-400,000

Question 5

Lifespan of platelets?

Answer 5

7-10 days

Question 6

What happens in primary hemostasis?

Answer 6

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.

Question 7

What is the final event in primary hemostasis?

Answer 7

Following adhesion, platelets initiate a release reaction that recruits other platelets from the circulating blood to seal the disrupted vessel.

Question 8

Principal mediators in platelet aggregation?

Answer 8

Adenosine diphosphate

Serotonin

Question 9

Can hemostasis occur in heparinized patients?

Answer 9

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.

Question 10

Origin of thromboxane A2 (TXA2)?

Answer 10

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.

Question 11

Effects of TXA2?

Answer 11

Thromboxane A2 has potent vasoconstriction and platelet aggregation effects.

Question 12

Arachidonic acid may also be shuttled to adjacent endothelial cells and converted to prostacyclin (PGI2). Actions of PGI2?

Answer 12

PGI2 is a vasodilator and acts to inhibit platelet aggregation.

Question 13

How is platelets cyclooxygenase affected by medications?

Answer 13

Platelet cyclooxygenase is irreversibly inhibited by aspirin and reversible blocked by NSAIDs.

But it is not affected by COX-2 inhibitors.

Question 14

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?

Answer 14

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.

Question 15

Thrombospondin is a protein secreted by the alpha-granules. What is its role in the second wave of platelet aggregation?

Answer 15

It stabilizes fibrinogen binding to the activated platelet surface and strengthens platelet-platelet interactions.

Question 16

Which substances inhibit the second wave of platelet aggregation?

Answer 16

Aspirin
NSAIDs
Cyclic adenosine mono phosphate (cAMP)
Nitric oxide (NO)

Question 17

The intrinsic pathway begins with?

Answer 17

The activation of factor XII, which subsequently activates factor XI, IX, and VIII.

Question 18

Why is the intrinsic pathway called as such?

Answer 18

In this pathway, each of the primary factors is “intrinsic” to the circulating plasma, whereby no surface is required to initiate the process.

Question 19

What initiates the extrinsic pathway?

Answer 19

Tissue factor (TF) is released or exposed on the endothelial surface, binding to circulating factor VII, facilitating its activation to VIIa.

Question 20

The common pathway begins with?

Answer 20

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.

Question 21

When does clot formation occur?

Answer 21

Clot formation occurs after fibrin monomers are cross-linked to polymers with the assistance of factor XIII.

Question 22

An elevated activated partial thromboplastin time (aPTT) is associated with which arm of the cascade?

Answer 22

Intrinsic arm (II,IX, X, XI, XII)

Question 23

An elevated prothrombin time (PT) is associated with which arm of the cascade?

Answer 23

Extrinsic arm (II, VII, X)

Question 24

Vitamin K deficiency or warfarin use affects which factors?

Answer 24

Factors II, VII, IX, X (27910)

Question 25

The primary pathway for coagulation is initiated by?

Answer 25

Tissue factor (TF) exposure following subendothelial injury.

Question 26

The prothrombinase complex, which converts prothrombin to thrombin, is formed by?

Answer 26

Factor Xa
Factor Va
Calcium
Phospholipid

Question 27

Actions of thrombin?

Answer 27

Thrombin is involved with the conversion of fibrinogen to fibrin, and activation of factors V, VII,VIII, XI, and XIII.

Question 28

The intrinsic factor complex is formed by?

Answer 28

Factor VIIIa combined with IXa

Question 29

Role of thrombin-activatable fibrinolysis inhibitor (TAFI)?

Answer 29

Acts to stabilize the resultant fibrin clot.

Question 30

Mechanisms to prevent clot propagation beyond the site of injury?

Answer 30

1. Feedback inhibition (deactivates enzyme complexes leading to thrombin formation)
2. Tissue plasminogen activator (tPA) release (cleaves plasminogen to initiate fibrinolysis)
3. APC system (forms complex with cofactor protein S, cleaving Va and VIIIa, preventing TF-VIIa or prothrombinase complexes)

Question 31

Genetic mutation in which factor V is resistant to cleavage by APC, thereby remaining active as a procoagulant, and leading to venous thromboembolic events?

Answer 31

Factor V Leiden

Question 32

Degradation of the fibrin clot is accomplished by?

Answer 32

Plasmin

Question 33

Effects of fibrinolysis?

Answer 33

Allows restoration of blood flow during the healing process following injury.

It begins at the same time clot formation is initiated.

Question 34

Mechanisms to keep fibrinolysis in check?

Answer 34

1. Plasmin is inhibited by alpha2-antiplasmin
2. Circulating Plasmin is inhibited by alpha2-antiplasmin, tPA or urokinase.
3. TAFI removes lysine residues from fibrin that are essential for binding plasminogen.