Hem & Onc - Physiology (Primary Hemostasis & Erythrocyte sedimentation rate)

Question 1

What are the names of the general steps of platelet plug formation?

Answer 1

(1) Injury (2) Adhesion & Activation (4) Aggregation

Question 2

What is the first step of platelet plug formation? What key event occurs here?

Answer 2

Injury; vWF binds exposed collagen upon endothelial damage

Question 3

What is the second step of platelet plug formation? What key events occur here?

Answer 3

Adhesion & Activation; (1) Platelets bind vWF via GpIb receptor at the site of injury (2) Platelets release ADP & Ca2+ (necessary for coagulation cascade) (3) ADP plays two roles: (a) helps platelets adhere to endothelium (b) ACTIVATION: binds to its receptor, inducing GpIIb/IIIa expression at platelet surface

Question 4

What is the third step of platelet plug formation? What makes this step possible?

Answer 4

Aggregation; Fibrinogen binds GpIIb/IIIa receptors & links platelets

Question 5

What is the ultimate goal of platelet plug formation?

Answer 5

Temporarily stop bleeding (until secondary hemostasis can stabilize clot)

Question 6

What are the pro-aggregation versus anti-aggregation factors that must be balanced in order for the third and final step of platelet plug formation to occur (i.e., aggregation)?

Answer 6

PRO-AGGREGATION: (1) TXA2 (released by platelets) (2) Decreased blood flow (3) Increased platelet aggregation; ANTI-AGGREGATION: (1) PGI2 and NO (released by endothelial cells) (2) Increased blood flow (3) Decreased platelet aggregation

Question 7

What is a deficiency in GpIb called? At what step of platelet plug formation does this interfere?

Answer 7

Bernard-Soulier syndrome; Adhesion

Question 8

What is a deficiency in GpIIb/IIIa called? At what step of platelet plug formation does this interfere?

Answer 8

Glanzmann’s thrombasthenia; Aggregation

Question 9

What irreversibly blocks the ADP receptor? At what step(s) of platelet plug formation does this interfere?

Answer 9

Clopidogrel & ticlopidine; Adhesion & Activation plus Aggregation

Question 10

What blocks the GpIIb/IIIa receptor? At what step of platelet plug formation does this interfere?

Answer 10

Abciximab; Aggregation

Question 11

What is a deficiency in vWF called? At what step of platelet plug formation does this interfere?

Answer 11

von Willebrand’s disease; Adhesion

Question 12

By what mechanism does Aspirin work? What effect does this have on platelet plug formation?

Answer 12

Inhibits cyclooxygenase; Inhibits TXA2 synthesis = impairs aggregation

Question 13

What activates protein C?

Answer 13

Thrombomodulin

Question 14

What key players in platelet plug formation are found in endothelial cells?

Answer 14

vWF, thromboplastin, tPA, PGI2, NO

Question 15

What key players in platelet plug formation are found in platelets?

Answer 15

vWF, fibrinogen, ADP, TXA2

Question 16

What is an example of acute phase reactant relevant to hemostasis? What effects do such acute phase reactants have on erythrocyte sedimentation rate, and why?

Answer 16

Fibrinogen; Cause RBC aggregation, thereby INCREASING RBC sedimentation rate; RBC aggregates have a higher density than plasma

Question 17

What are examples of conditions that increase erythrocyte sedimentation rate?

Answer 17

(1) Infections (2) Autoimmune diseases (e.g., SLE, rheumatoid arthritis, temporal arthritis) (3) Malignant neoplasms (4) GI disease (ulcerative colitis) (5) Pregnancy

Question 18

What are examples of conditions that decrease erythrocyte sedimentation rate?

Answer 18

(1) Polycythemia (2) Sickle Cell anemia (3) Congestive heart failure (4) Microcytosis (5) Hypofibrinogenemia

Question 19

What role does ristocetin play in hemostasis? What is the important clinical utility of ristocetin?

Answer 19

Ristocetin activates vWF to bind to GpIb; Useful for diagnosis: normal platelet aggregation response is not seen in von Willebrand disease.