Blood Coagulation

Question 1

2 functions of Von Willebrand Factor (vWF).

Answer 1

1. Allows platelets to bind sub-endothelial tissue

2. Stabilizes Factor VIII

Question 2

List the 4 major platelet activators

Answer 2

1. Exposed Collagen (usually from injury)
2. Thromboxane A2
3. Thrombin
4. ADP

Question 3

Drug that is an ADP receptor antagonist to decrease platelet activation.

Answer 3

Clopidogrel (Plavix)

Question 4

Drug that inhibits formation of Thromboxane A2 to reduce platelet activation.

Answer 4

ASA (Aspirin)

Question 5

Name one mediator that reduces platelet activation and how.

Answer 5

Prostacyclin

-increases cAMP levels to decrease intracellular calcium levels

Question 6

Protein found in platelets that promotes aggregation and activation of platelets.

Answer 6

Pleckstrin

Question 7

Only clotting factor not made in the liver

Answer 7

Factor VIII

Question 8

Which five clotting factors are serine proteases that signal in the clotting cascade and which 2 are merely co-factors?

Answer 8

Serine Proteases: VII, IX, X, XI, XII

Co-factors: V and VIII

Question 9

What converts prothrombin into thrombin?

Answer 9

Factor Xa + Factor Va

along with platelets and Calcium

Question 10

What converts fibrinogen into fibrin monomers and how?

Answer 10

Thrombin cleaves (-) charged fibrinogen peptide tails to convert it to fibrin monomer units. Without the (-) charges repelling each other, the fibrin units aggregate, ONLY by weak charge attraction, forming a “soft” clot.

Question 11

Function of Factor XIIIa

Answer 11

Cross links the fibrin monomer units COVALENTLY to form the “hard” clot

Question 12

What mediator activates the two cofactor coagulation factors?

Answer 12

Factors V and VIII are activated by thrombin.

Question 13

Protein produced in the liver that inactivates only FREE plasmin (not bound to fibrin).

Answer 13

Alpha-2 Antiplasmin

Question 14

Name two enzymes (medications) other than t-PA that activate plasminogen.

Answer 14

Urokinase

Streptokinase

Question 15

Name 3 circulating thrombin inhibitors that prevent random clot formation.

Answer 15

1. Antithrombin III (most important)
2. Alpha-1 antiprotease
3. Alpha-2 macroglobulin

Question 16

What activates Antithrombin III?

Answer 16

Heparin

Question 17

Name 3 endothelial cell mediators that inhibit clotting and how each works.

Answer 17

1. Thrombomodulin: binds thrombin, activates protein C
2. Heparan Sulfate: activates antithrombin III
3. Prostacyclin: binds platelets and increases cAMP levels to decrease calcium levels preventing activation

Question 18

What is the function of protein C and how does it work?

Answer 18

1. Thrombomodulin binds thrombin
2. This complex activates protein C
3. A cofactor (protein S) binds protein C so that the complex functions in anticoagulation.
4. Protein C inactivates Factor Va and Factor VIIIa preventing Va from combining with Xa and VIIIa from combining with IXa.

Question 19

What is a common symptom in patients with Protein S deficiency?

Answer 19

DVT

Question 20

inheritance pattern of Hemophilia A and the defect that occurs.

Answer 20

X-linked recessive

Def. of Factor VIII

Question 21

inheritance pattern of Hemophilia B and the defect that occurs.

Answer 21

X-linked recessive

Def of Factor IX

Question 22

inheritance pattern of Hemophilia C and the defect that occurs.

Answer 22

Autosomal Dominant

Def. of Factor XI

Question 23

Inheritance pattern of von Willebrand Disease and defect that occurs.

Answer 23

Autosomal Dominant
Def of vWF and Factor VIII

(vWF needed to stabilize factor VIII)

Question 24

Inheritance pattern of Leiden Mutation and defect that occurs.

Answer 24

Autosomal Dominant

• factor V resists inactivation by protein C/S complex
• results in hypercoagulability and DVT

Question 25

Why does ASA lower Thromboxane A2 levels but not prostacyclin levels since both are produced by COX enzymes?

Answer 25

TxA2 is made in platelets which have no DNA to synthesize new proteins. ASA permanently inhibits ability to produce new TxA2.

Prostacyclin is made in endothelial cells which have DNA to produce more COX enzyme after an ASA dose.

Question 26

MOA of heparin.

Answer 26

Activates Antithrombin III

-rapid onset

Question 27

MOA of Warfarin

Answer 27

Inhibits vitamin K epoxide reductase reducing concentration of clotting factor synthesis.
-slow onset

Question 28

MOA of Bivalirudin and when is it used?

Answer 28

Direct Thrombin inhibitor

Used short-term during coronary angioplasty

Question 29

Risk of using streptokinase.

Answer 29

because it is a bacterial enzyme it can be antigenic with repeated use causing an immune reaction.