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Flashcards in Blood Coagulation Deck (29)
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1
Q

2 functions of Von Willebrand Factor (vWF).

A
  1. Allows platelets to bind sub-endothelial tissue

2. Stabilizes Factor VIII

2
Q

List the 4 major platelet activators

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

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

A

Clopidogrel (Plavix)

4
Q

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

A

ASA (Aspirin)

5
Q

Name one mediator that reduces platelet activation and how.

A

Prostacyclin

-increases cAMP levels to decrease intracellular calcium levels

6
Q

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

A

Pleckstrin

7
Q

Only clotting factor not made in the liver

A

Factor VIII

8
Q

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

A

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

Co-factors: V and VIII

9
Q

What converts prothrombin into thrombin?

A

Factor Xa + Factor Va

along with platelets and Calcium

10
Q

What converts fibrinogen into fibrin monomers and how?

A

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.

11
Q

Function of Factor XIIIa

A

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

12
Q

What mediator activates the two cofactor coagulation factors?

A

Factors V and VIII are activated by thrombin.

13
Q

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

A

Alpha-2 Antiplasmin

14
Q

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

A

Urokinase

Streptokinase

15
Q

Name 3 circulating thrombin inhibitors that prevent random clot formation.

A
  1. Antithrombin III (most important)
  2. Alpha-1 antiprotease
  3. Alpha-2 macroglobulin
16
Q

What activates Antithrombin III?

A

Heparin

17
Q

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

A
  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
18
Q

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

A
  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.
19
Q

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

A

DVT

20
Q

inheritance pattern of Hemophilia A and the defect that occurs.

A

X-linked recessive

Def. of Factor VIII

21
Q

inheritance pattern of Hemophilia B and the defect that occurs.

A

X-linked recessive

Def of Factor IX

22
Q

inheritance pattern of Hemophilia C and the defect that occurs.

A

Autosomal Dominant

Def. of Factor XI

23
Q

Inheritance pattern of von Willebrand Disease and defect that occurs.

A

Autosomal Dominant
Def of vWF and Factor VIII

(vWF needed to stabilize factor VIII)

24
Q

Inheritance pattern of Leiden Mutation and defect that occurs.

A

Autosomal Dominant

  • factor V resists inactivation by protein C/S complex
  • results in hypercoagulability and DVT
25
Q

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

A

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.

26
Q

MOA of heparin.

A

Activates Antithrombin III

-rapid onset

27
Q

MOA of Warfarin

A

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

28
Q

MOA of Bivalirudin and when is it used?

A

Direct Thrombin inhibitor

Used short-term during coronary angioplasty

29
Q

Risk of using streptokinase.

A

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