Blood Coagulation Flashcards
2 functions of Von Willebrand Factor (vWF).
- Allows platelets to bind sub-endothelial tissue
2. Stabilizes Factor VIII
List the 4 major platelet activators
- Exposed Collagen (usually from injury)
- Thromboxane A2
- Thrombin
- ADP
Drug that is an ADP receptor antagonist to decrease platelet activation.
Clopidogrel (Plavix)
Drug that inhibits formation of Thromboxane A2 to reduce platelet activation.
ASA (Aspirin)
Name one mediator that reduces platelet activation and how.
Prostacyclin
-increases cAMP levels to decrease intracellular calcium levels
Protein found in platelets that promotes aggregation and activation of platelets.
Pleckstrin
Only clotting factor not made in the liver
Factor VIII
Which five clotting factors are serine proteases that signal in the clotting cascade and which 2 are merely co-factors?
Serine Proteases: VII, IX, X, XI, XII
Co-factors: V and VIII
What converts prothrombin into thrombin?
Factor Xa + Factor Va
along with platelets and Calcium
What converts fibrinogen into fibrin monomers and how?
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.
Function of Factor XIIIa
Cross links the fibrin monomer units COVALENTLY to form the “hard” clot
What mediator activates the two cofactor coagulation factors?
Factors V and VIII are activated by thrombin.
Protein produced in the liver that inactivates only FREE plasmin (not bound to fibrin).
Alpha-2 Antiplasmin
Name two enzymes (medications) other than t-PA that activate plasminogen.
Urokinase
Streptokinase
Name 3 circulating thrombin inhibitors that prevent random clot formation.
- Antithrombin III (most important)
- Alpha-1 antiprotease
- Alpha-2 macroglobulin
What activates Antithrombin III?
Heparin
Name 3 endothelial cell mediators that inhibit clotting and how each works.
- Thrombomodulin: binds thrombin, activates protein C
- Heparan Sulfate: activates antithrombin III
- Prostacyclin: binds platelets and increases cAMP levels to decrease calcium levels preventing activation
What is the function of protein C and how does it work?
- Thrombomodulin binds thrombin
- This complex activates protein C
- A cofactor (protein S) binds protein C so that the complex functions in anticoagulation.
- Protein C inactivates Factor Va and Factor VIIIa preventing Va from combining with Xa and VIIIa from combining with IXa.
What is a common symptom in patients with Protein S deficiency?
DVT
inheritance pattern of Hemophilia A and the defect that occurs.
X-linked recessive
Def. of Factor VIII
inheritance pattern of Hemophilia B and the defect that occurs.
X-linked recessive
Def of Factor IX
inheritance pattern of Hemophilia C and the defect that occurs.
Autosomal Dominant
Def. of Factor XI
Inheritance pattern of von Willebrand Disease and defect that occurs.
Autosomal Dominant
Def of vWF and Factor VIII
(vWF needed to stabilize factor VIII)
Inheritance pattern of Leiden Mutation and defect that occurs.
Autosomal Dominant
- factor V resists inactivation by protein C/S complex
- results in hypercoagulability and DVT
Why does ASA lower Thromboxane A2 levels but not prostacyclin levels since both are produced by COX enzymes?
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.
MOA of heparin.
Activates Antithrombin III
-rapid onset
MOA of Warfarin
Inhibits vitamin K epoxide reductase reducing concentration of clotting factor synthesis.
-slow onset
MOA of Bivalirudin and when is it used?
Direct Thrombin inhibitor
Used short-term during coronary angioplasty
Risk of using streptokinase.
because it is a bacterial enzyme it can be antigenic with repeated use causing an immune reaction.
