Hemostasis II Flashcards
Name 3 important anticoagulants
Antithrombin III
Protein C/ProteinS
Tissue factor pathway inhibitor (TFPI)
How does Tissue Factor Pathway Inhibitor (TFPI) work?
It inhibits the function of TF:VIIA complex and FXa
-Prevents TF-induced thrombogenesis (prothrombin–>thrombin)
Antithrombin III
STRONGLY inhibits FX and thrombin
Partially inhibits Factors, 9/11/12
-Require cofactor for Heparin
What happens when heparin binds to Antithrombin III
Antithrombin’s affinity for coagulation factor increases
What factors does activated Protein C inactivate?
Va (5a) and VIIIa (8a)
Protein C is activated when?
Thrombin is bound to thrombomodulin on the surface of intact endothelial cells.
APTT is part of what pathways?
Intrinsic + Common
PT is part of what pathways
Extrinsic + Common
Causes for prolonged PT
Deficiencies in extrinsic and common pathway factors
- Vitamin K. antagonists
- Liver Disease
Vitamin K. Antagonists
Coumarins
- Coumadin
- Bishydroxycoumarin
Blood levels of coumadin peak in ___minutes, and the t1/2 is___?
90minutes, 36-42 hours
Vit K. is responsible for making what amino acid?
Gama-carboxyglutamate
What is gama-carboxyglutamates purpose?
Allows clotting factors to undergo a calcium dependent conformational change which allows them to bind to phospholipid surfaces leading to generation of membrane bound macromolecule complexes
Why is APTT referred to as partial thromboplastin?
because no Tissue Factor was used
Causes of prolonged APTT
deficiency in factors specific to the intrinsic pathway -hemophilia A -VWD Heparin Lupus anticoagulant Liver disease DIC
Direct thrombin inhibitors
- Argatroban
- Hirudin (lepirudin)
What thrombocytopenic disorder is Argatroban frequently used?
HITT
Prolonged PT and normal APTT is indicative of what factor deficiency?
FVII
Normal PT and Prolonged APTT is indicative of what factor deficiencies?
Deficiency in any intrinsic pathway factors
Prolonged APTT and PT is indicative of what factor deficiencies?
Factors of the common pathway (X, V, II, I)
DDAVP is used in the Tx of what blood disorders?
VWD, and Hemophilia A
How does DDAVP work?
increases plasma levels of FVIII and VWF due to release from endogenous stores
After receiving DDAVP, how long does it take for plasma levels of FVII to increase?
30 minutes, max effect 1-2 hours.
What is Novoseven?
Recombinant factor VIIa
-activates FX and FIX which convert prothrombin to thrombin
