Hemostasis Flashcards
Where does factor X occur in the coagulation scheme? What does it do?
Factor X plays an important role at the beginning of the common pathway. It can be activated by either the intrinsic or extrinsic pathway. It is accelerated by a protein cofactor (Factor Va). Factor X activates prothrombin to thrombin.
What is the importance of vitamin K to the coagulation cascade?
Vitamin K is an important part because several factors (II,VII,IX,X, Protein C and S) use it as a cofactor for post transcriptional modification. It allows vitamin-K dependent factors to add an extra carboxyl group to the glutamate residue near the N-terminus that can then bind a molecule of Ca2+. The Ca2+ complexed portions of the clotting factors can interact with phospholipids on the membrane.
Does vitamin K participate directly at the site of clotting?
Vitamin K does NOT participate directly at the site of clotting.
What is the role of gamma-carboxyglutamate residues in clotting factors?
After synthesis of these factors, an extra carboxyl group is added to glutamate residues near the N-terminus. It does not act directly at the site of clotting. The extra carboxyl group gives these factors a divalent anion (2-) at the glutamyl residue, enabling Ca2+ binding. These calcium complexes enable the factors to interact with the phospholipids of plasma membranes.
Many activated coaculation factors are enzymes. What class of reactions do they catalyze?
Many of the coagulation factors are proteolytic enzymes (proteases) that converts the other proenzymes (zymogens) into their enzymatic forms.
What is the “antihemophilic” factor, and at what stage does it function?
Factor VIII is the antihemophilic factor. It is a protein cofactor that often circulates with vWF. Together with Factor IXa, they work to activate Factor X, thus initializing the common pathway.
Name the K-dependent factors.
Factors II (Prothrombin), VII, IX, X, Protein C and Protein S
How does factor XIIIa differ from the other enzymes of the coagulation cascade?
Factor XIIIa is the only non-proteolytic enzyme of the clotting cascades. It is a transamidase which catalyzes the formation of peptide bonds between the side chains of lysine and glutamine residues in fibrin chains (aka Fibrin Stabilizing Factor).
Name the factors of the common pathway of coagulation and discuss their roles.
Factor X, which is activated by Factor IX, to Factor Xa. Factor Va is an allosteric enhancer of activity of Factor Xa. Factor Xa activated Prothrombin (Factor II) to Thrombin (Factor IIa). Thrombin activates fibrinogen to fibrin. Thrombin also activates protein C, platelets, factor VII/vWF and factor XIII. Factor XIIa causes cross-linking of fibrin.
Which 2 proteins of the cascade are not enzymes?
Factor VIII and Factor V are not enzymes. Factor VIII is a cofactor for Factor IXa.
At which amino acid does K-dependent carboxylation occur?
Glutamate residue near the N-terminus
Where are the component os the cascade synthesized?
The liver synthesizes plasma clotting factors. Renal tissue and megakaryocytes produce Factor XIII and vWF.
Discuss the ways in which coagulation is regulated.
Coagulation can be regulated in several ways:
1) Blood flow can “sweep away” clotting elements, diluting their effects
2) Uptake by the liver and inactivation of activating factors
3) Endogenous antiproteases; inhibition of coagulation process during the very process of coagulation
4) Undamaged endothelial cells generate antiaggregant
5) Some activated factors can break down other factors
Discuss the merits and drawbacks of anticoagulant therapy with heparin versus vitamin K antagonists.
Heparin enhances the inhibitory action of antithrombin III (it binds to the active site of thrombin and inhibits its activity). Once the complex of antithrombin III and thrombin is made, the heparin molecule leaves and finds another antithrombin III and enhances its binding to thrombin. There is a drawback that heparin therapy will not work, and most likely signifies an antithrombin III deficiency. Vitamin K antagonists (Warfarin and coumadin) prevent the K-dependent carboxylation of Factors II, VII, IX, and X. They are used for long-term control of thrombotic tendencies and their effectiveness depends on protein turnover.
Name the sequence of participation of factors in the intrinsic pathway.
Factor XII -> Factor XIIa by contact with negatively charged surfaces.
Factor XIIa converts Factor XI -> Factor XIa
Factor XIa converts Factor IX -> Factor IXa
Factor IXa along with Factor VIIIa/vWF converts Factor X -> Xa
