Flashcards in Hemostasis Deck (100):
What is the protein that is activated by the coagulation cascade?
What is the function of thrombin?
Cleaves fibrinogen into fibrin
What is the protein found on platelets that interacts with vWF?
What is the glycoprotein on platelets that serves as the attachment point for other platelets?
What is the role of factor VIII?
Binds to vWF, and promotes coag
What is integrin Alpha2Beta1?
Receptor on the surface of platelets, that binds to collagen
What happens to platelets as they bind to vWF? What is the signal for this?
undergo a shape change (disc to sphere) in response to Ca
What are the two granules that platelets secrete?
What are the chemicals found in delta granules? (6)
What are the chemical found in alpha granules?
Activation of platelets causes the release of what precursor molecule for protaglandins?
What is the enzyme that converts arachidonic acid into prostaglandin G2?
What does prostaglandin g2 get turned into? What next?
Prostaglandin H2, then into thromboxane A2 via thromboxane synthase
What is the enzyme that converts prostaglandin H2 into thromboxane A2?
Thromboxane, 5HT, and epi serve to do what to blood vessels?
What are the two major aggregation signals for platelets?
What is the MOA of ADP increasing aggregation of platelets?
conformation change of GpIIb/IIIa, allowing fibrinogen to attache
What is von Willebrand disease?
decrease in vWF protein levels, function, and a decrease in factor VIII binding
What is the most common bleeding disorder?
What are the symptoms of von Willebrand disease?
Excessive bleeding and easy bruising/bleeding that presents in early childhood
What is the treatment for von Willebrand disease? MOA?
Desmopressin--stimulates the release of vWF and factor VIII
What is Bernard-Soulier syndrome?
Giant platelet secretion/thrombocytopenia, and defect in the interaction of gpIb and vWF
Causes an inability of platelet to adhere correctly
What is the treatment for Bernard-Soulier syndrome?
minimize bleeding risk
What is Glanzmann thrombasthenia?
Quantitative/qualitative defects in GpIIb/IIIa
Prolonged bleeding time d/t reduction in platelet aggregation
Defect in GpIb/vWF = what disease?
Defect in GP IIa/IIIb results i what disease?
Decreased vWF = what disease?
von Willebrand disease
What is the convergence point of the coagulation cascades?
Why is the extrinsic pathway named as such?
Exogenous material (tissue factor) was needed to activate it
Which pathway is activated upon exposure to negatively charged surfaces?
What are zymogens?
inactive precursors of proteins
factor I = ? Where is it produced?
factor II = ? Where is it produced?
factor III = ? Where is it produced?
factor VI = ? Where is it produced?
factor V= ? Where is it produced?
factor VI = ? Where is it produced?
no such thing
factor VII = ? Where is it produced?
What are the factors that need vit k to function? What is the molecule that they all have in common that needs vit K?
10, 9, 7, 2
What is the enzyme that requires vitamin K as a cofactor?
What is endothelin, and what does it do?
Local factor produced by endothelial cells that causes vasoconstriction
What is the cement part of the clot?
Do platelets have RNA?
What is the mineral that is secreted by platelets that causes activation of the coag cascade?
What is the cytokine that triggers the change in conformation of GpIIb/IIIa to allow for the receptor to bind to fibrinogen?
What is the basis of the partial thromboplastin time test?
Intrinsic pathway will clot with exposure to negative charges on glass
What is the purpose of the gamma carboxyglutamate on factors 10, 9, 7, and 2?
Chelates Ca a lot better than glutamate does, allowing for Ca ions to coordinate negatively charged lipid membranes and keeping them bound
What is the enzyme that is inhibited by warfarin? What does this do?
Vitamin K epoxide reductase, prevents Vitamin K from being reduced back to its usable form
What type of molecule is factor 7? What does it do?
Serine protease that cleaves factor X, another serine protease
What type of molecule is factor 10?
factor Xa catalyzes the slow or fast cleavage of prothrombin?
What type of molecule is factor X? What is its function?
Serine protease, that cleaves factor V
What are the two components of the prothrombinase complex? What does this do?
Factors V and X
cleaves prothrombin rapidly
What are the three major functions of thrombin?
1. Cleave fibrinogen
2. activates factor V and VII (positive feedback
3. Activate factor VIII (intrinsic pathway)
What is the test that is used to assess the intrinsic pathway?
What is the first factor that is activated in the intrinsic pathway? How?
Factor XII by exposure to negatively charged surfaces
What are the two factors that factor XII activates? What is this factor complexed with?
Factor XI, which is complexed with prekallikrein to form a high molecular weight kininogen (HMWK)
What is the factor that factor XI activates?
What is the factor that factor IX activates? Is this a fast or slow reaction?
factor X, slow
Thrombin cleaves what factor
What are the factors that form the intrinsic tenase complex? What is the function of this complex?
Rapid activation of factor X
What is the factor that must be activated to form the hard clot? What type of molecule is this?
What is the amino acid bond that factor XIII catalyzes in fibrin?
K to a E
What is the mode of inheritance for hemophilia A and B?
What is the most common hemophilia?
What is the pathophysiology of hemophilia A?
deficiency of factor 8 production
What is the pathophysiology of hemophilia B?
Deficiency of factor IX production
What is the treatment for hemophilia A and B?
Recombinant factor (8 or 9 for A and B respectively)
How does thrombin inhibit clotting?
when thrombin is bound to a membrane protein of endothelial cells referred to as thrombomodulin, the specificity of thrombin is altered. Rather than promoting clotting, thrombin instead converts a protein C, which is a serine protease, into its active form
What type of molecule is protein C? What does it do?
Binds to protein S, which degrades factor Va and VIIIa
What is the function of protein S?
Binds to protein C, which degrades factors V and VIII
What are the factors that the protein S/C complex degrades?
V and VIII
What is the molecule that thrombin binds to, to activate protein C?
What are the serpins?
Serine protease Inhibitors
What type of molecules is antithrombin III? How does it work?
Serpin (serine protease inhibitor)
Binds and inhibits thrombin, factors IX, X, XI, and XIII
The formation of antithrombin III is greatly enhanced by the presence of what chemical? How does this work?
Heparin binds to ATIII, and increases its affinity for thrombin
What is the function of the TFPI protein?
produced by endothelial cells, and inhibits factor VII and Xa
What is the pathophysiology of factor V leiden?
AA change leads to resistance to cleavage by protein C
What is the process that down regulates coagulation factors?
What is the molecule that is responsible for fibrinolysis?
What is the circulating form of plasmin? What organ produces this?
Plasminogen has a high affinity for what molecule? What happen when it binds to this?
fibrin-- gets incorporated into the developing clot
What is the molecule that activates plasminogen into plasmin? What cells produce this?
tPA produced by endothelial cells
Release of tPA is stimulated by what molecule? What else does this do to ensure that tPA is activated?
Also degrades PAI-1 (which inhibits tPA)
What is the function of PAI-1?
tPA has a high affinity for what molecule? Why is this important?
Goes to where plasminogen is
What are the circulating proteins in the blood that ensure active plasmin does not break down clots throughout the body?
What is the function of streptokinase?
Exogenous activator of plasminogen
What does ADP trigger on platelets?
Conformation change of GP IIb/IIIa, allowing to bind fibrinogen
Why do platelets fail to aggregate in bernard soulier syndrome?
Defect in the Gp-Ib
Why do platelets fail to aggregate in Glanzmann thrombasthenia?
Defect in GpIIb/IIIa
What do you add to the PT test to initiate the extrinsic pathway?
What is the only factor that is not produced by the liver? What is it produced by?
What is the function of the Ca that binds to gamma-carboxyglutamate?
Chelates Ca on phospholipids, keeping the factors near the site they're needed
Why are neonates given a Vit K shot?
Vit K produced by gut flora, of which neonates have none
What are the components of the extrinsic Xase complex?
Factors VII and X
What is the factor that factor X activates to generate the extrinsic pathway tenase complex?
What is the initial complex of proteins that sets off the intrinsic pathway? What is this called? What activates it?
Factor XI, prekallikrein, forming the HMWK
Carboxypeptidase on cell membrane activates it
What is the effect of factor XIII?
Activated by thrombin
Will crosslink E and K residues on platelets