w5- coagulation Flashcards
what triggers the activation of a hard and soft clot
Cleavage of fibrinogen (coagulation factor I) to fibrin (factor Ia) by thrombin results in aggregation to form a “soft clot.” Cross linking between Lys & Gln in an enzyme-mediated transamidation reaction subsequently transforms the soft clot to a “hard clot.”
what is Virchow’s triad
- Blood flow (stasis or impaired flow) - Composition of the blood (hypercoagulability) - Changes in the vessel wall (endothelial activation or damage important for venous thrombosis
how does tx of arterial and venous thrombosis differ
arterial- anti-platelet venous- anti-coat
would hyper coagulation encourage venous or arterial thrombosis
venous
how does deoxygenation impact stasis
Deoxygenation increases chance of forming blood clots Recirculation of blood very important for anti coag prop
how does hypoxia impact venous thrombosis
Cells in the vessel walls become inflamed Bleb of microvesicles that express tissue factor coag cascade
induces expression of P-selectin, which acts as a docking site for tissue-factor-positive microparticles, platelets, and leukocytes
differentiate TPA from an anti-plasmin drug
o TPA- targets plasminogen o Antiplasmin- targets plasmin and prevents its conversion of fibrin to degredation products
what phase of the arterial cycle does vWVF impact and how
von Willebrand factor (vWF) mediates the adhesion in response to injury by changing its MW at sites of injury recognize the change and platelets bind
deficit = bleeding disorder (most common inherited cause of bleeding disorders)
what are the four steps of arterial thrombus
adhesion
activation
secrection
aggregation
name 3 things that are secreted during arterial thrombosis
Thombin (enforces activation)
ADP
thromboxin A2
what are the targets of aspirin and clopidogrel
Aspirin is an irreversible cyclooxygenase-1 (COX-1) inhibitor that blocks production of TXA2 from arachidonicacid.
Clopidogrelis an ADP receptor blocker.
what phase of the arterial thombosis cycle influences microvascular constriction and immune mediators
secrection
what 2 phases does thrombin act on
activation and aggregation (clot formation by converting fibrin)
speds up the conversion of V, VIII, IX (feedback
outline the process of aggregation
Upon activation, interaction between platelets is promoted by increased surface area due to shape changes. Thrombin converts fibrinogen to fibrin. Fibrin and vWFform cross-bridges between activated platelets and stabilize the thrombus
what causes tissue factor from the extrinsic pathway to be present
what is its function
endothelial damage
activates XI and X
what is the function of factor 10
what activates it
what does it interact with and how
function: forms complex with V to convert prothrombin to thrombin
activates: tissue factor and VII, IX and VIII
interacts with PS
X has post translational modification of carboxyl groups that allow interaction of calcium ions which bring between neg charge of PS and -carboxyglutamic acid
which factors contain γ-carboxyglutamic acid residues and can be bound with citric chelator
VII, IX, X, prothrombin
what is the target of coumadin a VIT K antagonist
block -carboxyglutamic acid residues post trans modifications
difference between the intrinsic and extrinsic pathway
Xii –> XI –> IX
indep of tissue factor
can be initiated by foreign surface such as dialysis tube or trauma/surgery and works in parallel with extrinsic
what is the deficit in hemophillia A and B
A- VIII (cant activate X)
B- IX
(cant activate X)
what activates antithombin and what does it block
heparin
blocks: thrombin, Xa, IXa
what is blocked by the Tissue factor pathway inhibitor (TFPI)
VIIa and Xa
what is the protein C pathways and what does it block
feedback loop mediated by thrombomodulin TM
TM turns on ability of thrombin to activate protein C by proteolytic cleavage.
Blocks VIII and Va
turns on TPA, blocka PAI (which inhibits TPA)
