Exam 1: Hemostasis Flashcards by Kaitlyn Johnson

what are the basic events in normal clot formation after initial blood vessel injury

vasoconstriction
platelet adhesion
platelets undergo conformation change
platelet aggregation
clotting (coagulation) pathways activate
formation of fibrin meshwork
resolution of clot formation through fibrinolysis

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vasoconstriction occurs from release of _____

endothelin by endothelial cells

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vasoconstriction decreases ______

blood flow (but cant stop blood loss)

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vasoconstriction brings _______ to the site of injury

platelets and coagulation factors (tissue factor exposure for clotting activation)

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what facilitates the binding of platelet (platelet adhesion)

exposure of subendothelial collagen following injury

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binding is greatly enhanced by

von Wellebrand factor (vWF), especially in high flow rate blood vessels

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where is vWF stored

in endothelial cells and platelets and circulates in blood stream bound to factor VIII

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platelets undergo conformation change and release what?

stored products in their granules such as Ca, ADP, vWF, thromoxane A2, epinephrine, platelet activating factor

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what do these products do

activate platelets

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the conformation change also exposes ______

fibrinogen binding sites

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fibrinogen binding sites are important for what

platelets to bind to other platelets

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in the conformation change, there is a change in platelet membranes that expose

specific platelet phospholipids that are important in activation of the clotting cascade

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more platelets stick to site of injury by binding to each other via

fibrinogen (important in the platelet plug)

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clotting activation ocurs quickly after initial vascular injury by exposure of _____ which activates clotting cascade and eventual formation of thrombin

tissue factor

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thrombin, in turn, cleaves _____ which is vital to the formation of this stabilized clot

fibrinogen to fibrin

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______ is incorptated into the platelet mass to hold/glue the clot together, forming the ______

fibrin; fibrin meshwork

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the process of the fibrin meshwork ______ clot formation

stabilizes

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resolution of clot fomration occurs through

fibrinolysis

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fibrinolysis is mediated throguh

plasmin following activation from plasminogen

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must maintain appropriate balance of clot resolution vs. clot retention or will have

hemorrhage or thrombosis depending on the imbalance

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blood vessel endothelium has what kind of properties

anticoagulant and procoagulant properties

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what is the lifespan of platelets

about 7-10 days

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in high shear blood vessels, platelets bind to

vWF that has adhered to subendothelial collagen in damaged high shear blood vessels

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in low shear blood vessles plateelets bind to

directly to collagen or fibronogen that has bound to collagen in the damaged vesssel

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after binding to the site of injury, platelets undergo ____

conformational changes

what do these confomration changes do?

enhance platelet to platelt binding by interaction with fibrinogen expose membrane phospholipids which initiate clooting factor pathways releases stored products from granules

thromboxane TxA2 causes what

vasoconstriction and platelet aggregation

TxA2 inhibited by

aspirin

Ca increased after _____ release

TxA2

Ca is essential for

clotting factor pathways, contractile elements of platelts

where are the clotting pathways with formation of fibrin and fibrin cross-links essential?

after loose plug is formed, it must become stronger with stronger interactions

are factors numbered in order of activation?

is there a factor VI

factor I

fibrinogen

factor II

prothrombin

factor III

tissue factor

factor Ia

fibrin

factor IIa

thrombin

factor IV

factor V through factor

XIII

factor XIII

fibrin stabilizing factor

what factors require vitamin K for synthesis

II, VII, IX, X, protein C and S

where does vitamin K work?

most clotting factors are produced by the

liver

what factors are the only ones without enzymatic like activity

V and VIII and IV

what does this mean for these factors that have enzymatic activity

not necessarily consumed in the reaction ot activate the clotting pathway

so factors V and VIII are

consumed and have a risk of depletion if the liver cant keep up production levels

what are the two classical methods of clotting pathways

classical (in-vitro) or Y model | Cell-based or in-vivo model

in secondary hemostasis, what is needed for all stages?

calcium

1. after injury to vascular endothelium, the exposure of ____ on cells beneath the endothelium initiates the hemostatic reaction

tissue factor

what is the only relevant activator of hemostatic pathwayss in real life

tissue factor

tissue factor is expressed on what membranes

subendothelial fibroblasts, smooth muscle cells, other stromal cells and monocytes

______ then binds to tissue factor on the membrane of one or more of these cells to allow the formation of the extrinsic tenase complex

factor VIIia

what is the only factor that circulates in the blood in active form

factor VIIa (although only 1% is in active form)

what does the activated factorVIIa/TF complex do

activates more factor VII and VIIa, which will bind more TF and form more extrinsic tenase complexes

extrinsic tenase complexes now promotes _____

circulating factor X to bind and become activated to factor Xa

circulating factor V can now bind to the complex and become

factor Va by factor Xa

this activation is very ______ at this point

slow and inefficient

V to Va is much more dependent on _____ for activation

thrombin

small amounts of circulating _______ can also bind to the complex and become activated to _____

factor IX, IXa

this complex is now composed of

tissue factor, Ca, factors VIIa, Xa, Va, IXa

this complex with these factors is now called

1st prothrombinase complex

1st prothrombinase complex main purpose is to

allow binding and activation of prothrombin to thrombin

thrombin at this point will begin to perform its multitude of functions to include

activating platelets, cleaving circulating factor VIII from vWF that in turn allows activation of factor VII, activataing circulating factor V, activating circulating factor XI and cleaving fibrinogen to fibrin

only a small amount of prothrombin is activated to thrombin at this point, and if the reaction does not proceed to amplification stage of hemostasis, what will happen to the clot

will not form properly

what is the key to amplification step of secondary hemostasis

dissociation of some factor IXa from the 1st prothrombinase complex

why does this dissociation occur?

because some factors are not tightly bound to the copmplex and can dissociate

factor xa usually stays associated with the 1st prothrombin complex, but if it dissociates _____ or ______ can quickly break it down

antithrombin or tissue factor pathway inhibitor (TFPI)

once factor ixa dissociates from the 1st prothrombin complex, it is free to bind to

adjacent platelet membrane phospholipid

factor ixa is subject to degradation by

minimally by antithrombin

factor ixa is now available to bind with factor viiia on the surface of

platelet membrane

foactor viia becomes activated when

thrombin that was generated from 1st prothrombinase coplex cleaves circulating ffactor vii from vwf at the site of injury

the combination of factor viia, ixa, ca and platelet membrane is called

intrinsic tenase complex

intrinsic tenase complex is responsible for

binding and accelerating the formation of factor x to xa on the surface of platelets which previously was limited to the tissue factor/viia site

once intrinsic tenase complexs are adequately functioning on the surface of platelets, what happens to the extrinsic tenase complex

become relatively insignificant and are shutdown primarily by TFPI

at this point the reaction is ready to proceed to the second phase of amplification process with the formation of the

2nd prothrombinase complex

once factor xa has been generated, factor _____ must be incorporated into the complex in order for factor xa to optimally function

factor va has arlready been generated from

thrombin that was produced by the end product of the 1st prothrombinase complex

incorporation of factor Va, platelet membranes, Ca, factor IXa, factor VIIIa, and factor Xa make up the

2nd prothrombinase complex

this complex is now ready to activate ____ into _____

thrombin into prothrombin

which prothrombinase complex is higher for thrombin generation

2nd

during the course of this entire process, circulating _____ has been incorporated into the platelet mass; as well as

fibrinogen; binding platelets to platelets

high thrombin gneration is now responsible for

cleaving fibrinogen to fibrin and surrounding the clot

to stabilize the clot, thrombin activates what

circulating factor XIII to XIIIa

XIIIa does what

cross-links fibrin within the clot to strengthen it

at this point, thrombin is being generated by 2nd and will continue to be produced until

the reaction is shut down

thrombin strongly activates platelets, causing them to do what

release granules and alter their outer phospholipid membranes to expose phosphatidylserine (PS)

how does thrombin generate VIIIa and free vWF

activates factor V to Va and cleaves the circulating bound proteins factor VIII/vWF

thrombin activates

factor XIII to XIIIa

thrombin is a _____ for leukocytes

chemo-attractant

after the clot has formed, what must be done

clotting pathways must be inactivated

inactivation of the pathays occurs by what methods

tissue factor pathway inhibitor antithrombin thrombomodulin

TFPI is produced and stored in

endothelial cells (also stored in plateles)

TFPI primarily does what

inactivates factor VIIa and factor Xa, thrombin to a lesser degree

antithrombin does what

inativates factor IIa and Xa, But also prefers

thrombomodulin

small molecule produced on the endothelial surface combines with thrombin to perform actions

heparin sulfate molecules and exogenous heparin do wha

amplify antithrombin to maximize degradation of actor IIa and factor Xa

thrombomodulin and trhombin active ______ then in conjunctive with proein S. inactivates ncativation factor Va, and VIIIa

exogenous hyperia

lastly, what happens to the clot

it must be broken down to prevent thrombosis and without causing hemorrhage (fibrinolysis)

diruing initial clot formation, endothelial cells release

plasminogen activator inhibitor | PIa-1

PAI-1 does wht

prevents the activation of plasminogen to plasmin

as the clot stablizies and endothelial cells being healing, the endothelium releases

tiue plasminogen activator (t-pa)

t-PA does what

converts plasminogen to plasmin

what is plasminogen

a protein produced by the liver that circulates in the plasma and becomes incorporated with the clot but doesnt have any fibrinolytic activity until activated to plasmin

t-pa does not convert plasminogen to plasmin unless ______ is also present

fibrin or cross-linked fibrin (generally does not occur until clot has stabilized)

certain drugs or compounds can convert plasminogen to plasmin such as

urokinase or streptokinases

if plasmin is released into the plasma

alpha2-anthiplasmin (antip-plasmin) will inactivate it unless the system is overwhelemed

____ cells eventually move into and remove much of the material from the clot and normal resolution, the blood vessel heals normally and restores blood flow

phagocytic cells