Hemo-SLAy-sis - (this one's rough and also bad just btw)

hemostasis

____________ = arrest of bleeding; Physiologic response to vascular damage and a mechanism to seal an injured vessel to prevent blood loss

maintain blood in fluid state OR rapid formation of a local plus at site of damage

What are the two main functions of hemostasis? (one in normal and one in abnormal conditions)

formation of platelet plug

what is primary hemostasis?

formation of fibrin-platelet aggregate

what is secondary hemostasis?

dissolution of fibrin-platelet aggregate

what is thrombolysis/fibrinolysis

thrombolysis/fibrinolysis

______________________: dissolution of fibrin-platelet aggregate

vasoconstriction

what is the first step of hemostasis? after injury occurs and the collagen is exposed

platelet adhesion and primary hemostasis

what is step two of hemostasis?

secondary hemostasis

what is step 3 of hemostasis

thrombus and antithrombotic events

what is step 4 of hemolysis

i gotcha

there's some much clearer diagrams on slide 6-9 of these notes on the steps of clot forming that you should look at. But her ppt doesnt have notes and I don't really know how to turn this into a quizlet I'm sorry.

endothelium, platelets, coagulation factors

what are the "cast of characters" of hemostasis?

endothelium

what is the "dynamic interface" of hemostasis?

promotes smooth, nonturbulent flow of blood, vasodilation, antithrombotic, profibrinolytic

What are some of the properties of normal endothelium?

(opposite normal) vasoconstriction, enhance platelet adhesion and aggregation, stimulate coagulation, prothrombotic, antifibrinolytic

what are the properties of injured endothelum?

oxidative stress, hypoxia, inflammation, infectious agents, tissue injury

what can activate endothelium? (what puts it in an injured state)

megakaryocyte

platelets are anucleate cell fragments derived from ____________ circulating in blood

subendothelial collagen, leminin, fibronectin

platelets adhere to exposed _______, _______, -________, etc. but intact endothelium prevents this exposure

coagulation factors, IX, X

platelets provide a surface for the assembly of __________________; specifically _____ and _______

alpha, dense granules

platelets contain cytoplasmic granules split into ____ and ______ groups

PDGF, fibrinogen, factor V, vWF, thrombospondin, platelet factor 4

What are the growth factors in alpha cytoplasmic granules? (1)

And the coagulation factors? (5)

adenine nucleotides, calcium, inorganic phosphates, serotonin

what are the dense granules in the cytoplasmic granules?

coagulation

______________: process by which blood changes from a liquid to a gel, forming a blood clot

intrinsic, extrinsic, common

coagulation is classically organized into _______, ____________, and ________ Pathways

serine protease proenzymes, nonenzymatic proteins, platelet phospholipids, transmembrane cells surface receptors, calcium

coagulation factors can include: (5)

liver, hours to days, proenzymes or zymogens

coag factors are synthesized by the ________

circulate for ___[how long]_____

and require activation to become ________ or ___________

VII, 4-6 hours

which coag factor has the shortest half-life?

II, VII, IX, X

Vitamin K dependent factors

high molecular weight kininogen, prekallikrein, XII, XI, IX, VIII

what is included in the intrinsic pathway?:

_______, _____________, and factors: _____________________

Negatively charges substances (collagen, activated platelets, endotoxin)

contact activation for HMWK, prekallikrein and factors XII and XI are activated by ________________ (like ____________________(3))

factors IX and VIII activate factor X

what marks the start of the common pathway?

When factor III contacts factor VII, IX, X

the extrinsic pathway typically starts when __________________________________, then, this complex can activate factor _____ and factor _____________

tissue factor/factor III

__________________: cell surface glycoprotein expressed on subendothelial tissue

factor VII

___________________: Vit K-dependent, circulating, serine protease

either, factor V, plasma, platelet alpha granules

factor X can be activated by the [intrinsic/extrinsic] pathway and binds to factor _______ which can be found in _______ or within __________________

prothrombinase complex

what is the combination of X-V-Ca2+ complex called?

prothrombin (factor II, thrombin (IIa), thrombin, fibrinogen (factor I), fibrin (Ia), factor XIII, fibrin

prothrombinase complex converts ______________ to _________________

THEN ______________ converts ________ to ___________________.

Finally, ________cross links _____________

(sorry babe, write it out if it helps)

transient vasoconstriction

immediately upon tissue injury, what happens to reduce the volume of blood flowing through the affected areas and brings the endothelial surfaces closer together

collagen, fibronectin, ECM glycoproteins, proteoglycans, von willebrand factor

damage/disruption of the endothelium exposes ________________________(5) and attracts platelets

negatively charged ECM matrix, vWF

Platelets "recognize" endothelial damage by being attracted to the ______________________ and adhering to exposed _______________

shape change, release granules, phospholipid accdivation binds coag factors

when platelets become activated what happens?

platelet plug

Recruitment and aggregation of additional platelets forms a _________________

loosely

the initial fibrinogen bridges [loosely/tightly] link platelets,

platelet contraction, polymerization of fibrinogen to fibrin

_______________ and ___________________ turn the loose fibrinogen bridges into a dense consolidated platelet plug

secondary hemostasis

Mediators from endothelial cells, activated platelets, and the ECM trigger activation of the coagulation cascade and the formation of fibrin for ___________

fibrin

in many cases ________ is necessary for complete hemostasis

extrinsic tenase complex, Xa, intrinsic tenase complex

It is generally believed that the initiation of blood coagulation occurs via the _______________ following tissue injury. However, the sustained generation of factor ______ is dependent upon the ________________ which is 50 times more efficient and not as susceptible to inhibition.

release of factor III, binding of factor XII to negatively charged surface

What is the stimuli in the extrinsic pathway for secondary hemostasis?

And for the intrinsic pathway?

initiation

the release of tissue factor III and the combination of this with factor VII and Ca as well as the activation of factor X and IX BY that TF:VIIa complex is called ____________

extrinsic

initiation is associated with the __________ pathway

Factor V, Ca2+, and phospholipids

now active Factor X (Xa) binds to ___________ , _________ and _________ to form the prothrombinase complex

common

Amplification (Active Factor X (Xa) binds to Factor V, Ca2+,

and phospholipids) is associated with the ___________ pathway

factor Xa

what cleaves prothrombin II into thrombin IIa?

thrombin

what converts fibrinogen I to fibrin Ia?

thrombin

what activates platelets AND factors XI, VIII, V, and XIII

contact activation/binding of factor XII to negative surfaces

what is the stimulus for PROPOGATION

intrinsic

propagation is associated with the _______________ pathway

proenzymes, XII, XI, IX

Conversion of ______________ to active enzymes occurs on platelet surface and we follow the activation cascade

______ → _______ → ________

common

we return to the _____________ pathway for the formation of fibrin

prothrombin (II), thrombin (IIa), thrombin, fibrinogen (I), fibrin (Ia), XIII, thrombin

formation of firbin:

Factor Xa converts ____________ to ______________

__________ cleaves _____________ into ________________

factor __________ is activated by __________ in order to stabilize fibrin.

insoluble

crosslinked fibrin is [soluble/insoluble]

sticky, everything

freshy formed fibrin strands are "_______________" and adhere to _____________________

contracts

over time the fibrin _________ to allow blood to get past and to pull the edges of the damage closer together

fibrinous

The adjective that describes fibrin is ____________________

fibrin

What is this?

platelets are attracted to and adhere to damaged vessel wall and are activated

Quick! give me a one sentence overview of what happens in PRIMARY hemostasis

The plasma coagulation system attracts more platelets and binds them with fibrin. This then contracts and adds more fibrin to make a permanent plug.

And now... give me a two sentence horror story summing up what happens in SECONDARY hemostasis

(super general, this is just cus all the numbers and factors make me lose sight of whats actually happening)

thrombolysis/fibrinolysis

_______________________: Removal/dissolution of fibrin-platelet aggregate (thrombus)

plasminogen

_______________ is responsible for fibrinolysis

- Tissue plasminogen activator (tPA), Urokinases, Factor XIIa

- α2-antiplasmin, α2-macroglobin

Plasminogen is activated by ________________

and INactivated by _________________

Thrombin Activatable Fibrinolysis Inhibitor (TAFI), Plasminogen Activator Inhibitors (PAIs)

Fibrinolysis is regulated by ______________ and ___________________

true

true/false: coag factors are CONTINUOUSLY activated and ready to respond, so proteins that inhibit or degrade them are released at sites of injury to limit the hemostatic reactions.

hemostatic, fibrinolytic, anticoagulant

what three pathways must remain balanced during coagulation?

blood flow, liver, spleen

coagulation factors are diluted by the ______________ by removal from the site, and are removed by circulation by _____ and _______

antithrombin III

what is the most potent and most significant coagulation inhibitor

antithrombin III, heparin sulfate, tissue factor pathway inhibitor, protein C-protein S-thrombomodulin system

what are the anticoagulant molecules (4)

heparan sulfate, thrombomodulin

which anticoagulants are endothelial surface members?

Antithrombin III, Tissue Factor Pathway Inhibitor, Protein C, Protein S

Which anticoagulants are circulating members?

thrombin (IIa), procoagulant, anticoagulant, Xa, VIIa, VIIIa, V

the end result of the anticoagulant system is to convert _____________ from _________________ to _______________ and to inhibit factors ____________ (4)

true!

true/false; thrombin can act as a procoagulant (by cleaving fibrinogen or activating factors V, VIII, XI, XIII and platelets) OR can act as an anticoagulant in high concentrations (DESTROYING factor V and VII and activating protein C)

proinflammatory!

A prothrombic environment is ALSO __________________ because theres a lot of overlap in the mechanisms

II, VII, IX, X

which factors of the coag cascade are Vitamin K dependant?

extrinsic pathway/tissue factor III and VIIfactor IX -VIII

Which members of the coagulation cascade are mainly responsible for initiation coagulation in vivo?

Factor IX/VIII complex

In the cell based model, which is mostly responsible for the sustained generation of Factor Xa during the propagation phase of coagulation?

antithrombin III

what is the most potent and significant coagulation inhibitor