Normal Platelets and Coagulation

What is the function of Glycoprotein Ib (GPIb)

Binds to vWf and forms bridge between platelet and subendothelial collagen

What is the alternative name for GPIb? ______________ receptor

Von willebrand factor receptor

What is the function of Glycoprotein IIb/IIIa (GPIIb/IIIa)?

Binds to fibrinogen which acts like a rope tying the platelets together

what is an alternative name GPIIb/IIIa? ___________ receptor

Fibrinogen receptor

What adhesion molecule binds to vWf?

Glycoprotein Ib

What adhesion molecule binds to fibrinogen?

Glycoprotein IIb/IIIa

What is the major cytokine that stimulates megakaryocytic and platelet production?

Thrombopoietin

What is the function of Thrombopoietin?

stimulates megakaryocytic and platelet production

What must occur for primary hemostasis to happen (in normal animal)

Vascular damage

What are the 3 major categories of steps of primary hemostasis

Platelet adhesion

Platelet activation

Platelet plug formation

What occurs with Platelet adhesion

GPIb binds platelet to exposed vWf and forms a bridge between platelets and exposed collagen

Where are platelets adhered to

subendothelial matrix

What step of primary hemostasis is described with GPIb binds platelet to exposed vWf and forms a bridge between platelets and exposed collagen

Platelet adhesion

What are the three simultaneous steps of platelet activation

Platelet shape change

Release of granule contents

Recruitment of more platelets

T/F: The steps within platelet activation simultaneous

True

Describe the platelet shape changes within platelet activation

from discs (inactive) to elongated with cytoplasmic extensions (active)

What is the purpose of the platelet shape change

increase surface area

What are the granule contents released from platelets

platelet agonists- ADP and TXA2

vWf

Fibrinogen

Coagulation factors

What is the purpose of platelet agonists

recruit and activate additional platelets- PLATELET PARTY!!!!

What occurs with platelet plug formation

GPIIb/IIIa is activated by platelet agonists and bind fibrinogen/forms bridges between platelets to form platelet plug

What is a limitation of the platelet plug formed during primary hemostasis?

it is unstable

What is the initiating factor of the extrinsic pathway

release of tissue factor from damaged subendothelium

What is the initiating factor of the intrinsic pathway

initiated by Factor XII being activated to XIIa

How is Factor XII activated

when in contact with negatively changed surface (collagen)

The cascade of the extrinsic pathway up to start of common

release of tissue factor- complexes with factor VII activating it to VIIa

TF:VIIa complex activates both X to Xa and IX to IXa

The cascade of the intrinsic pathway up to start of common

Factor XII activates to XIIa when in contact with negative charged surface (collagen)

Factor XIIa activates XI to XIa

Factor XIa activates IX to IXa

IXa complexes with VIIIa to make IXa:VIIIa

IXa:VIIIa activates X to Xa

What is the first factor of the common pathway

Factor X

How is Factor X activated in common pathway

by TF:VIIa and IXa:VIIIa

The common pathway starting at Factor X

activated Xa complexes with Va to create Xa:Va

Xa:Va coverts prothrombin (II) to thrombin (IIa)

thrombin (IIa):

- cleaves fibrinogen to soluble fibrin

- activates XIII to XIIIa to cross link soluble fibrin to insoluble fibrin

- activates V, VIII, XI, XIII

What does XIIIa do

cross link soluble fibrin to insoluble fibrin

What are the factors in the extrinsic pathway

TF, and 7

What are the factors in the intrinsic pathway

12, 11, 9, 8

What are the factors in the common pathway

10, 5, 2, 8, 1

What is the major end product of the coagulation cascade

insoluble (cross-linked) fibrin

What is the purpose of insoluble fibrin as a product of the coagulation cascade

acts like concrete to hold platelets together- stabilize platelet plug

What factors are vitamin K dependent

II, VII, IX, X

How are factors II, VII, IX, X dependent on vitamin K

vitamin K is a cofactor for their carboxylation in the liver in order for the factors to be functional

How is vitamin K treated after the carboxylation of factors II, VII, IX, X

it is recycled in order to be used again

What happens with vitamin K deficiency or antagonism

carboxylation of II, VII, IX, X does not happen causing the halting of the coagulation cascade- leading to severe hemorrhagic disorder

What is the major fibrinolytic enzyme involved in fibrinolysis

plasmin

What is the 2 purposes of fibrinolysis in a normal patient

occurs simultaneously with coagulation to control size and spread of the clot

What does plasmin do

Cleaves and inactivates factor XIIIa preventing it's cross linking of fibrin

Breaks down fibrin into fibrinolysis breakdown products

What are the two breakdown products of fibrinolysis

Fibrinogen degradation products (FDPs)

D-dimers

What are FDPs

breakdown of fibrinogen and soluble fibrin

What is D-dimers

breakdown of cross-linked fibrin

What is Antithrombin III

an endogenous coagulation inhibitor

What is the function of Antithrombin III

inhibit thrombin (IIa), IXa, Xa, and XIa (shutting down intrinsic and common pathways)

Why is antithrombin III important

helps prevent unchecked clotting