Platelet Function Platelet Di

8/3/2019 Platelet Function Platelet Di

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Platelet adhesion, activation

aggregation


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What are the three major ste

involved in the platelet

response to vascular injury


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Platelet adhesion


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Interaction of platelets wit

non-platelet surfaces.


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Platelet activation


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In response to agonists,platelets undergo metaboli

activation resulting in shapchange and secretion.


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Platelet aggregation


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Cross linking of platelet-

platelet surfaces.


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Endothelial cells


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What is plasma Von

Willebrand factor (vWF)

derived from?


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GP Ib/IX complex


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Serves as the binding site o

platelets for vWF to mediat

platelet adhesion.


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collagen & fibronectin


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Multiple proteins in the

subendothelial matrix can bi

vWF, including ____ & ___


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vWF, GP Ib/IX (platelet

receptor), & subendothelia

binding site for vWF


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What are the three things

required for platelet adhesio


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calcium


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Platelet activation requires an

increase in cytoplasmic ____. Thcomes from internal storage sites

(dense tubular system) and theexternal environment through

membrane channels.


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Phospholipase C;

diacylglycerol (DG); inositol

trisphosphate (IP3); protein

kinase C; calcium; calmoduli

dependent protein kinases


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____ converts phosphatidyl-inositol-bisphosp

(PIP2) into ____ and ____. The former activ

____ in contact with the inner leaflet of the

platelet membrane, which phosphorylates

substrate proteins, including a 40-47 kd protei

involved in platelet secretion. The latter releas____ from its storage sites. The increased

cytoplasmic concentration activates ____ and

results in shape change and contraction.


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Phospholipase A2;

thromboxane A2 (TxA2)


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____ releases arachidonic acid from

membrane phospholipids, activating th

prostaglandin pathway. In the platelet

results in synthesis of ____, a potent

agonist which activates the phospholip

C pathway.


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adenylate cyclase;

phosphodiesterase;

Prostacyclin; nitric oxide (N


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cAMP and cGMP serve as regulators of

platelet response; increased levels ofcAMP is regulated by synthesis (____)

and degradation (____). ____ is a pot

stimulator of the former. cGMP issynergistic with cAMP and its level is

increased by ____.


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GP IIb-IIIa; ADP


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Platelet aggregation requires activation

____; in the resting state, it does not bfibrinogen or other adhesive proteins.

Once it has been activated (e.g., by ___

binding to its receptor), it binds fibrinoand other adhesive proteins, including

vWF.


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Fibrinogen


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____ is a dimeric molecule

and its two terminal ends are

mirror images of each other

Consequently, it serves as anexcellent cross-linking agent


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Monomeric


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____ forms of fibrinogen can ser

as fibrin degradation productsbecause they contain a single

binding domain that can competefor binding sites on GP IIb-IIIa an

block platelet aggregation.


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high shear stress; vWF;

fibrinogen


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Aside from ADP activation, ____ canactivate GP IIb-IIIa; with this mechanis

of activation, high molecular weight

multimers of ____, rather than ____ cmediate platelet-platelet interaction.


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Mucocutaneous bleeding, includiecchymoses, petechiae, oral muco

bleeding. Evidence of splenomeg

hepatomegaly andlymphadenopathy should be soug


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Bleeding time, platelet counPT, APTT, vWF:antigen,

vWF:Ristocetin cofactoractivity, & vWF multimers


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List the laboratory procedur

used to determine platelet

function.


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Von Willebrand's disease

(vWD) type 1


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Decrease in quantity of vW

which appears to function

normally.


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vWD type 2


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Mutated form of vWF, often

causing a decrease in highmolecular weight multimers o

vWF; total antigen may benormal. Mutation may affect

binding site for factor VIII.


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vWD type 3


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Absent vWF (autosomal

recessive).


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Recurrent mucocutaneousbleeding (epistaxis, bruisin

menorrhagia) & positive famhistory of bleeding


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What are the clinical featur

of vWD?


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Childhood & early adulthoo


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At what point in life are th

symptoms of vWD most

evident?


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Pregnancy and acute

inflammatory reactions


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When can vWF normalize fo

individuals with vWD?


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Bernard-Soulier syndrome


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Rare, autosomal recessivedisorder due to deficiency o

GP Ib.


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Bernard-Soulier syndrome


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Thrombocytopenia with gian

platelets, abnormal (absent)aggregation with ristocetin a

normal vWF concentration afunction.


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Glanzmann's thrombasthen


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A rare autosomal recessivehereditary disorder

characterized by a deficiencof GP IIb-IIIa.


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Glanzmann's thrombasthen


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A normal platelet count and

morphology, absent primary wavaggregation to ADP (and collagen

and epinephrine), normal

aggregation response to ristocetin

and absent clot retraction.


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Altered platelet membraneantigens (PIA1, Baka and

Leka).


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What is the defect associatewith in Glanzmann's

thrombasthenia?


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Immune thrombocytopeni

purpura (ITP)

P ti t b t ti


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Patients may be asymptomati

or complain of easy bruising opetechiae commonly found on

one the lower extremities whe

the platelet count is less than

20,000.


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Acute (childhood type) ITP


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Type of ITP in which a viral

prodrome is common, there frequent spontaneous

remission, and male:femaleratio close to 1.


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Chronic (adult type) ITP


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Type of ITP in which there is

no antecedent infection, theris infrequent spontaneous

remission, and a male:femalratio of less than 1.


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ITP

Caused by antibodies directed


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Caused by antibodies directed

the platelet membrane; GP Iband IIb-IIIa are frequent targ

of autoantibodies but may no

be the only antigen targeted o

the platelet.


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ITP


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Bone marrow megakaryocytes are often

increased with active platelet sheddingbut in some patients megakaryocytic

hyperplasia may not be present. No

microangiopathic changes (fragmentedRBC's) on peripheral blood film.


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Isolated thrombocytopeniawith an otherwise normal

complete blood count.


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What is the typical

presentation of an ITP?


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Thrombotic thrombocytopen

purpura (TTP)


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Patients typically present wi

an unexplained anemia anthrombocytopenia, and

typically were previously vehealthy.


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women; African Americans

Caucasians


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TTP is more common in ___and may have an increased

risk in ____ compared to

____.


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TTP


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Characterized by thespontaneous development o

microthrombi in multiple

arterioles throughout the bo


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TTP

S h b i


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Severe thrombocytopenia,

fever, neurologic signs,microangiopathic changes o

peripheral blood film, andimpaired renal function.


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Multi-organ microvascula

thrombosis


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What is the hallmark

pathologic lesion in TTP?

Platelet Function Platelet Di

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