HEMOSTASIS_drmohammed _ 3_2 (1).ppt

7/27/2019 HEMOSTASIS_drmohammed _ 3_2 (1).ppt

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Platelet Function

Platelet must be adequate in number and function toparticipate optimally in homeostasis.

The functions of platelets in homeostasis include;

Maintenance of vascular integrity

Initial arrest of bleeding by platelet plug formation

Stabilization of hemostatic plug by contributing to fibrinformation.


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Adhesion

Key Mediators in Platelet Adhesion, Activation andAggregation

INJURY

vWF

Thrombin

Collagen

Fibronectin

Shear Forces

vWF

ADP-receptorTHROMBUS

Activation Aggregation

Membrane changes

Granule secretion

GPIIb/IIIa expression

Multiple agonists

Feedback loops

GPIIb/IIIa-mediated

Fibrinogen

vWF


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Aggregation

of platelets into a

thrombus

Platelets

Endothelial cells

Platelets adheringto subendothelialspace

Plateletthrombus

Normal platelets

in flowing blood

Platelets adhering to

damaged endothelium

and undergoing activation

Platelet Adhesion and Activation

Subendothelial space

Adapted from: Ferguson JJ. The Physiology of Normal Platelet Function. In: Ferguson JJ,

Chronos N, Harrington RA (Eds).Antiplatelet Therapy in Clinical Practice. London: MartinDunitz; 2000: pp.1535.


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Platelet Function (Adhesion)

Following blood vessel injury, platelets adhere to theexposed subendothelial connective tissues.

Subendothelial bind to the larger multimers of vWF andthrough these react with Platelet membrane GPIb .

large number of adhesion proteins are involved in

plateletvessel wall and platelet- platelet interaction.Adhesion to collagen is facilitated by GPIa.


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Platelet Function

Platelet adhesion induces a series of metabolic reactionswhich initiate the platelet release reactions, shapechange and aggregation.

Following adhesion, platelets become more spherical andextrude long pseudopods which enhance interactionbetween adjacent platelets.

von Willebrand factor (VWF) is involved in plateletadhesion to the vessel wall and to other platelets(aggregation).


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Platelet Function

vWF is encoded by a gene on chromosome 12 and issynthesized by endothelial cells and Megakaryocytes.

Release of vWF from endothelial cells occurs under theinfluence of several hormones.


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Adapted from: Kuwahara M et al. Arterioscler Thromb Vasc Biol2002; 22: 32934.

Platelet Aggregation

FIRM, BUT REVERSIBLEADHESION

IRREVERSIBLEADHESION

Scanning electron micrograph

of discoid, dormant platelets

Activated, aggregating platelets

illustrating fibrin strands

Flowingdisc-shaped

platelet

Rollingball-shaped

platelet

Hemisphere-shapedplatelet

Spreadingplatelet


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Platelet Function (Release Reaction)

Collagen exposure or thrombin action results in thesecretion of platelet granule contents which include ADP,serotonin, fibrinogen, lysosomal enzymes, -thromboglobulin.

Collagen and thrombin activate platelet prostaglandinsynthesis.

Released ADP and thromboxane A2 cause additionalplatelets to aggregate at the site of vascular injury.

ADP causes platelets to swell and encourages the plateletmembranes of adjacent platelets to adhere to each other.


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Platelet Function (Platelet aggregation)

As they do so further release reactions occur liberatingmore ADP and thromboxane A2 causing secondaryplatelet aggregation.

This positive feedback process results in the formation ofa platelet mass large enough to plug the area ofendothelial injury.


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Platelet Function Test

Bleeding Time Principle: Bleeding time is defined as the time taken for a

standardized skin wound to stop bleeding.

Platelet aggregation

Platelets function in primary hemeostasis by forming aninitial platelet plug at the site of vascular injury. Thephenomenon occurs partly through the ability ofplatelets to adhere to one another, a process known asplatelet aggregation.


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Substances that can induce platelet aggregation include;

Collagen, ADP, epinephrine, thrombin, serotonin,arachidonic acid, restocetin, snake venoms.

Platelet aggregation is an essential part of theinvestigation of any patient with a suspected plateletdysfunction.

Platelet aggregation is studied by means a plateletaggregometer.


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A photo-optical instrument connected to a chartrecorder.

Platelet rich plasma (PRP) which is turbid in appearance,is placed in a cuvette warmed to 37C in the heat block ofthe instrument, and stirred by a small magnetic bar.

Light transmittance through the PRP is recorded.


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The addition of aggregating agent cause the formation oflarger platelet aggregates with a corresponding increasein light transmittance, owing to a clearing in the PRP.

The change in the light transmittance is converted toelectric signal and recorded as a tracing by the chartrecorder.


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There are some basic requirements for plateletaggregation as in vitro means of evaluating plateletfunctions.

1-A clean venipuncture is crucial. Hemolyzed samplesshould not be studied because RBCs contained ADP.

2- Plasma from fasting patients is preferred for testing.Lipemic samples may obscure change in optical densityowing to platelet aggregation.


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3- Sodium citrate is the anticoagulant used inaggregation studies. In vitro aggregation is dependent onthe presence of calcium ions.

4- Fibrinogen must be present in the test sample foraggregation to occur.

5- Aggregation studies should be performed at 37C at apH of 6.5 to 8.5. To help maintain platelet values, all

samples, once collected, should be capped to prevent Co2loss.


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6- Test samples, should be maintained at room tempduring processing. Cooling inhibits the plateletaggregation response.

7- Stirring is necessary to bring the platelets in close

contact with one another to allow aggregation to occur.

8- It is essential that the patient refrain from taking anyanti-inflammatory drugs, one week before the test. Thedrugs inhibit the platelets release reaction.

9- Aggregating reagents should be prepared fresh dailyand brought to room temp before use. They must haveknown potency and be added in small volume.

HEMOSTASIS_drmohammed _ 3_2 (1).ppt

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