Basic Clinician Training Module 7 PlateletMapping™ PlateletMapping™ Assays.

Basic Clinician TrainingModule 7

PlateletMapping™

PlateletMapping™ Assays

PlateletMapping™What is it?

• Special TEG assay to measure effects of anti-platelet drug therapy on platelet function Measure reduction in platelet function

(MA) due to anti-platelet drugs Provides individual’s potential total

platelet function as a reference point Identifies resistance or subtherapeutic

response to drug therapy

• ADP receptor inhibitors such as clopidogrel and ticlopidine

• Arachadonic acid pathway inhibitors such as aspirin

• GPIIb/IIIa inhibitors such as abciximab, tirofiban, eptifibatide

PlateletMapping™What drugs are monitored?

• Individual response to anti-platelet drugs determine clinical outcome

• Knowing percent platelet inhibition is insufficient to determine therapeutic efficacy

• Also require knowledge of total or potential platelet function as a reference point

Why PlateletMapping?Personalized platelet therapy

• Patient A: 50% platelet inhibition is insufficient to completely reduce the risk of a thrombotic or ischemic event

• Patient B: 50% platelet inhibition provides anti-thombotic protection

• Patient C: 50% platelet inhibition increases risk of bleeding

Why PlateletMapping?Personalized platelet therapy

The hemostatic process

• The end result of hemostasis is a 3-D network of fibrin and platelets linked by fibrinogen via the GPIIb/IIIa receptor

• The integrity of the fibrin-platelet network is expressed as the MA on the TEG analyzer.

The hemostatic process

• Hemostasis is a tightly regulated process consisting of three separate, but interrelated, steps: Platelet plug formation = primary hemostasis Fibrin clot formation Fibrinolysis

• Interruption of platelet plug formation is a common therapeutic strategy to reduce risk of ischemic events (arterial thrombosis)

Anti-thrombotic strategiesInhibit platelet aggregation response

• Inhibit platelet activation – ADP receptor inhibitors (e.g. clopidogrel)

• Inhibit platelet secretion – block synthesis and secretion of TxA2, a potent platelet activator (e.g. aspirin)

• Inhibit platelet aggregation – inhibit GPIIb/IIIa receptors (e.g. abciximab, tirofiban, eptifibatide)

PlateletMappingHow it works - platelets

ADP and TxA2 both mediate activation/expression of GPIIb/IIIa receptors aggregation

ADPInhibited by clopidogrel, ticlopidine

TxA2

Inhibited by aspirin

PlateletMappingHow it works - platelets

• Activation/expression of GPIIb/IIIa receptors on platelet surface platelet aggregation via interaction with fibrinogen

• Inhibited by abciximab, tirofiban, eptifibatide

PlateletMappingHow it works - platelets

• ADP & TxA2 sites can be activated, but if the GPIIb/IIIa receptor is inhibited, platelet aggregation will not take place

PlateletMappingHow it works - thrombin

• Most potent platelet agonist – overrides inhibition at other platelet activation pathways Maximally activates platelets Provides total platelet function during

TEG analysis (MA)

• Cleaves fibrinogen to fibrin• Converts Factor XIII to Factor XIIIa for

fibrin cross linking

PlateletMappingHow it works – the assay

• Channel 1: Thrombin-activated platelet function provides total platelet function (MAthrombin), even in presence of anti-platelet agents

• Channels 2-4: Performed in presence of heparin to inhibit thrombin activity Channel 2: Measures contribution of fibrin(ogen) to

MA(MAfibrin) by addition of ActivitorF which converts fibrinogen to fibrin and FXIII to FXIIIa

Channels 3 and 4: ADP or AA (arachadonic acid) + Activator F to measure platelet function and fibrin contribution to MA (MAADP or MAAA)

• Only non-inhibited platelets will be activated by ADP or AA

• Measures the reduction in platelet function due to anti-platelet agents

PlateletMapping assayAt a glance

PlateletMapping assayCalculation of platelet inhibition

% inhibition =

[100 – (MApi-MAf)/(MAt-MAf)] * 100

Where:

MApi = MAADP or MAAA

MAf= MAfibrin

MAt = MAthrombin or MAKH

PlateletMapping assayTEG analysis - MA

%Inhibition = 83.5

PlateletMapping assayTEG analysis – Clopidogrel resistance

%Inhibition = 8.4

PlateletMapping assayTEG analysis – aspirin resistance

MATHROMBIN

MAAA

MAFIBRIN

%Inhibition = 0.0

Summary

• PlateletMapping measures platelet inhibition along with total platelet function as a reference point

• Monitors platelet inhibition at GPIIb/IIIa, ADP, and TxA2 receptors

• Detects drug resistance as well as efficacy (i.e. inhibition)

• Provides for anti-platelet drug therapy personalized to patient’s hemostatic state.

Overview exercises

PlateletMapping assay

PlateletMapping results

#1

The MA parameter of TEG analysis

demonstrates clot strength due to the

contributions of ________ and ________.

Answer Next

#2

Which of the following component of the

PlateletMapping Assay allows for personalized

anti-platelet therapy?

a. Demonstrates percent platelet inhibition due to inhibitors of platelet activation

b. Demonstrates percent platelet inhibition due to inhibitors of platelet aggregration

c. Demonstrates total platelet function as a reference point

Answer Next

B

a. MAfibrin

b. MAthrombin

c. MAADP

d. MAAA

Answer

Next

A1. Demonstrates total platelet

function

2. Demonstrates contribution of platelets and fibrin not inhibited by aspirin

3. Demonstrates contribution of fibrin

4. Demonstrates contribution of platelets and fibrin not inhibited by clopidogrel or ticlopidine:

5. Demonstrates contribution of platelets and fibrin not inhibited by GPIIb/IIIa inhibitors

6. Also known as MAKH

#3 Match all the applicable descriptions in Column A tothe appropriate PlateletMapping parameters in Column B

#4

Answer Next

Although a 50% inhibition of platelet function was achieved withadministration of an anti-platelet agent in each patient:• Which patient is still at risk for an thromboembolic event? A, B or C?• Which patient received optimal anti-platelet therapy? A, B, or C?

#5

Answer Next

Each of the following patients were administered a standard dose ofclopidogrel in the catherization laboratory. Based on the results of thePlateletMapping assay, which patient likely demonstrates resistance to the drug? A or B?

A B

#6The following PlateletMapping assay was performed on a patient priorto cardiac surgery (on pump, CABG) and 5 days after discontinuation of clopidogrel therapy. Is this patient at high or low risk for bleeding after surgery?

Answer Next

End of Module 7

#1

The MA parameter of TEG analysis provides

demonstrates clot strength due to the

contributions of platelets and fibrin or fibrinogen.

Next

#2

Which of the following component of the

PlateletMapping Assay allows for personalized

anti-platelet therapy?

a. Demonstrates percent platelet inhibition due to inhibitors of platelet activation

b. Demonstrates percent platelet inhibition due to inhibitors of platelet aggregration

c. Demonstrates total platelet function as a reference point

Next

Ba. MAfibrin

b. MAthrombin

c. MAADP

d. MAAA

Next

A1. Demonstrates total platelet function: b

(MAthrombin)

2. Demonstrates contribution of platelets and fibrin not inhibited by aspirin: d (MAAA)

3. Demonstrates contribution of fibrin: a (MAfibrin)

4. Demonstrates contribution of platelets and fibrin not inhibited by clopidogrel or ticlopidine: c (MAADP)

5. Demonstrates contribution of platelets and fibrin not inhibited by GPIIb/IIIa inhibitors: c,d (MAADP, MAAA)

6. Also known as MAKH: b (MAthrombin)

#3 Match all the applicable descriptions in Column A tothe appropriate PlateletMapping parameters in Column B

#4

Next

Although a 50% inhibition of platelet function was achieved withadministration of an anti-platelet agent in each patient:• Which patient is still at risk for an thromboembolic event? A, B or C?• Which patient received optimal anti-platelet therapy? A, B, or C?

#5

Next

Both of the following patients were administered a standard dose ofclopidogrel in the catherization laboratory. Based on the results of thePlateletMapping assay, which patient likely demonstrates resistance to the drug? A or B?

A B

#6The following PlateletMapping assay was performed on a patient priorto cardiac surgery (on pump, CABG) and 5 days after discontinuation of clopidogrel therapy. Is this patient at high or low risk for bleeding after surgery? HIGH risk for bleeding due to a high level of platelet inhibition even after a 5 day period of not taking clopidogrel.

Next