PFA-100 Platelet Function Analyzer In vitro method for platelet function testing

PFA-100

®

Platelet Function Analyzer

Clinical issue

●

Insufficient bleeding tendency assessment before operation

-

---history taking, CBC,aPTT, PT, BT (

Koscient J.MD, Ziemer S.MD, 2004

)

●

The effectiveness of anti-platelet drug is UNKNOW

---23% of 283 ACS patients

Poulsen et al; ESC 2003

38% of 129 post-AMI patients

Andersen et al., 2003

10% of 325 patients with CVD

Gum et al., 2001

27% of 89 patients with CVD, CAD

Santos et al; ISTH 2001

42% of 31 pts. with stable angina

Crowe et al; ISTH 2001

25% of 105 pts. with CAD

von Pape et al; ASH 2000

58% of 43 pts. undergoing PTCA

von Pape et al; ASH 2000

45% of 100 pts. with ACS

Sambola et al; ISTH 2001

Average 25% No responder or non-complaint

Hemotology---Clinical issue

●

The diagnostic approach to abnormalities of primary hemostasis is still a major

challenge for clinical laboratories

●

Investigation of unexplained bleeding, we need

Hemostasis

●

Vessel function

vessel constriction

●

Platelet function

Formation of platelet plugs (primary hemostasis)

●

Coagulation

Formation of fibrin plugs (second hemostasis)

●

Fibrinolysis

Dissolution of blood clots (tertiary hemostasis)

Primary hemostasis

●

First physiological response to vascular injury

●

Platelet mediated process

●

Mechanism

-

Adhesion

-

Recruitment (secretion)

-

Aggregation

-

Formation of the first hemostatic plug - initial arrest of bleeding

●

Occurs in high shear flow environment

(5000-6000s

₎

●

Triggers the coagulation cascade leading to formation of a

clot (secondary hemostasis)

●

Affected by medications, blood composition, platelet

function status, vessel wall status

Clinical issue

Platelet Sharp Change and Aggregation

Primary hemostasis

Causes for Abnormal Platelet Hemostatic Capacity

●

Platelet Defects

-

Congenital: Storage Pool Disease, Receptor Deficiencies

-

Acquired:

-

Drug-induced

(ex. Aspirin),

-

Underlying Disease-related (Uremia),

-

Liver cirrhosis

-

Extra-Corporeal Circulation

●

von Willebrand Disease

●

Thrombocytopenia

Common anti-platelet drugs

collagen

thrombin

TXA

ADP

ADP

TXA

TXA

ADP

phosphodiesterase

phosphodiesterase

ADP

ADP

GP IIb/IIIa

GP IIb/IIIa

Activation

Plavix (clopidogrel)

Ticlid (ticlopidine)

COX

cAMP

Persantine (dipyridamole)

Aggrenox (dipyrid. + ASA)

ReoPro

Aggrastat

Integrilin

Fbg, vWF

Fbg, vWF

Primary hemostasis

Laboratory Test on Platelet

●

Platelet evaluation

-

Count

-

Morphology

●

Traditional platelet function tests

-

Bleeding time (Duke, Template)

-

Platelet aggregation (PRP, WB) with an agonist panel of different

concentrations

●

von Willebrand factor

-

Antigenic level

-

Activity

Traditional Platelet Function Tests

●

In-vivo bleeding time in laboratory and clinical practice

-

Widely used because a lack of reliable alternatives

-

Insensitive and non-specific (non-diagnostic)

-

Invasive and time-consuming (template BT)

-

High inter-operator CV (poorly reproducible)

-

Affected by thrombocytopenia

-

Hard to perform on Irritable children

Traditional Platelet Function Tests

●

Platelet aggregation

-

Not ready to use (routine)

-

Labor intensive

-

Non-physiological (low shear stress & PRP)

-

Specialized equipment (expensive)

-

Time consuming (more 3.5 hrs)

-

Expertise to perform and interpret

-

Lag phase

-

Shape change

-

Primary and secondary aggregation

-

Clinical significance of mildly abnormal

Traditional Platelet Function Tests

●

Mainly to identify

-

The potential causes of abnormal bleeding

-

To monitor pro-hemostatic therapy in patients with a high risk of

bleeding

-

To ensure normal platelet function either prior to or during surgery

●

The diagnostic approach to abnormalities of primary hemostasis is

still a major challenge for clinical laboratories

●

History taking

remains most important and helps in diagnosing

bleeding disorders

PFA-100® Introduction & Test Principle

●

In 1996, DB introduced PFA-100 analyzer to detect primary

hemostasis based on the design of Krazter and Born (1984)

PFA-100® Introduction & Test Principle

What is the PFA-100 test

●

A global POC test system for platelet function.

●

A

high shear flow

system to measure platelet

adhesion

and aggregation

in buffered sodium citrated whole blood.

●

Two tests : Col/EPI Col/ADP

●

The time taken for blood to form aplatelet plug that

occludes the aperture is an indication of global platelet

function and is referred to as the Closure Time (CT).

PFA-100® Introduction & Test Principle

The Instrument

PFA-100® Introduction & Test Principle

In Vivo Haemostasis

_PFA-100

®

capillary 200µm aperture 150µm epinephrine or ADP platelet vWF erythrocyte FLOW - 40 mbar collagen membrane lumen fibrinogen platelet collagen fibrils erythrocyte endothelial cell vWF

PFA-100® Introduction & Test Principle

Test Cartridge before and after a test

before

after

PFA-100® Introduction & Test Principle

PFA-100® Introduction & Test Principle

PFA-100

REV. 2.00

S/N: 00370

14/07/97

14:01

ID#:

23456.17

Test Type: Collagen/EPI

PFA-100

REV. 2.00

S/N: 00370

14/07/97

14:01

ID#:

23456.17

Test Type: Collagen/EPI

Final Result and Print-out

Closure Time

(sec.) indicating

“

Primary-Hemostasis Capacity

”

PFA-100® Introduction & Test Principle

Two type tests:

●

COL/EPI

-

每一檢測盒含塗覆

2 µg

馬第一型膠原蛋白

（

equine Type-I

collagen

）

和

10 µg

腎上腺素酸性酒石酸鹽

（

epinephrine

bitartrate

）

-

Primary screening cartridge

-

Sensitive to ASA, vWD, congenital platelet defects,

thrombocytopenia, low hematocrit, GPIIbIIIa antagonists and other

platelet inhibiting agents

●

COL/ADP

-

每一檢測盒含塗覆

2 µg

馬第一型膠原蛋白

（

equine Type-I

collagen

）

和

50 µg

二磷酸腺苷酸

（

adenosine-5’-diphosphate

）

-

Used to discriminate between ASA-induced dysfunction and

PFA-100® Introduction & Test Principle

●

1. Sample Collection

-

System : either vacuum- or plonger-based

-

Collection medium :

3.2% (106 mM)

or 3.8% (129mM) buffered

sodium citrate

-

Technique :

short cuff-time, needle-size

≥

21G

.

-

Thorough mixing of sample by inverting tube several times

●

2. Sample Processing

-

Transport and store the sample undisturbed at room temperature

-

Mix the sample carefully by inverting several times by hand

-

800-1,000 µl blood inserted in cartridge, taking care that no air

bubbles are introduced

-

“Tubing” has to be validated by the site that wants to use it

PFA-100® Introduction & Test Principle

Reference Ranges

Reference Ranges

●

3.8% Sodium Citrate (n=176)

-

Collagen/Epinephrine

-

Mean 132 sec

Range 94 - 193 sec

-

Collagen/ADP

-

Mean 92 sec

Range 71 - 118 sec

●

3.2% Sodium Citrate (n=309)

-

Collagen/Epinephrine

-

Mean 110 sec

Range

82 - 150

sec

-

Collagen/ADP

-

Mean 78 sec

Range

62 - 100

sec

PFA-100® Introduction & Test Principle

Data Interpretation

●

The Closure Time is dependent on platelet function, vWF level,

platelet count (> 100,000-150,000) and hematocrit > 30~35%.

●

Expected Patterns

Col/Epi normal and Col/ADP normal

---Platelet function is normal, If the patient’s history/physical check are

confirmed normal.

Col/Epi Porlong and Col/ADP normal

---Drug induced platelet dysfunction, review the patient’s chart and

medication.

Col/Epi Prolong and Col/ADP Prolong

--- Platelet function is abnormal, commonly seen in VWD or congenital

platelet defect, most patient with prolonged Col/ADP CT manifest

PFA-100 ® Introduction & Test Principle

PFA-100

REV. 2.00

S/N: 00370

14/07/2008

14:01

ID#: 23456.17

Test Type: Collagen/EPI

SAMPLE A: 146 SEC

ID#:

23456.17

Test Type: Collagen/ADP

SAMPLE A: 87 SEC

PFA-100

REV. 2.00

S/N: 00370

14/07/2008

14:01

ID#: 23456.17

Test Type: Collagen/EPI

SAMPLE A: 146 SEC

ID#:

23456.17

Test Type: Collagen/ADP

SAMPLE A: 87 SEC

PFA-100

REV. 2.00

S/N: 00370

14/07/2008

14:01

ID#: 23456.17

Test Type: Collagen/EPI

SAMPLE A: 289 SEC

ID#:

23456.17

Test Type: Collagen/ADP

SAMPLE A: 87 SEC

PFA-100

REV. 2.00

S/N: 00370

14/07/2008

14:01

ID#: 23456.17

Test Type: Collagen/EPI

SAMPLE A: 289 SEC

ID#:

23456.17

Test Type: Collagen/ADP

SAMPLE A: 87 SEC

Aspirin pattern or

Milder platelet dysfunction

Normal pattern

PFA-100 Introduction & Test Principle

PFA-100

REV. 2.00

S/N: 00370

14/07/2008

14:01

ID#: 23456.17

Test Type: Collagen/EPI

SAMPLE A: 246 SEC

ID#:

23456.17

Test Type: Collagen/ADP

SAMPLE A: 187 SEC

PFA-100

REV. 2.00

S/N: 00370

14/07/2008

14:01

ID#: 23456.17

Test Type: Collagen/EPI

SAMPLE A: 246 SEC

ID#:

23456.17

Test Type: Collagen/ADP

SAMPLE A: 187 SEC

Limitation-platelet count

PFA-100 “should” be

run only on normal Plt

count samples!

If a CT is normal in spite

of abnormal plt count,

the clinician still has an

indication that platelet

function per se is

present…

Limitation-Hct

PFA-100 “should” be run

only on normal Hct

samples!

If a CT is normal in spite of

abnormal Hct, the clinician

still has an indication that

platelet function per se is

present…

Sourav K., Eric J.,

Clin Appl

Thrombosis/Hemostasis

,

2(4):124-249,1996

Article review

●

Analytical variable-1

Haematocrit : low Hct can lead to prolong CT

25%~50%

(Rohit cariappa, Timothy R.

J pediatric Hematology/Oncology

2003)

20%~50%

(Platelet Function Testing; Proposed Guideline by Aggregometry,

CLSI(NCCLS)

2007)

Hemoglobin < 8 g/dL

(Paul Harrison, Helen Segal, Stroke 2007)

> 30%

(Luc Christiaens,

Blood Coagulation and Fibrinolysis

, 2007)

Platelet Count : low PC can also lead to prolong CT

100,000/

μ

l

(Rohit cariappa, Timothy R.

J pediatric Hematology/Oncology

2003)

> 50,000/

μ

l

(Platelet Function Testing; Proposed Guideline by Aggregometry,

Test Advantages and Benefits

Objective, Accurate, Cost Efficiency… Convenience

●

No special sample collection and preparation

●

Permanent availability in combination with STAT

●

Objective and quantitative results

●

Accurate and reproducible results

●

High sample stability

●

Less stress on personnel though a minimal hands-on time

●

Less stress on patient because a routine venous blood

PFA-100®: Technical Advantage

●

Collected by vacutainer or syringe technique

●

Same anticoagulant as coagulation screening tests

●

Simple to perform

●

Rapid (maximal CT of 300 sec.)

●

Reported within and day-to-day imprecision (CV) <12%

●

Relative small volume of citrate blood (0.8 mL per cartridge) up to

4 hour at RT from sampling

●

Daily instrument QC check

●

Available proficiency test from CAP-2006

Test Advantages and Benefits

High Diagnostic Value

●

High sensitivity to platelet-related dysfunctions of primary

hemostasis

Col/EPI : PPV-81.8%, NPV-93.4%

Col/ADP: PPV-77.3%, NPV-79.4%

●

High sensitivity to vWD

●

High sensitivity to Aspirin-related platelet deficiency

●

Medication efficacy monitoring possible

(DDAVP, Aspirin®, ReoPro®)

●

Highly suitable tool for pre-surgical screening

●

Aid to demonstrate platelet transfusion efficacy

●

Pre-screening of platelet-donors

Indication

●

類血友病及血小板功能障礙篩檢

●

DDAVP

在第一型類血友病患者之治療評估

●

阿斯匹靈之治療評估

●

術前之出血危險評估

Col/EPI & Col/ADP

二項得同時申請

*

中央健保局於

2008

年新核准之適應症及使用規模

Platelet function closure time-Col/Epi

註：不得與08018C、08019C、08069C同時申報。

v v v v _{367 增列}

Clinical experience and Applications

More 200 articles published for clinical studies and uses in

global

●

… in Hematology

●

… in Tertiary Care

●

… in Cardiology

●

… in Pediatrics

●

… in Neurology

●

… in Urology

Hemostasis

Define reasons for investigation

(recent ASA intake ?, drug monitoring, vWD?

Haemophilia,?platelet disorder,? DDAVP trial)

Bleeding disorder ?

Clinical History (If available)

Bleeding history, family history, age, gender (if female: oestrogen

therapy?, pregnant?, excessive menstrual bleeding?) blood group

Clinical index of Suspicion regarding likely present of vWD.

Haemophilia, and/or platelet disorder

Select test panel as appropriate

( ie. Considering specific history and testing urgency)

PT & aPTT

vWF Ag

FVIII:C vWF:CBA

Platelet count

+/- vWF: RCof

E.J. Favaloro, Haemophilia (2001.7.170-179)

Hemostasis

Normal

1. If initial suspicion

low: no further

investigation

2. If initial suspicion

strong. Repeat testing

for confirmation

Abnormal

Investigate further as

required and depending on

initial test resulets: eg more

extensive vWF studies.

RIPA, PFS, factor studies.?

Drug effect. ? Platelet

disorder.etc

Clinical experience and Applications

Comparison of the PFA-100

_{with in vivo Bleeding Time Test}

0

1

0

1

Sensitivity

1 - Specificity

Bleeding Time test

PFA-100®

Area Under Curve 0.977 0.70 Error _{0.008 0.04}

Bleeding Time test

Receiver/Operator characteristics (ROC) of PFA (Col/Epi)

and Bleeding Time test

Population of 206 normal

and 176 abnormal subjects

Clinical experience and Applications

Study Design Bleeding Time

Sensitivity Sensitivity PFA-100 Reference

12 volunteers on 250 mg ASA daily, for 5

days. (estimated) 30% (estimated) 70% Marshall etal. Br J Clin Pharmacol 1997; 44: 151-155

60 von Willebrand Disease patients (vWD) 66% 97% Fressinaud et al. Blood 1998; 91:

1325-1331

120 donors after 1 bolus of 325 mg ASA

44 vWD, 5 Glanzmann Thrombasthenia 59% 96% Mammen Hemost 1998; 24: 195-202 etal. Semin Thromb

52 vWD 65% 87% Cattaneo etal. Thromb Haemost

1999; 82: 35-39

23 type 1 vWD pre- & post-desmopressin

(DDAVP) recorded in Correction 90% of cases

Correction recorded in 100% of cases

Fressinaud et al. Br J Haematol 1999; 106: 777-783

32 vWD; 5 Hermansky-Pudlak, 1 Glanzmann 55% 84% Kerenyi et al. Thromb Res 1999; 96: 487-492

113 hospital inpatients

BT and PFA agreed on 74% of the cases. In 86% of the discordant cases, PFA-100 was in concordance with Francis et al. Platelets 1999; 10: 132-136

Clinical experience and Applications

Bleeding time better

_{PFA-100 better}

Von Willebrand’s Disease

Aspirin Ingestion

Congenital platelet receptor disorders

Platelet secretion defect (col/EPI)

Platelet secretion defect (c/ADP)

1. PFA and BT ‘agree” in 70~80% cases

2. PFA correlation more closely with aggregation

3. PFA is more useful in clinical practice

Clinical experience and Applications

Study on 60 von Willebrand Disease Patients

36 Type 1

10 Type 2A

3 Type 2B

4 Type 3

2 Type 2N

5 Acquired

Clinical experience and Applications

Comparing the PFA-100

_{with Aggregometry}

Overall agreement between PFA-100® and Platelet Aggregometry

is 87.5% normal abnormal normal abnormal

Platelet Function

Platelet Function

PFA-100 ®

Aggregometry

Article review

●

Newborns and neonates have relatively short CTs compared

to shool-age childern and adults.

(probably by high vWF

conc.)

●

No correlation with age and gender.

* Bock M, De Haan J,

Br J haematol

1999

* Carcao MD, Blanchette VS,

Br J haematol

1998.

* Knofler R, Weissbach G,

Semin Thromb Hemost

1998.

* Rand ML, Carcao MD,

Semin Thromb Hemost

1998.

Article review

Conclusion:

Given the difficulties of offering and interpreting BT in pediatric patients and

compares the performance of PFA with BT, PFA could replace BT for detection

platelet dysfunction and vWD.

Rohit Cariappa. Ph D., Timothy R. B.A., Curtis A. Parvin, Ph.D., & Lori Luchtman-Jones, M.D. Comparison of

PFA-C/EPI

C/ADP

BT

97% (32/33)

80%(12/15)

88%(29/33)

100%(19/19)

87%(13/15)

37%(7/19)

98% (51/52)

83%(25/30)

69%(36/52)

100%(12/12)

80%(8/10)

17%(2/12)

98%(44/45)

80%(20/25)

69%(31/45)

Combined platelet deficiencies

vWD

Preoperative management of patients with impaired primary

hemostasis-1

●

Transient Platelet dysfunction : occurrence with

3%~5%

in

acquired (drug-induced) and congenital platelet dysfunction

or

vWD

.

●

Both of severe thrombocytopenia or hemophilia are

easily

identified via history taking, physical examination or Palelet

count

, aPTT, PT and BT.

But PC and BT are poor reliably

and reproducible.

●

There is no validated concept of when use drugs or how to

assess their effects before or during a surgical intervention.

●

PFA-100 enable to identify all patients with impaired

primary hemostasis.

Preoperative management of patients with impaired primary

hemostasis-2

●

Setting: Berlin German

●

Sample: A total of

5649 unselected

adult patients were

enrolled to identify impaired hemostasis before surgical

intervention.

254 having acquired and inherited impaired

primary hemostasis.

●

Method: A standardized questionnaire concerning bleeding

history. aPTT, PT, platelet count, PFA (CPI and ADP) were

routine processed.

And BT, vWF Ag were performed in additional with positive

bleeding history and /or evidence of impaired hemostasis,

Preoperative management of patients with impaired primary

hemostasis-3

Intervention (treatment):

●

All patient (254) with impaired primary hemostasis were

preoperatively treat with 30-minute infusion of 0.3

μ

g/kg

DDAVP (Minirin

®

_{) desmopressin acetate, and retest by}

PFA-100. All responders underwent with same drug as below table.

●

vWD patient were treated with factor VIII containing vWF

after non-responding DDAVP.

●

All other non-responders were treated with aprotinin

(Trasyol

®

_{) or tranexamic acid (Ugurol}

®

₎

Preoperative management of patients with impaired primary

hemostasis-4

Drug

_Preoperative

Doses

Perioperative

Total Cost

_(€)

DDAVP

Factor VIII

with vWF

Aprotinin

Tranexamic

acid

Conjugated

estrogens

0.3

μ

g/kg i.v.

50-80IE/kg i.v.

1,000,000 KIE i.v.

500 mg/kg i.v.

25 mg i.v.

3 x 0.3

μ

g/kg i.v.

(interval: 12h)

50-80IE/kg i.v.

(interval: 12h)

5-7 d postoperatice

500,000 KIE i.v.

intraoperative

250 mg/kg i.v. intraoperative

Until 4h of OP-end 3x250 mg

p.o. 3 d postoperative

25 mg intraoperative i.v. and

25 mg postoperative i.v.

220 (€)

26,000 (€)

450 (€)

40 (€)

90 (€)

Preoperative management of patients with impaired primary

hemostasis-5

Patients

N=5,649

Negative bleeding

history

N=5,021 (88.8%)

Positive bleeding

history

N=628 (11.2%)

Abnormal screening

test

N=9 (0.2%)

Abnormal screening

test

N=256 (40.8%)

aPTT n=9 (0.2%)

PC n=0

PFA C/EPI n=250 (97.7%)

PFA C/ADP n= 199(77.7%)

BT n=188(73.4%)

aPTT n=24(9.4%)

Result:

Preoperative management of patients with impaired primary

hemostasis-6

Result1:

Hemostasis

Tests

(Abnormal)

Normal Hemostasis

(n=5393)

Impaired Hemostasis

(n=256)

PFA-100: C/EPI

PFA-100: C/ADP

aPTT (sec)

PT (%)

Platelet count

0 of 5393

0 of 5393

9 of 5393

0 of 5393

0 of 5393

250* of 256 (97.7%)

199 of 256 (77.7%)

24 of 256 (9.4%)

10 of 256 (3.9%)

2 of 256 (0.8%)

Preoperative management of patients with impaired primary

hemostasis-7

Result2:

●

DDAVP administration resulted in correction of platelet

dysfunction in 229 of 254 (90.2%), as tested by C/EPI,

66.9% by C/ADP, 60% by BT.

●

Tranexamic acid was effective in 12 of 16.

Aprptinin was effective in 3 0f 5.

Factor VIII with vWF was effective in 4.

Koscient J.MD, Ziemer S.MD, Radtke H.MD, Schmutzler M.MD, Kiesemutzler M.MD, A Practical Concept for Preoperative Identification of Patients with Impaired Primary Hemostasis. Clin Appl Thrombosis/Hemostasis,

Preoperative management of patients with impaired primary

hemostasis-8

Result3:

_{Impaired hemostasis}

N=256

Second hemostasis

disorders

N=2 (0.8%)

Primary hemostasis

disorders

N=187 (73.0%)

Combined hemostasis

disorders

N=67 (26.2%)

Congenital

Dysfibrinogenaemia

N=1

age:26

Hereditary

Factor VII-deficiency

N=1

age: 34

Acquired

thrombopathies

N=169

age=37~78

Uremia associate n=7

Drug induced n=162

ASA n=87

, dicofenac,

ibuprofen, clopidogrel

vWD

N=34 age:17~47

vWD-1

N=40

vWD-possible 1

N=12

vWD-2a

N=2

Preoperative management of patients with impaired primary

hemostasis-9

Retrospective study similar

group at same hospital

in 1999 (n=5102)

Impaired hemostasis

N=317

Second hemostasis

disorders

N=0 (0%)

Primary hemostasis

disorders

N=299 (94.3%)

Combined hemostasis

disorders

N=19 (5.7%)

Acquired

thrombopathies

N=291

age=33~80

Drug induced n=291

ASA, dicofenac,

ibuprofen, clopidogrel

Hereditary

thrombopathies

vWD

N=10

age:19~41

Liver cirrhosis

N=8

age: 29~65

Preoperative management of patients with impaired primary

hemostasis-10

Elective operations

Prospective study

Retrospective study

Patients N=5102

Normal hemostasis

N=4785

Nontreated

abnormal hemostasis

N=317

Blood transfusions

N=541 (11.3%)

Blood transfusions

N=283 (89.3%)

Patients N=5649

Normal

haemostasis

N=5393

Corrected

abnormal hemostasis

N=256

Blood transfusions

N=660 (12.2%)

Blood transfusions

N=24 (9.4%)

Preoperative management of patients with impaired primary

hemostasis-11

Discussion-1:

●

There are two reasons for DDAVP use, low cost and

low side effect compared with other two drugs.

●

DDAVP may lead to improvement of hemostasis by

increasing the level of factor VIII, vWF and

plasminogen activator. Others ,may increase the

expression GP-Ib receptor, conjugated estrogens seem

to increase aggregation.

●

The improvement was confirmed by platelet function

assay, C/EPI.

Koscient J.MD, Ziemer S.MD, Radtke H.MD, Schmutzler M.MD, Kiesemutzler M.MD, A Practical Concept for Preoperative Identification of Patients with Impaired Primary Hemostasis. Clin Appl Thrombosis/Hemostasis,

Preoperative management of patients with impaired primary

hemostasis-12

Discussion-2:

●

Preoperative correction of platelet dysfunction was

found to

reduce the need for blood transfusion

in

almost all cases.

●

Recommend initial treatment with DDAVP and

second-line with others drugs.

Preoperative management of patients with impaired primary

hemostasis-13

Discussion-3:

●

Based on the data (retrospective group), the positive and

negative predictive values for blood transfusion are 91.7%

and 89.6% for PFA C/EPI, 86.5% and 86.6% for PFA C/ADP.

●

Area under ROC curve=0.9237.

●

Findings of groups, the PFA is clearly superior to BT.aPTT,

PT,vWF:Ag. Sensitivity : 90.8%.

●

All patients with positive bleeding history to primary or

combined hemostasis disorder could be identified using

PFA-100, and

they are also detected abnormalities who 14

patient failed to report anti-platelet drug use.

Clinical experience and Applications

●

Assessing the Response to ASA

•

Aspirin is the most widely consumed drug in the world

and a cost-effective medication for the prevention and

treatment of heart disease and stroke.

•

Aspirin inhibits platelet function and may dampen the role

of platelets as inflammatory mediators, two factors

strongly implicated in promoting acute coronary

syndromes (ACS).

Clinical experience and Applications

●

Assessing the Response to ASA

•

However, studies suggest that significant insensitivity (5%

- 60%) to aspirin occurs among patients with defined

coronary disease, cardiovascular disease and stroke.

•

“…Despite the demonstrated benefit of aspirin in secondary

prevention and its possible beneficial effects in selected

individuals for primary prevention, there remains a large

segment of the population at risk that does not benefit from

Clinical experience and Applications

●

Assessing the Response to ASA

•

23% of 283 ACS patients

Poulsen et al; ESC 2003

•

38% of 129 post-AMI patients

Andersen et al., 2003

•

10% of 325 patients with CVD

Gum et al., 2001

•

27% of 89 patients with CVD, CAD

Santos et al; ISTH 2001

•

42% of 31 pts. with stable angina

Crowe et al; ISTH 2001

•

25% of 105 pts. with CAD

von Pape et al; ASH 2000

•

58% of 43 pts. undergoing PTCA

von Pape et al; ASH 2000

•

45% of 100 pts. with ACS

Sambola et al; ISTH 2001

Σ

Review of the literature on 1,105 patients...

Cardiac Population

Article review

●

A systemic review of 53 studies (64 population, 6,450

subjects) for ASA no-responding detected by PFA-100.

●

Pooling these studies, the risk of vascular clinical events

appeared to be

significantly higher

in non- responders to

aspirin.

(RR: 1.63, 95% CI: 1.16-2.28)

●

Cutoff of Col/EPI:

174 ~193 sec.

●

Non-responding : 27%

Article review

Recommendation:

Prolonged CT can reflect other abnormalities (vWD), and as such,

abnormal results require further diagnostic evaluations.

Normal CT can help exclude some severe platelet defect.

C.P.M. Hayward, P. Harrison, M. Cattaneo, T.L. Ortel & A.K. Rao, Platelet function analyzer(PFA)-100 closure time in the evaluation of platelet disorders and platelet function. Journal of Thrombosis and Haemostasis ,

THE END

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