Utility of the Platelet Function Analyzer in Patients with Suspected Platelet Function Disorders: Diagnostic Accuracy Study

Abstract Introduction The platelet function analyzer (PFA) is widely used as a screening tool for bleeding disorders in various settings. The diagnostic performance regarding platelet function disorders (PFDs), which are among the most common inherited bleeding disorders, is however still elusive. We aimed to assess the diagnostic value of PFA for PFD in clinical practice. Methods Comprehensive clinical and laboratory data of all consecutive patients referred to a specialized outpatient between January 2012 and March 2017 with a suspected bleeding disorder were prospectively recorded. The diagnostic work-up was performed according to a prespecified protocol following current guidelines and platelet function was tested using light transmission aggregometry as well as flow cytometry. Results Five hundred and fifty-five patients were included (median age 43.7 years; interquartile range [IQR] 29.3, 61.7; 66.9% female). Possible PFD was diagnosed in 64 patients (11.5%) and confirmed PFD in 54 patients (9.7%). In patients with confirmed PFD, median closure times were 107 seconds (ADP or adenosine diphosphate; IQR 89, 130) and 169 seconds (EPI; IQR 121, 211). In patients without bleeding disorders, PFA closure times were 96 seconds (ADP; IQR 83, 109) and 137 seconds (EPI; IQR 116, 158). The sensitivity was 19.5% in case of PFA ADP (95%CI 12.6, 30.0; specificity 86.4%; 95% CI 82.4, 89.8), and 44.3% in case of PFA EPI (95% CI 34.9, 53.9; specificity 75.6%; 95% CI 70.8, 79.9). Conclusion The diagnostic performance of PFA for PFD was moderate to poor. Our results do not support the utilization of PFA for screening of PFD in clinical practice.

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Adequate Platelet Function Inhibition Confirmed by Two Inductive Agents Predicts Lower Recurrence of Ischemic Stroke/Transient Ischemic Attack

BioMed Research International ◽

10.1155/2017/3504950 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Lulu Zhang ◽

Xiaowei Hu ◽

Juehua Zhu ◽

Xiuying Cai ◽

Yan Kong ◽

...

Keyword(s):

Ischemic Stroke ◽

Antiplatelet Therapy ◽

Platelet Function ◽

Adenosine Diphosphate ◽

Aggregation Rate ◽

Function Analyzer ◽

Ischemic Attack ◽

Platelet Function Analyzer ◽

Platelet Functions

Background. The correlation between platelet function and recurrent ischemic stroke or TIA remains uncertain. Objective. To investigate two inductive agents to detect platelet functions and assess associations with recurrent ischemic stroke/TIA. Method. The study included 738 ischemic stroke/TIA patients. On days 0, 3, and 9 after antiplatelet therapy, platelet function tests were determined by maximum aggregation rate (MAR) using a PL-11 platelet function analyzer and phase matching reagents. Two induction agents were used: arachidonic acid (AA) and adenosine diphosphate (ADP). At 3-month follow-up, recurrence of stroke/TIA was recorded. Result. Cut-off values of adequate platelet function inhibition were MARADP < 35% and MARAA < 35%. Data showed that antiplatelet therapy could reduce the maximum aggregation rate. More importantly, adequate platelet function inhibition of either MARADP or MARAA was not associated with the recurrence of stroke/TIA, but adequate platelet function inhibition of not only MARADP but also MARAA predicts lower recurrence (0/121 (0.00%) versus 18/459 (3.92%), P = 0.0188). Conclusion. The platelet function tested by PL-11 demonstrated that adequate inhibition of both MARADP and MARAA could predict lower risk of ischemic stroke/TIA recurrence.

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Sevoflurane Inhibits Unstimulated and Agonist-induced Platelet Antigen Expression and Platelet Function in Whole Blood In Vitro

Anesthesiology ◽

10.1097/00000542-200111000-00028 ◽

2001 ◽

Vol 95 (5) ◽

pp. 1220-1225 ◽

Cited By ~ 9

Author(s):

Nicola A. Horn ◽

Lothar de Rossi ◽

Tilo Robitzsch ◽

Klaus E. Hecker ◽

Gabriele Hutschenreuter ◽

...

Keyword(s):

Platelet Function ◽

Whole Blood ◽

Control Sample ◽

Antigen Expression ◽

Adenosine Diphosphate ◽

Color Flow ◽

Platelet Antigen ◽

Function Analyzer ◽

Platelet Function Analyzer

Background Previous studies have reported conflicting results about the effect of sevoflurane on platelet aggregation. To clarify this point, we investigated the effects of sevoflurane on platelet antigen expression and function in vitro. Methods Human whole blood was incubated for 1 h with 0.5 and 1 minimum alveolar concentration sevoflurane, 21% O(2), and 5% CO(2). A control sample was kept at the same conditions without sevoflurane. After stimulation with adenosine diphosphate or thrombin receptor agonist peptide 6, samples were stained with fluorochrome conjugated antibodies, and the expression of platelet glycoproteins GPIIb/IIIa, GPIb, and P-selectin, as well as activated GPIIb/IIIa, were measured with two-color flow cytometry. In addition, platelet function was assessed by means of thromboelastography and using the platelet function analyzer 100. Results Already in subanesthetic concentrations, sevoflurane inhibits unstimulated and agonist-induced GPIIb/IIIa surface expression and activated GPIIb/IIIa expression on platelets in whole blood. The agonist-induced redistribution of GPIb into the open canalicular system was also impaired by sevoflurane, whereas no effect on P-selectin expression in activated platelets could be found. Sevoflurane significantly reduced the maximum thromboelastographic amplitude. Furthermore, platelet function analyzer 100 closure times were significantly prolonged. Conclusion The results show that sevoflurane significantly impairs platelet antigen expression in vitro. It is especially the inhibition of GPIIb/IIIa expression and activation that impairs bleeding time as reflected in thromboelastographic measurements and platelet function analyzer 100 closure times. The exact inhibitory mechanism remains unclear.

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Quantifying the Effect of Antiplatelet Therapy

Anesthesiology ◽

10.1097/00000542-200610000-00011 ◽

2006 ◽

Vol 105 (4) ◽

pp. 676-683 ◽

Cited By ~ 68

Author(s):

Seema Agarwal ◽

Margaret Coakely ◽

Kalpana Reddy ◽

Anne Riddell ◽

Susan Mallett

Keyword(s):

Antiplatelet Therapy ◽

Platelet Function ◽

Light Transmission ◽

Point Of Care ◽

Perioperative Bleeding ◽

Light Transmission Aggregometry ◽

Function Analyzer ◽

Platelet Function Analyzer ◽

Ischemic Events ◽

Good Agreement

Background Antiplatelet therapy with aspirin and clopidogrel is known to confer protection against ischemic events. Increasing numbers of patients are presenting for surgery while taking these drugs. This may lead to an increase in perioperative blood loss, particularly in those who have a heightened response to the drugs. Identifying these patients preoperatively would allow us to plan appropriate management. Methods The antiplatelet effect of aspirin and/or clopidogrel was measured using two point-of-care monitors: the platelet function analyzer (PFA-100; Dade, Miami, FL) and the modified thromboelastograph (mTEG; Haemoscope Corp., Niles, IL). This was compared with optical light transmission aggregometry. Results All people taking aspirin displayed a definitive aspirin effect on aggregometry (n = 20). Ninety percent of these were identified by modified thromboelastography (n = 18). Seventy percent were identified by the platelet function analyzer (n = 14). Fifty percent of people taking clopidogrel displayed a definitive response to the drug on aggregometry. Seventy percent of these were identified on modified thromboelastography (n = 7). None were identified by the platelet function analyzer. There was good agreement between the results of the aggregometry and modified thromboelastography in clopidogrel patients (kappa = 0.81). Conclusion The search for a point-of-care monitor of platelet function has been the focus of much research. This study has shown that the modified thromboelastograph can be used for monitoring the effect of clopidogrel as well as aspirin. It potentially has a wide scope to be used for the monitoring of effectiveness of therapy as well as a possible predictor of perioperative bleeding.

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Platelet function in cats with hyperthyroidism

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x20920585 ◽

2020 ◽

Vol 22 (12) ◽

pp. 1214-1218

Author(s):

Elizabeth C Hiebert ◽

David L Panciera ◽

Katie M Boes ◽

Lara Bartl

Keyword(s):

Platelet Count ◽

Platelet Function ◽

Adenosine Diphosphate ◽

Control Group ◽

Closure Time ◽

Function Analyzer ◽

The Mean ◽

Platelet Function Analyzer ◽

Von Willebrand ◽

Willebrand Factor

Objectives Cats with hyperthyroidism have been reported to develop thromboembolism, with and without echocardiographic abnormalities consistent with hyperthyroidism. The objective of this study was to compare platelet function in cats with hyperthyroidism with euthyroid age-matched cats. We hypothesized that cats with hyperthyroidism have shortened collagen and adenosine diphosphate (C-ADP) closure times as measured with the platelet function analyzer (PFA-100) in comparison with healthy, age-matched controls. Methods Sixteen hyperthyroid and nine euthyroid healthy cats >7 years of age were recruited from the hospital population. Platelet function, measured using the C-ADP closure times by the PFA-100, and platelet count were measured in healthy euthyroid cats and cats with hyperthyroidism. Results Mean ± SD closure times were not significantly different between control (66.3 ± 9.6 s) and hyperthyroid cats (65.9 ± 11.5 s; P = 0.75). The mean ± SD closure times of hyperthyroid cats that either were untreated or received methimazole for ⩽3 weeks (n = 6; mean 68.5 ± 15.4 s) was not different than that of cats treated for >3 weeks (n = 10; mean 64.3 ± 8.9 s; P = 0.57). The mean automated platelet count was higher in the hyperthyroid group than in the control group ( P = 0.023). Conclusions and relevance Platelet function, as measured by closure time under high shear conditions using C-ADP as an agonist, was not affected by hyperthyroidism in this group of cats. Further research is needed to determine if a hypercoagulable state exists in hyperthyroid cats and the potential roles platelets and von Willebrand factor may have.

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Comparison of current platelet functional tests for the assessment of aspirin and clopidogrel response

Thrombosis and Haemostasis ◽

10.1160/th15-11-0870 ◽

2016 ◽

Vol 116 (10) ◽

pp. 638-650 ◽

Cited By ~ 40

Author(s):

Jean-Claude Bordet ◽

Claude Negrier ◽

Yesim Dargaud ◽

Sandra Le Quellec

Keyword(s):

Platelet Function ◽

Light Transmission ◽

Platelet Response ◽

Platelet Function Tests ◽

Clopidogrel Resistance ◽

Function Tests ◽

Function Analyzer ◽

Clopidogrel Therapy ◽

Whole Blood Aggregometry ◽

Platelet Function Analyzer

SummaryThe two most widely used antiplatelet drugs in the world are aspirin and clopidogrel. However, some patients on aspirin and/or clopidogrel therapy do not respond appropriately to either aspirin or clopidogrel. This phenomenon is usually called “aspirin/clopidogrel resistance”. Several platelet function tests have been used in various studies for the assessment of aspirin and clopidogrel resistance in healthy individuals and patients admitted in cardiology departments. An accurate assessment of platelet response to aspirin/clopidogrel could benefit patients by proposing tailored-antiplatelet therapy based on test results. However, there is a clear lack of standardisation of such techniques and their analytical variability may induce misinterpretation. After a quick report of the mechanisms responsible for aspirin/clopidogrel resistance, we describe the pre-analytical aspects and the analytical performances of current platelet function tests (Light-transmission aggregometry, whole-blood aggregometry, VerifyNow®, Platelet Function Analyzer®, thromboelastography, VASP assay) that are used for the assessment of aspirin/clopidogrel resistance in clinical studies. Considering the different variables that have to be taken into account with each of the platelet function tests, a particular attention should be paid when interpreting results.

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Monitoring of Aspirin (ASA) Pharmacodynamics with the Platelet Function Analyzer PFA-100®

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613805 ◽

2000 ◽

Vol 83 (02) ◽

pp. 316-321 ◽

Cited By ~ 155

Author(s):

Monika Homoncik ◽

Nicole Hergovich ◽

Petra Stohlawetz ◽

Simon Panzer ◽

Wolfgang Speiser ◽

...

Keyword(s):

Platelet Function ◽

Adenosine Diphosphate ◽

Rapid Onset ◽

Response Curves ◽

Double Blind ◽

Platelet Aggregometry ◽

Function Analyzer ◽

Anti Platelet Drug ◽

Stress Dependent ◽

Platelet Function Analyzer

SummaryAnti-platelet drug therapy is currently performed without monitoring, because the established method of platelet aggregometry is cumbersome. The recently developed platelet function analyzer PFA-100® measures shear stress dependent, collagen epinephrine (CEPI) and collagen adenosine diphosphate (CADP) induced platelet plug formation. As the PFA-100 provides a valuable tool to detect patients with platelet dysfunction more efficiently and cost-effectively than aggregometry, we investigated its potential to monitor the efficacy of aspirin treatment.All healthy volunteers (n = 10) received a fractionated infusion of L-aspirin to establish individual dose-response curves. Further, in a randomized, double-blind, placebo controlled two-way cross over study the same volunteers received either 50 or 100 mg aspirin/day p.o. for a period of 11 days to determine the day-to-day variability CEPI induced closure time (CT) under constant intake of low dose aspirin, and to compare the efficacy of those two doses.Intra- and intersubject variability of CEPI-CT averaged 9% and 22%, respectively. Seven volunteers exceeded the maximum of CEPI-CT (>300 s) already after infusion of 100 mg L-aspirin. Intake of 100 mg of aspirin elicited a more rapid onset of effect than 50 mg, which was only significant on days 3 and 4 of aspirin intake. The aspirin induced CEPI-CT prolongation correlated positively with basal CEPI-CT values (r = 0.86; p = 0.001) and were strongly dependent on von Willebrand Factor levels (r = -0.9; p = 0.001).Thus, the PFA-100 system appears suitable to demonstrate an aspirin-induced platelet effect in a longitudinal study, and may be adequate to monitor a patient’s compliance. However, prospective trials have to be conducted to demonstrate whether the EPI-CT achieved under ASA-intake has predictive value for cardiovascular outcome.

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Cross validation of the Multiple Electrode Aggregometry

Thrombosis and Haemostasis ◽

10.1160/th08-10-0669 ◽

2009 ◽

Vol 102 (08) ◽

pp. 397-403 ◽

Cited By ~ 43

Author(s):

Jolanta Siller-Matula ◽

Ghazaleh Gouya ◽

Michael Wolzt ◽

Bernd Jilma

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Cross Validation ◽

Platelet Reactivity ◽

Adenosine Diphosphate ◽

Multiple Electrode Aggregometry ◽

Vasp Phosphorylation ◽

Function Analyzer ◽

Platelet Function Analyzer ◽

Multiple Electrode

SummarySeveral test systems exist for assessment of platelet function in patients under clopidogrel or aspirin therapy. The objective was to cross-validate the Multiple Electrode Aggregometry (MEA) with three other methods used for determining platelet reactivity under treatment with clopidogrel and aspirin. Platelet function was assessed by the MEA, Vasodilator Stimulated Phosphoprotein (VASP) phosphorylation assay, Platelet Function Analyzer-100 (PFA-100) and the Cone and Platelet Analyzer. Measurements were performed in blood from nine healthy volunteers at baseline, 2, 4, 6 and 72 hours after clopidogrel and aspirin loading. The apparent effect size for clopidogrel and aspirin was greatest for the MEA: treatment induced a 19-fold difference in the arachidonic acid-induced platelet aggregation and an 11-fold difference in the adenosine diphosphate-induced platelet aggregation before/after treatment. For comparison, aspirin and clopidogrel induced only 2.0– to 2.6 -fold changes in other tests (VASP assay, Cone and Platelet Analyzer and PFA-100). Maximal effects were seen 2 hours after aspirin loading and shorter than 72 hours after clopidogrel loading. In conclusion, aspirin and clopidogrel produce stronger signals in the MEA compared to several other methods.

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