Thrombelastography (TEG) measured by the TEG5000 Hemostasis Analyzer is an established but the labor-intensive method for assessing global hemostasis. The first true point-of-care TEG, the TEG6s ...system, uses resonance-frequency viscoelasticity measurements and a disposable multi-channel microfluidic cartridge to assess hemostasis and response to antiplatelet therapy. TEG assays (n = 5,100) were performed on the blood of healthy volunteers (n = 157) and patients undergoing coronary revascularization at three hospitals (n = 300). The results from the TEG6s were compared with the conventional TEG5000 in accordance with Clinical and Laboratory Standards Institute (CLSI) and FDA recommendations. Precision testing was conducted using blood from healthy donors, all assays were run for 5 consecutive days in duplicate using multiple operators, lots, and instruments. Reference ranges were comparable between the TEG systems.
Deming regression analysis demonstrated a strong correlation between the two systems for the standard hemostasis tests (R r = 0.932, MA r = 0.972, LY30 r = 0.938). Method comparison analysis showed an acceptable agreement between PlateletMapping (PM) assays for measuring arachidonic acid (indicator of aspirin response)- and adenosine diphosphate (indicator of P2Y
12
inhibitor response)-induced platelet aggregation (total agreement = 90%, and 72%, respectively). TEG6s precision testing yielded low variability (CV 0-13%) in all measures. The new point-of-care TEG6s is associated with greater ease of use than the TEG5000 and provides precise results. The results correlated between methods for all variables. TEG6s is a promising device for near-patient hemostasis monitoring and future trials of personalized therapy designed to reduce bleeding and thrombosis.
Summary
The guideline writing group was selected to be representative of UK‐based medical experts. MEDLINE was systematically searched for publications in English up to the Summer of 2010 using key ...words platelet, platelet function testing and platelet aggregometry. Relevant references generated from initial papers and published guidelines/reviews were also examined. Meeting s were not included. The writing group produced the draft guideline, which was subsequently revised and agreed by consensus. Further comment was made by members of the Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. The guideline was then reviewed by a sounding board of approximately 40 UK haematologists, the British Committee for Standards in Haematology (BCSH) and the British Society for Haematology Committee and comments incorporated where appropriate. Criteria used to quote levels and grades of evidence are as outlined in appendix 7 of the Procedure for Guidelines Commissioned by the BCSH http://www.bcshguidelines.com/BCSH_PROCESS/EVIDENCE_LEVELS_AND_GRADES_OF_RECOMMENDATION/43_GRADE.html. The objective of this guideline is to provide healthcare professionals with clear guidance on platelet function testing in patients with suspected bleeding disorders. The guidance may not be appropriate to patients receiving antiplatelet therapy and in all cases individual patient circumstances may dictate an alternative approach.
Accurate assessment of blood haemostasis is essential for the management of patients who use extracorporeal devices, receive anticoagulation therapy or experience coagulopathies. However, current ...monitoring devices do not measure effects of haemodynamic forces that contribute significantly to platelet function and thrombus formation. Here we describe a microfluidic device that mimics a network of stenosed arteriolar vessels, permitting evaluation of blood clotting within small sample volumes under pathophysiological flow. By applying a clotting time analysis based on a phenomenological mathematical model of thrombus formation, coagulation and platelet function can be accurately measured in vitro in patient blood samples. When the device is integrated into an extracorporeal circuit in pig endotoxemia or heparin therapy models, it produces real-time readouts of alterations in coagulation ex vivo that are more reliable than standard clotting assays. Thus, this disposable device may be useful for personalized diagnostics and for real-time surveillance of antithrombotic therapy in clinic.
Summary
Background
Diagnosis of inherited platelet function disorders (IPFDs) is important for appropriate management and to improve epidemiologic and clinical knowledge. However, there remains a ...lack of consensus on the diagnostic approach.
Objectives
To gain knowledge on the current practices for the diagnosis of IPFD worldwide.
Methods
A 67‐item questionnaire was distributed to the ISTH members and to the members of several national hemostasis and thrombosis societies.
Results
A total of 202 laboratories from 37 countries participated in the survey. The most frequent criterion to define patients with a suspected IPFD was a history of mucocutaneous bleeding and no acquired cause, but heterogeneity on the identification criteria was evident. Only 64.5% of respondents performed a direct clinical interview. On average, each laboratory studied 72 patients per year. The most commonly used laboratory equipment were the light‐transmission aggregometer, the Platelet Function Analyzer‐100, and the flow cytometer. Screening tests were platelet count, peripheral blood smear, light‐transmission aggregometry, and Platelet Function Analyzer‐100. Second‐step tests were flow cytometry, molecular genetic analysis, and electron microscopy. Methodologies varied widely. In total, ~ 14 000 patients were investigated yearly and 60% turned out to not have a defect. Of the remaining 40%, only 8.7% received a diagnosis at a molecular level.
Conclusions
Many laboratories worldwide are involved in the diagnosis of IPFD. A large fraction of the patients studied remain without a diagnosis. A high variability in the diagnostic approaches is evident.
The level of platelet aggregation, measured with light transmission aggregometry (LTA) in platelet rich plasma (PRP), has been shown to predict outcomes after percutaneous coronary intervention ...(PCI). However, measuring parameters of platelet function with LTA is time consuming and weakly standardized. Thus, a fast and standardized method to assess platelet function after clopidogrel treatment would be of great value for clinical practice. A new method, multiple electrode platelet aggregometry (MEA), to rapidly measure platelet aggregation in whole blood has recently been developed. The aim of this study was to assess parameters of platelet function with MEA and LTA before and after administration of 600 mg clopidogrel. Blood samples from 149 patients scheduled for coronary angiography were taken after clopidogrel treatment; in addition, in 60 of the patients samples were available before clopidogrel treatment. ADP-induced platelet aggregation was measured with LTA and simultaneously in whole blood with MEA on the Multiplate analyzer. Platelet aggregation measured with MEA decreased significantly after clopidogrel treatment (P < 0.0001). ADP-induced platelet aggregation assessed with MEA and LTA correlated significantly (Spearman rank correlation coefficient = 0.71; P < 0.0001). The results of MEA, a fast and standardized method to assess the platelet response to ADP prior to and after clopidogrel treatment, correlate well with LTA.
Platelet Function Tests Lordkipanidzé, Marie
Seminars in thrombosis and hemostasis,
04/2016, Volume:
42, Issue:
3
Journal Article
Peer reviewed
Open access
Traditionally developed for diagnosis of bleeding disorders, platelet function assays have become increasingly used in basic research on platelet physiology, in phenotype-genotype associations in ...bleeding disorders, in drug development as surrogate endpoints of efficacy of new antiplatelet therapy, and to an extent, in the monitoring of antiplatelet therapy in clinical practice to predict thrombotic and bleeding risk. A multiplicity of platelet function assays is available to measure the level of platelet activity in various settings. These include assays that are restricted to a specialized laboratory as well as point-of-care instruments meant to investigate platelet function at patient bedside. Unlike tests that determine a defined quantity or measurement of a clinical biomarker (e.g., cholesterol or blood pressure), platelet function testing assesses the dynamics of living cells, which immediately presents a series of unique problems to any laboratory or clinic. This article presents currently used platelet function assays and discusses important variables to take into account when performing these assays, including preanalytical issues and difficulties in interpreting platelet function test results.
Platelet function tests: a comparative review Paniccia, Rita; Priora, Raffaella; Liotta, Agatina Alessandrello ...
Vascular health and risk management,
01/2015, Volume:
11, Issue:
default
Journal Article
Peer reviewed
Open access
In physiological hemostasis a prompt recruitment of platelets on the vessel damage prevents the bleeding by the rapid formation of a platelet plug. Qualitative and/or quantitative platelet defects ...promote bleeding, whereas the high residual reactivity of platelets in patients on antiplatelet therapies moves forward thromboembolic complications. The biochemical mechanisms of the different phases of platelet activation - adhesion, shape change, release reaction, and aggregation - have been well delineated, whereas their complete translation into laboratory assays has not been so fulfilled. Laboratory tests of platelet function, such as bleeding time, light transmission platelet aggregation, lumiaggregometry, impedance aggregometry on whole blood, and platelet activation investigated by flow cytometry, are traditionally utilized for diagnosing hemostatic disorders and managing patients with platelet and hemostatic defects, but their use is still limited to specialized laboratories. To date, a point-of-care testing (POCT) dedicated to platelet function, using pertinent devices much simpler to use, has now become available (ie, PFA-100, VerifyNow System, Multiplate Electrode Aggregometry MEA). POCT includes new methodologies which may be used in critical clinical settings and also in general laboratories because they are rapid and easy to use, employing whole blood without the necessity of sample processing. Actually, these different platelet methodologies for the evaluation of inherited and acquired bleeding disorders and/or for monitoring antiplatelet therapies are spreading and the study of platelet function is strengthening. In this review, well-tried and innovative platelet function tests and their methodological features and clinical applications are considered.
In the context of interventional cardiology, platelet function testing may identify patients treated with P2Y12-inhibitors at an increased risk of mortality, thrombosis and bleeding. Several whole ...blood point-of-care platelet function analyzers are available; however, inter-device differences have not been examined systematically. To compare three platelet function tests under standardized in vitro conditions. Healthy volunteer (n = 10) blood samples were spiked with increasing concentrations of ticagrelor (0–7500 ng/mL) and/or ASA (0–3280 ng/mL), measured on three platelet function analyzers (TEG
®
6s, Multiplate
®
, and VerifyNow
®
) and respective Effective Concentration (EC) levels EC10, EC50 and EC90 were calculated. Repeatability was assessed in a separate group of pooled blood samples (n = 10) spiked with ticagrelor at EC10, EC50 and EC90. ASA had no impact on ADP-activated channels for all three devices. TEG
®
6s was able to distinguish (p ≤ 0.05) between all ticagrelor EC zones; VerifyNow
®
and Multiplate
®
were able to distinguish between three and two zones, respectively. Multiplate
®
showed the largest window between EC10 and EC90 (19–9153 ng/mL), followed by TEG
®
6s (144–2589 ng/mL), and VerifyNow
®
(191–1100 ng/mL). Drug effect models distribution of disagreements were identified for TEG
®
6s (5.0%), VerifyNow
®
(8.3%), and Multiplate
®
(13.3%). TEG
®
6s showed the smallest average coefficient of variation between EC conditions (5.1%), followed by Multiplate
®
(14.1%), and VerifyNow
®
(17.7%). Linear models could be generated between TEG
®
6s and Multiplate
®
, but not VerifyNow
®
. Significant differences were found between whole blood point-of-care platelet function analyzers and the clinical impact of these differences needs to be further investigated.
Background
Platelet function testing may be warranted to assess response to aspirin and clopidogrel.
Hypothesis/Objectives
To evaluate the effects of aspirin, clopidogrel, or combination therapy ...using 3 platelet function tests: Multiplate Analyzer (MP), Platelet Function Analyzer‐200 (PFA), and Plateletworks (PW).
Animals
Six healthy laboratory Beagles.
Methods
Randomized double‐blind placebo‐controlled study (crossover design). Dogs were given aspirin 1 mg/kg, clopidogrel 2 mg/kg, or combination therapy for 1 week each, with a washout period of 2 weeks. Platelet function was assessed on days 0 and 7 of each phase using MP (adenosine diphosphate ADP, arachidonic acid AA, collagen COL agonists), PFA (P2Y, COL‐ADP CADP, COL‐Epinephrine CEPI cartridges), and PW (ADP, AA, COL agonists). Platelet counts were obtained with impedance and optical counters.
Results
For MP, mean aggregation was decreased for COL and AA with combination therapy and for ADP with all treatments. For PFA, mean CT was increased for the CEPI cartridge with aspirin; and for the P2Y and CADP cartridges with clopidogrel or combination therapy. More dogs receiving clopidogrel showed an increase in PFA CT using the P2Y than the CADP cartridge. For PW, mean aggregation was decreased for AA with all treatments; for ADP with clopidogrel or combination therapy; and for COL with clopidogrel. The PW results with the 2 hematology counters showed almost perfect agreement.
Conclusion and Clinical Importance
All platelet function tests detected treatment effects in some dogs and may have utility for monitoring therapy.
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