Platelet function tests: a comparative review

Abstract

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.

Population pharmacodynamics of cilostazol in healthy Korean subjects

“…After first dosing on Day 8, blood samples were collected at 0 (predose), 1,2,3,4,6,8,10,12,13,14,15,16,18,20,22,24,36,48, and 72 hours for PK. In the case of PD, blood samples were collected at 0 hour (baseline) on Day 1 and 0 (predose), 3,6,8,10,12,15,18,20,22,24,36, 48 and 72 hours after first dosing on Day 8.…”

“…Although LTA has been considered to be the gold standard assay for the assessment of platelet functions, it has problems such that the technique is affected by pre-analytical and procedural conditions and highly skillful and experienced laboratory staff is needed. [13] On the other hand, Platelet Function Analyzer (PFA-100), which was introduced in 1994 and used closure time (CT) as a PD marker, [14] Cilostazol is used for the treatment of intermittent claudication, ulceration and pain. This study was conducted to develop a population pharmacodynamic (PD) model for cilostazol's closure time (CT) prolongation effect in healthy Korean subjects based on a pharmacokinetic (PK) model previously developed.…”

“…CT data were best described by a turnover model with a fractional turnover rate constant (K out ) inhibited by drug effects (Eff), which were represented by a sigmoid E max model used due to assay results compatible with LTA and additional benefits. [13] One of the benefits is that PFA can be used as a screening tool for existing tests and has a highly negative predictive value; when the CT result is normal in a suspected platelet disease, a further platelet function test does not need to be performed. However, no work has been reported on cilostazol's effect on CT in a Korean population.…”

Platelet testing in flow diversion: a review of the evidence

“…Advantages of multiple electrode aggregometry include its relative speed and the ability to use whole blood. 37 VerifyNow (Accumetrics) is a bedside assay that involves ADP stimulation of platelets in whole blood that bind to fibrinogen-coated polystyrene beads. As these platelet-bead complexes fall out of solution, the change in light transmittance is measured to assess the level of aggregation.…”

“…This test has become increasingly popular as it is a fully automated bedside system that eliminates the need for experienced laboratory technicians. 27,37 The platelet function analyzer (PFA-100) test attempts to mimic certain in vivo conditions. PFA-100 measures the time required for occlusion of the apparatus by platelet plugs under high shear rates while reproducing the pressure of the capillary in vivo.…”