Platelet Function Monitors

Despite tremendous advances in point-of-care monitoring of plasma coagulation, bedside assessment of platelet function has remained problematic. Although platelet function influences many point-of-care coagulation monitoring methods currently in use, these platelet-mediated effects are often nonspecific and unpredictable. The ACT is influenced only by profound platelet dysfunction,^[820] and even though the TEG and Sonoclot are capable of detecting platelet abnormalities, their sensitivity and specificity are limited in terms of defining platelet dysfunction in the context of a complex perioperative coagulopathy. The standard method for identifying qualitative platelet dysfunction is laboratory-based optical aggregometry performed with specific platelet agonists in platelet-rich plasma. Unfortunately, this form of testing is technically demanding and cannot be performed at the bedside. Furthermore, alteration of platelet function by the method of sample preparation may affect the results.^[849] Flow cytometry using fluorescent-labeled antibodies provides a sensitive method for quantitating platelet activation and platelet surface receptor availability. A further advantage of this form of platelet function analysis is the ability to use whole blood, thereby minimizing the potential for blood sampling and processing artifacts. However, as with platelet aggregation studies, flow cytometry requires substantial technical expertise and laboratory-based support.

Several platelet function assays specifically designed for use at the bedside have entered clinical trials. The HemoSTATUS (Medtronic Blood Systems, Parker, CO) platelet function test exploits the ability of platelet-activating factor (PAF) to accelerate clot formation of a kaolin-activated ACT. HemoSTATUS testing is performed on the Medtronic HMS coagulation analyzer by using a six-channel kaolin ACT cartridge preloaded with serially increasing concentrations of PAF. A clot ratio is determined for each individual patient assay based on the ratio of the PAF-accelerated ACT to the standard ACT. An individual patient's clot ratio is compared with a maximal clot ratio derived from normal volunteers to provide a relative

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Currently undergoing clinical trials, the Rapid Platelet Function Analyzer (RPFA; Accumetrix, San Diego, CA) is an automated turbidimetric whole blood assay of platelet function that assesses the ability of activated platelets to bind fibrinogen-coated polystyrene beads.^[853] On addition of the test blood, thrombin receptor-activating peptide directly activates platelets within the sample, thereby stimulating expression of glycoprotein IIb/IIIa platelet surface receptors. As activated platelets bind and aggregate fibrinogen-coated beads, light transmission through the sample increases to generate a measurable signal. Although the RPFA is simple to operate and provides a rapid bedside measure of platelet function, a baseline reference measurement is required for each patient to calculate the extent of subsequent changes in platelet function, and the potential for application of this methodology in the perioperative setting remains unclear.

Plateletworks, a diagnostic assay of platelet aggregation, is performed with the Ichor hematology analyzer (Helena Labortories, Beaumont, TX). The Plateletworks assay uses a hemocytometer to perform automated platelet counts on whole blood samples collected in the presence and absence of platelet-stimulating agonists such as collagen or adenosine diphosphate. The difference in platelet counts before and after addition of the agonist provides a direct measure of platelet aggregation and is reported as percent aggregation. Although applicability of the Plateletworks assay to the perioperative setting remains to be determined, preliminary investigations have demonstrated reasonable correlations between cell counts performed with the Ichor hematology analyzer and traditional laboratory-based instruments.^[854] In addition, the Plateletworks assay has proved effective in identifying platelet dysfunction in the setting of glycoprotein IIb/IIIa antagonists and appears to correlate relatively well with laboratory-based measures of platelet aggregation.^{[855] [856]}

The PFA-100 (Platelet Function Analyzer; Dade International Inc, Miami) is unique among both laboratory-based and point-of-care platelet function monitors in that it incorporates high-shear conditions to simulate primary hemostasis after injury to a small vessel. Citrate-containing blood added to a disposable test cartridge is aspirated through a 200-µm capillary and then forced through a 150-mm aperture in a membrane containing collagen and either adenosine diphosphate or epinephrine.^[857] Exposure of platelets within the blood sample to activating agents within the membrane under high-shear conditions stimulates platelet adherence and aggregation. As the platelet plug forms, blood flow through the aperture decreases and the time to aperture occlusion is displayed as the "closure time."

Although clinical trials with this instrument remain in progress, preliminary findings have demonstrated that the PFA-100 detects both congenital and acquired disorders of platelet function with a high degree of sensitivity and specificity. ^{[858] [859]} Furthermore, the PFA-100 has proved effective as a measure of platelet function during cardiopulmonary bypass in adults, with preliminary data suggesting potential to identify postoperative coagulopathies.^{[846] [860]}

The Hemodyne Hemostasis Analyzer (Hemodyne, Richmond, VA), currently in clinical trials, specifically measures the force developed between platelets during clot formation and subsequent retraction. Using a sample of whole blood, the Hemodyne analyzer provides measures of platelet contractile force, the force produced by platelets during clot retraction, and clot elastic modulus, a measure of clot rigidity.^[861] In preliminary investigations, platelet contractile force was reduced after cardiopulmonary bypass and modestly correlated with perioperative blood loss.^[862]

Advances in our understanding of hemostasis and thrombosis at the molecular level have directly contributed to recent biotechnologic innovations in the assessment of perioperative hemostasis. Further advances in point-of-care coagulation monitoring offer the opportunity for clinicians to make more informed decisions about transfusion therapy and hemostatic drug administration to minimize bleeding in the perioperative setting.