Assessment of Mechanical Properties of Platelets

Because they are performed on anticoagulated blood, aggregation studies cannot be used to test platelets under conditions of maximal activation, and they are incapable of assessing the role of platelets in thrombin production (36).

Assays capable of assessing platelet function during clotting and thus allowing measurement of the contribution of platelets to thrombin generation are available. Because platelets are monitored in the presence of thrombin, the test gages platelets under conditions of maximal activation. Different parameters are simultaneously assessed on one 700-^L sample of citrated whole blood. Platelet contractile force (PCF), the force produced by platelets during clot retraction, is sensitive to platelet number, Gpllb/IIIa status, and the presence of antithrombin activities. Clot elastic modulus (CEM) is sensitive to fibrinogen concentration, platelet concentration, rate of thrombin generation, and production of force by platelets. Finally, the thrombin generation time (TGT) is determined from the PCF kinetics curve (Fig. 4). Because PCF is absolutely thrombin dependent (no thrombin, no force), the initial upswing in PCF occurs at the moment of thrombin production. The combination ofPCF, CEM, and TGT measured on the same sample may allow rapid assessment of global hemostasis and the response to a variety of procoagulant and antithrombotic medications. Because PCF is relatively insensitive to fibrinogen concentration, the combination of PCF and CEM allows a degree ofseparation ofclot structure from platelet effects. However, the direct establishment of the degree of risk associated with increasingly abnormal assay values needs to be established in clinical trials.

This type of investigation has been correlated with morphological analysis of ex vivo blood clots, assessed by confocal microscopy, in patients with AMI. The impact of both platelets and IIb/IIIa receptor antagonists on physical properties of platelet-rich clots as well as fibrinolysis has been successfully investigated (37-39). These new techniques are

Fig. 5. Dynamic assessment of impact ofboth platelets and Ilb/IIIa receptor antagonists on lysis speed using confocal microscopy (38). (A) Lysis speed is decreased around platelet-rich areas. (B) The use of IIb/IIIa receptor antagonists decreases the size of platelet-rich areas, giving rise to a more homogeneous architecture of the fibrin network, which is more sensitive to the effect of lytics. The photographs represent an overlap (arrowheads) of the same clot taken 5 min apart.

Fig. 5. Dynamic assessment of impact ofboth platelets and Ilb/IIIa receptor antagonists on lysis speed using confocal microscopy (38). (A) Lysis speed is decreased around platelet-rich areas. (B) The use of IIb/IIIa receptor antagonists decreases the size of platelet-rich areas, giving rise to a more homogeneous architecture of the fibrin network, which is more sensitive to the effect of lytics. The photographs represent an overlap (arrowheads) of the same clot taken 5 min apart.

easy to perform and effective in assessing the properties of new antiplatelet agents administered in addition to recommended antithrombotic therapy in patients with ACS (Fig. 5).

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