Use of the PFA-100 apparatus to assess platelet function in patients undergoing PTCA during and after infusion of c7E3 Fab in the presence of other antiplatelet agents.

The PFA-100 (Dade) is a new functional whole blood analyzer, the accuracy and reliability of which have been evaluated in von Willebrand disease and during acetyl salicylate acid therapy. This new test has the advantages of rapidity and simplicity. It may be useful to monitor new antiplatelet agents, such as GPIIb/IIIa receptor antagonists. The objective of this study was to assess the PFA-100 in comparison with aggregometry and with the percentage of blockaded receptors GPIIb/IIIa during and after c7E3 Fab infusion in fifteen patients undergoing PTCA. Our results showed a change of closure time values from normal to abnormal within a small margin of flow cytometric values (60-75% of blockaded receptors), and moreover a variable platelet response to long-term low dose aspirin treatment in agreement with aggregometry. No influence with heparin was observed. In conclusion, this study shows that PFA-100 may be helpful in the decision making for additional antiaggregant therapy before PTCA or in monitoring long-term GPIIb/IIIa receptor antagonist treatment.

[Platelet-leukocyte interactions in coronary heart disease: pathophysiology, clinical relevance, pharmacological modulation]. / Interactions leucoplaquettaires au cours de l'insuffisance coronarienne. Physiopathologie, pertinence clinique, modulation pharmacologique.

The interactions between leukocytes and endothelial cells have been studied extensively under conditions of ischemia and reperfusion. In contrast, attraction of leukocytes by platelets at the site of damage is poorly understood. This recruitment facilitates inflammation and atherogenesis. Studies performed ex vivo in coronary artery disease show that neutrophil-platelet adhesion increases in unstable angina, coronary angioplasty and coronary artery bypass surgery, in comparison with stable angina. Experimental works have shown the major role of platelet P-selectin in platelet-leukocyte interactions, and of fibrinogen, which is the ligand of both platelets and leukocytes (B2 integrins). Studied performed in anti-GPIIb/IIIa-treated patients demonstrate a modulation, as inhibition, of platelet-leukocyte interactions. This new drug inhibits platelet function and coagulation, and moreover inflammation.

[Platelet activation in cardiology: methods, indications and therapeutic perspectives]. / Activation plaquettaire en cardiologie: méthodes, indications et perspectives thérapeutiques.

Platelet activation and/or platelet reactivity have been reported to be associated with coronary heart disease. Whole blood flow cytometry allows to analyze platelets in their physiological environment, while other assays need platelet separation, susceptible to induce platelet modifications. But flow cytometric assay also have limitations. We studied preanalytical conditions in healthy volunteers, using two monoclonal antibodies directed against CD62 and CD63 (two specific markers of platelet degranulation), and two markers which recognize GPIIb/IIIa activation (PAC1 and bound fibrinogen). Preanalytical requirements were as follow: 1) whole blood samples need antagonists of platelet activation i.e., a mixture of theophylline, adenosine and dipyridamole, since artefactual platelet activation rapidly occurred in citrated whole blood, 2) whole blood should be immediately immunolabeled when samples arrived to laboratory, because fixation did not prevent artefactual time dependent activation, 3) the stability of immunolabeling was determined for each monoclonal antibody: paraformaldehyde as fixative solution was mandatory for both CD62 and CD63, whereas it enhanced bound fibrinogen and PAC1 expression, 4) platelets can be easily identified and gating on a dual scatter (forward scatter x side scatter) dot plot with no specified labeling. The whole blood flow cytometric assay must be standardized in future clinical studies, especially regarding to preanalytical requirements.

[Interference of anaesthesia and transfusion on rheological parameters (author's transl)]. / Interférence de l'anesthésie et de la transfusion sur les paramètres rhéologiques.

This study was designed to investigate the rheological and plasmatic parameters from multiple transfused patients and patients undergoing surgery non transfused. Blood filtrability compared with the erythrocyte electrophoretic mobility shows the perturbance resulting from the delay of conservation and the importance of the transfused blood. The 2-3 DPG, ATP and oxygen-hemoglobin affinity suggest the excellent recuperation of the erythrocyte metabolic function in vitro. The rheological parameters seems to be a good mean in the supervision of red massive transfusion blood cell.