Ativação plaquetária e outros fatores condicionantes da resposta à transfusão de plaquetas

Abstract

Platelet transfusions (PT) play an important role in the treatment of hemato-oncological patients with thrombocytopenia, in particular for their contribution in supporting the therapy. However, the response to PT is hightly variable and often multifactorial, depending on platelet-related or patient-related variables. In some cases, the clinical success is very limited, as patients develop a state of platelet refractoriness. In clinical daily practice, assessment of the effectiveness of platelets transfusion in thrombocytopenic patients is based primarily on the clinical response as well as on the evaluation of the increase in platelet counts, using the corrected increment count and the percentage of platelets recovery, but the functional aspect of the transfused platelets are usually not taken in consideration. P-selectin (CD62P) is a good indicator of platelet activation. In quiescent platelets, this protein is located on the inner wall of the α-granules. Platelet activation results in “membrane flipping” where the platelet releases α granules and the inner walls of the granules are exposed on the outside of the platelet; because of that, CD62P becomes expressed on the platelet membrane, leading to recognition and destruction of platelets by macrophages. Thus, CD62P expression on the platelet surface correlates with platelet activation and the accelerated destruction of circulating platelets. In this work, we reviewed the literature on the platelet structural and functional aspects, the causes of thrombocytopenia, the preparation of platelet concentrates, as well as the factors affecting the response to platelet transfusion, the evaluation of this response and the development of a refractoriness state. In addition, we have also investigated whether the effectiveness of platelet transfusion, as measured by the corrected platelet count increment, is related to the clinical and demographic profile of transfused patients, and with the characteristics of the transfused platelets. For the latter, we have analyzed, amongst other aspects, the storage time, the similarity and compatibility between blood groups from donors and recipients as well as, the baseline platelet activation and the platelet response to thrombin, evaluated, among others, by the expression of CD62P quantified by flow cytometry. Thirteen hemato-oncological patients were studied, from which 20% were refractory to platelet transfusion. Regarding the increase in corrected platelet count increment 1 hour after transfusion, there was no statistically significant association with the demographic and clinical factors analyzed. Moreover, the activation of the transfused platelets was higher than expected, probably as a consequence of the processing method, and their responsiveness to thrombin decreased with the storage time. It was further observed that there was a positive correlation between the responsiveness to thrombin of the transfused platelets and the responsiveness to thrombin of the platelets from venous blood collected 1 hour after PT. Key-words: Platelets, Thrombocytopenia, Platelet transfusion, Platelet activation, Platelet refractoriness, Flow cytometry, Platelet glycoproteins, P-selectin

Date of Award	Aug 2012
Original language	Portuguese
Awarding Institution	Universidade Católica Portuguesa
Supervisor	Margarida Lima (Supervisor)