Pharmacological modulation of thalassemia platelet mediators and functions

การควบคุมสารสื่อและการทำงานของเกร็ดเลือดในผู้ป่วยธาลัสซีเมีย

Name: Vipa Chaipatikul

MeSH: Blood Platelet Disorders

MeSH: Dipyridamole -- therapeutic use

MeSH: Platelet Aggregation

MeSH: Splenectomy

MeSH: Thalassemia

Abstract: The defects that occurred to the platelets in a splenectomized thalassemia patient (NiT) were closely followed in this study. This repressents an effort to avoid the uncontrollable variation of data derived from studies with groups of subjects, in which the "thalassemia syndrome" represents a wide spectrum of pathological defects. Blood samples were taken into siliconzied-glass tubes containing sodium citrate (9:1). Impedence aggregation was performed in the half diluted whole blood with normal saline. Platelet counts in the whole blood and in the plateiet rich plasma were respectively readed from the Technicon H-1 and Coulter-thrombocyte counters. The ratio of pletelet counts in the freshly prepared PRP (F-WS PRP) to that in the PRP from 2-hous settled blood(S-WB PRP) was recorded as FS-Platelet Count Ratio, representing the "integrity index" of platelets. Conventional optical aggregation was performed in both F-WB PRP and 5-WB PRP with a Both-type aggrego-meter. The release of ATP from the activated platelets was simultaneously monitored of the emitted chemiluminescent light from the coupline reaction of ATP and firefly luciferase. It was found that splenectomized thalassemia blood was in hyperaggregated state. Spontaneous eggregation frequently occurred following mechanical stimulation and the responsiveness of the whole blood to ADP stimulation was greatly enhanced in the impedance method. The freagility of platelets in splenectomized thalassemia blood was further supported by the lower value of F5-Platelet Count Ratio. In addition, the lesser extent of optical aggregation in F-WB PRP was in contrast with that of the S-WB PRP suggesting that contamination of RBCs, debris cells and microaggregated platelets in the F-WB PRP might be the likely responsible factors. Blood samples taken following an ingestion of 50 mg dipyridamole (1-hour after) started to show a number of changes that occurred to some detectable parameters. For an acute effect of dipyridamole, the Add-stimulated release of ATP from the platelets was the very first parameter affected. The enhanced release of ATP was abruptly reduced and disappeared within 24 hours. The FS-Platelet Count Ratio and Whole blood response to ADP stimulation were unaffected with brief dispyridamole exposure. Other parameters were gradually improved following prolonged dipyridamole treatment (with a daily dose of 50 or 100 mg dipyridamole) for upto 2 months. The effectiveness of therapy was slowly faded away as the patient was withdrawn from medication. This study suggested that thalassemia platelets were under continuous presures (stimulation) in the body and continuously destroyed by the pathological mediators resulting from the ineffective erythropoiesis, short-life red blood cells and heavily iron-overload in the tissues. The acute effect of dipyridamole suggested that short-life chemical mediators that modulate platelet funchtion were affected. Prolonged dipyridamole treatment could modulete the excessive expression of those pathological mediators and further lead to the eventual control in the progression of pathological process and thus the improvement of those derived parameters in the splenectomized thalassemia. Its concluded from this study that the controlling mechanism in the release of pletelet mediators is the likely primary site of defect in the splenectomized thal-assemia pletelets. Should such pathway is properly modulated then the griveous consequences could be accordingly controlled. This fiding provides a rational therapuetic basis for further assessment of dipyridamole in thalassumia.

Mahidol University. Mahidol University Library and Knowledge Center

Address: NAKHONPATHOM

Email: liwww@mahidol.ac.th

Name: Udom Chantharaksri

Role: Thesis Advisors

Name: Suthat Fucharoen

Role: Thesis Advisors

Name: Kovit Pattanapanyasat

Role: Thesis Advisors

Created: 1990

Modified: 2018-04-25

Issued: 2018-04-25

วิทยานิพนธ์/Thesis

application/pdf

eng

DegreeName: Master of Science

Level: Master's Degree

Descipline: Pharmacology

Grantor: Mahidol University

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