The influence of low-dose aspirin and hydroxyurea on platelet-leukocyte interactions in patients with essential thrombocythemia.
Essential thrombocythemia is associated with an increased risk of thromboembolic complications. Recently, there has been a growing evidence that platelet-leukocyte interactions may contribute to pathogenesis of thrombosis in essential thrombocythemia. Low-dose aspirin (ASA) is generally recommended in the therapy of low-risk patients for thrombosis, whereas hydroxyurea in high-risk patients. The aim of the present study was to determine the effect of ASA and hydroxyurea on platelet, leukocyte functions and on formation of platelet/leukocyte conjugates in vivo in patients with essential thrombocythemia. Markers of platelet and leukocyte activation were assessed in 40 patients with essential thrombocythemia at diagnosis and in 20 controls using flow cytometry assays. In second part of the study, the tests were repeated after either ASA treatment (in 25 low-risk patients) or hydroxyurea therapy (in 15 high-risk patients). On diagnosis, significantly elevated expression of P-selectin on platelets (4.98 +/- 3.31 vs. 0.99 +/- 0.69 P < 0.001) and increased percentage of platelet-polymorphonuclear leukocyte CD11b/CD42b conjugates [10.12 (4.21-31.22) vs. 3.17 (1.43-5.99) P < 0.001] and platelet-monocyte CD11b/CD14/CD61 conjugates [36.62 (12.23-51.62) vs. 13.86 (7.14-23.51) P < 0.001] were found in essential thrombocythemia group as compared with the healthy control group. Therapy with ASA significantly reduced platelet-polymorphonuclear leukocyte [10.72 (4.21-26.97) vs. 8.12 (1.13-26.94) P < 0.05] and platelet-monocyte conjugates [38.6 (13.45-51.62) vs. 25.76 (13.52-45.02) P < 0.05]. Surprisingly, therapy with hydroxyurea was poorly effective in reduction of platelet/leukocyte conjugates. These data document an increased platelet and leukocyte activation at the time of diagnosis. This is the first report showing enhanced platelet-leukocyte aggregate formation in low-risk essential thrombocythemia patients and the efficacy of ASA in its reduction.
Treliński
Jacek
J
Department of Hematology, Medical University of Lodz, Lodz, Poland. jtrel2001@yahoo.com
Tybura
Marzena
M
Smolewski
Piotr
P
Robak
Tadeusz
T
Chojnowski
Krzysztof
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D016022:Case-Control Studies; D002450:Cell Communication / Q000187:drug effects*; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage*; D007962:Leukocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018570:Risk Assessment; D013920:Thrombocythemia, Essential / Q000188:drug therapy*; D013927:Thrombosis / Q000209:etiology
D015415:Biomarkers; D001241:Aspirin; D006918:Hydroxyurea