Graff J, Andries D, Elsner M, Westrup D, Bassus S, Franz N, Klinkhardt U, Harder S
Institute of Clinical Pharmacology, Medical School of the J.W. Goethe University, Frankfurt am Main, Germany.
Br J Clin Pharmacol. 2001 Jun;51(6):577-82. doi: 10.1046/j.1365-2125.2001.01392.x.
To investigate a correlation of the platelet activation marker CD62 and secretion of the growth factor PDGF from platelets in coronary patients under therapy with the GPIIb/IIIa-inhibitor abciximab.
Flow cytometric assessment of fibrinogen binding (GPIIb/IIIa-binding site) and CD62 expression, as well as PDGF release of human platelets (immunoassay) and platelet aggregation with 20 microM ADP and 2 microg ml(-1) collagen were evaluated in nine patients with stable coronary artery disease. Patients were undergoing elective balloon angioplasty and were treated with aspirin (100 mg day(-1)), heparin (ACT < 220 s) and abciximab (bolus and infusion over 12 h). Blood samples were obtained before initiation of abciximab therapy (under aspirin and heparin) (I), 3 h after angioplasty under abciximab (II) and 12 h after termination of abciximab infusion (III).
Compared with sample I before abciximab therapy, fibrinogen binding was reduced to 37% (+/- 34 s.d., P < 0.05) (II) and 55% (+/- 40 s.d., P < 0.05) (III). Reduced fibrinogen binding also led to a significant reduction of the aggregation response to ADP (down to 37% +/- 20) and collagen (down to 0%). Mean fluorescence intensity of CD62-expression was 78 units (+/- 20 s.d.) (I), 72 units (+/- 14 s.d.) (II) and 64 units (+/- 12 s.d., P < 0.05) (III). PDGF release from isolated, washed platelets was 99 (+/- 33 s.d.) ng/10(9) platelets at (I), 82 (+/- 31 s.d.) ng/10(9) platelets and 96 (+/- 30 s.d.) ng/10(9) platelets.
The results indicate that despite a strong reduction of GPIIb/IIIa-binding and platelet aggregation, CD62 as a marker of platelet secretion and the secretion product PDGF were only slightly reduced under abciximab treatment. No direct correlation between CD62 expression and PDGF release could be demonstrated.
研究在接受糖蛋白IIb/IIIa抑制剂阿昔单抗治疗的冠心病患者中，血小板活化标志物CD62与血小板源性生长因子（PDGF）分泌之间的相关性。
对9例稳定型冠状动脉疾病患者进行了流式细胞术评估纤维蛋白原结合（糖蛋白IIb/IIIa结合位点）和CD62表达，以及人血小板的PDGF释放（免疫测定），并评估了血小板与20微摩尔ADP和2微克/毫升胶原蛋白的聚集情况。患者接受选择性球囊血管成形术，并接受阿司匹林（每日100毫克）、肝素（活化凝血时间<220秒）和阿昔单抗（静脉推注并持续输注12小时）治疗。在阿昔单抗治疗开始前（服用阿司匹林和肝素时）（I）、血管成形术后3小时（使用阿昔单抗时）（II）和阿昔单抗输注结束后12小时（III）采集血样。
与阿昔单抗治疗前的样本I相比，纤维蛋白原结合在（II）时降至37%（±34标准差，P<0.05），在（III）时降至55%（±40标准差，P<0.05）。纤维蛋白原结合减少也导致对ADP的聚集反应显著降低（降至37%±20）和对胶原蛋白的聚集反应（降至0%）。CD62表达的平均荧光强度在（I）时为78单位（±20标准差），在（II）时为72单位（±14标准差），在（III）时为64单位（±12标准差，P<0.05）。从分离、洗涤后的血小板中释放的PDGF在（I）时为99（±33标准差）纳克/10⁹血小板，在（II）时为82（±31标准差）纳克/10⁹血小板，在（III）时为96（±30标准差）纳克/10⁹血小板。
结果表明，尽管糖蛋白IIb/IIIa结合和血小板聚集大幅降低，但在阿昔单抗治疗下，作为血小板分泌标志物的CD62和分泌产物PDGF仅略有降低。未证实CD62表达与PDGF释放之间存在直接相关性。
