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。