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接受经皮冠状动脉腔内血管成形术(PTCA)并使用阿昔单抗治疗的患者血小板CD62表达及血小板衍生生长因子AB(PDGFAB)分泌情况

Platelet CD62 expression and PDGFAB secretion in patients undergoing PTCA and treatment with abciximab.

作者信息

Graff J, Andries D, Elsner M, Westrup D, Bassus S, Franz N, Klinkhardt U, Harder S

机构信息

Institute of Clinical Pharmacology, Medical School of the J.W. Goethe University, Frankfurt am Main, Germany.

出版信息

Br J Clin Pharmacol. 2001 Jun;51(6):577-82. doi: 10.1046/j.1365-2125.2001.01392.x.

Abstract

AIMS

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.

METHODS

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).

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

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。

方法

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。

结果

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。

结论

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。

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