Gurbel Paul A, Galbut Brian, Bliden Kevin P, Bahr Raymond D, Roe Matthew T, Serebruany Victor L, Gibler W Brian, Christenson Robert H, Ohman E Magnus
Sinai Center for Thrombosis Research, Baltimore, Maryland 21215, USA.
J Thromb Thrombolysis. 2002 Dec;14(3):213-9. doi: 10.1023/a:1025048726396.
Receptors other than GP IIb/IIIa may mediate leukocyte-platelet-endothelial interactions that obstruct the microvasculature in acute coronary syndromes (ACS) and cause microinfarcts. The effect of eptifibatide on these receptors was investigated in a substudy of the EARLY Trial.
Patients received early (in the Emergency Department, n = 27) or late (12-24 h, n = 28) eptifibatide. Ten platelet receptors by flow cytometry and platelet aggregation (10 micromol/L ADP) were measured serially at baseline, and at 3, 6, 12 and 24 h after randomization.
Platelet aggregation was rapidly inhibited by early eptifibatide therapy (baseline, 72 +/- 20%; 3 h post, 7 +/- 9%; p < 0.001). No significant differences were seen in either group for CD 31, CD 63, CD 107a, CD 107b, CD 41 (GPIIb/IIIa expression), or CD 62p. Leukocyte-platelet aggregate formation (mean fluorescense intensity) trended upward after presentation (early baseline, 43.1 +/- 26.0 versus 65.8 +/- 35.6, p =.09). PAC-1 (GP IIb/IIIa activity), CD 51/61 (vitronectin receptor) and CD 42b (GP Ib) were inhibited by eptifibatide (p <.05).
In Emergency Department patients with unstable angina, early eptifibatide rapidly and profoundly inhibits platelet aggregation and reduces GP IIb/IIIa activity and the expression of CD51/61 and CD 42b; the latter two effects may also contribute to the drug's anti-thrombotic effect. However, platelet-leukocyte aggregate formation, a marker of platelet activity rises within 24 h after presentation despite eptifibatide therapy and is a potential mechanism for microvascular obstruction.
除糖蛋白IIb/IIIa外的其他受体可能介导白细胞-血小板-内皮细胞相互作用，这种相互作用会阻塞急性冠状动脉综合征（ACS）的微血管并导致微梗死。在EARLY试验的一项子研究中，对依替巴肽对这些受体的作用进行了研究。
患者接受早期（在急诊科，n = 27）或晚期（12 - 24小时，n = 28）依替巴肽治疗。通过流式细胞术测定10种血小板受体，并在基线以及随机分组后3、6、12和24小时连续测量血小板聚集（10微摩尔/升二磷酸腺苷）。
早期依替巴肽治疗可迅速抑制血小板聚集（基线时为72±20%；给药后3小时为7±9%；p < 0.001）。两组在CD 31、CD 63、CD 107a、CD 107b、CD 41（糖蛋白IIb/IIIa表达）或CD 62p方面均未观察到显著差异。白细胞-血小板聚集体形成（平均荧光强度）在就诊后呈上升趋势（早期基线时为43.1±26.0，而后期为65.8±35.6，p = 0.09）。依替巴肽可抑制PAC - 1（糖蛋白IIb/IIIa活性）、CD 51/61（玻连蛋白受体）和CD 42b（糖蛋白Ib）（p < 0.05）。
在急诊科不稳定型心绞痛患者中，早期依替巴肽可迅速且显著抑制血小板聚集，并降低糖蛋白IIb/IIIa活性以及CD51/61和CD 42b的表达；后两种作用可能也有助于该药物的抗血栓作用。然而，尽管采用了依替巴肽治疗，但血小板-白细胞聚集体形成（血小板活性的一个标志物）在就诊后24小时内仍会升高，这是微血管阻塞的一个潜在机制。
