Basora M, Gomar C, Escolar G, Pacheco M, Fita G, Rodriguez E, Ordinas A
Department of Anesthesiology, Hospital Clínic, University of Barcelona, Spain.
J Cardiothorac Vasc Anesth. 1999 Aug;13(4):382-7. doi: 10.1016/s1053-0770(99)90207-0.
To determine whether two low-dose regimens of aprotinin influence platelet function.
Prospective, randomized, single-blinded trial.
University teaching hospital performing 600 cardiac operations per year.
Fifty-nine patients scheduled for cardiac surgery undergoing cardiopulmonary bypass (CPB) of expected duration of 60 minutes or more.
Patients were randomized into three groups. Group C (control) included 21 patients who did not receive aprotinin. In group A2, 17 patients received 14,286 kallikrein inhibitor units (KIU)/kg (2 mg/kg) of aprotinin before surgery, followed by a continuous infusion of 7,143 KIU/kg/h (1 mg/kg/h) until the end of surgery. In group A4, 19 patients received 28,572 KIU/kg (4 mg/kg) of aprotinin before surgery, followed by the same infusion.
Postoperative bleeding and transfusion requirements were significantly less in group A4. Changes in platelet number and function were similar in the three groups. Platelet aggregation was assessed in four periods: before CPB (T1), post-CPB (T2), and 2 hours (T3) and 4 hours (T4) after CPB. Platelet aggregation induced by adenosine diphosphate, 1 and 2 micromol/L; ristocetin, 1 mg/mL; and arachadonic acid (AA), 1.4 mmol/L, decreased at T2 (p < 0.001) in all groups, and for the ristocetin and AA groups, remained at less than baseline values at T3 and T4. In five patients from each group, platelet receptors for glycoprotein IIb-IIIa (GPIIb-IIIa) and expression of platelet activation markers, guanosine monophosphate 140 (GMP-140) and lysosomal protein, were measured by flow cytometry before and after CPB. Modifications in the expression of GPIIb-IIIa were always modest and without statistical significance. Platelet activation markers, GMP-140 or lysosomal protein, nearly doubled from baseline to post-CPB only in the A4 group, whereas they remained stable in both other groups (statistically not significant).
The two regimens of aprotinin, both considered low dosage, did not exert a protective effect on platelet function. Neither dose produced changes in platelet GPIIb-IIIa or platelet activation markers. However, bleeding and transfusion needs were decreased.
确定两种低剂量抑肽酶方案是否会影响血小板功能。
前瞻性、随机、单盲试验。
每年进行600例心脏手术的大学教学医院。
59例计划接受心脏手术且预计体外循环（CPB）持续时间达60分钟或更长时间的患者。
患者被随机分为三组。C组（对照组）包括21例未接受抑肽酶的患者。A2组17例患者在手术前接受14286激肽释放酶抑制单位（KIU）/kg（2mg/kg）的抑肽酶，随后持续输注7143KIU/kg/h（1mg/kg/h）直至手术结束。A4组19例患者在手术前接受28572KIU/kg（4mg/kg）的抑肽酶，随后进行相同的输注。
A4组术后出血和输血需求显著减少。三组患者血小板数量和功能的变化相似。在四个时间段评估血小板聚集情况：CPB前（T1）、CPB后（T2）以及CPB后2小时（T3）和4小时（T4）。在所有组中，由1和2微摩尔/升二磷酸腺苷、1毫克/毫升瑞斯托霉素以及1.4毫摩尔/升花生四烯酸（AA）诱导的血小板聚集在T2时降低（p<0.001），对于瑞斯托霉素和AA组，在T3和T4时仍低于基线值。对每组中的5例患者，在CPB前后通过流式细胞术测量糖蛋白IIb-IIIa（GPIIb-IIIa）的血小板受体以及血小板活化标志物鸟苷单磷酸140（GMP-140）和溶酶体蛋白的表达。GPIIb-IIIa表达的变化始终较小且无统计学意义。血小板活化标志物GMP-140或溶酶体蛋白仅在A4组中从基线到CPB后几乎翻倍，而在其他两组中保持稳定（无统计学意义）。
两种抑肽酶方案，均被视为低剂量，对血小板功能未发挥保护作用。两种剂量均未引起血小板GPIIb-IIIa或血小板活化标志物的变化。然而，出血和输血需求减少。
