Vilahur G, Choi B G, Zafar M U, Viles-Gonzalez J F, Vorchheimer D A, Fuster V, Badimon J J
Cardiovascular Biology Research Laboratory, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Thromb Haemost. 2007 Jan;5(1):82-90. doi: 10.1111/j.1538-7836.2006.02245.x.
Aspirin (ASA) + clopidogrel are commonly used in acute coronary syndrome (ACS), but persistent antiplatelet effects may complicate surgery.
To study the possibility of normalizing platelet reactivity after ASA + clopidogrel treatment, 11 healthy subjects received a 325-mg ASA + clopidogrel loading dose (300 or 600 mg dependent on study arm), followed by 81 mg of ASA + 75 mg of clopidogrel daily for 2 days. Platelet reactivity was assessed by light transmittance aggregometry (LTA) [challenged by adenosine diphosphate (ADP), arachidonic acid (AA), collagen, and thrombin receptor activating peptide (TRAP)] and flow cytometry for platelet activation by GPIIb/IIIa receptor exposure pretreatment, 4 and 72 h postload. To normalize platelet reactivity, increasing amounts of pooled platelets from five untreated volunteers [volunteers (V)-platelet-rich plasma (PRP)] were added ex vivo to the subject's PRP (S-PRP). At both 4 and 72 h, 40% and 50% V-PRP were needed to overcome platelet disaggregation in the 300 or 600 mg arms, respectively, after ADP challenge; an additional 10% V-PRP fully normalized aggregation. Recovery of function was linear with each incremental increase of V-PRP. ADP-induced GPIIb/IIIa activation showed the same pattern as LTA (r = 0.74). Forty percent V-PRP was required to normalize platelet function to AA, collagen, and TRAP.
Our results suggest that the pre-operative transfusion of 10 platelet concentrate units (the equivalent of 40% V-PRP) after a 300-mg clopidogrel loading or 12.5 units (50% V-PRP) after a 600 mg loading may adequately reverse clopidogrel-induced platelet disaggregation to facilitate postoperative hemostasis. An additional 2.5 units fully normalized platelet function. The potential clinical implications of our observations could include shorter hospitalizations and reduced bleeding complications. But these observations should be fully explored in an in vivo clinical setting with clopidogrel-treated patients before and after surgery.
阿司匹林（ASA）+氯吡格雷常用于急性冠状动脉综合征（ACS），但其持续的抗血小板作用可能使手术复杂化。
为研究ASA +氯吡格雷治疗后使血小板反应性恢复正常的可能性，11名健康受试者接受325 mg ASA +氯吡格雷负荷剂量（根据研究分组为300或600 mg），随后每日服用81 mg ASA + 75 mg氯吡格雷，共2天。通过光透射聚集法（LTA）[用二磷酸腺苷（ADP）、花生四烯酸（AA）、胶原和凝血酶受体激活肽（TRAP）进行刺激]以及流式细胞术检测血小板糖蛋白IIb/IIIa受体暴露情况来评估血小板反应性，检测时间为负荷前、负荷后4小时和72小时。为使血小板反应性恢复正常，将来自5名未治疗志愿者的血小板富集血浆（V-PRP）中逐渐增加的血小板量体外加入受试者的血小板富集血浆（S-PRP）中。在4小时和72小时时进行ADP刺激后，300 mg组和600 mg组分别需要加入40%和50%的V-PRP来克服血小板解聚；再额外加入10%的V-PRP可使聚集完全恢复正常。随着V-PRP的每次递增，功能恢复呈线性关系。ADP诱导的糖蛋白IIb/IIIa激活与LTA显示出相同的模式（r = 0.74）。使血小板功能恢复至对AA、胶原和TRAP的正常反应需要40%的V-PRP。
我们的结果表明，在服用300 mg氯吡格雷负荷剂量后术前输注10个血小板浓缩单位（相当于40%的V-PRP）或服用600 mg负荷剂量后输注12.5个单位（50%的V-PRP）可能足以逆转氯吡格雷诱导的血小板解聚，以促进术后止血。再额外加入2.5个单位可使血小板功能完全恢复正常。我们观察结果的潜在临床意义可能包括缩短住院时间和减少出血并发症。但这些观察结果应在体内临床环境中，对接受氯吡格雷治疗的患者在手术前后进行充分探索。
