Kuliczkowski Wiktor, Żurawska-Płaksej Ewa, Podolak-Dawidziak Maria, Cielecka-Prynda Magdalena, Karolko Bożena, Dębski Jakub, Kaaz Konrad, Protasiewicz Marcin, Prajs Iwona, Mysiak Andrzej, Wróbel Tomasz, Usnarska-Zubkiewicz Lidia
Department of Cardiology, Wroclaw Medical University, Wrocław, Poland.
Department of Pharmaceutical Biochemistry, Wroclaw Medical University, Wrocław, Poland.
Cardiol Res Pract. 2021 Apr 17;2021:6637799. doi: 10.1155/2021/6637799. eCollection 2021.
Platelet reactivity and response to antiplatelet drugs, acetylsalicylic acid (ASA) and clopidogrel, in patients with thrombocytopenia and thrombocythemia can have a potentially important effect on the outcome. The effectiveness and safety of antiplatelet drugs in such patients has not been well examined. Measuring the effect of ASA and clopidogrel on platelets could help guide the therapy. Nevertheless, platelet response to antiplatelet drugs is not routinely measured in platelet count disorders and relevant evidence is scarce.
The study aimed to measure platelet reactivity and response to ASA and clopidogrel in patients with platelet count disorders.
This was a cross-sectional study of consecutive patients hospitalized in cardiology and hematology departments in the years 2018-2019. The study included patients with thrombocytopenia (PLT < 150 G/L) and thrombocythemia (PLT > 450 G/L) on ASA or dual antiplatelet therapy (DAPT; ASA plus clopidogrel). Controls included patients on antiplatelet drugs with normal platelet count. Platelet reactivity was measured in whole blood (Multiplate aggregometer, Roche, Switzerland) using arachidonic acid (AA), adenosine-5'-diphosphate (ADP), and thrombin receptor agonist peptide-6 (TRAP) as agonists. Platelet aggregation was expressed in arbitrary units (AU). AA-induced aggregation was used as a measure of response to ASA with a cut-off above 30 AU showing high on-treatment platelet reactivity to ASA (HTPR-A). ADP-induced aggregation measured response to clopidogrel with a cut-off above 48 AU for high on-treatment platelet reactivity to clopidogrel (HTPR-C). TRAP-induced aggregation measured baseline platelet reactivity not affected by oral antiplatelet drugs.
The study included 174 patients. There were 64 patients with thrombocytopenia, 30 patients with chronic thrombocythemia, and 80 controls. All patients were on 75 mg of ASA and 32% of them additionally on 75 mg of clopidogrel due to a history of recent coronary artery angioplasty. AA- and ADP-induced aggregation was comparable between thrombocytopenic patients and controls (median (IQR) 19 (7-28) vs. 23 (15-38) for AA AU and 32 (16-44) vs. 50 (32-71) for ADP AU, respectively), while it was significantly higher in thrombocythemic patients (median (IQR) 80 (79-118) for AA AU and 124 (89-139) for ADP AU). TRAP-induced aggregation showed significantly lowest aggregation in thrombocytopenic (median (IQR) 41 (34-60) for TRAP AU) and highest in thrombocythemic patients (median (IQR) 137 (120-180) for TRAP AU). HTPR-A was frequent in thrombocythemic patients in comparison with thrombocytopenic patients and controls (60% vs. 4% vs. 15%, respectively; < 0.0002). HTPR-C was highly common in thrombocythemic patients and least common in thrombocytopenic ones in comparison with controls (80% vs. 8% vs. 40%, respectively; < 0.001).
Chronic thrombocytopenia does not significantly affect platelet reactivity and response to ASA and clopidogrel in comparison with controls. Thrombocytosis significantly increases platelet reactivity and attenuates response to both ASA and clopidogrel.
血小板减少症和血小板增多症患者的血小板反应性以及对抗血小板药物（乙酰水杨酸（ASA）和氯吡格雷）的反应可能对治疗结果产生潜在的重要影响。此类患者使用抗血小板药物的有效性和安全性尚未得到充分研究。测量ASA和氯吡格雷对血小板的作用有助于指导治疗。然而，在血小板计数异常的情况下，血小板对抗血小板药物的反应并非常规检测项目，相关证据也很匮乏。
本研究旨在测量血小板计数异常患者的血小板反应性以及对ASA和氯吡格雷的反应。
这是一项对2018年至2019年在心脏病科和血液科住院的连续患者进行的横断面研究。研究纳入了正在接受ASA或双联抗血小板治疗（DAPT；ASA加氯吡格雷）的血小板减少症（血小板计数（PLT）<150×10⁹/L）和血小板增多症（PLT>450×10⁹/L）患者。对照组包括血小板计数正常且正在接受抗血小板药物治疗的患者。使用花生四烯酸（AA）、腺苷-5'-二磷酸（ADP）和凝血酶受体激动肽-6（TRAP）作为激动剂，通过全血（Multiplate血小板聚集仪，罗氏公司，瑞士）测量血小板反应性。血小板聚集以任意单位（AU）表示。AA诱导的聚集用作衡量对ASA反应的指标，截断值高于30 AU表示对ASA的治疗期高血小板反应性（HTPR-A）。ADP诱导的聚集用于衡量对氯吡格雷的反应，截断值高于48 AU表示对氯吡格雷的治疗期高血小板反应性（HTPR-C）。TRAP诱导的聚集测量不受口服抗血小板药物影响的基线血小板反应性。
本研究共纳入174例患者。其中血小板减少症患者64例，慢性血小板增多症患者30例，对照组80例。所有患者均服用75 mg ASA，其中32%因近期有冠状动脉血管成形术史而额外服用75 mg氯吡格雷。血小板减少症患者与对照组之间，AA和ADP诱导的聚集情况相当（AA诱导的聚集：中位数（四分位间距）分别为19（7 - 28）AU和23（15 - 38）AU；ADP诱导的聚集：中位数（四分位间距）分别为32（16 - 44）AU和50（32 - 71）AU），而血小板增多症患者的上述指标显著更高（AA诱导的聚集：中位数（四分位间距）为80（79 - 118）AU；ADP诱导的聚集：中位数（四分位间距）为124（89 - 139）AU）。TRAP诱导的聚集在血小板减少症患者中显示出显著最低的聚集水平（TRAP诱导的聚集：中位数（四分位间距）为41（34 - 60）AU），在血小板增多症患者中最高（TRAP诱导的聚集：中位数（四分位间距）为137（120 - 180）AU）。与血小板减少症患者和对照组相比，HTPR-A在血小板增多症患者中更为常见（分别为60%、4%和15%；P<0.0002）。与对照组相比，HTPR-C在血小板增多症患者中极为常见，在血小板减少症患者中最少见（分别为80%、8%和40%；P<0.001）。
与对照组相比，慢性血小板减少症对血小板反应性以及对ASA和氯吡格雷的反应无显著影响。血小板增多症显著增加血小板反应性，并减弱对ASA和氯吡格雷的反应。
