From the Università Vita Salute San Raffaele.
Advanced Heart Failure and Mechanical Circulatory Support Program, San Raffaele Scientific Institute.
ASAIO J. 2020 Apr;66(4):415-422. doi: 10.1097/MAT.0000000000001064.
We characterized the biologic background of prothrombotic platelet function in the setting of durable left ventricular assist devices (LVADs) evaluating the role of different antithrombotic regimens. Platelet-mediated thrombin generation was quantified using the Platelet Activity State (PAS) Assay and the Thrombin Generation Test (TGT) in 78 patients implanted with the HeartMate II (n = 10, 13%), the HeartMate 3 (HM3) (n = 30, 38%), or the HVAD (n = 38, 49%) and managed with oral anticoagulation plus aspirin (n = 46, 59%) or anticoagulation alone (n = 32, 41%). Coagulation parameters (platelet count, International Normalized Ratio (INR), activated Partial Thromboplastin Time, Fibrinogen and D-Dimer levels) and hemolysis (lactate dehydrogenase levels [LDH]) were also recorded to comprehensively characterize the hemostatic profile in the two groups. In patients without aspirin, the PAS assay revealed low-intensity increase in platelet prothrombinase activity (1.11-fold, p = 0.03). Similarly the TGT revealed moderate higher platelet reactivity when compared with patients receiving aspirin, consistent with reduction in lag time (0.87-fold, p < 0.001), increase in peak of thrombin generation (1.5-fold, p = 0.002) and thrombin generation rate (2-fold, p = 0.02), but comparable endogenous thrombin potential (p = 0.50). Coagulation parameters and LDH were comparable in the two groups (p > 0.05). Moreover, no differences were noted in platelet prothrombinase activity of patients implanted with the HM3 or HVAD. Our results suggest that, in the setting of durable LVADs, aspirin minimally modulates the biochemical pathway of platelet-mediated thrombin generation. Accordingly, re-evaluation of current antithrombotic management criteria in patients stratified according to bleeding/thromboembolic risk might be safe and beneficial to prevent adverse events.
我们研究了在持久性左心室辅助装置（LVAD）中，不同抗血栓治疗方案对促血栓形成血小板功能的生物学背景。我们采用血小板活性状态（PAS）检测和血栓生成检测（TGT），对 78 名植入 HeartMate II（n=10，13%）、HeartMate 3（HM3）（n=30，38%）或 HVAD（n=38，49%）的患者进行了血小板介导的凝血酶生成情况评估，并对接受口服抗凝加阿司匹林治疗（n=46，59%）或仅抗凝治疗（n=32，41%）的患者进行了评估。我们还记录了凝血参数（血小板计数、国际标准化比值（INR）、活化部分凝血活酶时间、纤维蛋白原和 D-二聚体水平）和溶血（乳酸脱氢酶水平[LDH]），以全面描述两组患者的止血特征。在未使用阿司匹林的患者中，PAS 检测显示血小板凝血酶原酶活性呈低强度增加（1.11 倍，p=0.03）。同样，与接受阿司匹林治疗的患者相比，TGT 显示血小板反应性较高，这与凝血酶生成的延迟时间减少（0.87 倍，p＜0.001）、凝血酶生成峰值增加（1.5 倍，p=0.002）和凝血酶生成率增加（2 倍，p=0.02）有关，但内源性凝血酶潜力相当（p=0.50）。两组的凝血参数和 LDH 相似（p＞0.05）。此外，植入 HM3 或 HVAD 的患者的血小板凝血酶原酶活性没有差异。我们的研究结果表明，在持久性 LVAD 中，阿司匹林最小程度地调节了血小板介导的凝血酶生成的生化途径。因此，根据出血/血栓栓塞风险对患者进行分层，重新评估当前的抗血栓治疗管理标准可能是安全和有益的，可以预防不良事件的发生。
