Background: Persistent low-level hemolysis (LLH) during continuous-flow mechanical circulatory support is associated with subsequent thrombosis. Free hemoglobin from ongoing hemolysis scavenges nitric oxide (NO) to create an NO deficiency which can augment platelet function leading to a prothrombotic state. The phosphodiesterase-5 inhibitor, sildenafil, potentiates NO signaling to inhibit platelet function. Accordingly, we investigated the association of sildenafil administration and thrombotic events in patients with LLH during Heart Mate II support.

Methods and Results: A single-center review of all patients implanted with a Heart Mate II who survived to discharge (n=144). LLH was defined by a discharge lactate dehydrogenase level of 400 to 700 U/L. Patients were categorized as (1) LLH not on sildenafil, (2) LLH on sildenafil, (3) no LLH not on sildenafil, and (4) no LLH on sildenafil. Age, sex, platelet count, and mean platelet volume were similar between groups. Seventeen patients had either device thrombosis or ischemic stroke. Presence of LLH was associated with a greater risk of thrombosis (adjusted hazard ratio, 15; 95% confidence interval, 4.5–50; P<0.001 versus no LLH, not on sildenafil). This risk was reduced in patients with LLH on sildenafil (adjusted hazard ratio, 1.7; 95% confidence interval, 0.2–16.1; P=0.61). Device thrombosis and ischemic stroke were associated with an increase in mean platelet volume (9.6±0.5 to 10.9±0.8 fL, P<0.001). Patients with LLH not on sildenafil had a greater increase in mean platelet volume in comparison to those with LLH on sildenafil (P<0.001).

Conclusions: Sildenafil is associated with reduced device thrombosis and ischemic stroke during ongoing LLH on Heart Mate II support.

背景：在持续流动的机械循环支持过程中持续的低水平溶血（LLH）与随后的血栓形成有关。正在进行的溶血过程中释放出的血红蛋白会清除一氧化氮（NO），造成NO缺乏，从而增加血小板功能，导致血栓形成前状态。磷酸二酯酶5抑制剂西地那非可增强NO信号传导，从而抑制血小板功能。因此，我们在心脏伴侣II支持期间调查了LLH患者中西地那非给药与血栓形成事件之间的关系。

方法和结果：对所有植入心脏伴侣II且存活至出院的患者进行单中心评估（n = 144）。LLH定义为排出乳酸脱氢酶水平为400至700U / L。患者分为（1）西地那非未使用LLH，（2）西地那非未使用LLH，（3）西地那非未使用LLH和（4）西地那非未使用LLH。两组之间的年龄，性别，血小板计数和平均血小板体积相似。17名患者发生了设备血栓形成或缺血性中风。LLH的存在与更大的血栓形成风险相关（调整后的危险比为15； 95％置信区间为4.5-50；P <0.001，与没有LLH相比，未使用西地那非）。西地那非LLH患者的这种风险降低（调整后的危险比为1.7； 95％置信区间为0.2-16.1；P= 0.61）。装置血栓形成和缺血性中风与平均血小板体积增加有关（9.6±0.5至10.9±0.8 fL，P <0.001）。与未接受西地那非的LLH患者相比，未接受西地那非的LLH患者的平均血小板体积增加更大（P <0.001）。

结论：西地那非与在Heart Mate II支持下持续进行的LLH期间的装置血栓形成减少和缺血性中风有关。