Bulanov Andrey Y, Bulanova Ekaterina L, Simarova Irina B, Bovt Elizaveta A, Eliseeva Olesya O, Shakhidzhanov Soslan S, Panteleev Mikhail A, Roumiantsev Aleksandr G, Ataullakhanov Fazoil I, Karamzin Sergey S
Moscow City Clinical Hospital №52 of Healthcare Department, Moscow, Russia.
Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
PLoS One. 2023 Jun 2;18(6):e0282939. doi: 10.1371/journal.pone.0282939. eCollection 2023.
Blood coagulation abnormalities play a major role in COVID-19 pathophysiology. However, the specific details of hypercoagulation and anticoagulation treatment require investigation. The aim of this study was to investigate the status of the coagulation system by means of integral and local clotting assays in COVID-19 patients on admission to the hospital and in hospitalized COVID-19 patients receiving heparin thromboprophylaxis.
Thrombodynamics (TD), thromboelastography (TEG), and standard clotting assays were performed in 153 COVID-19 patients observed in a hospital setting. All patients receiving treatment, except extracorporeal membrane oxygenation (ECMO) patients (n = 108), were administered therapeutic doses of low molecular weight heparin (LMWH) depending on body weight. The ECMO patients (n = 15) were administered unfractionated heparin (UFH).
On admission, the patients (n = 30) had extreme hypercoagulation by all integral assays: TD showed hypercoagulation in ~75% of patients, while TEG showed hypercoagulation in ~50% of patients. The patients receiving treatment showed a significant heparin response based on TD; 77% of measurements were in the hypocoagulation range, 15% were normal, and 8% remained in hypercoagulation. TEG showed less of a response to heparin: 24% of measurements were in the hypocoagulation range, 59% were normal and 17% remained in hypercoagulation. While hypocoagulation is likely due to heparin treatment, remaining in significant hypercoagulation may indicate insufficient anticoagulation for some patients, which is in agreement with our clinical findings. There were 3 study patients with registered thrombosis episodes, and all were outside the target range for TD parameters typical for effective thromboprophylaxis (1 patient was in weak hypocoagulation, atypical for the LMWH dose used, and 2 patients remained in the hypercoagulation range despite therapeutic LMWH doses).
Patients with COVID-19 have severe hypercoagulation, which persists in some patients receiving anticoagulation treatment, while significant hypocoagulation is observed in others. The data suggest critical issues of hemostasis balance in these patients and indicate the potential importance of integral assays in its control.
凝血异常在新型冠状病毒肺炎(COVID-19)病理生理过程中起主要作用。然而,高凝状态及抗凝治疗的具体细节仍需研究。本研究旨在通过整体和局部凝血检测方法,调查COVID-19患者入院时及接受肝素血栓预防治疗的住院COVID-19患者的凝血系统状态。
对一家医院观察的153例COVID-19患者进行血栓动力学(TD)、血栓弹力图(TEG)及标准凝血检测。除体外膜肺氧合(ECMO)患者(n = 108)外,所有接受治疗的患者均根据体重给予治疗剂量的低分子量肝素(LMWH)。ECMO患者(n = 15)给予普通肝素(UFH)。
入院时,所有整体检测显示患者(n = 30)存在极度高凝状态:TD显示约75%的患者存在高凝,而TEG显示约50%的患者存在高凝。接受治疗的患者基于TD显示出显著的肝素反应;77%的检测结果处于低凝范围,15%正常,8%仍处于高凝状态。TEG显示对肝素的反应较小:24%的检测结果处于低凝范围,59%正常,17%仍处于高凝状态。虽然低凝可能是由于肝素治疗,但仍处于显著高凝状态可能表明部分患者抗凝不足,这与我们的临床发现一致。有3例研究患者发生血栓事件,且所有患者均超出有效血栓预防典型TD参数的目标范围(1例患者处于弱低凝状态,与所用LMWH剂量不符,另外2例患者尽管接受了治疗剂量的LMWH,但仍处于高凝范围)。
COVID-19患者存在严重高凝状态,部分接受抗凝治疗的患者高凝状态持续存在,而其他患者则出现显著低凝。数据表明这些患者止血平衡存在关键问题,并提示整体检测在控制止血平衡方面的潜在重要性。