Department of Hepatology, Postgraguate Institute of Medical Education and Research, Chandigarh, India.
Department of Anaesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
BMJ Open. 2022 May 2;12(5):e051971. doi: 10.1136/bmjopen-2021-051971.
Coagulation changes associated with COVID-19 suggest the presence of a hypercoagulable state with pulmonary microthrombosis and thromboembolic complications. We assessed the dynamic association of COVID-19-related coagulation abnormalities with respiratory failure and mortality.
Single-centre, prospective cohort study with descriptive analysis and logistic regression.
Tertiary care hospital, North India.
Patients with COVID-19 pneumonia requiring intensive care unit (ICU) admission between August 2020 and November 2020.
We compared the coagulation abnormalities using standard coagulation tests like prothrombin time, D-dimer, platelet count, etc and point-of-care global coagulation test, Sonoclot (glass beaded(gb) and heparinase-treated(h)). Incidence of thromboembolic or bleeding events and presence of endogenous heparinoids were assessed. Cox proportional Hazards test was used to assess the predictors of 28-day mortality.
All patients underwent Sonoclot (glass beaded) test at admission apart from the routine investigations. In patients at risk of thromboembolic or bleeding phenomena, paired tests were performed at day 1 and 3 with Sonoclot. Activated clotting time (ACT) <110 s and peak amplitude >75 units were used as the cut-off for hypercoagulable state. Presence of heparin-like effect (HLE) was defined by a correction of ACT ≥40 s in h-Sonoclot.
Of 215 patients admitted to ICU, we included 74 treatment naive subjects. A procoagulant profile was seen in 45.5% (n=5), 32.4% (n=11) and 20.7% (n=6) in low-flow, high-flow and invasive ventilation groups. Paired Sonoclot assays in a subgroup of 33 patients demonstrated the presence of HLE in 17 (51.5%) and 20 (62.5%) at day 1 and 3, respectively. HLE (day 1) was noted in 59% of those who bled during the disease course. Mortality was observed only in the invasive ventilation group (16, 55.2%) with overall mortality of 21.6%. HLE predicted the need for mechanical ventilation (HR 1.2 CI 1.04 to 1.4 p=0.00). On multivariate analysis, the presence of HLE (HR 1.01; CI 1.006 to 1.030; p=0.025), increased C reactive protein (HR 1.040; CI 1.020 to 1.090; p=0.014), decreased platelet function (HR 0.901; CI 0.702 to 1.100 p=0.045) predicted mortality at 28days.
HLE contributed to hypocoagulable effect and associated with the need for invasive ventilation and mortality in patients with severe COVID-19 pneumonia.
NCT04668404; ClinicalTrials.gov.in. Available from https://clinicaltrials.gov/ct2/show/NCT04668404.
与 COVID-19 相关的凝血变化表明存在高凝状态，伴有肺微血栓形成和血栓栓塞并发症。我们评估了 COVID-19 相关凝血异常与呼吸衰竭和死亡率的动态关联。
单中心、前瞻性队列研究，描述性分析和逻辑回归。
印度北部的一家三级护理医院。
2020 年 8 月至 2020 年 11 月期间需要入住重症监护病房（ICU）的 COVID-19 肺炎患者。
我们比较了使用标准凝血试验（如凝血酶原时间、D-二聚体、血小板计数等）和即时凝血试验（Sonoclot[玻璃珠（gb）和肝素酶处理（h）]）的凝血异常。评估了血栓栓塞或出血事件的发生率和内源性肝素样物质的存在。Cox 比例风险检验用于评估 28 天死亡率的预测因素。
所有患者在入院时除常规检查外均进行 Sonoclot（玻璃珠）试验。对于有血栓栓塞或出血风险的患者，在第 1 天和第 3 天进行 Sonoclot 配对检测。激活凝血时间（ACT）<110 s 和峰值幅度>75 单位被用作高凝状态的截止值。肝素样效应（HLE）的存在通过 h-Sonoclot 中 ACT 纠正≥40 s 来定义。
在入住 ICU 的 215 名患者中，我们纳入了 74 名未接受治疗的患者。在低流量、高流量和有创通气组中，分别有 45.5%（n=5）、32.4%（n=11）和 20.7%（n=6）的患者表现出促凝特征。在 33 名患者的亚组中进行的配对 Sonoclot 检测显示，在第 1 天和第 3 天，分别有 17（51.5%）和 20（62.5%）例存在 HLE。在疾病过程中出血的患者中，有 59%（n=10）存在 HLE。只有在有创通气组（16 例，55.2%）观察到死亡率，总死亡率为 21.6%。HLE 预测需要机械通气（HR 1.2，CI 1.04 至 1.4，p=0.00）。多变量分析显示，HLE（HR 1.01；CI 1.006 至 1.030；p=0.025）、C 反应蛋白升高（HR 1.040；CI 1.020 至 1.090；p=0.014）、血小板功能降低（HR 0.901；CI 0.702 至 1.100；p=0.045）预测 28 天死亡率。
HLE 导致低凝效应，并与严重 COVID-19 肺炎患者需要有创通气和死亡相关。
NCT04668404；ClinicalTrials.gov.in。可从 https://clinicaltrials.gov/ct2/show/NCT04668404 获得。
