INTEM, EXTEM, and FIBTEM MCF were all elevated above the upper normal reference limit in greater than or equal to 10 of 12 patients in cohort 1, indicating hypercoagulation. cohort 1 (low-molecular-weight heparin dose: 129 53 U/kg/24?hr), 50% had pulmonary embolism, and thromboelastography analysis revealed hypercoagulation in a majority of patients and greater than 80% had detectable antiphospholipid antibodies. In the second cohort (enhanced low-molecular-weight heparin dose: 200 82 U/kg/24?hr; = 0.04 vs cohort 1), we found a nonsignificantly lower prevalence of pulmonary embolism (21%; = 0.22), lower fibrinogen (6.3 2.5 vs 8.7 2.0; = 0.02), reduced fibrinogen-dependent thromboelastography ( 0.001), and lower inflammatory markers. Conclusions: In these two cross-sectional cohorts of ICU-treated coronavirus disease 2019 patients, thromboembolic complications, hypercoagulation, and antiphospholipid antibodies were common. A more aggressive anticoagulation regime was associated with a reduction in inflammatory biomarkers including plasma fibrinogen and a reduction in fibrinogen-dependent hypercoagulation, as indicated by thromboelastography analyses. tests or Mann-Whitney tests, as appropriate. Belotecan hydrochloride Fisher exact test was used for categorical variables. All statistical analyses were performed using GraphPad Prism Version 8.3.0 (GraphPad Software, La Jolla, CA). A value of less than 0.05 was determined as statistically significant and a value of 0.05C0.10 was determined a trend. RESULTS Table ?Table11 outlines the patient characteristics. The patients were all male with a high proportion of comorbidity. All patients were on mechanical ventilation and approximately half on renal replacement therapy. As expected, a higher background dose of LMWH was seen in the second cohort (200 82 U/kg/24?hr) compared with the first cohort (129 53 U/kg/24?hr; = 0.04) (Fig. ?Fig.11= 0.22). Figure ?Figure22 displays a representative ROTEM analysis and individual patient data. Most patients in both cohorts displayed INTEM and EXTEM CT within the normal reference range, whereas FIBTEM was prolonged. INTEM, EXTEM, and FIBTEM MCF were all elevated above the upper normal reference limit in greater than or equal to 10 of 12 patients in cohort 1, indicating hypercoagulation. In the second cohort, INTEM and EXTEM MCF were similarly elevated, whereas fibrinogen-dependent (FIBTEM) MCF was significantly lower than the first cohort ( 0.01). The lower FIBTEM MCF in cohort 2 was accompanied by significantly lower plasma fibrinogen, a trend toward lower d-dimer (Fig. ?Fig.33= 12)= 14)(%) for categorical variables and mean sd for continuous variables with normal distribution and median (interquartile range) for continuous variables with skewed distribution. Open in a separate window Figure 1. Low molecular weight heparin dosing and prevalence of pulmonary embolism and deep vein thrombosis in the two study Belotecan hydrochloride cohorts. A, Significantly higher low-molecular-weight heparin (LMWH) in Rabbit polyclonal to ZFP161 cohort 2 after changing to an enhanced anticoagulation strategy. B, High prevalence of pulmonary embolism (PE) and deep vein thrombosis (DVT) in cohort 1 that decreased nonsignificantly after introducing a more aggressive anticoagulation regime. TE = thrombotic event. Open in a separate window Figure 2. Thromboelastometry point-of-care coagulation test (ROTEM) was markedly increased in ICU-treated coronavirus disease 2019 (COVID-19) patients, but fibrinogen-dependent maximum clot firmness (MCF) was significantly reduced in cohort 2. A, Representative ROTEM analysis of intrinsic thromboelastometry (INTEM), extrinsic thromboelastometry Belotecan hydrochloride (EXTEM), and fibrinogen-dependent thromboelastometry (FIBTEM) clot formation from one COVID-19 patient. B, Individual (denote the reference range. ROTEM = thromboelastography. Open in a separate window Figure 3. Blood markers of cloth formation propensity and inflammation in the two study cohorts. The reduction in FIBTEM MCF between the two cohorts was associated with a significant reduction in (A) plasma levels of fibrinogen and a trend toward Belotecan hydrochloride decrease in d-dimer as well as (B) inflammation parameters. CRP = C-reactive protein, ESR = erythrocyte sedimentation rate. Open in a separate window Figure 4. High prevalence of detectable ( 2 U/mL) anticardiolipin and Belotecan hydrochloride anti-2-glycoprotein I antibodies in critically ill coronavirus disease 2019 patients. In the sensitivity analysis, ICU stay at the time of ROTEM analysis was similar in cohort 1 (13 d [7C16 d]; = 12) and cohort 2 (14 d [12C24]; = 11; = 0.10). As in the main analysis, LMWH-dosing was higher (= 0.09), whereas the prevalence of PE (= 0.03) and plasma fibrinogen (= 0.048) and FIBTEM-MCF ( 0.001) were lower in the second cohort. Similarly, markers of inflammation were lower in cohort 2 (= 0.02 for C-reactive protein (CRP) and = 0.01 for erythrocyte sedimentation rate). The results are detailed in Supplemental Table 1 (http://links.lww.com/CCX/A467). DISCUSSION In this study, we report a high prevalence of hypercoagulation, thrombotic.