Inadequate prophylactic effect of low-molecular weight heparin in critically ill COVID-19 patients

Abstract

Purpose The aim of this study was to investigate potential markers of coagulopathy and the effects of thromboprophylaxis with low-molecular-weight heparin (LMWH) on thromboelastography (TEG) and anti-factor Xa in critically ill COVID-19 patients. Material and Methods We conducted a prospective study in 31 consecutive adult intensive care unit (ICU) patients. TEG with and without heparinase and anti-factor Xa analysis were performed. Standard thromboprophylaxis was given with dalteparin (75–100 IU/kg subcutaneously). Results Five patients (16%) had symptomatic thromboembolic events. All patients had a maximum amplitude (MA) > 65 mm and 13 (42%) had MA > 72 mm at some point during ICU stay. Anti-factor Xa activity were below the target range in 23% of the patients and above target range in 46% of patients. There was no significant correlation between dalteparin dose and anti-factor Xa activity. Conclusions Patients with COVID-19 have hypercoagulability with high MA on TEG. The effect of LMWH on thromboembolic disease, anti-factor Xa activity and TEG was variable and could not be reliably predicted. This indicates that standard prophylactic doses of LMWH may be insufficient. Monitoring coagulation and the LMWH effect is important in patients with COVID-19 but interpreting the results in relation to risk of thromboembolic disease poses difficulties.

Elevated Angiopoietin-2 inhibits thrombomodulin-mediated anticoagulation in critically ill COVID-19 patients

“…In this study, all patients had MA ≥ 65 mm, and at the late timepoint, 3 out of 4 non-recovering patients had MA ≥ 77 mm (Table 2). Increased MA has previously been reported in critically ill COVID-19 patients ( 5, 39, 40 ). Platelet count and D-dimer were not different between recovering and non-recovering patients, but both were significantly increased compared to healthy controls (Table 2).…”

“…SARS-CoV-2 infection may be paucisymptomatic, or lead to coronavirus disease-2019 (COVID-19), which has a wide range of symptoms and may cause severe illness, in particular in individuals with other cardiovascular risk factors ( 1 ). Thrombotic and thromboembolic disease has emerged as a major COVID-19 complication despite routine thrombosis prophylaxis now being standard of care ( 2-5 ). Microthrombosis has been suggested to contribute to both respiratory failure and neurological complications ( 6, 7 ), and activation of the coagulation system indicates a poor prognosis among COVID-19 patients in intensive care ( 1, 7-9 ).…”

The Role of TEG Analysis in Patients with COVID-19-Associated Coagulopathy: A Systematic Review

“…Reduced fibrinolytic activity was also observed in patients with COVID-19, with all studies reporting LY30 less than 1%, including three which showed complete fibrinolytic shutdown (LY30 of 0%) [ 18 , 23 , 25 ]. A shortened R-time of less than 5 min was observed in patients from four studies [ 18 , 20 , 22 , 26 ], indicating a shorter time to clot formation in hypercoagulable patients, although the R-value was within the range of normal in most studies ( Figure 4 ), implying that the change in R-time is less consistent than the increased MA [ 5 , 14 , 15 , 19 ] and fibrinolytic shutdown in the characterization of COVID-19.…”

Viscoelastometric Testing to Assess Hemostasis of COVID-19: A Systematic Review

“…VETs were performed using ROTEM (25 studies), TEG (15 studies), Quantra (two prospective studies [66,67]) and ClotPro (one retrospective study [24] and one case report [68]); no study compared two devices. Among articles reporting data about TEG, four were prospective studies [52,[59][60][61], ten were retrospective studies [51,[53][54][55][56][57][58][62][63][64], and one was a case report [65]. Among articles dealing with ROTEM, thirteen were prospective studies [28][29][30][31][32][39][40][41][42][43][44][45][46], seven were retrospective studies [27,[33][34][35][36]48,49], one was a cross-sectional study [47], and four were case reports [26,37,38,50].…”

“…Testing was carried out either on admission or within the following days, but the timing of blood collection for VET was specified only for 29 studies [24,26,27,[29][30][31]33,[35][36][37][38]41,[43][44][45][46][47][48]50,53,[55][56][57][58][59][65][66][67]. In some studies, the measurements were repeated during the patientʹs stay, either because of a pre-established protocol [26,27,29,45,53,59,60,67] or because of the occurrence of a thromboembolic event [65,68]. Number of VETs performed during a patient's stay ranged from 1 to 5 [29].…”