Anticoagulation with tinzaparin in COVID-19 patients in icu: Are low anti-XA levels associated with thedevelopment of thrombo-embolic events?

Background : During the first wave of COVID-19 infections, a significantly higher incidence of thrombo-embolic events (TE) was reported. This led to some international guidelines favouring the administration of a higher dose of low molecular weight heparin (LMWH) as a prophylactic anticoagulation strategy. Despite switching to a dose of 100 IU/kg tinzaparin in COVID-19 infected patients in our intensive care unit (ICU), we still experienced several ischemic events. Aims : To establish if anti-Xa plasma levels can determine the development of TE in COVID-19 infected ICU patients. Methods : After obtaining ethical approval, we retrospectively collected data on anti-Xa levels from all COVID-19 infected ICU patients, treated once daily with tinzaparin, on 2 random dates in November 2020 in UZ Brussel. Samples were obtained 4 h after injection, as required to measure reliable peak levels. We investigated whether these patients developed a TE within 14 days following sample collection. Results : We analysed 32 anti-Xa plasma levels from 24 patients, 19 from patients receiving a high prophylactic dose of tinzaparin (median dose = 103 IU/kg) and 13 from patients receiving a therapeutic dose (median dose = 177 IU/kg). None of the patients in the therapeutic group developed a TE within 14 days, in contrast with 6 patients in the high prophylactic group (Figure 1). All patients with anti-Xa levels below 0.23 IU/mL ( n = 4) developed a TE, as opposed to only 2 out of 15 with higher levels. However, due to a wide range in anti-Xa levels and a small sample size, there was no statistically significant difference in anti-Xa levels in patients with and without TE ( P -value = 0.123). Conclusions : Anti-Xa peak levels below 0.23 IU/mL might predict TE within 14 days in COVID-19 infected ICU patients receiving a high prophylactic dose of LMWH. After validation in larger patient groups, this could lead to integration of systematic anti-Xa level monitoring in future COVID-19 guidelines.