Anticoagulation with Tinzaparin in COVID-19 patients in ICU: are low anti-Xa levels associated with the development of trombo-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).