Scientific reports, Volume 15, Issue 1, 25 4 2025, Pages 10321 Assessing differential application of thromboprophylaxis regimes related to risk of pulmonary embolism and mortality in COVID-19 patients through instrumental variable analysis. Nab L, Visser C, van Bussel BCT, Beishuizen A, Bemelmans RHH, Ten Cate H, Croles FN, van Guldener C, de Jager CPC, Huisman MV, Nijziel MR, Kamphuisen PW, Klok FA, Koster SCE, Kuşadasi N, Meijer K, den Uil CA, Schutgens REG, Stam F, Vlaar APJ, Vlot EA, Linschoten MPM, Asselbergs FW, Kruip MJHA, le Cessie S, Cannegieter SC, Dutch Covid and Thrombosis Coalition & the CAPACITY-COVID collaborative consortium
Thrombotic complications are common in Coronavirus disease 2019 (COVID-19) patients, with pulmonary embolism (PE) being the most frequent. Randomised trials have provided inconclusive results on the optimal dosage of thromboprophylaxis in critically ill COVID-19 patients. We utilized data from the multicentre CAPACITY-COVID patient registry to assess the effect of differential application of Low Molecular Weight Heparin (LMWH) dose protocols on PE and in-hospital mortality risk in critically ill COVID-19 patients. An instrumental variable analysis was performed to estimate the intention-to-treat effect, utilizing differences in thromboprophylaxis prescribing behaviour between hospitals. We included 939 patients with PCR confirmed SARS-CoV-2 infection from 34 hospitals. Two-hundred-and-one patients (21%) developed a PE. The adjusted cause-specific HR of PE was 0.92 (95% CI: 0.73-1.16) per doubling of LMWH dose. The adjusted cause-specific HR for in-hospital mortality was 0.82 (95% CI: 0.65-1.02) per doubling of LMWH dose. This dose-response relationship was shown to be non-linear. To conclude, this study did not find evidence for an effect of LMWH dose on the risk of PE, but suggested a non-linear decreased risk of in-hospital mortality for higher doses of LMWH. However, uncertainty remains, and the dose-response relationship between LMWH dose and in-hospital mortality needs further investigation in well-designed studies.
