Elevated Unfractionated Heparin Requirement in COVID-19 ICU Patients: Exploring Influencing Factors

Patients with COVID-19-associated pulmonary embolism have been reported to require higher doses of unfractionated heparin (UFH) to achieve therapeutic activated partial thromboplastin time (APTT) levels. This study aimed to compare the UFH dose in ICU patients with COVID-19 and control ICU patients, exploring possible explanatory factors. In this retrospective cohort study at Leiden University Medical Center, 162 COVID-19 ICU patients (admitted between 15 March 2020 and 1 January 2022) and 1006 control patients (admitted from 1 January 2014 to 1 January 2020) were included. All patients had an indication for therapeutic UFH. The primary endpoint was the UFH dose. A mixed linear model was used to assess the relationship between UFH dose, APTT, antithrombin (AT), c-reactive protein (CRP), and BMI. COVID-19 patients received a median UFH dose of 383 IU/kg/day compared to 308 IU/kg/day in controls (p < 0.001). Median APTT was lower in COVID-19 patients (63 vs. 66 s, p < 0.001). Median CRP was lower and median AT higher in COVID-19 patients. In the mixed linear model, only UFH dose showed a significant relationship with APTT (p = 0.0316). COVID-19 patients received higher UFH doses but had lower APTT values compared to controls. These differences could not be explained by BMI, CRP, or AT levels, suggesting other patient-related factors may influence heparin dosing, for example, factor VIII and fibrinogen.