Unfractionated Heparin in COVID-19 and Non-COVID-19 Patients

CoVID-19 is a viral disease caused by SARS-CoV-2 virus that may affect many organ systems. Patients with severe disease almost invariably have profound pulmonary inflammation and may require mechanical ventilation and prolonged ICU admission. Mortality in ICU patients may be up to 50%. In the majority of patients with CoVID-19 in the ICU, profound activation of coagulation is present as reflected by d-dimer levels up to 20.000 mg/L or higher. Patients with proven pulmonary thrombosis are commonly treated with unfractionated heparin (UFH). Typically, it seemed that very high dosages of UFH were necessary to achieve therapeutic values of aPTT and anti-Xa levels in COVID-19 patients. Though, the question remains whether dosages given in COVID-19 patients were indeed extravagant compared to non-COVID-19 patients and what potential causes of these high dosages might be. Earlier research already implied that APTT, which is a primarily used parameter to dose UFH, is not accurate and rather anti-Xa levels should be used. Other potential reasons for the high doses are that COVID-19 patients show signs of heparin resistance, possible due to high inflammation parameters. As overdosing of heparin can lead to serious bleeding complications, more understanding on heparin dosage, e.g. parameters to rely on and potential influencing factors, in COVID-19 patients is needed. The primary objective of this study is to determine whether heparin dosages are higher in COVID-19 patients compared to non COVID-19 patients. The secondary objective is to determine the correlation between aPTT and anti-Xa values and to explore possible causes for non-correlating aPTT and anti-Xa, including CRP and AT plasma levels.

Inclusion criteria

Covid-19 group:

• Covid-19 disease proven by PCR of nose- or airway sample
• Age ≥ 18 years
• Admitted to the ICU from the 15th of March 2020 until 1st of January 2022
• Treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa level 0.3-0.7 iE/ml

Inclusion criteria

non-Covid-19 group:

• Age ≥ 18 years
• Admitted to the ICU between the 1st of January 2014 and 1st of January 2020
• Treated with unfractionated heparin aiming at aPTT 60-80 sec and/or anti-Xa level 0.3-0.7 iE/ml

Exclusion criteria

• Treatment with anticoagulants other than UFH or fibrinolytics