Heparin resistance in COVID-19 patients in the intensive care unit

Patients with COVID-19 have a coagulopathy and high thrombotic risk. In a cohort of 69 intensive care unit (ICU) patients we investigated for evidence of heparin resistance in those that have received therapeutic anticoagulation. 15 of the patients have received therapeutic anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH), of which full information was available on 14 patients. Heparin resistance to UFH was documented in 8/10 (80%) patients and sub-optimal peak anti-Xa following therapeutic LMWH in 5/5 (100%) patients where this was measured (some patients received both anticoagulants sequentially). Spiking plasma from 12 COVID-19 ICU patient samples demonstrated decreased in-vitro recovery of anti-Xa compared to normal pooled plasma. In conclusion, we have found evidence of heparin resistance in critically unwell COVID-19 patients. Further studies investigating this are required to determine the optimal thromboprophylaxis in COVID-19 and management of thrombotic episodes.