Discussion
Discussions regarding anticoagulation for COVID-19 patients have been intensifying as evidence of hypercoagulability in this population continues to accumulate. Decisions about anticoagulation must, in part, take the risk of ICH following anticoagulation into consideration. Our data will certainly be helpful in this regard. We found that 4.4% of 755 patients diagnosed with positive COVID-19 and with concurrent neuroimaging had ICH. The majority of these patients received therapeutic anticoagulation, most commonly UFH. The most frequent indication for starting anticoagulation was elevated D-dimer levels, reflecting a trend among centers to intensify anticoagulation regimens in COVID-19 positive patients based on evidence of hypercoagulability including increased D-dimer.4 Although the large hemorrhages causing herniation were thought to be the result of primary intracranial hemorrhage, the majority of the other hemorrhages were hemorrhagic transformation of ischemic stroke.
Of particular interest is our subgroup of 5 patients with large parenchymal hemorrhages causing mass effect and herniation. Mortality was 100% in these patients, all of whom were on continuous UFH and were found to have hemorrhages many days into their hospitalization. Although two of these patients were placed on therapeutic anticoagulation due to known or suspected thrombosis, the other three were started on therapeutic anticoagulation because of increasing D-dimer levels. Although empiric anticoagulation has been shown to lower 28-day mortality in COVID-19 patients with severely elevated D-dimer,14 this sobering outcome underscores the need for randomized clinical trials to properly assess benefit versus risk regarding anticoagulation strategies in COVID-19. It also raises the question of whether a screening head CT should be done prior to starting anticoagulation in patients with mental status too impaired to obtain a good neurological assessment, so as to avoid the risk of catastrophic hemorrhage in an unsuspected large acute infarct.
In our study, many patients had punctate hemorrhages that were characterized as cortical in nature on MRI, but that were either mischaracterized as subarachnoid hemorrhage or not seen on CT. MRI is known to have better sensitivity than CT for detecting small ICH,15 but as neuroimaging use, and particularly MRI use, has decreased significantly during the COVID-19 pandemic, some patients with ICH may have an ICH that is diagnosed late or missed entirely.
Our study has multiple limitations, most importantly its descriptive nature as well as a small sample size. It is possible that additional patients with ICH in this cohort were not identified either because the patients were heavily sedated and there was no opportunity for a detailed neurological examination and there was a desire to limit transport out of the room for neuroimaging. As such, MRI use was limited in this cohort and adjudication of ICH etiology were made to the best of our ability. We were not able to review all COVID-19 patients getting anticoagulation to see how many of them had ICH, and we did not include patients with neuroimaging but no hemorrhage in this descriptive paper. We did not compare our patients to COVID-19 patients who had neuroimaging without evidence of hemorrhage.
Nevertheless, we believe our study provides important initial data regarding ICH and anticoagulation in patients hospitalized with COVID-19. Future work must look more deeply into the benefits and consequences of anticoagulation for COVID-19 patients, through outcomes analysis and well-powered, prospective, randomized clinical trials.