Anticoagulation use and Hemorrhagic Stroke in SARS-CoV-2 Patients Treated at a New York Healthcare System

Abstract

Background and purpose: While the thrombotic complications of COVID-19 have been well described, there are limited data on clinically significant bleeding complications including hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this particular subset of patients are especially salient as therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19.

Methods: We conducted a retrospective cohort study of patients with hemorrhagic stroke (both non-traumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between March 1, 2020, and May 15, 2020, within a major healthcare system in New York, during the coronavirus pandemic. Patients with hemorrhagic stroke on admission and who developed hemorrhage during hospitalization were both included. We compared the clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital system between March 1, 2020, and May 15, 2020 (contemporary controls), and March 1, 2019, and May 15, 2019 (historical controls). Demographic variables and clinical characteristics between the individual groups were compared using Fischer's exact test for categorical variables and nonparametric test for continuous variables. We adjusted for multiple comparisons using the Bonferroni method.

Results: During the study period in 2020, out of 4071 patients who were hospitalized with COVID-19, we identified 19 (0.5%) with hemorrhagic stroke. Of all COVID-19 with hemorrhagic stroke, only three had isolated non-aneurysmal SAH with no associated intraparenchymal hemorrhage. Among hemorrhagic stroke in patients with COVID-19, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% of these patients versus 4.2% in contemporary controls (p ≤ .001) and 10.0% in historical controls (p ≤ .001). Compared to contemporary and historical controls, patients with COVID-19 had higher initial NIHSS scores, INR, PTT, and fibrinogen levels. Patients with COVID-19 also had higher rates of in-hospital mortality (84.6% vs. 4.6%, p ≤ 0.001). Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results.

Conclusion: We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in patients with COVID-19 infection occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in patients with COVID-19.

Keywords: COVID-19; Coagulopathy; Coronavirus; Hemorrhagic stroke; Intracerebral hemorrhage; Pandemic; Subarachnoid hemorrhage.

Fig. 1

The number of COVID-19 hospitalizations and hemorrhagic strokes during the study period. a Overall number of COVID-19 hospitalizations in all of NYC hospitalizations. b The number of COVID-19 hospitalizations at NYU Langone Health System over the study period. c Number of COVID-19 patients diagnosed with hemorrhagic stroke. d Time graph of point at which anticoagulation was started and when hemorrhagic stroke was diagnosed

Fig. 2

Two patients with hemorrhagic stroke in the setting of coronavirus disease 2019 (COVID-19). The left column shows thoracic X-ray, and the right column shows brain non-contrast CT for both patients. CT demonstrates primarily peripheral, parenchymal hematomas in patient 1 (top row), including a large, dominant paramedian parietal hemorrhage on the right and generalized sulcal effacement and cerebral edema. Patient 2 (bottom row) demonstrates a solitary but large parenchymal hematoma in the perirolandic vertex of the right hemisphere with severe, unilateral sulcal effacement. Thoracic imaging in both patients revealed severe, multifocal airspace disease consistent with atypical pneumonia