Failure of Therapeutic Anticoagulation in COVID-19 Patients With Acute Ischemic Stroke. A Retrospective Multicenter Study

Abstract

BackgroundAcute ischemic stroke (AIS) is a possible complication of coronavirus disease 2019 (COVID-19) infection. Although peculiar clinical features and underlying specific mechanisms of thrombogenesis have been suggested so far, there is no consensus on the appropriate vascular preventive drug regimen in patients with COVID-19.Aim and MethodsFrom a larger clinical series of consecutive acute ischemic strokes related to COVID-19 admitted to three cerebrovascular units in Northern Italy, herein, we describe the clinical features of a subgroup of patients in whom stroke occurred despite therapeutic anticoagulation.ResultsA total of seventeen/80 AIS related to COVID-19 (21.2%) occurred in anticoagulated patients. Although no blood level was available for Direct Oral AntiCoagulant, the drug dosage was appropriate according to guidelines. Their National Institute of Health Stroke Scale (NIHSS) at admission was 12.0 (SD = 7.4) and 58.8% of them had evidence of large vessel occlusion. The case fatality rate was as high as 64.7%.Discussion and ConclusionsThe occurrence of an anticoagulation failure seems to be increased in the setting of COVID-19 infection, with worse clinical outcomes if compared to non-COVID-19 related ischemic strokes. We discuss the diagnostic and therapeutic implications of such evidence, suggesting that some arterial thrombotic complications might be either resistant to or independent of the anticoagulation effect.

Longitudinal viscosity of blood plasma for rapid COVID-19 prognostics

“…Though a significant increase of FDPs can conceivably result in viscoelastic changes, these in of themselves would be too small in size to explain the observed spatial heterogeneities, and would not explain the lack of any significant hysteresis in up-down temperature sweeps observed (which also rule out the denaturing of proteins). Our observations are somewhat surprising given that our samples were collected and stored in anticoagulation tubes (Methods), although reports have hinted at the reduced effectiveness of anticoagulants in COVID-19 patients 31,32 . While ultrastructural and biochemical studies on suspensions is still needed, one can speculate whether these might be related to crosslinked microfibrin/fibrin microclots reported to exist in COVID patient samples 33 .…”

Cerebrovascular Manifestations of SARS-CoV-2: A Comprehensive Review

“…The American Society of Hematology (ASH) guidelines recommended prophylactic dose anticoagulation over intermediate and therapeutic intensity regimens due to small absolute risk difference, with no preference for any specific agent [ 108 ]. A case series of 17 patients receiving therapeutic doses of various anticoagulation medications pointed out the probability of resistance due to COVID-19 coagulopathy [ 109 ]. In a study comparing thrombotic outcomes between 108 patients receiving prophylactic dose and 71 receiving therapeutic dose heparin, the latter presented no AIS, while in the former group 6 patients (5.6%) eventually developed AIS.…”

Neurological complications of coronavirus disease 2019 and the underlying mechanisms

“…Of note, the occurrence rate of arterial or venous thromboembolism in hospitalized COVID-19 patients has been reported to be between 8% and 31% despite the fact that prophylactic anticoagulant therapy was adopted [52,53] . A multicenter study conducted in Italy has reported that COVID-19 patients to whom stroke occurred despite the use of anticoagulant therapy had a worse clinical outcome, along with 64.7% of fatality rate [54] . The treatment for stroke is similarly administered to patients with or without COVID-19; however, there are few studies about the safety and feasibility of thrombectomy treatment in COVID-19 patients with acute ischemic stroke.…”