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Acute ischemic strokes were seen in six British COVID-19 patients, including two who had breakthrough strokes despite therapeutic anticoagulation, researchers reported.

All six patients had large vessel occlusion and in three patients, occlusions were in multiple territories, wrote David Werring, PhD, of UCL Queen Square Institute of Neurology in London, and co-authors in a letter to the on Friday.

All patients had D-dimer levels greater than 1,000 μg/L; five had levels greater than 7,000 μg/L. "We also found the lupus anticoagulant, a protein associated with thrombosis, in five of the six people," Werring told MedPage Today.

Stroke occurred 8 to 24 days after COVID-19 symptom onset in five patients and before COVID-19 symptoms started in one. Two patients had concurrent venous thromboses.

The paper adds to previous reports from China, France, and the United States, linking ischemic stroke with COVID-19 infection. Endothelial damage and abnormal clotting appear to be COVID-19 complications, but why they occur is unknown.

"The prothrombotic state of COVID-19 is a real concern," said Edwin van Beek, MD, PhD, of the University of Edinburgh, who was not involved with the report.

"We have seen that even in patients with prophylactic therapy, their blood clotting is still high, as shown by very high plasma D-dimer levels," van Beek noted. "It has also been seen as a problem in patients requiring hemodialysis for kidney failure, that these systems are much more prone to blood clotting compared to what is normally observed."

"It is entirely feasible that low therapeutic levels of anticoagulation may not be sufficient in some patients with COVID-19," he told MedPage Today. "Doses of anticoagulants may need to be higher depending on individual requirements and measurements of blood clotting, such as higher plasma D-dimer levels."

The fact that two patients had breakthrough strokes "emphasizes the striking tendency for thrombosis in this situation," Werring said. "The implication here is that early preventive anticoagulation in COVID-19, before arterial or venous thromboses have occurred, would be ideal. But this might not always be possible: in one of the patients in our paper, the stroke occurred during the pre-symptomatic phase of COVID-19."

The report included six cases assessed between April 1 and April 16 at the National Hospital for Neurology and Neurosurgery in London. All tested positive for SARS-CoV-2, the virus that causes COVID-19. Four had severe or critical COVID-19, one had moderate-to-severe disease, and one had moderate.

Four of the six patients had hypertension and two had atrial fibrillation. Patient ages ranged from 53 to 85. The youngest was taking warfarin for atrial fibrillation and presented with stroke 24 days after COVID-19 symptom onset; she died after respiratory problems due to COVID-19 pneumonia.

How COVID-19 and stroke are related is not clear, observed Tim Chico, MD, of the University of Sheffield in England, who was not involved with the paper.

"I would expect COVID-19 multiplies the previous risk of stroke, such that people with other risk factors such as age, smoking, and previous stroke are more likely to suffer stroke with COVID-19," Chico told MedPage Today. "However, we still do not have a good estimate of how much COVID-19 increases the risk of blood clots or what we can do to reduce this."

But there is "more and more evidence of both thrombotic and arterial thromboembolism" with COVID-19, said van Beek, who co-authored guidance for the Dutch National Institute for Public Health that advocated prophylactic-dose low-molecular-weight heparin for all hospitalized confirmed or suspected COVID-19 patients and an based on close D-dimer monitoring.

"We firmly believe there is a much wider vascular problem giving rise to multiple organs being affected by COVID-19," van Beek said.

"The fact that mortality rates in intensive care units have normalized in the Netherlands since the institution of more rigorous D-dimer testing, use of anticoagulants, and appropriate diagnostic imaging where feasible gives us positive feedback on what we have proposed," he noted.

"In the U.K., there is still some hesitation to using anticoagulants in many intensive care units, as they can cause complications," he added. "However, we think that many patients with acute deterioration actually suffer from thromboembolism, and organ perfusion is a major contributor to both low oxygen levels and direct organ failure."

Other groups, including a consensus panel of the International Society on Thrombosis and Haemostasis and other societies, also have issued recent guidance about anticoagulation treatment for hospitalized and discharged COVID-19 patients.

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