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. 2023 Apr 29;7(4):100170. doi: 10.1016/j.rpth.2023.100170

Poststroke venous thromboembolism and neutrophil activation: an illustrated review

Nirav Dhanesha 1,∗, Junaid Ansari 2, Nilesh Pandey 1, Harpreet Kaur 1, Chiranjiv Virk 3, Karen Y Stokes 4
PMCID: PMC10236222  PMID: 37274177

Abstract

Patients with acute ischemic stroke are at a high risk of venous thromboembolism (VTE), such as deep vein thrombosis (DVT), estimated to affect approximately 80,000 patients with stroke each year in the United States. The prevalence of symptomatic DVT after acute stroke is approximately 10%. VTE is associated with increased rates of in-hospital death and disability, with higher prevalence of in-hospital complications and increased 1-year mortality in patients with stroke. Current guidelines recommend the use of pharmacologic VTE prophylaxis in patients with acute ischemic stroke. However, thromboprophylaxis prevents only half of expected VTE events and is associated with high risk of bleeding, suggesting the need for targeted alternative treatments to reduce VTE risk in these patients. Neutrophils are among the first cells in blood to respond after ischemic stroke. Importantly, coordinated interactions among neutrophils, platelets, and endothelial cells contribute to the development of DVT. In case of stroke and other related immune disorders, such as antiphospholipid syndrome, neutrophils potentiate thrombus propagation through the formation of neutrophil-platelet aggregates, secreting inflammatory mediators, complement activation, releasing tissue factor, and producing neutrophil extracellular traps. In this illustrated review article, we present epidemiology and management of poststroke VTE, preclinical and clinical evidence of neutrophil hyperactivation in stroke, and mechanisms for neutrophil-mediated VTE in the context of stroke. Given the hyperactivation of circulating neutrophils in patients with stroke, we propose that a better understanding of molecular mechanisms leading to neutrophil activation may result in the development of novel therapeutics to reduce the risk of VTE in this patient population.

Keywords: deep vein thrombosis, ischemic stroke, neutrophils, thromboprophylaxis, venous thromboembolism

Essentials

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    Patients with acute ischemic stroke are at a high risk of venous thromboembolism (VTE).

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    VTE is associated with increased risk of death and disability in patients with stroke.

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    Interactions between neutrophils and other cells and factors contribute to risk of VTE.

  • •

    Current literature supports a key role of neutrophil-dependent mechanisms in promoting VTE.

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Acknowledgment

The authors are thankful to Aadhya Dhanesha (11-year-old daughter of N.D.) for creating an illustration of a stroke patient in slide 11.

Funding

The efforts of N.D. for this publication were supported by grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL158546-01) and by the Career Development Award (20CDA3560123) from American Heart Association. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. The efforts of K.Y.S. for this publication were supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number R01HL134959. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author contributions

N.D. developed the concepts, wrote the manuscript, and produced the illustrations. N.P., H.K., and C.V. edited the manuscript. J.A. and K.Y.S. cowrote the manuscript and edited the illustrations.

Relationship disclosure

There are no competing interests to disclose.

Footnotes

Handling Editor: Dr Michelle Sholzberg

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