Von Willebrand factor
Editor – Ladikou et al have elegantly shown in their series that levels of factor VIII and von Willebrand factor (VWF) are markedly raised in patients with COVID-19 and that there is a reduced level of ADAMTS13 which may be secondary to depletion of the enzyme through consumption.1 Similar results have been reported by others and there is a growing recognition that COVID-19 may trigger a ‘thrombo-inflammatory’ cascade that should be targeted.2–5 Endothelialitis, whether caused by COVID-19 or another septic process, triggers the release of VWF, including the highly biologically active and more adhesive ultra-long VWF that can bind platelets spontaneously via glycoprotein Ib receptors. The ultra-long VWF multimers released from the Weibel–Palade bodies have a lower shear stress for unfolding and therefore may represent the initiating molecules for this self-assembly process which leads to hyper-adhesive strings capturing platelets and the microthrombosis that is now well established as part of the disease.6–10 This represents the first step in platelet activation and thrombus growth. Under normal conditions ADAMTS13 cleaves VWF and regulates the VWF/platelet interaction, however, this regulatory mechanism may be overwhelmed by the degree of microthrombosis seen in COVID-19 as is suggested by the results presented by Ladikou et al. We believe that targeting the initial VWF/platelet interaction with caplacizumab presents an attractive target that may prevent widespread microthrombosis and its clinical sequelae and that this drug may prove be particularly effective for patients that present with abnormally raised VWF, and abnormal VWF/factor VIII ratio or reduced ADAMTS13. We believe that investigation of caplacizumab in these patients warrants urgent investigation. Anfibatide represents an alternative drug with a similar mode of action to caplacizumab and should also be considered high on the list of drugs to be investigated.
- © Royal College of Physicians 2020. All rights reserved.
References
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- Ladikou EE
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- Goshua G
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- Guglielmetti G
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- Carsana L
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- Tee A
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- Ciceri F
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- Fox SE
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- Jung EM
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