Could antiphospholipid antibodies contribute to coagulopathy in COVID-19?
Authors: Aurora Parodi, Giulia Gasparini, Emanuele Cozzani
Journal: Journal of the American Academy of Dermatology (2020)

To the Editor: We read with great interest the article by Manalo et al.1Manalo I.F. Smith M.K. Cheeley J. Jacobs R. A dermatologic manifestation of COVID-19: transient livedo reticularis.J Am Acad Dermatol. 2020; 83: 700Abstract Full Text Full Text PDF PubMed Scopus (178) Google Scholar Coronavirus disease 2019 (COVID-19) patients may develop a thrombophilic state, and extensive microthrombosis has been found at autoptic examination in numerous organs.2Zhang Y. Cao W. Xiao M. et al.Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia.Zhonghua Xue Ye Xue Za Zhi. 2020; 41: E006PubMed Google Scholar We agree with Manalo et al1Manalo I.F. Smith M.K. Cheeley J. Jacobs R. A dermatologic manifestation of COVID-19: transient livedo reticularis.J Am Acad Dermatol. 2020; 83: 700Abstract Full Text Full Text PDF PubMed Scopus (178) Google Scholar that it is likely that this phenomenon does not spare the skin, where it plausibly expresses itself through livedo reticularis and acral ischemia.1Manalo I.F. Smith M.K. Cheeley J. Jacobs R. A dermatologic manifestation of COVID-19: transient livedo reticularis.J Am Acad Dermatol. 2020; 83: 700Abstract Full Text Full Text PDF PubMed Scopus (178) Google Scholar,2Zhang Y. Cao W. Xiao M. et al.Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia.Zhonghua Xue Ye Xue Za Zhi. 2020; 41: E006PubMed Google Scholar Hypercoagulability in COVID-19 patients should not be underestimated because in the worst-case scenario it may lead to death by causing pulmonary embolism or disseminated intravascular coagulation.2Zhang Y. Cao W. Xiao M. et al.Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia.Zhonghua Xue Ye Xue Za Zhi. 2020; 41: E006PubMed Google Scholar The pathogenesis underlying thrombophilia in COVID-19 patients is not clear yet. A recent report described 3 cases of Chinese patients affected by COVID-19 who had coagulopathy and antiphospholipid antibodies.3Zhang Y. Xiao M. Zhang S. et al.Coagulopathy and antiphospholipid antibodies in patients with COVID-19.N Engl J Med. 2020; 382: e38Crossref PubMed Scopus (1602) Google Scholar Indeed, livedo reticularis and acral ischemia can be observed in antiphospholipid syndrome. Disseminated intravascular coagulation also may be substantially indistinguishable from the most severe form of antiphospholipid syndrome; namely, catastrophic antiphospholipid syndrome, in which a "thrombotic storm" affects 3 or more organs or systems simultaneously, leading to multiorgan failure.4Linnemann B. Antiphospholipid syndrome - an update.Vasa. 2018; 47: 451-464Crossref PubMed Scopus (64) Google Scholar Zhang et al3Zhang Y. Xiao M. Zhang S. et al.Coagulopathy and antiphospholipid antibodies in patients with COVID-19.N Engl J Med. 2020; 382: e38Crossref PubMed Scopus (1602) Google Scholar cautioned that this might be a fortuitous coincidence because antiphospholipid antibodies may arise transiently in patients with critical illness and various infections. Moreover, the presence of these antibodies may rarely lead to thrombotic events that are difficult to differentiate from other causes of multifocal thrombosis in critically patients, such as disseminated intravascular coagulation, heparin-induced thrombocytopenia, and thrombotic microangiopathy.3Zhang Y. Xiao M. Zhang S. et al.Coagulopathy and antiphospholipid antibodies in patients with COVID-19.N Engl J Med. 2020; 382: e38Crossref PubMed Scopus (1602) Google Scholar Nonetheless, antiphospholipid syndrome often arises after infectious triggers.4Linnemann B. Antiphospholipid syndrome - an update.Vasa. 2018; 47: 451-464Crossref PubMed Scopus (64) Google Scholar Viral induction of autoimmunity can be explained by various phenomena, including epitope spreading, molecular mimicry, cryptic antigen, and bystander activation.5Lyons-Weiler J. Pathogenic priming likely contributes to serious and critical illness and mortality in COVID-19 via autoimmunity.J Transl Autoimmun. 2020; 3: 100051Crossref PubMed Scopus (99) Google Scholar Remarkably, greater than one-third of the immunogenic proteins in severe acute respiratory syndrome corona virus 2 have potentially problematic homology to proteins that are key to the human adaptive immune system.5Lyons-Weiler J. Pathogenic priming likely contributes to serious and critical illness and mortality in COVID-19 via autoimmunity.J Transl Autoimmun. 2020; 3: 100051Crossref PubMed Scopus (99) Google Scholar Moreover, severe acute respiratory syndrome corona virus 2 seems to induce organ injury through alternative mechanisms beyond direct viral infection, including immunologic injury.2Zhang Y. Cao W. Xiao M. et al.Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia.Zhonghua Xue Ye Xue Za Zhi. 2020; 41: E006PubMed Google Scholar Could antiphospholipid antibodies play a role in inducing coagulopathy in COVID-19 patients? Is coagulopathy in COVID-19 patients a manifestation of mild to very severe forms of antiphospholipid syndrome? This is could be a far-fetched hypothesis but perhaps worth perusing to better understand the pathologic mechanisms underlying the very dangerous coagulopathy observed in COVID-19 patients. Moreover, antiphospholipid antibody testing is simple, rapid, and easily accessible. Further studies are needed to investigate the validity of this hypothesis and its possible clinical implications on anticoagulant therapy management in COVID-19 patients. A dermatologic manifestation of COVID-19: Transient livedo reticularisJournal of the American Academy of DermatologyVol. 83Issue 2Preview Full-Text PDF