Role of lupus anticoagulant and von Willebrand factor in chronic reactive endotheliitis in COVID-19
Authors: Manuel Lorenzo López Reboiro, Rebeca Suárez Fuentetaja, Raquel Gutiérrez López, Beatriz Ares Castro-Conde, Cristina Sardiña González, Inés Navarro Menéndez, Marco Francisco Pereyra Barrionuevo, M. Teresa Alves Pérez, José López Castro
Journal: Journal of Infection (2021)

We read with interest the excellent letter of Falcinelli et at.1Falcinelli E. Petito E. Becattini C. De Robertis E. Paliani U. Sebastiano M. Vaudo G. Guglielmini G. Paciullo F. Cerotto V. Malvestiti M. Gori F. Bury L. Lazzarini T. Gresele P. Role of endotelial dysfunction in the thrombotic complications of COVID-19 patients.J Infect. 2020; (Dec 2:S0163-4453(20)30760-X)https://doi.org/10.1016/j.jinf.2020.11.041Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar entitled "Role of endothelial dysfunction in the thrombotic complications of COVID-19 patients" recently published in the Journal. By the way of having being cited in this letter,2López Castro J COVID-19 and thrombosis: beyond a casual association.Med Clin. 2020; 155: 44https://doi.org/10.1016/j.medcle.2020.04.004Crossref PubMed Google Scholar we would like to present some practical considerations based on our experience in a small series of patients with severe SARS-CoV-2 pneumonia. Currently, there is a better understanding of the pathophysiological mechanisms underlying disseminated microthrombosis at the endothelial level, reactive chronic endotheliitis,3López Castro J Post-COVID-19 syndrome (PC19S): chronic reactive endotheliitis and disseminated vascular disease.Acta Med Port. 2020; 33: 855Crossref PubMed Google Scholar release of von Willebrand (vWF) multimers4Teuwen L.A. Geldhof V. Pasut A. Carmeliet P. COVID-19: the vasculature unleashed.Nat Rev Immunol. 2020; 20: 389-391Crossref PubMed Scopus (755) Google Scholar and the coagulopathy as a hallmark of severe COVID-19, mainly characterized by a pro-coagulative state with high D-dimer and thrombin levels. Measurement of increasing D-dimer and thrombin levels have prognostic value since all genetic variants of SARS-CoV-2 show a high thrombogenic potential, particularly in patients of advanced age. In our limited group of 35 patients with severe SARS-CoV-2 pneumonia, 20 men with a mean age of 76.7 ± 12.8 years, the levels of activity of vWF were randomly determined in 17 patients, and in all of which were above 200% (upper limit of normal 150%). This is in agreement with the results reported by Falcinelli et al.1Falcinelli E. Petito E. Becattini C. De Robertis E. Paliani U. Sebastiano M. Vaudo G. Guglielmini G. Paciullo F. Cerotto V. Malvestiti M. Gori F. Bury L. Lazzarini T. Gresele P. Role of endotelial dysfunction in the thrombotic complications of COVID-19 patients.J Infect. 2020; (Dec 2:S0163-4453(20)30760-X)https://doi.org/10.1016/j.jinf.2020.11.041Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar In addition, lupus anticoagulant (LA) testing was performed, with significantly higher values in patients requiring non-invasive mechanical ventilation (NIMV) as compared to those requiring conventional oxygen therapy only (1.41 ± 0.32 vs. 1.1 ± 0.07 IU; P = 0.024) (Fig. 1a). In 8 patients, LA values were higher than 1.1 IU and 4 of them needed NIMV, whereas none of the patients with LA levels < 1.1 IU required ventilatory support. These data indicate that in addition to vWF and other molecules, such as fibrinogen, thrombin, and beta-2 glycoprotein I (beta-2 GPI), LA plays a crucial role in thrombogenesis induced by SARS-CoV-2 infection. Beta-2 GPI promotes LA activity, with platelet adhesion, aggregation, release of tissue factor and activation of the coagulation cascade (Fig. 1b), leading to a hypercoagulable state, which may be frequently irreversible in advanced stages.5Aoi S. Kakkar A.M. Golowa Y. Grushko M. Coyle C.M. Elrafei T. Langston M.D. Faillace R.T. Bangalore S. Sokol S.I. Saddle pulmonary embolism and clot in transit in COVID-19 infection: a case report of catastrophic venous thromboembolism.Eur Heart J Case Rep. 2020; 4: 1-6Crossref PubMed Scopus (7) Google Scholar On the other hand, the cytokine storm can amplify platelets' thrombotic response by increasing platelet production and development of disseminated microthrombi in different territories of the vasculature, with direct involvement in the pathogenesis of thrombosis in COVID-19. Another consequence is that high LA levels are directly related to a higher risk for prothrombotic complications, progression to the need of mechanical ventilation, and poor clinical outcome. The combination of both parameters, vWF and LA, would be a very useful predictive tool to assess the risk of hospitalization as well as to assess which patients would be candidates for mechanical ventilation or even to evaluate the risk of death. Therefore, it would be advisable to evaluate in prospective studies the possibility of routinely measuring serum levels of vWF and LA as prognostic predictive markers of severe COVID19 and at risk of acute respiratory distress syndrome.6Sieiro Santos C. López Castro J Post-coronavirus disease syndrome and disseminated microthrombosis: the role of von Willebrand factor and antiphospholipid antibodies.Clinics. 2021; 76: e2784Crossref PubMed Google Scholar Assessment of these parameters may contribute to determine which of the patients that recover from the acute phase of the disease will present chronic or permanent endothelial damage, and in some cases, for predicting reactivation in different microvasculature territories, such as vasa vasorum of the peripheral nerves and cerebral microvasculature causing a proinflammatory status (endotheliitis)1Falcinelli E. Petito E. Becattini C. De Robertis E. Paliani U. Sebastiano M. Vaudo G. Guglielmini G. Paciullo F. Cerotto V. Malvestiti M. Gori F. Bury L. Lazzarini T. Gresele P. Role of endotelial dysfunction in the thrombotic complications of COVID-19 patients.J Infect. 2020; (Dec 2:S0163-4453(20)30760-X)https://doi.org/10.1016/j.jinf.2020.11.041Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar leading to chronic neuropathic or neuropsychiatric late sequelae. The authors declare no conflict of interest. None to be declared.