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Letters to the Editor
high likelihood of DIC according to the ISTH criteria).11 The vast majority of patients had a score of 2 or less and only one had a score of 4, driven by remarkably high lev- els of D-dimer (38,847 ng/mL). Similarly, SIC scores were similar in the three groups and were all below the cut-off value of 4 and these patients, thus, differed from those with sepsis. FVIII, one of the most potent procoagulants, was strikingly increased with a gradient from low- to high-intensity care, suggesting a state of hypercoagulabil- ity roughly proportional to disease severity. VWF:Ag was even higher than FVIII, causing a proportional reduction of the FVIII/VWF:Ag ratio to the degree of disease sever- ity and, thus, suggesting that endothelial cell perturba- tion concurs with hypercoagulability to explain mecha- nistically the clinical manifestations of VTE associated with COVID-19. These views are supported by the find- ings of Goshua et al.13 who recently showed that VWF and D-dimer were significantly higher in ICU versus non- ICU patients.
Overall, the above findings are consistent with a com- plex crosstalk between inflammation, hemostasis and endothelial cells that, once activated during inflamma- tion, acquire a prothrombotic phenotype which in turn contributes to the procoagulant imbalance. These find- ings are mechanistically plausible with the increased VTE risk in COVID-19 patients, with a possible added contri- bution from fibrinolysis derangement not explored in this study.
The clinical picture of hospitalized COVID-19 patients in Milan differed not only from DIC3 but also from other disorders characterized by hypercoagulability and endothelial perturbation, triggered by systemic inflam- mation, such as the hemophagocytic lymphohistiocyto- sis/macrophage activation syndrome14 and bacterial sep- sis.15 The reasons for such differences may be caused by the evaluation of patients at different disease stages and/or the early start of LMWH prophylaxis, even though striking hypercoagulability was present notwith- standing the implementation of prophylaxis.
In conclusion, this study in COVID-19 patients charac- terizes an acquired coagulopathy associated with hyper- acute inflammation, hypercoagulability and endothelial perturbation broadly proportional to the clinical severity of the infection and to the levels of intensity of care need- ed by the patients.
Flora Peyvandi,1,2 Andrea Artoni,1 Cristina Novembrino,1 Stefano Aliberti,2,3 Mauro Panigada,4 Marco Boscarino,1 Roberta Gualtierotti,1,2 Federica Rossi,1 Roberta Palla,2
Ida Martinelli,1 Giacomo Grasselli,2,4 Francesco Blasi2,3 and Armando Tripodi1
1Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan; 2Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan; 3Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, UOC Pneumologia, Milan and 4Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, UOC Anestesia e Terapia Intensiva Adulti, Milan, Italy
Correspondence:
ARMANDOTRIPODI- armando.tripodi@unimi.it doi:10.3324/haematol.2020.262634
Received: June 19, 2020.
Accepted: August 18, 2020.
Pre-published: August 27, 2020.
Disclosures: FP received personal fees from Roche, Sanofi, Sobi, Spark, and Takeda; CN received personal fees from Instrumentation Laboratory, Roche, Bayer, Novonordisk and Sobi; SA received grants
and personal fees from Bayer Healthcare, Aradigm Corporation, Grifols, Chiesi, and INSMED, Astra Zeneca, Basilea, Zambon, Novartis, Raptor, Actavis UK Ltd, and Horizon; RG received personal fees from Biomarin and Takeda; IM received personal fees from Bayer, Daiichi-Sankyo, Pfizer, Werfen, Grifols and Italfarmaco;
RP reports personal fees from Novonordisk; GG received personal fees from Biotest, Draeger Medical, Getinge Thermofisher and Fisher&Paykel; FB received grants and personal fees from Astrazeneca, Chiesi, GSK, Insmed, and Pfizer, grants from Bayer, personal fees from Guidotti, Grifols, Menarini, Mundipharma, Novartis, and Zambon; AT received speaker’s fees from Werfen, Stago and Sobi; AA, MP, MB and FR have no conflicts of inerest to disclose.
Contributions: FP, AA and AT conceived the study; AA supervised blood samples and data collection; SA, MP, RG, IM, GG and FB managed patients; CN, FR and RP performed tests; MB performed statistical analysis; FP and AT wrote the manuscript; all authors reviewed the data and revised the manuscript.
Acknowledgments: the authors would like to thank Prof Pier Mannuccio Mannucci for his critical revision of the manuscript.
Funding: this work was partially supported by the Italian Ministry of Health - Bando Ricerca Corrente and partially financed by Italian fiscal contribution "5x1000" 2017 devolved to Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico.
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