Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study
MD, A B Pine MD, N Bar MD George Goshua, Alexander B Pine, Matthew L Meizlish, PhD C-Hong Chang, PhD Hanming Zhang, MS, C Tormey MD Parveen Bahel, Audrey Baluha, Noffar Bar, MD Robert D Bona, Adrienne J Burns, Charles S Dela Cruz, Anne Dumont, MD Stephanie Halene, Prof John Hwa, MD Jonathan Koff, Hope Menninger, MD Natalia Neparidze, Christina Price, MD Jonathan M Siner, Christopher Tormey, Henry M Rinder, Hyung J Chun, MD Alfred I Lee
The Lancet Haematology, doi:10.1016/s2352-3026(20)30216-7
Background An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19associated coagulopathy, characterised by increased thrombotic and microvascular complications. Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy. To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19. Methods In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital. Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range. We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes. We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable. We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality. Kaplan-Meier analysis was used to further explore the association between biochemical markers and survival. Findings 68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls. Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0•0001) and soluble P-selectin (15•9 ng/mL [4•8] vs 11•2 ng/mL [3•1]; p=0•0014). VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients. We found mortality to be significantly correlated with VWF antigen (r=0•38; p=0•0022) and soluble thrombomodulin (r=0•38; p=0•0078) among all patients. In all patients, soluble thrombomodulin concentrations greater than 3•26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0•0050) and lower likelihood of survival on Kaplan-Meier analysis (hazard ratio 5•9, 95% CI 1•9-18•4; p=0•0087). Interpretation Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death. Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19.
Contributors GG, ABP, MLM, CT, HMR, HJC, and AIL designed the study. C-HC, HZ, and PB did assays to measure haemostatic factors and endothelial cell and platelet biomarkers. AB, RDB, AJB, AD, SH, HM, NN, HMR, HJC, and AIL contributed to sample collection. NB, RDB, CSDC, SH, JH, JK, NN, CP, and JMS contributed valuable ideas and input during the study. GG, ABP, MLM, HJC, and AIL wrote the manuscript and all authors participated in editing the manuscript. GG, ABP, and MLM contributed equally as first authors. HJC and AIL contributed equally as senior investigators.
Declaration of interests NN reports research funding support from Janssen and GlaxoSmithKline and is an advisory board member for Sanofi, outside of the submitted work. All other authors declare no competing interests.
References
Ackermann, Verleden, Kuehnel, Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2015432Asakura, Ontachi, Mizutani, An enhanced fibrinolysis prevents the development of multiple organ failure in disseminated intravascular coagulation in spite of much activation of blood coagulation, Crit Care Med
Aso, Fujiwara, Tayama, Takebayashi, Inukai et al., Relationship between soluble thrombomodulin in plasma and coagulation or fibrinolysis in type 2 diabetes, Clin Chim Acta
Bunte, Patnaik, Pritzker, Burns, Pulmonary venoocclusive disease following hematopoietic stem cell transplantation: a rare model of endothelial dysfunction, Bone Marrow Transplant
Diurno, Numis, Porta, Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience, Eur Rev Med Pharmacol Sci
Escher, Breakey, Lämmle, Severe COVID-19 infection associated with endothelial activation, Thromb Res
Gralinski, Bankhead A 3rd, Jeng, Mechanisms of severe acute respiratory syndrome coronavirus-induced acute lung injury, MBio
Handt, Jerome, Tietze, Hantgan, Plasminogen activator inhibitor-1 secretion of endothelial cells increases fibrinolytic resistance of an in vitro fibrin clot: evidence for a key role of endothelial cells in thrombolytic resistance, Blood
Helms, Tacquard, Severac, High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study, Intensive Care Med
Johansen, Johansson, Ostrowski, Profound endothelial damage predicts impending organ failure and death in sepsis, Semin Thromb Hemost
Kayal, Jaïs, Aguini, Chaudière, Labrousse, Elevated circulating E-selectin, intercellular adhesion molecule 1, and von Willebrand factor in patients with severe infection, Am J Respir Crit Care Med
Kerr, Stirling, Ludlam, Interleukin 6 and haemostasis, Br J Haematol
Klok, Kruip, Van Der Meer, Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis, Thromb Res
Levi, Scully, How I treat disseminated intravascular coagulation, Blood
Levi, Scully, Singer, The role of ADAMTS-13 in the coagulopathy of sepsis, J Thromb Haemost
Liu, Li, Liu, Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19, Acta Pharm Sin B,
doi:10.1016/j.apsb.2020.04.008Llitjos, Leclerc, Chochois, High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients, J Thromb Haemost,
doi:10.1111/jth.14869López-Aguirre, Páramo, Endothelial cell and hemostatic activation in relation to cytokines in patients with sepsis, Thromb Res
Makrilakis, Fragiadaki, Smith, Sfikakis, Kitas, Interrelated reduction of chemerin and plasminogen activator inhibitor-1 serum levels in rheumatoid arthritis after interleukin-6 receptor blockade, Clin Rheumatol
Mehta, Mcauley, Brown, Sanchez, Tattersall et al., COVID-19: consider cytokine storm syndromes and immunosuppression, Lancet
Nawroth, Häring, Thrombomodulin and coronary heart disease, Lancet
Panigada, Bottino, Tagliabue, Hypercoagulability of COVID-19 patients in intensive care unit. A report of thromboelastography findings and other parameters of hemostasis, J Thromb Haemost,
doi:10.1111/jthRubin, Wiener-Kronish, Murray, Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome, J Clin Invest
Siddiqi, Mehra, COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal, J Heart Lung Transplant
Tang, Li, Wang, Sun, Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia, J Thromb Haemost
Varga, Flammer, Steiger, Endothelial cell infection and endotheliitis in COVID-19, Lancet
Yadav, Kor, Platelets in the pathogenesis of acute respiratory distress syndrome, Am J Physiol Lung Cell Mol Physiol
Yasmeen, Akram, Hainsworth, Kruuse, Cyclic nucleotide phosphodiesterases (PDEs) and endothelial function in ischaemic stroke. A review, Cell Signal
DOI record:
{
"DOI": "10.1016/s2352-3026(20)30216-7",
"ISSN": [
"2352-3026"
],
"URL": "http://dx.doi.org/10.1016/S2352-3026(20)30216-7",
"alternative-id": [
"S2352302620302167"
],
"assertion": [
{
"label": "This article is maintained by",
"name": "publisher",
"value": "Elsevier"
},
{
"label": "Article Title",
"name": "articletitle",
"value": "Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study"
},
{
"label": "Journal Title",
"name": "journaltitle",
"value": "The Lancet Haematology"
},
{
"label": "CrossRef DOI link to publisher maintained version",
"name": "articlelink",
"value": "https://doi.org/10.1016/S2352-3026(20)30216-7"
},
{
"label": "CrossRef DOI link to the associated document",
"name": "associatedlink",
"value": "https://doi.org/10.1016/S2352-3026(20)30215-5"
},
{
"label": "Content Type",
"name": "content_type",
"value": "article"
},
{
"label": "Copyright",
"name": "copyright",
"value": "© 2020 Elsevier Ltd. All rights reserved."
}
],
"author": [
{
"affiliation": [],
"family": "Goshua",
"given": "George",
"sequence": "first"
},
{
"affiliation": [],
"family": "Pine",
"given": "Alexander B",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Meizlish",
"given": "Matthew L",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Chang",
"given": "C-Hong",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Zhang",
"given": "Hanming",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Bahel",
"given": "Parveen",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Baluha",
"given": "Audrey",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Bar",
"given": "Noffar",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Bona",
"given": "Robert D",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Burns",
"given": "Adrienne J",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Dela Cruz",
"given": "Charles S",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Dumont",
"given": "Anne",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Halene",
"given": "Stephanie",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Hwa",
"given": "John",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Koff",
"given": "Jonathan",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Menninger",
"given": "Hope",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Neparidze",
"given": "Natalia",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Price",
"given": "Christina",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Siner",
"given": "Jonathan M",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Tormey",
"given": "Christopher",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Rinder",
"given": "Henry M",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Chun",
"given": "Hyung J",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Lee",
"given": "Alfred I",
"sequence": "additional"
}
],
"container-title": "The Lancet Haematology",
"container-title-short": "The Lancet Haematology",
"content-domain": {
"crossmark-restriction": true,
"domain": [
"clinicalkey.jp",
"clinicalkey.com",
"clinicalkey.es",
"clinicalkey.com.au",
"clinicalkey.fr",
"thelancet.com",
"elsevier.com",
"sciencedirect.com"
]
},
"created": {
"date-parts": [
[
2020,
6,
30
]
],
"date-time": "2020-06-30T22:38:44Z",
"timestamp": 1593556724000
},
"deposited": {
"date-parts": [
[
2020,
7,
29
]
],
"date-time": "2020-07-29T01:39:12Z",
"timestamp": 1595986752000
},
"indexed": {
"date-parts": [
[
2025,
9,
29
]
],
"date-time": "2025-09-29T11:54:46Z",
"timestamp": 1759146886816
},
"is-referenced-by-count": 907,
"issue": "8",
"issued": {
"date-parts": [
[
2020,
8
]
]
},
"journal-issue": {
"issue": "8",
"published-print": {
"date-parts": [
[
2020,
8
]
]
}
},
"language": "en",
"license": [
{
"URL": "https://www.elsevier.com/tdm/userlicense/1.0/",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2020,
8,
1
]
],
"date-time": "2020-08-01T00:00:00Z",
"timestamp": 1596240000000
}
}
],
"link": [
{
"URL": "https://api.elsevier.com/content/article/PII:S2352302620302167?httpAccept=text/xml",
"content-type": "text/xml",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://api.elsevier.com/content/article/PII:S2352302620302167?httpAccept=text/plain",
"content-type": "text/plain",
"content-version": "vor",
"intended-application": "text-mining"
}
],
"member": "78",
"original-title": [],
"page": "e575-e582",
"prefix": "10.1016",
"published": {
"date-parts": [
[
2020,
8
]
]
},
"published-print": {
"date-parts": [
[
2020,
8
]
]
},
"publisher": "Elsevier BV",
"reference": [
{
"DOI": "10.1016/j.healun.2020.03.012",
"article-title": "COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal",
"author": "Siddiqi",
"doi-asserted-by": "crossref",
"first-page": "405",
"journal-title": "J Heart Lung Transplant",
"key": "10.1016/S2352-3026(20)30216-7_bib2",
"volume": "39",
"year": "2020"
},
{
"DOI": "10.1016/S0140-6736(20)30628-0",
"article-title": "COVID-19: consider cytokine storm syndromes and immunosuppression",
"author": "Mehta",
"doi-asserted-by": "crossref",
"first-page": "1033",
"journal-title": "Lancet",
"key": "10.1016/S2352-3026(20)30216-7_bib3",
"volume": "395",
"year": "2020"
},
{
"DOI": "10.1111/jth.14768",
"article-title": "Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia",
"author": "Tang",
"doi-asserted-by": "crossref",
"first-page": "844",
"journal-title": "J Thromb Haemost",
"key": "10.1016/S2352-3026(20)30216-7_bib4",
"volume": "18",
"year": "2020"
},
{
"DOI": "10.1111/jth.14850",
"article-title": "Hypercoagulability of COVID-19 patients in intensive care unit. A report of thromboelastography findings and other parameters of hemostasis",
"author": "Panigada",
"doi-asserted-by": "crossref",
"journal-title": "J Thromb Haemost",
"key": "10.1016/S2352-3026(20)30216-7_bib5",
"year": "2020"
},
{
"DOI": "10.1111/jth.14869",
"article-title": "High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients",
"author": "Llitjos",
"doi-asserted-by": "crossref",
"journal-title": "J Thromb Haemost",
"key": "10.1016/S2352-3026(20)30216-7_bib6",
"year": "2020"
},
{
"DOI": "10.1016/j.thromres.2020.04.041",
"article-title": "Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis",
"author": "Klok",
"doi-asserted-by": "crossref",
"first-page": "148",
"journal-title": "Thromb Res",
"key": "10.1016/S2352-3026(20)30216-7_bib7",
"volume": "191",
"year": "2020"
},
{
"article-title": "Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy",
"author": "Carsana",
"journal-title": "medRxiv",
"key": "10.1016/S2352-3026(20)30216-7_bib8",
"year": "2020"
},
{
"DOI": "10.1056/NEJMoa2015432",
"article-title": "Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19",
"author": "Ackermann",
"doi-asserted-by": "crossref",
"journal-title": "N Engl J Med",
"key": "10.1016/S2352-3026(20)30216-7_bib9",
"year": "2020"
},
{
"DOI": "10.1016/S0140-6736(20)30937-5",
"article-title": "Endothelial cell infection and endotheliitis in COVID-19",
"author": "Varga",
"doi-asserted-by": "crossref",
"first-page": "1417",
"journal-title": "Lancet",
"key": "10.1016/S2352-3026(20)30216-7_bib10",
"volume": "395",
"year": "2020"
},
{
"DOI": "10.1007/s00134-020-06062-x",
"article-title": "High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study",
"author": "Helms",
"doi-asserted-by": "crossref",
"first-page": "1089",
"journal-title": "Intensive Care Med",
"key": "10.1016/S2352-3026(20)30216-7_bib11",
"volume": "46",
"year": "2020"
},
{
"DOI": "10.1016/j.thromres.2020.04.014",
"article-title": "Severe COVID-19 infection associated with endothelial activation",
"author": "Escher",
"doi-asserted-by": "crossref",
"first-page": "62",
"journal-title": "Thromb Res",
"key": "10.1016/S2352-3026(20)30216-7_bib12",
"volume": "190",
"year": "2020"
},
{
"DOI": "10.1016/S0049-3848(98)00200-X",
"article-title": "Endothelial cell and hemostatic activation in relation to cytokines in patients with sepsis",
"author": "López-Aguirre",
"doi-asserted-by": "crossref",
"first-page": "95",
"journal-title": "Thromb Res",
"key": "10.1016/S2352-3026(20)30216-7_bib13",
"volume": "94",
"year": "1999"
},
{
"DOI": "10.1016/S0140-6736(99)90039-9",
"article-title": "Thrombomodulin and coronary heart disease",
"author": "Nawroth",
"doi-asserted-by": "crossref",
"first-page": "1722",
"journal-title": "Lancet",
"key": "10.1016/S2352-3026(20)30216-7_bib14",
"volume": "353",
"year": "1999"
},
{
"DOI": "10.1016/S0009-8981(00)00335-1",
"article-title": "Relationship between soluble thrombomodulin in plasma and coagulation or fibrinolysis in type 2 diabetes",
"author": "Aso",
"doi-asserted-by": "crossref",
"first-page": "135",
"journal-title": "Clin Chim Acta",
"key": "10.1016/S2352-3026(20)30216-7_bib15",
"volume": "301",
"year": "2000"
},
{
"DOI": "10.1097/00003246-200106000-00015",
"article-title": "An enhanced fibrinolysis prevents the development of multiple organ failure in disseminated intravascular coagulation in spite of much activation of blood coagulation",
"author": "Asakura",
"doi-asserted-by": "crossref",
"first-page": "1164",
"journal-title": "Crit Care Med",
"key": "10.1016/S2352-3026(20)30216-7_bib16",
"volume": "29",
"year": "2001"
},
{
"DOI": "10.1007/s10067-014-2704-1",
"article-title": "Interrelated reduction of chemerin and plasminogen activator inhibitor-1 serum levels in rheumatoid arthritis after interleukin-6 receptor blockade",
"author": "Makrilakis",
"doi-asserted-by": "crossref",
"first-page": "419",
"journal-title": "Clin Rheumatol",
"key": "10.1016/S2352-3026(20)30216-7_bib17",
"volume": "34",
"year": "2015"
},
{
"DOI": "10.1128/mBio.00271-13",
"article-title": "Mechanisms of severe acute respiratory syndrome coronavirus-induced acute lung injury",
"author": "Gralinski",
"doi-asserted-by": "crossref",
"first-page": "1",
"journal-title": "MBio",
"key": "10.1016/S2352-3026(20)30216-7_bib18",
"volume": "4",
"year": "2013"
},
{
"DOI": "10.1182/blood.V87.10.4204.bloodjournal87104204",
"article-title": "Plasminogen activator inhibitor-1 secretion of endothelial cells increases fibrinolytic resistance of an in vitro fibrin clot: evidence for a key role of endothelial cells in thrombolytic resistance",
"author": "Handt",
"doi-asserted-by": "crossref",
"first-page": "4204",
"journal-title": "Blood",
"key": "10.1016/S2352-3026(20)30216-7_bib19",
"volume": "87",
"year": "1996"
},
{
"DOI": "10.1172/JCI114733",
"article-title": "Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome",
"author": "Rubin",
"doi-asserted-by": "crossref",
"first-page": "474",
"journal-title": "J Clin Invest",
"key": "10.1016/S2352-3026(20)30216-7_bib20",
"volume": "86",
"year": "1990"
},
{
"DOI": "10.1164/ajrccm.157.3.9705034",
"article-title": "Elevated circulating E-selectin, intercellular adhesion molecule 1, and von Willebrand factor in patients with severe infection",
"author": "Kayal",
"doi-asserted-by": "crossref",
"first-page": "776",
"journal-title": "Am J Respir Crit Care Med",
"key": "10.1016/S2352-3026(20)30216-7_bib21",
"volume": "157",
"year": "1998"
},
{
"DOI": "10.1152/ajplung.00266.2015",
"article-title": "Platelets in the pathogenesis of acute respiratory distress syndrome",
"author": "Yadav",
"doi-asserted-by": "crossref",
"first-page": "L915",
"journal-title": "Am J Physiol Lung Cell Mol Physiol",
"key": "10.1016/S2352-3026(20)30216-7_bib22",
"volume": "309",
"year": "2015"
},
{
"DOI": "10.1038/sj.bmt.1705990",
"article-title": "Pulmonary veno-occlusive disease following hematopoietic stem cell transplantation: a rare model of endothelial dysfunction",
"author": "Bunte",
"doi-asserted-by": "crossref",
"first-page": "677",
"journal-title": "Bone Marrow Transplant",
"key": "10.1016/S2352-3026(20)30216-7_bib23",
"volume": "41",
"year": "2008"
},
{
"DOI": "10.1055/s-0034-1398377",
"article-title": "Profound endothelial damage predicts impending organ failure and death in sepsis",
"author": "Johansen",
"doi-asserted-by": "crossref",
"first-page": "16",
"journal-title": "Semin Thromb Hemost",
"key": "10.1016/S2352-3026(20)30216-7_bib24",
"volume": "41",
"year": "2015"
},
{
"DOI": "10.1182/blood-2017-10-804096",
"article-title": "How I treat disseminated intravascular coagulation",
"author": "Levi",
"doi-asserted-by": "crossref",
"first-page": "845",
"journal-title": "Blood",
"key": "10.1016/S2352-3026(20)30216-7_bib25",
"volume": "131",
"year": "2018"
},
{
"DOI": "10.1111/jth.13953",
"article-title": "The role of ADAMTS-13 in the coagulopathy of sepsis",
"author": "Levi",
"doi-asserted-by": "crossref",
"first-page": "646",
"journal-title": "J Thromb Haemost",
"key": "10.1016/S2352-3026(20)30216-7_bib26",
"volume": "16",
"year": "2018"
},
{
"DOI": "10.1016/j.cellsig.2019.05.011",
"article-title": "Cyclic nucleotide phosphodiesterases (PDEs) and endothelial function in ischaemic stroke. A review",
"author": "Yasmeen",
"doi-asserted-by": "crossref",
"first-page": "108",
"journal-title": "Cell Signal",
"key": "10.1016/S2352-3026(20)30216-7_bib27",
"volume": "61",
"year": "2019"
},
{
"article-title": "Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19",
"author": "Liu",
"journal-title": "Acta Pharm Sin B",
"key": "10.1016/S2352-3026(20)30216-7_bib28",
"year": "2020"
},
{
"article-title": "Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience",
"author": "Diurno",
"first-page": "4040",
"journal-title": "Eur Rev Med Pharmacol Sci",
"key": "10.1016/S2352-3026(20)30216-7_bib29",
"volume": "24",
"year": "2020"
},
{
"DOI": "10.1046/j.1365-2141.2001.03061.x",
"article-title": "Interleukin 6 and haemostasis",
"author": "Kerr",
"doi-asserted-by": "crossref",
"first-page": "3",
"journal-title": "Br J Haematol",
"key": "10.1016/S2352-3026(20)30216-7_bib30",
"volume": "115",
"year": "2001"
}
],
"reference-count": 29,
"references-count": 29,
"relation": {},
"resource": {
"primary": {
"URL": "https://linkinghub.elsevier.com/retrieve/pii/S2352302620302167"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"title": "Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study",
"type": "journal-article",
"update-policy": "http://dx.doi.org/10.1016/elsevier_cm_policy",
"volume": "7"
}
