ENDOTHELIOPATHY IS ESSENTIAL IN COVID-19 ASSOCIATED COAGULOPATHY
Author(s): ,
George Goshua
Affiliations:
Hematology,Yale University School of Medicine,New Haven,United States
,
Alexander Pine
Affiliations:
Hematology,Yale University School of Medicine,New Haven,United States
,
Matthew Meizlish
Affiliations:
Yale University School of Medicine,New Haven,United States
,
C. Hong Chang
Affiliations:
Cardiology,Yale University School of Medicine,New Haven,United States
,
Hanming Zhang
Affiliations:
Cardiology,Yale University School of Medicine,New Haven,United States
,
Parveen Bahel
Affiliations:
Lab Medicine,Yale University School of Medicine,New Haven,United States
,
Audrey Baluha
Affiliations:
Hematology,Yale Cancer Center,New Haven,United States
,
Noffar Bar
Affiliations:
Hematology,Yale University School of Medicine,New Haven,United States
,
Robert Bona
Affiliations:
Hematology,Yale University School of Medicine,New Haven,United States
,
Adrienne Burns
Affiliations:
Hematology,Yale Cancer Center,New Haven,United States
,
Charles Dela Cruz
Affiliations:
Pulmonary, Critical Care, and Sleep Medicine,Yale University School of Medicine,New Haven,United States
,
Anne Dumont
Affiliations:
Hematology,Yale Cancer Center,New Haven,United States
,
Stephanie Halene
Affiliations:
Hematology,Yale University School of Medicine,New Haven,United States
,
John Hwa
Affiliations:
Cardiology,Yale University School of Medicine,New Haven,United States
,
Hope Menninger
Affiliations:
Hematology,Yale Cancer Center,New Haven,United States
,
Natalia Neparidze
Affiliations:
Hematology,Yale University School of Medicine,New Haven,United States
,
Christina Price
Affiliations:
Immunology,Yale University School of Medicine,New Haven,United States
,
Henry Rinder
Affiliations:
Lab Medicine,Yale University School of Medicine,New Haven,United States
,
Jonathan Siner
Affiliations:
Pulmonary, Critical Care, and Sleep Medicine,Yale University School of Medicine,New Haven,United States
,
Hyung Chun
Affiliations:
Cardiology,Yale University School of Medicine,New Haven,United States
Alfred Ian Lee
Affiliations:
Hematology,Yale University School of Medicine,New Haven,United States
EHA Library. Goshua G. 06/14/20; 303393; LB2605
George Goshua
George Goshua
Contributions
Abstract

Abstract: LB2605

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: Late-breaking Oral Session

Background
A striking feature of SARS-CoV-2 pathogenesis is COVID-19 associated coagulopathy (CAC), characterized by increased thrombotic and microvascular complications. To better understand the pathophysiology of CAC, we measured markers of endothelial cell (EC) and platelet activation, PAI1 and coagulation factors in stable and critically ill patients hospitalized with COVID-19. 

Aims
 

1. Evaluate for evidence of endotheliopathy in CAC

2. Evaluate for evidence of platelet activation in CAC

3. Evaluate the involvement of the secondary hemostatic and fibrinolytic system in CAC

4. Identify biomarkers of critical illness and/or mortality in CAC

Methods
Adult patients (≥18 years of age) with COVID-19 treated according to our hospital system’s COVID-19 treatment algorithm were included in this study. EC and platelet activation, PAI-1 and hemostatic studies, were measured with the first morning draw. 

Results
Forty-eight patients in a medical Intensive Care Unit (ICU) and 20 non-ICU patients were included in the study. Soluble P-selectin (sP-sel) was significantly elevated in ICU patients over non-ICU patients or healthy controls. Soluble CD40 ligand (sCD40L) was greater in ICU patients than in controls. Soluble thrombomodulin (sTM) was significantly correlated with mortality, and sTM levels above 3.26 ng/mL segregated with mortality in survival analyses of the entire patient cohort and of ICU patients. Von Willebrand factor (vWF) levels were elevated in both ICU and non-ICU patients albeit at much higher levels in ICU patients. Plasminogen activator inhibitor-1 (PAI-1) was elevated in the vast majority of patients.



Conclusion
As measured by sTM, sP-sel, sCD40L, PAI-1, and vWF, CAC is a prothrombotic state driven by endotheliopathy and platelet activation. These processes occur early in the pathogenesis of COVID-19 infection and becomes more pronounced with worsening severity of disease. sTM levels in particular are significantly associated with mortality in ICU patients.

Session topic: 34. Thrombosis and vascular biology - Biology & Translational Research

Keyword(s): COVID-19, Endothelial dysfunction, Thrombomodulin, Thrombosis

Abstract: LB2605

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: Late-breaking Oral Session

Background
A striking feature of SARS-CoV-2 pathogenesis is COVID-19 associated coagulopathy (CAC), characterized by increased thrombotic and microvascular complications. To better understand the pathophysiology of CAC, we measured markers of endothelial cell (EC) and platelet activation, PAI1 and coagulation factors in stable and critically ill patients hospitalized with COVID-19. 

Aims
 

1. Evaluate for evidence of endotheliopathy in CAC

2. Evaluate for evidence of platelet activation in CAC

3. Evaluate the involvement of the secondary hemostatic and fibrinolytic system in CAC

4. Identify biomarkers of critical illness and/or mortality in CAC

Methods
Adult patients (≥18 years of age) with COVID-19 treated according to our hospital system’s COVID-19 treatment algorithm were included in this study. EC and platelet activation, PAI-1 and hemostatic studies, were measured with the first morning draw. 

Results
Forty-eight patients in a medical Intensive Care Unit (ICU) and 20 non-ICU patients were included in the study. Soluble P-selectin (sP-sel) was significantly elevated in ICU patients over non-ICU patients or healthy controls. Soluble CD40 ligand (sCD40L) was greater in ICU patients than in controls. Soluble thrombomodulin (sTM) was significantly correlated with mortality, and sTM levels above 3.26 ng/mL segregated with mortality in survival analyses of the entire patient cohort and of ICU patients. Von Willebrand factor (vWF) levels were elevated in both ICU and non-ICU patients albeit at much higher levels in ICU patients. Plasminogen activator inhibitor-1 (PAI-1) was elevated in the vast majority of patients.



Conclusion
As measured by sTM, sP-sel, sCD40L, PAI-1, and vWF, CAC is a prothrombotic state driven by endotheliopathy and platelet activation. These processes occur early in the pathogenesis of COVID-19 infection and becomes more pronounced with worsening severity of disease. sTM levels in particular are significantly associated with mortality in ICU patients.

Session topic: 34. Thrombosis and vascular biology - Biology & Translational Research

Keyword(s): COVID-19, Endothelial dysfunction, Thrombomodulin, Thrombosis

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