Abstract Number: OC 68.2
Meeting: ISTH 2021 Congress
Theme: COVID and Coagulation » COVID and Coagulation, Basic Science
Background: Hemostasis activation is a hallmark of COVID-19, and an integral part of a broader host response known as immunothrombosis. Microvesicles (MVs) are lipid-bilayer particles released from cells, and thought to be relevant mediators of immunothrombosis, due to their capacity to transfer proteins such as tissue factor (TF) and fibrinolytic mediators between different cells.
Aims: To quantify platelet, endothelial cell (EC) and red blood cell (RBC) MVs in plasma from patients with COVID-19 and to explore their association with immunothrombosis mediators.
Methods: Samples were obtained from patients admitted to a COVID-19 ward as part of a clinical trial. Samples were collected at admission, before any study intervention. MVs levels were measured in double centrifuged platelet poor plasma by flow cytometry. Coagulation, fibrinolysis and endothelial activation markers were measured by functional or immunological methods. The study was approved by the IRB and all participants provided written informed consent.
Results: Data were obtained from 30 patients and 30 age and sex-matched healthy individuals. Mean time from symptoms onset and length of hospital stay (LOS) were 8.1 ± 2.3 days and 12.9 ± 9.8 days respectively. Twelve patients (40%) required intensive care (ICU), and 28/30 patients survived. Mean D-dimer was 3,609 ± 14,440 ng/mL. Platelet, EC and RBC MV counts are shown in table 1. No association was observed between MV counts and clinical markers of disease severity such as LOS (total or in ICU), oximetry, and lung CT extension score. Associations between MV counts and biomarkers of coagulation, fibrinolysis and EC activation are shown in table 2.
Table 1.
Patients (n=30) |
Healthy individuals (n=30) |
P** | |
Total MV counts (events/ μL) | |||
Platelet (CD41+)¶ | 137.2 ± 74.5 | 37.0 ± 17.0 | <0.0001 |
Endothelial cells (CD144+146+)* | 0.04 (0.02 – 0.09) | 0.02 (0.01 – 0.04) | 0.02 |
Red blood cells (CD235+)* | 0.4 (0.1 – 1.1) | 0.3 (0.1 – 0.7) | 0.4 |
Tissue factor+ MV (events/ μL) | |||
Platelet (CD41+)* | 2.2 (1.36 – 8.16) | 3.2 (1.89 – 7.84) | 0.8 |
Endothelial cell (CD144+146+)* | 0.07 (0.03 – 0.12) | 0.02 (0.02 – 0.05) | 0.005 |
Red blood cells (CD235+)* | 0.0 (0.00 – 0.01) | 0.0 (0.00 – 0.01) | 0.9 |
¶ mean ± SD; * median (interquartile range); **Mann-Whitney test or t-test for non-parametric and parametric data respectively. |
Microvesicle counts in COVID-19 patients at admission
Table 2.
Marker of coagulation, fibrinolysis or EC activation |
Correlation coefficient * | P | |
Total MV counts | |||
Platelet (CD41+) | Fibrinogen Factor VIII:C Factor IX:C VWF:Ag Angiopoietin-1 Tie-2 VEGF-A Soluble uPAR |
0.677 0.377 0.444 0.411 0.534 0.308 0.512 0.480 |
<0.0001 0.004 0.0004 0.001 <0.0001 0.02 <0.0001 0.0001 |
Endothelial cell (CD144+146+) | – | ||
Red blood cells (CD235+) | – | ||
Tissue factor+ MV | |||
Platelet (CD41+) | – | ||
Endothelial cell (CD144+146+) | CT score Platelet Factor IX:C VWF:Ag Tie2 |
-0.370 -0.311 0.303 0.352 0.324 |
0.04 0.02 0.02 0.006 0.01 |
Red blood cells (CD235+) | – | ||
Coagulation factor activities were measured using one-stage coagulometric assays; *Pearson or Spearman correlation coefficient for parametric and non-parametric data respectively. Correlations < 0.3 are not shown. |
Association between MV counts and markers of coagulation, fibrinolysis and endothelial activation in COVID-19
Conclusions: Increased levels of MV from platelets and EC were observed in COVID-19. The association of these MVs with markers of coagulation and fibrinolytic activation, and with elements of the Tie2/Ang1 pathway warrant additional studies on the contribution of these pathways to the pathogenesis of COVID-19.
To cite this abstract in AMA style:
Barbosa MS, Lima F, Moraes CRP, Santos IP, Borba Junior IT, Huber SC, Montalvao SAL, Annichino-Bizzacchi JM, Palma AC, Ulaf RG, Bernardes AF, Mansour E, Moretti ML, Velloso LA, De Paula EV. Circulating Levels of Platelet, Endothelial and Red Blood Cell Microvesicles in COVID-19: Association with Biomarkers of Coagulation, Fibrinolysis and Angiogenesis [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/circulating-levels-of-platelet-endothelial-and-red-blood-cell-microvesicles-in-covid-19-association-with-biomarkers-of-coagulation-fibrinolysis-and-angiogenesis/. Accessed November 29, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/circulating-levels-of-platelet-endothelial-and-red-blood-cell-microvesicles-in-covid-19-association-with-biomarkers-of-coagulation-fibrinolysis-and-angiogenesis/