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. 2023 Jan 3;12(1):193.
doi: 10.3390/cells12010193.

Pervasive Platelet Secretion Defects in Patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Johannes Kalbhenn  1 , Jan-Steffen Pooth  2 , Georg Trummer  3 , David Kranzhöfer  4 , Axel Schlagenhauf  5 , Barbara Zieger  6
Affiliations

Pervasive Platelet Secretion Defects in Patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Johannes Kalbhenn et al. Cells. .

Abstract

Critically ill COVID-19 patients suffer from thromboembolic as well as bleeding events. Endothelial dysfunction, spiking of von Willebrand factor (vWF), and excessive cytokine signaling result in coagulopathy associated with substantial activation of plasmatic clotting factors. Thrombocytopenia secondary to extensive platelet activation is a frequent finding, but abnormal platelet dysfunction may also exist in patients with normal platelet counts. In this study, we performed analyses of platelet function and of von Willebrand factor in critically ill COVID-19 patients (n = 13). Platelet aggregometry was performed using ADP, collagen, epinephrin, and ristocetin. VWF and fibrinogen binding of platelets and CD62 and CD63 expression after thrombin stimulation were analyzed via flow cytometry. In addition, VWF antigen (VWF:Ag), collagen binding capacity (VWF:CB), and multimer analysis were performed next to routine coagulation parameters. All patients exhibited reduced platelet aggregation and decreased CD62 and CD63 expression. VWF binding of platelets was reduced in 12/13 patients. VWF:CB/VWF:Ag ratios were pathologically decreased in 2/13 patients and elevated in 2/13 patients. Critically ill COVID-19 patients exhibit platelet secretion defects independent of thrombocytopenia. Platelet exhaustion and VWF dysfunction may result in impaired primary hemostasis and should be considered when treating coagulopathy in these patients.

Keywords: COVID-19; platelet secretion; von Willebrand factor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Platelet counts (a) and platelet aggregation analysis of COVID-19 patients (n = 13) after stimulation with ADP, collagen, epinephrin, or ristocetin. (b) Gray area marks normal range. Bars depict mean ± SD.
Figure 2
Figure 2
Surface expression of CD62 (a) and CD63 (b) in diluted platelet-rich plasma obtained from COVID-19 patients (n = 13) in comparison to day controls after stimulation with increasing concentrations of thrombin. (c) Von Willebrand binding after stimulation with increasing concentrations of ristocetin. (d) Fibrinogen binding after stimulation with increasing concentrations of ADP. Results are presented as mean ± SD. Gray area marks normal range; for difference from day controls.
Figure 3
Figure 3
VWF:Ag and VWF:CB (a), and VWF:CB/VWF:Ag ratio (b) in COVID-19 patients (n = 13). Gray area marks normal range.
Figure 4
Figure 4
Spearman correlation analyses between maximum CD62/CD63 expression after incubation with 1 U/mL thrombin with platelet counts (a,b), VWF:CB/VWF:Ag ratio (c,d), and aPTT (e,f).
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