Von Willebrand factor with increased binding capacity is associated with reduced platelet aggregation but enhanced agglutination in COVID-19 patients: another COVID-19 paradox?
Patients with Coronavirus-associated disease-2019 (COVID-19) display alterations of the hemostatic system and the presence
of a prothrombotic status frequently leading to vascular complications. However, the impact of COVID-19 on platelet
activity, aggregation and agglutination still needs to be clarified. We measured total levels of von Willebrand factor (vWF)
and vWF binding to the platelet glycoprotein (Gp) complex (GPIb-IX-V), in a cohort of COVID-19 patients admitted to the
intensive care unit of our Institution. Moreover, we evaluated platelet aggregation in response to agonists (ADP, collagen,
arachidonic acid) and platelet agglutination in response to ristocetin. We found that levels of vWF antigen and the active
form of vWF binding to platelets (vWF:RCo), were markedly increased in these patients. These results were associated
with higher agglutination rates induced by ristocetin, thereby indirectly indicating an increased capability of vWF to bind
to platelets. Conversely, we found that platelet aggregation in response to both ADP and collagen was lower in COVID-
19 patients compared to healthy volunteers. This study shows that COVID-19 is associated with increased vWF-induced
platelet agglutination but reduced platelet responsivity to aggregation stimuli. Our findings have translational relevance
since platelet adhesion to vWF may represent a marker to predict possible complications and better delineate therapeutic
strategies in COVID-19 patients.