Platelet Distribution Width Is Associated with P-Selectin Dependent Platelet Function: Results from the Moli-Family Cohort Study

Abstract

Defined as an index of platelet size heterogeneity, the platelet distribution width (PDW) is still a poorly characterized marker of platelet function in (sub)clinical disease. We presently validated PDW as a marker of P-selectin dependent platelet activation in the Moli-family cohort. Platelet-bound P-selectin and platelet/leukocyte mixed aggregates were measured by flow cytometry in freshly collected venous blood, both before and after in vitro platelet activation, and coagulation time was assessed in unstimulated and LPS- or TNFα-stimulated whole blood. Closure Times (CT) were measured in a Platelet Function Analyzer (PFA)-100. Multivariable linear mixed effect regression models (with age, sex and platelet count as fixed and family structure as random effect) revealed PDW to be negatively associated with platelet P-selectin, platelet/leukocyte aggregates and von Willebrand factor (VWF), and positively with PFA-100 CT, and LPS- and TNF-α-stimulated coagulation times. With the exception of VWF, all relationships were sex-independent. In contrast, no association was found between mean platelet volume (MPV) and these variables. PDW seems a simple, useful marker of ex vivo and in vitro P-selectin dependent platelet activation. Investigations of larger cohorts will define the usefulness of PDW as a risk predictor of thrombo-inflammatory conditions where activated platelets play a contributing role.

Mineralocorticoid Receptor Pathway Is a Key Mediator of Carfilzomib-induced Nephrotoxicity: Preventive Role of Eplerenone

“…Decreased PDW is associated with decreased platelet activity and thus decreased thrombogenicity. 16 Moreover, Cfz led to an increased ADAM-TS13 activity and increased cleavage of vWF ( Figure S3B-D ). Since TMA is associated with decreased ADAM-TS13 activity, which leads to decreased vWF cleavage, 17 it seems that TMA does not contribute to the molecular mechanism of Cfz’s nephrotoxicity in mice.…”

BTK Inhibitors Impair Platelet-Mediated Antifungal Activity

“…In perspective, additional studies are required to (i) precisely assess the risk of IFIs occurring in patients treated with ibrutinib and, more importantly, with other BTKis; (ii) disclose whether the multifunctional impairment in innate immunity is strictly caused by the inhibition of BTK outside the BCR (i.e., on unwanted cellular targets expressing BTK) or, more likely, is also mediated by unselective molecular inhibition of other kinases (such as TEC); (iii) fully characterize platelet proteomic and structural modifications occurring in the presence of BTKis; and (iv) test new immunological tools and specific inflammatory biomarkers, including platelet parameters, such as mean platelet volume (MPV) and platelet distribution width (PDW) [68,69], aiming to identify and monitor 'protective vs. permissive' immune profiles in patients with or at risk for IFIs.…”

High platelet distribution width is an independent risk factor of postoperative pneumonia in patients with type A acute aortic dissection

“…In this study, we confirmed a straight-line relationship between admission PDW and postoperative pneumonia in patients with AAAD and demonstrated that high PDW was significantly associated with an increased risk of postoperative pneumonia in patients with AAAD after adjustment for potential confounders. PDW, routinely measured by automated cell counters, has emerged as a relatively reliable marker of thrombopoiesis and platelet function (18). PDW is used to reflect the variability in platelet size and detect fractions of larger platelets that are more active, both enzymatically and metabolically (8).…”

“…PDW, routinely measured by automated cell counters, has emerged as a relatively reliable marker of thrombopoiesis and platelet function ( 18 ). PDW is used to reflect the variability in platelet size and detect fractions of larger platelets that are more active, both enzymatically and metabolically ( 8 ).…”