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.
Highlights
Women had lower platelet distribution width (PDW), higher platelet count (Plt), ADP/collagen stimulated P-selectin and platelet/leukocyte aggregates compared to men (Supplementary Table S1)
We investigated how PDW distribution relates to a number of P-selectin dependent platelet activation tests as measured in the Moli-family cohort [18]
Our data link for the first time PDW to P-selectin dependent platelet activation and function in a general population, in the absence of acute cardiovascular disease events. This relationship indicates that PDW is a simple, inexpensive, useful marker of platelet activation in both women and men and is influenced by age
Summary
PDW is an index of platelet size heterogeneity, measuring the spread in platelet volumes [3,4,5] It is a marker of platelet anisocytosis, accompanying platelet activation, during which pseudopods form, increasing platelet diameter and apparent volume [5]. PDW is commonly used for the differential diagnosis of clinical conditions that present with increased platelet destruction or decreased platelet production. These conditions, characterized by modulated megakaryocyte differentiation and thrombopoiesis, in turn affecting platelet size and morphology, include (immune) thrombocytopenia [6] essential thrombocythemia [7] liver cirrhosis with altered platelet homeostasis [8] and idiopathic thrombocytopenic purpura [9]
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