Platelet Distribution Width as a marker of platelet reactivity and platelet activation status in men and women of the Moli-family cohort

Objective Platelets are a key player in (patho)physiological processes as primary haemostasis, thrombosis, tissue inflammation and immune regulation. As a measure of platelet size heterogeneity, the platelet distribution width (PDW) has been explored in several clinical conditions but its value as a marker of platelet function in (sub)clinical disease is still uncertain. Making use of the elaborate set of platelet activation markers available for the Moli-family cohort, we aimed at validating the strength of PDW as a marker of platelet reactivity and platelet activation status and its gender-specific differences.

Material and Methods Flow cytometric measurements of platelet-bound P-selectin, leukocyte/platelet mixed aggregates of resting and in vitro activated whole blood, PFA-100 Closure Time, soluble P-selectin, pro-coagulant activity in unstimulated and LPS- or TNFalpha-stimulated blood were measured on freshly isolated blood of the Moli-family participants (N = 753). Multivariable linear mixed effects regression models (adjusted for age, gender and other platelet indices) were used to evaluate associations between PDW with the above mentioned platelet activation/function markers taking into account the possible effect of Platelet count (Plt) and Mean Platelet Volume (MPV). These analyses were performed on the whole population and in women and men, separately.

Results PDW was associated with platelet/leukocyte aggregates (ß= -0.149, CI(-0.220 – (-0.079), p=3.7E-5,) and with platelet P-selectin expression in unstimulated conditions (ß= 0.149, CI(-0,223 – (-0.075)), p=8.4E-5). These associations remained significant after adjustement for Plt and MPV and were independent on the gender. PDW was positively associated with LPS- and TNFα-stimulated procoagulant activity (ß= 0.720, CI(0.376 - 1.065), p=4.5E-5, and ß= 0.658, CI(0.293 – 1.024), p=4.4E-4, respectively) and negatively with vWF levels (ß= -0.306, p=0.002, CI(-0.502 – (-0.111)), independently from gender differences. A positive association was observed with PFA-100 Closure time in the whole population (ß= 0.005, CI(0.003-0.008), p=3.4E-5) and in women, but not in men.

Conclusion PDW is an overall better predictive marker of platelet activation whose effect is largely independent of both Plt and MPV and is not influenced by gender. PDW might be a useful tool to assess platelet reactivity and activation status in population studies.

Publication History

Article published online:
18 June 2021