Inflammasome, clonal stability and the thrombotic circuit in myeloproliferative neoplasms: an antecedent framework

El-Sehrawy and colleagues recently proposed a model of clonal thrombo-inflammation in myeloproliferative neoplasms organised around the inflammasome, clonal stability and a multi-compartmental thrombotic niche. Each of these elements was addressed in two reviews published by our group in 2021, neither of which is cited. The first set out the pathogenetic role of the NLRP3 and AIM2 inflammasomes and their link to hypercoagulable states; the second formalised the vascular consequence as the Circulating Wound, a self-sustaining lesion in which tissue-factor-rich clonal platelets, thrombin generation, protease-activated receptor signalling and TGF-β crosstalk reinforce one another. This coagulative arm is absent from the more recent model. We summarise experimental findings from 53 therapy-naive patients that support the earlier formulation, and set out where the two accounts diverge and why the difference bears on the therapeutic reading.