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Exercising this role requires expression of pattern recognition receptors by platelets, including toll\u2010like receptor 4 (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4) and nucleotide\u2010binding domain leucine rich repeat containing protein 3 (<jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3), the latter forming intraplatelet multiprotein inflammasome complexes. Platelets are a potential target of various damage\u2010associated molecular pattern (<jats:styled-content style=\"fixed-case\">DAMP<\/jats:styled-content>) molecules, such as free haem, a degradation by\u2010product of haemoglobin oxidation during haemolysis, and high\u2010mobility group box 1 (<jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>1), a <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010binding protein released by dying or stressed cells and activated platelets. We have recently identified platelet <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4, <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3, and Bruton tyrosine kinase (<jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content>) as critical regulators of platelet aggregation and thrombus formation, suggesting that the <jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content> inhibitor ibrutinib is a potential therapeutic target. Increasing evidence suggests that these and other <jats:styled-content style=\"fixed-case\">DAMP<\/jats:styled-content>\u2010driven signalling mechanisms employed by platelets might be key in mediating inflammation and thrombosis encountered in haemolytic disorders. However, the precise regulatory triggers and their clinical relevance are poorly understood. We provide new insights into these less\u2010well characterised platelet mechanisms, which are potentially targetable in haemolytic disorders.<\/jats:p>","DOI":"10.1111\/bjh.15117","type":"journal-article","created":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T04:18:39Z","timestamp":1517372319000},"page":"761-767","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Platelets at the crossroads of thrombosis, inflammation and haemolysis"],"prefix":"10.1111","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3284-0464","authenticated-orcid":false,"given":"Sebastian","family":"Vogel","sequence":"first","affiliation":[{"name":"Sickle Cell Branch National Heart Lung and Blood Institute National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swee Lay","family":"Thein","sequence":"additional","affiliation":[{"name":"Sickle Cell Branch National Heart 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