Pathophysiology of thrombosis in myeloproliferative neoplasms

Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer?

“…52,53 In the context of cardiovascular disease burden, the general concept has been that these complications were primarily attributed to abnormal rheology consequent to the raised hematocrit, leukocytosis, and thrombocytosis, and in vivo activation of leukocytes, thrombocytes, and endothelial cells. [24][25][26][27][28] Consequently, activated clonal cells release several proinflammatory products, which altogether elicit a state of chronic inflammation. 25 However, another supplementary mechanism may imply that chronic inflammation per se elicits and drives clonal evolution toward the burnt-out myelofibrosis phase.…”

“…[24][25][26][27][28] Consequently, activated clonal cells release several proinflammatory products, which altogether elicit a state of chronic inflammation. 25 However, another supplementary mechanism may imply that chronic inflammation per se elicits and drives clonal evolution toward the burnt-out myelofibrosis phase. This novel concept is supported by the known link between chronic inflammation and cancer being recognized for several years and most recently also substantiated in myeloid cancer by the association between chronic inflammatory/autoimmune diseases and the subsequent development of MDS and AML.…”

“…31 In patients with ET and PV, the elevated CRP levels have been explained consequent to clonal myeloproliferation with in vivo cell activation (leukocytes and platelets), giving rise to release of proinflammatory cytokines and other proinflammatory products from leukocytes and platelets. 25 In the study by Barbui et al, levels of hsCRP also correlated significantly with the JAK2V617F allele burden. 3 Accordingly, chronic inflammation might be considered a secondary event elicited by clonal cells.…”

“…The pathogenesis of thrombosis in these patients is multifactorial. 24,25 Thus, in PV patients, the increased hematocrit is considered of importance, although the significance of the hematocrit in the range of 40% to 55% for cardiovascular morbidity has most recently been questioned. 26 Other contributing factors to abnormal rheology in these patients are leukocytosis, thrombocytosis, circulating leukocyte-platelet aggregates, and in vivo leukocyte, platelet, and endothelial cell activation.…”

The Clinical Course and Prognosis of Patients With Essential Thrombocythemia Treated With Hydroxyurea and Low-Dose Aspirin in an 11-Year Follow-Up

“…have been described with in vivo leukocytes, platelets and endothelial cells activation [17]. Chronic inflammation triggers in vivo activation of platelets, leukocytes, and endothelial cells and the activation of platelets by inflammatory triggers have major importance in coagulation and thrombus formation [18].…”