Pathologic thrombopoiesis of rheumatoid arthritis

Rheumatoid arthritis (RA) is frequently complicated by thrombocytosis correlated with disease activity. The exact pathogenetic mechanism(s) that cause increased platelet counts in RA are still unknown. Recent investigations indicate that proinflammatory pleiotropic cytokines of RA also have megakaryocytopoietic/thrombopoietic properties. Moreover, several lineage-dominant hematopoietic cytokines can also act as acute phase responders and contribute to the inflammation. This review focuses on the current literature and our experience regarding the dual relationships of the pathologic thrombopoiesis of RA. Growth factors contributing to it, namely interleukin (IL)-6, IL-11, stem cell factor, leukemia inhibitory factor, granulocyte colony stimulating factor, thrombopoietin (TPO), and the regulation of megakaryocytopoiesis during the inflammatory cascade are reviewed. Some data indicate that thrombopoietin could contribute to the reactive thrombocytosis of RA. In the non-lineage-specific gp130 cytokine family, IL-6 appears to predominate for the induction of megakaryopoiesis. However, other cytokines and growth factors may also contribute to the pathologic megakaryocytopoiesis of RA. Those pleiotropic mediators seem to act in concert to regulate this enigmatic process. Clarification of the pathobiologic basis of thrombopoiesis in RA may improve understanding of the disease pathogenesis and management of the inflammatory thrombocytosis.