Thrombopoietic Cytokines in Patients with Iron Deficiency Anemia with or without Thrombocytosis

Abstract

Iron deficiency anemia is a cause of reactive thrombocytosis. A moderate increase in platelet numbers is common but sometimes counts may exceed 1,000 × 10⁹/l. The mechanisms causing reactive thrombocytosis are unclear. In this study, we evaluated 15 women with iron deficiency anemia and thrombocytosis (platelets >450 × 10⁹/l) and 16 women with iron deficiency anemia with normal platelet counts. Serum samples were taken before oral iron replacement therapy, after 1 and 3 months and at the end of replacement therapy. Thrombopoietin, erythropoietin (EPO), leukemia inhibitory factor, interleukin-6 and interleukin-11 levels were assayed. There was no change in the levels of thrombopoietic cytokines except for EPO. The correlation between high EPO levels and high platelet counts may suggest that EPO increases platelet counts, but the same EPO level changes can also be demonstrated in women with iron deficiency anemia but normal initial platelet counts. The fact that the levels of other cytokines remained unchanged during treatment suggests that either these cytokines have no effect on reactive thrombocytosis or the change in platelet counts in our patients is in a narrow range and is thus not affected by the cytokine levels.

Iron deficiency alters megakaryopoiesis and platelet phenotype independent of thrombopoietin

“…Unfortunately, serum was unavailable to confirm the mRNA data on protein level. EPO mRNA was elevated in ID rats, probably due to anemia and hypoxia 24. There is an ongoing debate whether EPO may directly stimulate platelet production.…”

Quantitative data on the magnitude of the systemic inflammatory response and its relationship with serum measures of iron status

“…Indeed, thrombocytosis is well recognised to be associated with both systemic inflammation and iron deficiency. [22][23] Components of the differential white cell count including a variety of ratios derived from neutrophils, monocytes and lymphocytes have been of interest, particularly in the setting of clinical oncology. [24][25] However relationships between these ratios, such as the neutrophil lymphocyte ratio (NLR) and lymphocyte monocyte ratio (LMR) and iron status are unclear.…”

Eisenmangel, Thrombozytose und Thromboembolie

“…Ein indirekter Effekt auf die Thrombopoese über Zytokine und hämatopoetische Faktoren erscheint eher unwahrscheinlich. Der Thrombopoetinspiegel, der wichtigste Stimulators der Thrombopoese, korreliert nicht gut mit der Ausprägung der Thrombozytose [10,[32][33][34]. Weitere thrombopoetische Faktoren wie IL-6 und IL-11 sind unverändert im Rahmen der eisenmangelinduzierten Thrombozytose.…”

“…Weitere thrombopoetische Faktoren wie IL-6 und IL-11 sind unverändert im Rahmen der eisenmangelinduzierten Thrombozytose. Das einzige thrombopoetische Zytokin, dessen Konzentration erhöht ist, ist das Erythropoetin [10,32], dessen Rolle in der Thrombopoese sehr umstritten ist. Erythropoetin erhöht die Plättchenanzahl in vivo [35], und stimuliert (synergistisch mit weiteren megakaryopoetischen Faktoren) die Megakaryozytenproliferation in vitro [36].…”

“…Eine ursprünglich vermutete direkte Wirkung über den Thrombopoetinrezeptor c-mpl [39] konnte nicht nachgewiesen werden [37,40]. Der EPO Spiegel korreliert schlecht mit der Plättchenanzahl und kann auch in der Abwesenheit einer Thrombozytose erhöht sein [32,37,40] [128] 2α und VEGF (vascular endothelial growth factor)-A mediiert sein [42]. Weiters ist die klinische Bedeutung der reaktiven Thrombozytose unklar.…”