GHT improves IBS-related QOL, is superior to SMT alone, and shows a long-term effect even in refractory IBS.

Iron deficiency is a common cause of reactive thrombocytosis, however, the exact pathways have not been revealed. Here we aimed to study the mechanisms behind iron deficiency‐induced thrombocytosis. Within few weeks, iron‐depleted diet caused iron deficiency in young Sprague–Dawley rats, as reflected by a drop in hemoglobin, mean corpuscular volume, hepatic iron content and hepcidin mRNA in the liver. Thrombocytosis established in parallel. Moreover, platelets produced in iron deficient animals displayed a higher mean platelet volume and increased aggregation. Bone marrow studies revealed subtle alterations that are suggestive of expansion of megakaryocyte progenitors, an increase in megakaryocyte ploidy and accelerated megakaryocyte differentiation. Iron deficiency did not alter the production of hematopoietic growth factors such as thrombopoietin, interleukin 6 or interleukin 11. Megakaryocytic cell lines grown in iron‐depleted conditions exhibited reduced proliferation but increased ploidy and cell size. Our data suggest that iron deficiency increases megakaryopoietic differentiation and alters platelet phenotype without changes in megakaryocyte growth factors, specifically TPO. Iron deficiency‐induced thrombocytosis may have evolved to maintain or increase the coagulation capacity in conditions with chronic bleeding. Am. J. Hematol. 89:524–529, 2014. © 2014 Wiley Periodicals, Inc.

SummaryAutoimmune gastritis is a chronic inflammatory disease with destruction of parietal cells of the corpus and fundus of the stomach. The known consequence is vitamin B12 deficiency and, consequently, pernicious anemia. However, loss of parietal cells reduces secretion of gastric acid which is also required for absorption of inorganic iron; thus, iron deficiency is commonly found in patients with autoimmune gastritis. This usually precedes vitamin B12 deficiency and is found mainly in young women. Patients with chronic iron deficiency, especially those refractory to oral iron therapy, should therefore be evaluated for the presence of autoimmune gastritis.

FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis.

Background and Aims Secondary thrombocytosis is a clinical feature of unknown significance. In inflammatory bowel disease (IBD), thrombocytosis is considered a marker of active disease; however, iron deficiency itself may trigger platelet generation. In this study we tested the effect of iron therapy on platelet counts in patients with IBD-associated anemia. Methods Platelet counts were analyzed before and after iron therapy from four prospective clinical trials. Further, changes in hemoglobin, transferrin saturation, ferritin, C-reactive protein, and leukocyte counts, before and after iron therapy were compared. In a subgroup the effect of erythropoietin treatment was tested. The results were confirmed in a large independent cohort (FERGIcor). Results A total of 308 patient records were available for the initial analysis. A dose-depended drop in platelet counts (mean 425 G/L to 320 G/L; p<0.001) was found regardless of the type of iron preparation (iron sulphate, iron sucrose, or ferric carboxymaltose). Concomitant erythropoietin therapy as well as parameters of inflammation (leukocyte counts, C-reactive protein) had no effect on the change in platelet counts. This effect of iron therapy on platelets was confirmed in the FERGIcor study cohort (n=448, mean platelet counts before iron therapy: 383 G/L, after: 310 G/L, p<0.001). Conclusion Iron therapy normalizes elevated platelet counts in patients with IBD-associated anemia. Thus, iron deficiency is an important pathogenetic mechanism of secondary thrombocytosis in IBD.

No abstract

BackgroundIron deficiency anemia (IDA) is a common complication of inflammatory bowel disease (IBD). In clinical practice, many patients receive initial treatment with iron tablets although intravenous (i.v.) iron supplementation is often preferable.AimThis study investigated whether systemic inflammation at initiation of treatment (assessed by C-reactive protein [CRP] and interleukin-6 [IL-6] measurements) predicts response to iron therapy.MethodsData from a previously published phase III trial were retrospectively analyzed after stratification of patients according to baseline CRP (>4 vs. ≤4 mg/L) and IL-6 (>6 vs. ≤6 pg/mL) levels. The study population consisted of patients with Crohn’s disease or ulcerative colitis and IDA (Hb ≤ 110 g/L and TSAT < 20 % or serum ferritin < 100 ng/mL), randomized to either oral (ferrous sulfate) or i.v. iron (ferric carboxymaltose).ResultsA total of 196 patients were evaluated (oral iron: n = 60; i.v. iron: n = 136). Baseline CRP and IL-6 levels were independent of patients’ initial Hb levels and iron status (serum ferritin and TSAT; all p > 0.05). Among iron tablet-treated patients, Hb increase was significantly smaller in the high- versus low-CRP subgroup (1.1 vs. 2.0, 2.3 vs. 3.1, and 3.0 vs. 4.0 g/dL at weeks 2, 4, and 8, respectively; all p < 0.05). Differences were less pronounced with stratification according to baseline IL-6. Response to i.v. iron was mainly independent of inflammation.ConclusionsPatients with high baseline CRP achieved a lower Hb response with oral iron therapy. Our results suggest that CRP may be useful to identify IBD patients who can benefit from first-line treatment with i.v. iron to improve their IDA.

SummaryBackgroundIron deficiency is associated with reactive thrombocytosis; however, the mechanisms driving this phenomenon remain unclear. We previously demonstrated that this occurs alongside enhanced megakaryopoiesis in iron‐deficient rats, without alterations in the megakaryopoietic growth factors thrombopoietin, interleukin‐6, or interleukin‐11.ObjectivesThe aim of this study was to evaluate megakaryocyte differentiation under iron deficiency in an in vitro model and to investigate potential genes involved in this process.MethodsHuman erythroleukemia and megakaryoblastic leukemia cell lines, as well as cord‐blood derived hematopoietic stem cells were cultured under iron deficiency. Cell morphology, ploidy, expression of CD41, CD61, and CD42b, and proplatelet formation were assessed in iron‐deficient cultures. Polymerase chain reaction arrays were used to identify candidate genes that were verified using real‐time polymerase chain reaction. Hypoxia‐inducible factor 1, α subunit (HIF2α) protein expression was assessed in bone marrow sections from iron‐deficient rats and vascular endothelial growth factor (VEGF)‐A in culture supernatants.Results and ConclusionsIron deficiency enhanced megakaryoid features in cell lines, increasing ploidy and initiating formation of proplatelet‐like structures. In cord blood cell cultures, iron deficiency increased the percentage of cells expressing megakaryopoietic markers and enhanced proplatelet formation. HIF2α and VEGF were identified as potential pathways involved in this process. HIF2α protein expression was increased in megakaryocytes from iron‐deficient rats, and VEGF‐A concentration was higher in iron‐deficient culture supernatants. Addition of VEGF‐A to cell cultures increased percentage expression of megakaryocyte CD41. In conclusion, the data demonstrate that iron deficiency augments megakaryocytic differentiation and proplatelet formation and a potential role of HIF2α in megakaryopoiesis.