Celiac disease (CD) is a systemic autoimmune disease driven by gluten-ingestion in genetically predisposed individuals. Although it primarily affects the small bowel, CD can also involve other organs and manifest as an extraintestinal disease. Among the extraintestinal features of CD, hematologic ones are rather frequent and consist of anemia, thrombocytosis (thrombocytopenia also, but rare), thrombotic or hemorrhagic events, IgA deficiency, hyposplenism, and lymphoma. These hematologic alterations can be the sole manifestation of the disease and should prompt for CD testing in a suggestive clinical scenario. Recognition of these atypical, extraintestinal presentations, including hematologic ones, could represent a great opportunity to increase the diagnostic rate of CD, which is currently one of the most underdiagnosed chronic digestive disorders worldwide. In this review, we summarize recent evidence regarding the hematological manifestations of CD, with focus on practical recommendations for clinicians.

Anemia is a frequent finding in children with celiac disease but the detailed pathophysiological mechanisms in the intestine remain obscure. One possible explanation could be an abnormal expression of duodenal iron transport proteins. However, the results have so far been inconsistent. We investigated this issue by comparing immunohistochemical stainings of duodenal cytochrome B (DCYTB), divalent metal transporter 1 (DMT1), ferroportin, hephaestin and transferrin receptor 1 (TfR1) in duodenal biopsies between 27 children with celiac disease and duodenal atrophy, 10 celiac autoantibody-positive children with potential celiac disease and six autoantibody-negative control children. Twenty out of these 43 subjects had anemia. The expressions of the iron proteins were investigated with regard to saturation and the percentage of the stained area or stained membrane length of the enterocytes. The results showed the stained area of ferroportin to be increased and the saturation of hephaestin to be decreased in celiac disease patients compared with controls. There were no differences in the transporter protein expressions between anemic and non-anemic patients. The present results suggest an iron status-independent alteration of ferroportin and hephaestin proteins in children with histologically confirmed celiac disease.

Aim: The European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) allows a no-biopsy diagnostic of celiac disease under certain conditions. We assessed the impact of the diagnostic algorithm on the patient's long-term outcome by comparing the serology-based diagnosed patients to biopsy-proven ones.Methods: We reviewed the charts of children presenting with antitransglutaminase IgA titers above ten times upper limit of normal and consecutively diagnosed with celiac disease between 2010 and 2014, a time-period overlapping with ESPGHAN diagnostic guideline change in 2012. Outcome measures for no-biopsy vs. biopsy-proven diagnosed patients were clinical and laboratory findings, compliance to gluten-free diet and to regular visits after one, two and 8–10 years of follow-up.Results: Clinical and laboratory, i.e., serum chemistry and autoantibody outcome measures on gluten-free diet clearly showed worse patient healing in the 33 serology-based diagnosed children compared to the 30 biopsy-proven ones. The attendance of the follow-up visits was also higher in the biopsy group.Conclusions: Our results indicate that dietary transgressions are common in childhood celiac disease resulting in slow healing. Therefore, there is a need of improvement of the management, with special attention regarding the ESPGHAN no-biopsy criteria diagnosed patients. Our study also indicates that novel treatments adjunctive to diet are warranted in children.