title: Histologic Features of Intestinal Thrombotic Microangiopathy in Pediatric and Young Adult Patients after Hematopoietic Stem Cell Transplantation.
abstract: High-risk transplantation-associated thrombotic microangiopathy (TMA) can present with multisystem involvement and is associated with a poor outcome after hematopoietic stem cell transplantation (HSCT), with < 20% 1-year survival. TMA may involve the intestinal vasculature and can present with bleeding and ischemic colitis. There are no established pathologic criteria for the diagnosis of intestinal TMA (iTMA). The goal of our study was to identify histologic features of iTMA and describe associated clinical features. We evaluated endoscopic samples from 50 consecutive HSCT patients for 8 histopathologic signs of iTMA and compared findings in 3 clinical groups based on the presence or absence of systemic high-risk TMA (hrTMA) and the presence or absence of clinically staged intestinal graft-versus-host disease (iGVHD): TMA/iGVHD, no TMA/iGVHD, and no TMA/no iGVHD. Thirty percent of the study subjects had a clinical diagnosis of systemic hrTMA. On histology, loss of glands, intraluminal schistocytes, intraluminal fibrin, intraluminal microthrombi, endothelial cell separation, and total denudation of mucosa were significantly more common in the hrTMA group (P < .05). Intravascular thrombi were seen exclusively in patients with hrTMA. Mucosal hemorrhages and endothelial cell swelling were more common in hrTMA patients but this difference did not reach statistical significance. Patients with hrTMA were more likely to experience significant abdominal pain and gastrointestinal bleeding requiring multiple blood transfusions (P < .05). Our study shows that HSCT patients with systemic hrTMA can have significant bowel vascular injury that can be identified using defined histologic criteria. Recognition of these histologic signs in post-transplantation patients with significant gastrointestinal symptoms may guide clinical decisions.
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: Javier.El-Bietar@cchmc.org.
authors.forename: Javier
authors.initials: J
authors.lastname: El-Bietar
authors.affiliation: Division of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Mikako
authors.initials: M
authors.lastname: Warren
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Christopher
authors.initials: C
authors.lastname: Dandoy
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Kasiani C
authors.initials: KC
authors.lastname: Myers
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Adam
authors.initials: A
authors.lastname: Lane
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Gregory
authors.initials: G
authors.lastname: Wallace
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.affiliation: Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Sonata
authors.initials: S
authors.lastname: Jodele
mesh_terms: D015746:Abdominal Pain / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic; D001855:Bone Marrow Diseases; D000080983:Bone Marrow Failure Disorders; D002648:Child; D002675:Child, Preschool; D017091:Colitis, Ischemic / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D007223:Infant; D007413:Intestinal Mucosa / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D007422:Intestines / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D057049:Thrombotic Microangiopathies / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D019653:Myeloablative Agonists
keywords: Endothelial injury; Graft-versus-host disease TA-TMA; Intestinal thrombotic microangiopathy; Thrombotic microangiopathy (TMA)