title: Microangiopathy in patients on cyclosporine prophylaxis who developed acute graft-versus-host disease after HLA-identical bone marrow transplantation.
abstract: Severe microangiopathy has been reported as a rare complication of cyclosporine A (CsA) prophylaxis in allogeneic bone marrow transplantation (BMT). We found morphological and biochemical changes indicative of generalized endothelial damage in 49 of 66 allogeneic marrow graft recipients receiving cyclosporine, but none in 11 patients treated with methotrexate for prophylaxis of graft-v-host disease (GVHD). Changes occurred after engraftment of bone marrow and consisted of intravascular hemolysis with red cell fragmentation and de novo thrombocytopenia. They were preceded by a decrease in activated partial thromboplastin time and fibrinogen indicating activation of coagulation. Endothelial damage as the central lesion of microangiopathy was confirmed by a simultaneous increase of factor VIII related antigen. Severe microangiopathy was observed in ten patients and was fatal in seven. Risk factor analysis revealed a highly significant association of microangiopathy with severity of acute GVHD (aGVHD) (P less than .001) and use of CsA prophylaxis (P less than .001). Our data suggest endothelial damage as a result of cellular activation and subsequent release of cytokines in the course of a aGVHD, which is not inhibited by CsA prophylaxis.
authors.affiliation: Medizinische Klinik III, Ludwig-Maximilians-Universität, München, FRG.
authors.forename: E
authors.initials: E
authors.lastname: Holler
authors.forename: H J
authors.initials: HJ
authors.lastname: Kolb
authors.forename: E
authors.initials: E
authors.lastname: Hiller
authors.forename: W
authors.initials: W
authors.lastname: Mraz
authors.forename: W
authors.initials: W
authors.lastname: Lehmacher
authors.forename: B
authors.initials: B
authors.lastname: Gleixner
authors.forename: C
authors.initials: C
authors.lastname: Seeber
authors.forename: U
authors.initials: U
authors.lastname: Jehn
authors.forename: H H
authors.initials: HH
authors.lastname: Gerhartz
authors.forename: G
authors.initials: G
authors.lastname: Brehm
mesh_terms: D000328:Adult; D001778:Blood Coagulation Disorders / Q000097:blood / Q000139:chemically induced*; D016026:Bone Marrow Transplantation; D003524:Cyclosporins / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D005169:Factor VIII / Q000032:analysis; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000209:etiology*; D006650:Histocompatibility Testing; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D011183:Postoperative Complications / Q000097:blood / Q000209:etiology; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D003524:Cyclosporins; D005169:Factor VIII; D007770:L-Lactate Dehydrogenase