Microangiopathy in Patients on Cyclosporine Prophylaxis Who Developed Acute Graft-Versus-Host Disease After HLA-Identical Bone Marrow Transplantation

• Published in: Blood Vol. 73; no. 7; pp. 2018 - 2024
• Main Authors: Holler, E., Kolb, H.J., Hiller, E., Mraz, W., Lehmacher, W., Gleixner, B., Seeber, Ch, Jehn, U., Gerhartz, H.H., Brehm, G., Wilmanns, W.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.05.1989; The Americain Society of Hematology
• Subjects: Adult; Biological and medical sciences; Blood Coagulation Disorders - blood; Blood Coagulation Disorders - chemically induced; Bone Marrow Transplantation; Cyclosporins - adverse effects; Drug toxicity and drugs side effects treatment; Endothelium, Vascular - drug effects; Endothelium, Vascular - pathology; Factor VIII - analysis; Female; Graft vs Host Disease - blood; Graft vs Host Disease - etiology; Histocompatibility Testing; Humans; L-Lactate Dehydrogenase - blood; Male; Medical sciences; Microcirculation - drug effects; Middle Aged; Pharmacology. Drug treatments; Postoperative Complications - blood; Postoperative Complications - etiology; Retrospective Studies; Risk Factors; Toxicity: cardiovascular system; Human; HLA-System; Drug combination; Toxicity; Coagulation; Graft versus host reaction; Hemopathy; Endothelium; Vascular disease; Microangiopathy; Bone marrow; Graft; Immunosuppressive agent
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V73.7.2018.2018

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 microangi-opathy 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 < .001) and use of CsA prophylaxis (P < .001). Our data suggest endothelial damage as a result of cellular activation and subsequent release of cytokines in the course of aGVHD, which is not inhibited by CsA prophylaxis. ©1989 by Grune & Stratton, Inc. 0006-4971/89/7307-0022$3.00/0