title: Activity of C1 esterase inhibitor in patients with vascular leak syndrome after bone marrow transplantation.
abstract: Vascular-leak syndrome (VLS) is a common complication in the first 3 weeks after bone marrow transplantation (BMT). The patients present with weight gain, generalized edema, ascites, pericardial or pleural effusions, tachycardia, arterial hypotonia, and/or pre-renal failure. The aim of our study was to investigate the role of the complement system in VLS. The protein concentrations of C3 and C4 were studied by immunodiffusion, and total hemolytic complement activity was studied by assessment of CH50. C1 esterase inhibitor (C1 Inh), the major inhibitor of the classical pathway of complement, was assessed by a functional test. Activation of complement was assessed by C4d (a C4 activation product). Twelve patients were followed prospectively from start of conditioning therapy to day +21 after bone marrow transplantation. Eight of 12 patients did not develop VLS. These patients had an increase of C3 between day +9 and day +13 (range: 1.3- to 1.5-fold, median: 1.4-fold), C4 (range: 1.3- to 1.9-fold, median: 1.4-fold), CH50 (range: 1.3- to 1.6-fold, median: 1.4-fold), and C1 Inh (range: 1.2- to 1.5-fold, median: 1.3-fold). Four of 12 patients developed VLS. C1 Inh activity was decreased to 0.60- to 0.80-fold. This decrease began 2-6 days prior to clinical diagnosis of VLS (n = 3), or at onset of VLS (n = 1). Patients with VLS showed elevated C4d concentrations (up to 2.4 mg/dl, upper normal threshold value: 0.9 mg/dl). Patients with VLS reveal an activated state of the complement system which is accompanied by a reduced activity of C1 Inh. Insufficient control of complement activation may contribute to VLS in patients after BMT.
authors.affiliation: Department for Pediatric Hematology and Oncology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Nürnberger
authors.forename: I
authors.initials: I
authors.lastname: Michelmann
authors.forename: K
authors.initials: K
authors.lastname: Petrik
authors.forename: S
authors.initials: S
authors.lastname: Holthausen
authors.forename: R
authors.initials: R
authors.lastname: Willers
authors.forename: G
authors.initials: G
authors.lastname: Lauermann
authors.forename: B
authors.initials: B
authors.lastname: Eisele
authors.forename: U
authors.initials: U
authors.lastname: Delvos
authors.forename: S
authors.initials: S
authors.lastname: Burdach
authors.forename: U
authors.initials: U
authors.lastname: Göbel
mesh_terms: D000293:Adolescent; D000328:Adult; D001835:Body Weight; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003174:Complement C1 Inactivator Proteins / Q000502:physiology*; D015941:Complement Hemolytic Activity Assay; D005260:Female; D006801:Humans; D008297:Male; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D003174:Complement C1 Inactivator Proteins