ACTIVITY OF C1 ESTERASE INHIBITOR IN PATIENTS WITH VASCULAR LEAK SYNDROME AFTER BONE-MARROW TRANSPLANTATION

Vascular-leak syndrome (VLS) is a common complication in the first 3 w eeks after bone marrow transplantation (BMT). The patients present wit h weight gain, generalized edema, ascites, pericardial or pleural effu sions, 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 immuno diffusion, and total hemolytic complement activity was studied by asse ssment of CH50. C1 esterase inhibitor (C1 Inh), the major inhibitor of the classical pathway of complement, was assessed by a functional tes t. Activation of complement was assessed by C4d (a C4 activation produ ct). Twelve patients were followed prospectively from start of conditi oning therapy to day +21 after bone marrow transplantation. Eight of 1 2 patients did not develop VLS. These patients had an increase of C3 b etween 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- t o 1.6-fold, median: 1.4-fold), and Cl Inh (range: 1.2- to 1.5-fold, me dian: 1.3-fold). Four of 12 patients developed VLS. Cl Inh activity wa s 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). Pati ents with VLS showed elevated C4d concentrations (up to 2.4 mg/dl, upp er normal treshold value: 0.9 mg/dl). Patients with VLS reveal an acti vated state of the complement system which is accompanied by a reduced activity of Cl Inh. Insufficient control of complement activation may contribute to VLS in patients after BMT.