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.

Evaluation of noninvasive determinants for capillary leakage syndrome in septic shock patients

“…While this is an interesting approach, the sophisticated technique is obviously not available in many hospitals at the bedside. Recently published studies define CLS as noncardiogenic generalized edema and hemodynamic instability [31] or more than 3 % increase in BW within 24 h combined with generalized edema [5]. These definitions must be considered as nonspecific and inappropriate for difficult pathophysiological situations in septic shock.…”

“…Conclusion: These results suggest that measurements of an increased ECW using bioelectrical impedance analysis combined with a different response of colloid osmotic pressure to administration of albumin can discriminate noninvasively between drome (CLS). Proposed criteria for clinical assessment of CLS are either nonspecific, for example, generalized edema combined with increase in body weight (BW) [5], or have limited bedside applicability. For instance, the, dual-radionuclide method ( 67 Ga-labeled circulating transferrin and 99 Tc-labeled red blood cells) for measuring pulmonary edema is not widely available, and the disadvantages of radioactive contamination and dye accumulation especially in repeated measurements are obvious [6].…”

Hepatic veno-occlusive disease with severe capillary leakage after peripheral stem cell transplantation: treatment with recombinant plasminogen activator and C1-esterase inhibitor concentrate

“…Regarding the pathophysiology of CLS, we measured the C5a level as a significant parameter for complement activation in these patients. 8 Because the VOD treatment (anticoagulants) does not influence the associated vascular hyperpermeability, we intended to inhibit complement activation by C1-INH-C. 4,8 C5a levels decreased from 2.4 g/l on day +14 to 0.94 g/l on day +19. We observed clinical resolution of the symptoms as decreased weight to baseline, improved jaundice and cardiovascular function during therapy with rt-PA and C1-INH-C.…”

“…2,3 A condition of vascular hyperpermeability classified as systemic capillary leak syndrome (CLS) is known as associated with or isolated from VOD. 1,4 Hypovolemic shock and organ dysfunction are the clinical consequences of a fluid and protein shift from the intravascular to the inter- stitial space. 4 CLS is considered to be a systemic, inflammatory reaction.…”

“…1,4 Hypovolemic shock and organ dysfunction are the clinical consequences of a fluid and protein shift from the intravascular to the inter- stitial space. 4 CLS is considered to be a systemic, inflammatory reaction. An activation of the complement system via the classical pathway has been described in CLS after interleukin-2 therapy as well as after BMT.…”