Summary
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 treshold 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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Abbreviations
- BMT:
-
bone marrow transplantation
- VLS:
-
vascular leak syndrome
- BW:
-
body weight
- C1 Inh:
-
C1 esterase inhibitor
- CH50:
-
total hemolytic complement
- C3:
-
third component of complement
- C4:
-
fourth component of complement
- C4d:
-
C4 activation product
References
Agostini A de, Lijnen HR, Pixley RA, Colman RW, Schapira M (1984) Inactivation of factor XII active fragment in normal plasma-predominant role of C1-inhibitor. J Clin Invest 73:1542–1549
Atkinson JP, Waldmann TA, Stein SF, Gelfand JA, McDonald JW, Heck LW, Cohen EL, Kaplan AP, Frank MM (1977) Systemic capillary leak syndrome and monoclonal gammopathy. Medicine (Baltimore) 56:225–239
Blume KG, Forman SJ, O'Donnell MR, Doroshow JH, Krance RA, Nademanee AP, Snyder DS, Schmidt GM, Fahey JL, Metter GE, Hill LR, Findley DO, Sniecinski IJ (1987) Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematological malignancies. Blood 69:1015–1020
Bork K, Witzke G (1989) Long-term prophylaxis with C1 inhibitor concentrate in patients with recurrent angioedema caused by hereditary and acquired C1 inhibitor deficiency. J Allergy Clin Immunol 83:677–682
Brower MS, Harpel PC (1982) Proteolytic cleavage and inactivation of alpha-2-plasmin-inhibitor and C1 inactivator by human polymorphonuclear leucocyte elastase. J Biol Chem 257:9849–9854
Burdach S (1991) The granulocyte/macrophage-colony-stimulating factor (GM-CSF): basic science and clinical application. Klin Padiatr 203:302–310
Burdach St, Peters C, Paulussen M, Nürnberger W, Wurm R, Wernet P, Dilloo D, Voehringer R, Gadner H, Göbel U, Jürgens H (1991) Improved relapse-free survival in patients with poor-prognosis Ewing's sarcoma after consolidation with hyperfractionated total body irradiation and fractionated high-dose melphalan followed by high-dose etoposide and hematopoietic rescue. Bone Marrow Tranplant 7 [Suppl 2]:95
Ghebrehiwet B, Randazzo BR, Dunn JT, Silverberg M, Kaplan AP (1983) Mechanisms of activation of the classical pathway of complement by Hageman factor fragment. J Clin Invest 71:1450–1456
Gluckman E, Barrett AJ, Arcese W, Devergie A, Degoulet P (1981) Bone marrow transplantation in severe aplastic anemia: a survey of the European Group for Bone Marrow Transplantation (EGBMT). Br J Haematol 49:165–176
Hack CE, Nuijens JH, Felt-Bersma RJF, Schreuder WO, Ehrenberg-Belmer AJM, Paardekooper J, Bronsveld W, Thijs LG (1989) Elevated plasma levels of the anaphylatoxins C3a and C4a are associated with a fatal outcome in sepsis. Am J Med 86:20–26
Hack CE, Wagstaff J, Strack van Schijndel RJM, Ehrenberg AJM, Pinedo HM, Thijs LG, Nuijens JH (1991) Studies of the contact system of coagulation during therapy with high doses of recombinant IL-2: implications for septic shock. Thromb Haemost 65:497–503
Heber H, Kolde HJ, Heimburger N, Svendsen G (1983) A chromogenic substrate assay for Cl-inhibitor. Thromb Haemost 50:227–230
Killeen AA, Meyer KC, Vogt JM, Edson JR (1987) Kallikrein inhibition and C1 esterase inhibitor levels in patients with the lupus inhibitor. Am J Clin Pathol 88:223–228
Lint TF (1982) Laboratory detection of complement activation and complement deficiencies. Am J Med Technol 48:743–748
Mammen EF (1990) Contact activation: the interaction of clotting, fibrinolytic, kinin and complement systems. Biomed Prog 2:31–34
Nürnberger W, Stannigel H, Müntel V, Michelmann I, Wahn V, Göbel U (1990) In vivo activation of the fourth component of the complement system (C4) in premature and term infants with generalized bacterial infection. Klin Padiatr 202:141–146
Rosenstein M, Ettinghausen SE, Rosenberg SA (1986) Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin-2. J Immunol 137:1735–1738
Schapira M, Scott CF, Colman RW (1982) Contribution of plasma protease inhibitors to the inactivation of kallikrein in plasma. J Clin Invest 426–466
Schapira M, de Agostini A, Schifferli JA, Colman RW (1985) Biochemistry and pathophysiology of human C1 inhibitor: current issues. Complement 2:111–126
Späth PJ, Baumgartner C, Gratwohl A, Doran JE, Elisa A, Bachmann P, Scherz R, Berger C, Morell A, Tichelli A, Speck B (1989) Complement and humoral immune response in bone marrow transplant recipients: effects of intravenous immunoglobulin administration. Transplant Proc 21/1:3064–3066
Spitzer TR, Cottier-Fox M, Torrisi J, Cahill R, Greenspan A, Lynch M, Deeg HJ (1989) Escalating doses of etoposide with cyclophosphamide and fractional total body irradiation or busulfan as conditioning for bone marrow transplantation. Bone Marrow Transplant 4:559–566
Thijs LG, Hack CE, Strack van Schijndel RJM, Nuijens JH, Wolbink GJ, Ehrenberg AJM, van der Vail H, Wagstaff J (1990) Activation of complement system during immunotherapy with recombinant IL-2. J Immunol 144:2419–2424
Vachino G, Gelfand JA, Atkins MB, Tamerius JD, Demchak P, Meir JW (1991) Complement activation in cancer patients undergoing immunotherapy with interleukin-2: binding of complement and C-reactive protein by IL-2-activated lymphocytes. Blood 78:2505–2513
Author information
Authors and Affiliations
Additional information
This work was supported by theElterninitiative Kinderkrebs-klinik e.V., Düsseldorf.
Rights and permissions
About this article
Cite this article
Nürnberger, W., Michelmann, I., Petrik, K. et al. Activity of C1 esterase inhibitor in patients with vascular leak syndrome after bone marrow transplantation. Ann Hematol 67, 17–21 (1993). https://doi.org/10.1007/BF01709661
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01709661