Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-28T07:14:00.171Z Has data issue: false hasContentIssue false
  • English
  • Français

Evidence of endothelial dysfunction in patients with functionally univentricular physiology before completion of the Fontan operation

Published online by Cambridge University Press:  14 April 2005

Maria A. Binotto ,
Nair Y. Maeda  and
Antonio A. Lopes
Maria A. Binotto
Affiliation:
Department of Paediatric Cardiology and Adult Congenital Heart Disease, Heart Institute, University of São Paulo Medical School, São Paulo, Brazil
Nair Y. Maeda
Affiliation:
Pró-Sangue Foundation, São Paulo, Brazil
Antonio A. Lopes
Affiliation:
Department of Paediatric Cardiology and Adult Congenital Heart Disease, Heart Institute, University of São Paulo Medical School, São Paulo, Brazil
Get access Rights & Permissions [Opens in a new window]

Abstract

Introduction: Postoperative thrombosis after a cavopulmonary connection has been widely described. Abnormalities in coagulation seem to occur early in the course of patients with functionally univentricular physiology, and may precede surgery. Endothelial abnormalities due to chronic hypoxia, and hyperviscosity, may contribute to this scene. The purpose of our study was to investigate if patients with a superior cavopulmonary connection have altered levels of endothelial and coagulative markers in the plasma. Methods: We compared findings in 10 patients, aged from 4 to 19 years, with 6 age-matched normal controls. We measured levels of von Willebrand factor antigen, thrombomodulin, tissue-type plasminogen activator, plasminogen activator inhibitor-1 and d-dimer in the plasma using enzyme-linked immunosorbent assay. Results: We found increased levels of von Willebrand factor antigen (p = 0.01), tissue-type plasminogen activator (p = 0.01), and decreased levels of thrombomodulin (p = 0.008) in the patients when compared to controls, while levels of plasminogen activator inhibitor-1 were not different. Values of d-dimer were within the reference range. Levels of tissue-type plasminogen activator had a positive correlation with von Willebrand factor antigen (r = 0.66, p = 0.008). Conclusions: Altered levels of endothelial markers in the plasma, in the presence of normal levels of d-dimer, suggest that endothelial dysfunction may precede the occurrence of intravascular coagulation and thrombosis in patients with functionally univentricular physiology. These observations may have therapeutical implications.

Keywords

Functionally single ventricleendotheliumcavopulmonary connection
Type
Original Article
Information
Cardiology in the Young , Volume 15 , Issue 1 , January 2005 , pp. 26 - 30
Copyright
2005 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Forbes TJ, Rosenthal GL, Reul Jr GR, Ott DA, Feltes TF. Risk factors for life-threatening cavopulmonary thrombosis in patients undergoing bidirectional superior cavopulmonary shunt: an exploratory study. Am Heart J 1997; 134: 865–871.Google Scholar
Hanséus K, Björkhem G, Jögi P, Sonesson S. Formation of thrombus and thromboembolism after the bidirectional Glenn anastomosis, total cavopulmonary connection and the Fontan operation. Cardiol Young 1998; 8: 211–216.Google Scholar
Day RW, Boyer RS, Tait VF, Ruttenberg HD. Factors associated with stroke following the Fontan procedure. Pediatr Cardiol 1995; 16: 270–275.Google Scholar
du Plessis AJ, Chang AC, Wessel DL, et al. Cerebrovascular accidents following the Fontan operation. Pediatr Neurol 1995; 12: 230–236.Google Scholar
Jahangiri M, Shore D, Kakkar V, Lincoln C, Shinebourne E. Coagulation factor abnormalities after the Fontan procedure and its modifications. J Thorac Cardiovasc Surg 1997; 113: 989–992.Google Scholar
Rosenthal DN, Friedman AH, Kleinman CS, et al. Thromboembolic complications after Fontan operations. Circulation 1995; 92: II287–II293.Google Scholar
Cromme-Dijkhuis AH, Henkens CM, Bijleveld CM, et al. Coagulation factor abnormalities as possible thrombotic risk factors after Fontan operations. Lancet 1990; 336: 1087–1090.Google Scholar
Jahangiri M, Kreutzer J, Zurakowski D, Bacha E, Jonas RA. Evaluation of hemostatic and coagulation factor abnormalities in patients undergoing the Fontan operation. J Thorac Cardiovasc Surg 2000; 120: 778–782.Google Scholar
Monagle P, Andrew M. Coagulation abnormalities after Fontan procedures. J Thorac Cardiovasc Surg 1998; 115: 732–733.Google Scholar
Odegard KC, McGowan Jr FX, DiNardo JA, et al. Coagulation abnormalities in patients with single-ventricle physiology precede the Fontan procedure. J Thorac Cardiovasc Surg 2002; 123: 459–465.Google Scholar
Odegard KC, McGowan Jr FX, Zurakowski D, et al. Coagulation factor abnormalities in patients with single-ventricle physiology immediately prior to the Fontan procedure. Ann Thorac Surg 2002; 73: 1770–1777.Google Scholar
Rauch R, Ries M, Hofbeck M, et al. Hemostatic changes following the modified Fontan operation (total cavopulmonary connection). Thromb Haemost 2000; 83: 678–682.Google Scholar
Ravn HB, Hjortdal VE, Stenbog EV, et al. Increased platelet reactivity and significant changes in coagulation markers after cavopulmonary connection. Heart 2001; 85: 61–65.Google Scholar
Ten VS, Pinsky DJ. Endothelial response to hypoxia: physiologic adaptation and pathologic dysfunction. Curr Opin Crit Care 2002; 8: 242–250.Google Scholar
Caramurú LH, Maeda NY, Lopes AA, Bydlowski SP. Age-dependent likelihood of in situ thrombosis in secondary pulmonary hypertension. Clin Appl Thrombosis/Hemostasis 2004; 10: 217–223.Google Scholar
Wu KK, Matijevic-Aleksic N. Thrombomodulin: a linker of coagulation and fibrinolysis and predictor of risk of arterial thrombosis. Ann Med 2000; 32: I73–I77.Google Scholar
Shreeniwas R, Ogawa S, Cozzolino F, et al. Macrovascular and microvascular endothelium during long-term hypoxia: alterations in cell growth, monolayer permeability, and cell surface coagulant properties. J Cell Physiol 1991; 146: 8–17.Google Scholar
Ogawa S, Gerlach H, Esposito C, et al. Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium. J Clin Invest 1990; 85: 1090–1098.Google Scholar
Goerge T, Niemeyer A, Rogge P, et al. Secretion pores in human endothelial cells during acute hypoxia. J Membrane Biol 2002; 187: 203–211.Google Scholar
Pinsky DJ, Naka Y, Liao H, et al. Hypoxia-induced exocytosis of endothelial cell Weibel-Palade bodies. A mechanism for rapid neutrophil recruitment after cardiac preservation. J Clin Invest 1996; 97: 493–500.Google Scholar
Blann AD, Taberner DA. A reliable marker of endothelial cell dysfunction: does it exist? Br J Haematol 1995; 90: 244–248.Google Scholar
Olli R, Celermajer DS. Testing for endothelial dysfunction. Ann Med 2000; 32: 293–304.Google Scholar
Mavromatis BH, Kessler CM. D-dimer testing: the role of the clinical laboratory in the diagnosis of pulmonary embolism. J Clin Pathol 2001; 54: 664–668.Google Scholar
Morgan VL, Graham Jr TP, Roselli RJ, Lorenz CH. Alterations in pulmonary artery flow patterns and shear stress determined with three-dimensional phase-contrast magnetic resonance imaging in Fontan patients. J Thorac Cardiovasc Surg 1998; 116: 294–304.Google Scholar
Khambadkone S, Li J, de Leval MR, et al. Basal pulmonary vascular resistence and nitric oxide responsiveness late after Fontan-type operation. Circulation 2003; 107: 3204–3208.Google Scholar
Mahle WT, Todd K, Fyfe DA. Endothelial function following the Fontan operation. Am J Cardiol 2003; 91: 1286–1288.Google Scholar