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Thromb Haemost 2000; 83(05): 678-682
DOI: 10.1055/s-0037-1613891
Review Article
Schattauer GmbH

Hemostatic Changes following the Modified Fontan Operation (Total Cavopulmonary Connection)

Ralf Rauch
1   From the Children‘s Hospital of the Friedrich-Alexander-Universität, Erlangen-Nuernberg, Germany
,
Martin Ries
1   From the Children‘s Hospital of the Friedrich-Alexander-Universität, Erlangen-Nuernberg, Germany
,
Michael Hofbeck
1   From the Children‘s Hospital of the Friedrich-Alexander-Universität, Erlangen-Nuernberg, Germany
,
Gernot Buheitel
1   From the Children‘s Hospital of the Friedrich-Alexander-Universität, Erlangen-Nuernberg, Germany
,
Helmut Singer
1   From the Children‘s Hospital of the Friedrich-Alexander-Universität, Erlangen-Nuernberg, Germany
,
Jens Klinge
1   From the Children‘s Hospital of the Friedrich-Alexander-Universität, Erlangen-Nuernberg, Germany
› Author Affiliations
Further Information

Publication History

Received 31 October 1998

Accepted after resubmission 07 December 1999

Publication Date:
08 December 2017 (online)

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Summary

Thromboembolism is a serious complication after Fontan operation, which may be caused by alterations of the coagulation system. We therefore investigated pro- and anticoagulant factors in 20 patients aged 4 to 21 years, 4 to 63 months following total cavopulmonary connection. Furthermore we compared markers of thrombin activation and fibrinolysis and in vitro clotting and clot-lysis to age-matched healthy subjects.

Compared to results of age-matched controls, the Fontan operated individuals had significant decreases in levels of protein C (0.88 U/ml in controls, 0.67 U/ml in patients; p <0.001) and protein S (1.05 in controls, 0.93 U/ml in patients; p <0.05). Moreover, half of the patients had high values of FVIII (>1.5 IU/ml), which are associated with an increased thrombotic risk. These changes may result in enhanced generation of thrombin and plasmin, indicated by our finding of increased thrombin-antithrombin III (TAT) and plasmin-antiplasmin (PAP) levels and a similar trend in prothrombin fragments F1+2. Clot lysis tests, global coagulation tests, red blood cell count, liver enzymes AST, ALT, but not GGT, were generally within the normal ranges.

Keywords

Fontan-operation - TCPC - thrombosis - coagulation cascade - D-dimer - TAT - PAP - F1+2
 

  • References

  • 1 Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax 1971; 26: 240-8.
    CrossrefPubMedSearch in Google Scholar
  • 2 Neudorf U, Schmaltz AA, Singer H. Kreislauftrennung auf Vorhofebene: Fontan-Operation und ihre Modifikationen. In: Herzoperierte Kinder und Jugendliche. Ein Leitfaden zur Langzeitbetreuung in Klinik und Praxis. Schmaltz AA, Singer H. Stuttgart: Wissenschaftliche Verlagsgesellschaft mbH; 1994: 249-57.
    Search in Google Scholar
  • 3 Lemmer JH, Coran AG, Behrendt DM, Heidelberger KP, Stern AM. Liver fibrosis (cardiac cirrhosis) five years after modified Fontan operation for tricuspid atresia. J Thorac Cardiovasc Surg 1983; 86: 757-60.
    PubMedSearch in Google Scholar
  • 4 Rosenthal DN, Friedman AH, Kleinman CS, Kopf GS, Rosenfeld LE, Hellenbrand WE. Thromboembolic complications after Fontan operations. Circulation. 1995 92. (Suppl II): II-287-II-293.
    PubMedSearch in Google Scholar
  • 5 Dobell ARC, Trusler GA, Smallhorn JF, Williams WG. Atrial thrombi after the Fontan operation. Ann Thorac Surg 1986; 42: 664-7.
    CrossrefPubMedSearch in Google Scholar
  • 6 Olson TM, Driscoll DJ, Edwards WD, Puga FJ, Danielson GK. Pulmonary microthrombi – caveat for successful modified Fontan operation. J Thorac Surg 1993; 106: 739-44.
    PubMedSearch in Google Scholar
  • 7 Okita Y, Miki S, Kusuhara K, Ueda Y, Tahata T, Komeda M, Tamura T. Massive systemic venous thrombosis after Fontan operation: report of a case. Thorac cardiovasc Surgeon 1988; 36: 234-6.
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Driscoll DJ, Offord KP, Feldt RH, Schaff HV, Puga J, Danielson GK. Fiveto-fifteen-year follow-up after Fontan operation. Circulation 1992; 85: 469-96.
    CrossrefPubMedSearch in Google Scholar
  • 9 Jahangiri M, Ross DB, Redington AN, Lincoln C, Shinebourne EA. Thromboembolism after the Fontan procedure and its modifications. Ann Thorac Surg 1994; 58: 1409-14.
    CrossrefPubMedSearch in Google Scholar
  • 10 Cromme-Dijkhuis Henkens CMA, Bijleveld CMA, Hillege HL, Bom VJJ, van der Meer J. Coagulation factor abnormalities as possible thrombotic risk factors after Fontan operations. Lancet 1990; 336: 1087-90.
    CrossrefPubMedSearch in Google Scholar
  • 11 Cromme-Dijkhuis AH, Hess J, Hählen K, Henkens CMA, Bink-Boelkens MThE, Eygelaar AA, Bos E. Specific sequelae after Fontan operation at mid- and long-term follow-up. J Thorac Cardiovasc Surg 1993; 106: 1126-32.
    PubMedSearch in Google Scholar
  • 12 Jahangiri M, Shore D, Lincoln C, Shinebourne E. Coagulation factor abnormalities after the Fontan procedure and its modifications. J Thorac Cardiovasc Surg 1997; 113: 989-93.
    CrossrefPubMedSearch in Google Scholar
  • 13 Comp PG, Doray D, Patton P, Esmon CT. An abnormal plasma distribution of protein S occurs in functional protein S deficiency. Blood 1986; 67: 504-8.
    PubMedSearch in Google Scholar
  • 14 Nicolson JF, Pesce MA. Laboratory medicine and reference tables. In: Behrman R. Textbook of pediatrics. 14th ed.. Philadelphia, London, Toronto, Montreal, Sydney, Tokio: Saunders Company; 1992: 1809-19.
    Search in Google Scholar
  • 15 Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood 1992; 80: 1998-2005.
    PubMedSearch in Google Scholar
  • 16 Mondorf W, Kuhnt R, Reitz H, Kozlowski A, Berlet A, Robbins KC, Scharrer I. Ein neuer Test zur Untersuchung der individuellen Ansprechbarkeit von Streptokinase, Urokinase und t-PA-induzierter Fibrinolyse. In: Hämophilie-Symposion Hamburg 1992. Scharrer I, Schramm W. Berlin, Heidelberg: Springer Verlag; 1993: 184-91.
    Search in Google Scholar
  • 17 Ries M, Zenker M, Klinge J, Keuper H, Harms D. Age related Differences in a clot lysis assay after adding different plasminogen activators in a plasma milieu in vitro. J Pediatr Hematol Oncol 1995; 17 (03) 260-4.
    CrossrefPubMedSearch in Google Scholar
  • 18 Geggel RL. Update on the modified Fontan procedure. Curr Opin Cardiol 1997; 12: 51-62.
    CrossrefPubMedSearch in Google Scholar
  • 19 Monagle P, Cochrane A, McCrindle B, Benson L, Williams W, Andrew M. Thromboembolic complications after Fontan procedures – the role of prophylactic anticoagulation. J Thorac Cardiovasc Surg 1998; 115: 493-9.
    CrossrefPubMedSearch in Google Scholar
  • 20 Kelly DA, O’Brien FJ, Hutton RA, Tuddenham EG, Summerfield JA, Sherlock S. The effect of liver disease on factors V, VIII and protein C. Br J Haematol 1985; 61 (03) 541-8.
    CrossrefPubMedSearch in Google Scholar
  • 21 Koster T, Blann AD, Briet E, Vandenbroucke JP, Rosendaal FR. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152-5.
    CrossrefPubMedSearch in Google Scholar
  • 22 O’Donnell J, Tuddenham EG, Manning R, Kemball-Cook G, Johnson D, Laffan M. High prevalence of elevated factor VIII in patients referred for thrombophilia screening: role of increased synthesis and relationship to the acute phase reaction. Thromb Haemost 1997; 77 (05) 825-8.
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 Kawasaki T, Kaida T, Arnout J, Vermylen J, Hoylaerts MF. A new animal model of thrombophilia confirms that high plasma VIII factor levels are thrombogenic. Thromb Haemost 1999; 81 (02) 306-11.
    Thieme ConnectPubMedSearch in Google Scholar
  • 24 Goodnough LT, Saito H, Ratnoff OD. Thrombosis or myocardial infarction in congenital clotting factor abnormalities and chronic thrombocytopenias: a report of 21 patients and a review of 50 previously reported cases. Medicine (Baltimore) 1983; 62 (04) 248-55.
    CrossrefPubMedSearch in Google Scholar
  • 25 Halbmayer WM, Mannhalter C, Feichtinger C, Rubi K, Fischer M. The prevalence of factor XII deficiency in 103 orally anticoagulated outpatients suffering from recurrent venous and/or arterial thromboembolism. Thromb Haemost 1992; 68 (03) 285-90.
    Thieme ConnectPubMedSearch in Google Scholar
  • 26 Koster T, Rosendaal FR, Briet E, Vandenbroucke JP. John Hageman’s factor and deep-vein thrombosis: Leiden thrombophilia Study. Br J Haematol 1994; 87 (02) 422-4.
    CrossrefPubMedSearch in Google Scholar
  • 27 Tripodi A, Manucci PM. Markers of activated coagulation and their usefulness in the clinical laboratory. Clin Chem 1996; 42 (05) 664-9.
    PubMedSearch in Google Scholar
  • 28 Bauer KA. New markers for in vivo coagulation. Curr Opin Hematol 1994; 01 (05) 341-6.
    PubMedSearch in Google Scholar
  • 29 Bauer KA, Broekmans AW, Bertina RM, Conard J, Horrelou MH, Samama MM, Rosenberg RD. Hemostatic enzyme generation in the blood of patients with hereditary protein C deficiency. Blood 1988; 71: 1418-26.
    PubMedSearch in Google Scholar
  • 30 Manucci PM, Tripodi A, Botasso B, Baudo F, Finazzi G, De Stefano V, Palareti G, Manotti C, Mazzucconi MG, Castaman G. Markers of procoagulant imbalance in patients with inherited thrombophilic syndromes. Thromb Haemost 1992; 67: 542-4.
    Thieme ConnectPubMedSearch in Google Scholar
  • 31 Conard J, Bauer KA, Gruber A, Griffin JH, Schwarz HP, Horrelou MH, Samana MM, Rosenberg RD. Normalization of markers of coagulation activation with a purified protein C concentrate in adults with homozygous protein C deficiency. Blood 1993; 82: 1059-64.
    PubMedSearch in Google Scholar