Surgery of a Cyanotic Heart Defect in an 11-year-old Boy with Thrombocytopenic Thrombocytopathy and Severe Anemia due to a GATA-1 Defect: Hemostatic Therapy

Abstract

A child was admitted to our hospital for repair of a ventricular septal defect (VSD) characterized by a predominantly right-to-left shunt and a severe stenosis of the right ventricular outflow tract (Tetralogy of Fallot). Severe congenital anemia (hemoglobin 72 g/L), thrombocytopenia (42×G/L) and profound platelet dysfunction led a stem cell defect to be suspected. X-linked thrombocytopenia (GATA-1 mutation) was diagnosed. GATA-1 defect may complicate medical interventions due to excessive bleeding and partial or complete bone marrow failure. Maintaining a platelet count of 100 G/L and a maximal clot firmness (EXTEM-MCF) >50 mm allowed repair of the congenital heart defect without bleeding or hematological complications. Anemia and thrombocytopenia persisted after cardiac surgery, while the spontaneous bleeding tendency improved.

Zusammenfassung

Ein Kind wurde zur Korrektur eines angeborenen Ventrikel-Septum-Defekts (VSD) mit erheblichem Rechts-links Shunt und hochgradiger Stenose des rechtsventrikulären Ausflusstrakts (Fallot’schen Tetralogie) an unserer Klinik vorstellig. Eine bekannte schwere kongenitale Anämie (Hb 72 g/L), Thrombozytopenie (42×G/L), sowie ausgeprägte Thrombozytenfunktionsstörung führten zur Verdachtsdiagnose eines Stammzelldefektes. In der Folge konnte eine GATA-1 Mutation diagnostiziert werden. Im Rahmen dieses Defektes können Interventionen zu lebensbedrohlichen Blutungen führen oder ein partielles oder völliges Versagen des Knochenmarkes auslösen. Anheben der Thrombozytenzahl auf 100 G/L und Aufrechterhalten einer maximalen Gerinnselfestigkeit von 50 mm (EXTEM-MCF) ermöglichte die Korrektur des zyanotischen Herzfehlers ohne Komplikationen. Anämie und Thrombozytopenie persistierten nach dem herzchirugischen Eingriff, wobei sich die spontane Blutungsneigung deutlich besserte.

Key words

congenital heart surgery - GATA-1 defect - dyserythropoietic anemia - thrombocytopenia - thrombocytopathy

• References

• 1 Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology 2006; 105: 198-208
• 2 Alamelu J, Liesner R. Modern management of severe platelet function disorders. Br J Haematol 2010; 149: 813-823
• 3 Andreasen JB, Hvas AM, Christiansen K et al. Can RoTEM(R) analysis be applied for haemostatic monitoring in paediatric congenital heart surgery?. Cardiol Young 2011; 21: 684-691
• 4 Balduini CL, Cattaneo M, Fabris F et al. Inherited thrombocytopenias: a proposed diagnostic algorithm from the Italian Gruppo di Studio delle Piastrine. Haematologica 2003; 88: 582-592
• 5 Cattaneo M, Hayward CP, Moffat KA et al. Results of a worldwide survey on the assessment of platelet function by light transmission aggregometry: a report from the platelet physiology subcommittee of the SSC of the ISTH. J Thromb Haemost 2009; 7: 1029
• 6 Freson K, Devriendt K, Matthijs G et al. Platelet characteristics in patients with X-linked macrothrombocytopenia because of a novel GATA1 mutation. Blood 2001; 98: 85-92
• 7 Haas T, Fries D, Velik-Salchner C et al. Fibrinogen in craniosynostosis surgery. Anesth Analg 2008; 106: 725-731 table of contents
• 8 Halimeh S, Angelis G, Sander A et al. Multiplate whole blood impedance point of care aggregometry: preliminary reference values in healthy infants, children and adolescents. Klin Padiatr 2010; 222: 158-163
• 9 Heimpel H, Anselstetter V, Chrobak L et al. Congenital dyserythropoietic anemia type II: epidemiology, clinical appearance, and prognosis based on long-term observation. Blood 2003; 102: 4576-4581
• 10 Hennewig U, Laws HJ, Eisert S et al. Bleeding and surgery in children with Glanzmann thrombasthenia with and without the use of recombinant factor VII a. Klin Padiatr 2005; 217: 365-370
• 11 Henriksson P, Varendh G, Lundstrom NR. Haemostatic defects in cyanotic congenital heart disease. Br Heart J 1979; 41: 23-27
• 12 Jambor C, Bremerich D, Moritz A et al. Management of hemostasis disorders after extracorporeal circulation. A clinical therapy algorithm. Anaesthesist 2008; 57: 374-381
• 13 Klingebiel T, Creutzig U, Christaras A et al. Milestones of health policy and rare diseases. Klin Padiatr 2010; 222: 121-123
• 14 Lang T, Johanning K, Metzler H et al. The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia. Anesth Analg 2009; 108: 751-758
• 15 Lill MC, Perloff JK, Child JS. Pathogenesis of thrombocytopenia in cyanotic congenital heart disease. Am J Cardiol 2006; 98: 254-258
• 16 Lundin A, Richardsson A, Thore A. Continous monitoring of ATP-converting reactions by purified firefly luciferase. Anal Biochem 1976; 75: 611-620
• 17 Mehaffey MG, Newton AL, Gandhi MJ et al. X-linked thrombocytopenia caused by a novel mutation of GATA-1. Blood 2001; 98: 2681-2688
• 18 Mittermayr M, Streif W, Haas T et al. Effects of colloid and crystalloid solutions on endogenous activation of fibrinolysis and resistance of polymerized fibrin to recombinant tissue plasminogen activator added ex vivo. Br J Anaesth 2008; 100: 307-314
• 19 O’Connell BA, Lee EJ, Rothko K et al. Selection of histocompatible apheresis platelet donors by cross-matching random donor platelet concentrates. Blood 1992; 79: 527-531
• 20 Olbrich P, Parrilla Parrilla J, Caballero Eraso C et al. Combined Use of Recombinant Activated Factor VII and ECMO in Severe Postoperative Bleeding after Cardiac Surgery in a Newborn: Death due to Ventricular Dysfunction. Klin Padiatr 2012; 224: 193-194
• 21 Rahe-Meyer N, Winterhalter M, Boden A et al. Platelet concentrates transfusion in cardiac surgery and platelet function assessment by multiple electrode aggregometry. Acta Anaesthesiol Scand 2009; 53: 168-175
• 22 Sacher RA, Kickler TS, Schiffer CA et al. Management of patients refractory to platelet transfusion. Arch Pathol Lab Med 2003; 127: 409-414
• 23 Streif W, Knofler R, Eberl W. Inherited disorders of platelet function in pediatric clinical practice: a diagnostic challenge. Klin Padiatr 2010; 222: 203-208
• 24 Streif W, Oliveri M, Weickardt S et al. Testing for inherited platelet defects in clinical laboratories in Germany, Austria and Switzerland. Results of a survey carried out by the Permanent Paediatric Group of the German Thrombosis and Haemostasis Research Society (GTH). Platelets 2010; 21: 470-478
• 25 Tauer JT, Gneuss A, Lohse JE et al. Evaluation of desmopressin effect on primary haemostasis in pediatric patients with aspirin-like defect as hereditary thrombocytopathy. Klin Padiatr 2011; 223: 169-172
• 26 Terai M, Nakazawa M, Takao A et al. Thrombocytopenia in patients with aortopulmonary transposition and an intact ventricular septum. Br Heart J 1987; 57: 371-374
• 27 Thies WR, Gobel U, Liersch R. Fibrinogen half-life in children with cyanotic congenital heart disease. Eur J Pediatr 1982; 139: 43-47
• 28 Velik-Salchner C, Haas T, Innerhofer P et al. The effect of fibrinogen concentrate on thrombocytopenia. J Thromb Haemost 2007; 5: 1019-1025
• 29 Vyas P, Ault K, Jackson CW et al. Consequences of GATA-1 deficiency in megakaryocytes and platelets. Blood 1999; 93: 2867-2875
• 30 Wedemeyer AL, Edson JR, Krivit W. Coagulation in cyanotic congenital heart disease. Am J Dis Child 1972; 124: 656-660