Kubisz et al. Journal of Medical Case Reports 2012, 6:350 http://www.jmedicalcasereports.com/content/6/1/350 C A S E R E P O R T JOURNAL OF MEDICAL CASE REPORTS Open Access Successful immune tolerance induction consisting of high-dose factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin: a case report Peter Kubisz*, Ivana Plamenova, Pavol Holly and Jan Stasko Abstract Introduction: The development of factor VIII inhibitors is a serious complication of replacement therapy in patients with congenital hemophilia A. Immune tolerance induction has been accepted as the only clinically proven treatment allowing antigen-specific tolerance to factor VIII. However, some of its issues, such as patient selection, timing, factor VIII dosing, use of immunosuppressive or immunomodulatory procedures, still remain the subject of debate. Case presentation: A case of a 3-year-old Caucasian boy with severe congenital hemophilia A, intron 22 inversion of the F8 gene and high-titer inhibitor, who underwent an immune tolerance induction according to the modified Bonn regimen (high doses of plasma-derived factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin) is presented. The treatment lasted for 13 months and led to the eradication of inhibitor. Conclusion: Addition of intravenous immunoglobulin did not negatively affect the course of immune tolerance induction and led to the rapid eradication of factor VIII inhibitor. Keywords: Coagulation factor VIII inhibitor, Hemophilia A, Immune tolerance induction, Intravenous immunoglobulin, Recombinant activated factor VII Introduction The development of factor VIII (FVIII) inhibitors is a serious complication of replacement therapy in patients with congenital hemophilia A, affecting up to 35%, pre- dominantly those with severe disease [1]. It leads to the failure of previously efficient replacement therapy or prophylaxis with FVIII and thus to an increased risk of bleeding, joint impairment and reduced quality of life. Immune tolerance induction (ITI) has been accepted as the only clinically proven treatment allowing antigen- specific tolerance to FVIII [2,3]. However, some of its issues, such as patient selection, timing, FVIII dosing, use of immunosuppressive or immunomodulatory * Correspondence: hema@jfmed.uniba.sk Department of Hematology and Transfusion Medicine, Jessenius Faculty of Medicine of the Comenius University and University Hospital Martin, Kollarova 2, Martin 036 59, Slovakia procedures, still remain unclear. Several modifications of the first ITI treatment proposed in Bonn (Bonn regimen) have been described, but none have been proved to be superior [3-7]. Case presentation We present a successful use of the high-dose FVIII regimen for ITI: plasma-derived FVIII rich in von Willebrand factor (vWF) and pulsed intravenous immunoglobulin (IVIG). The high-dose FVIII regimen was used in a 3-year-old Caucasian boy with severe con- genital hemophilia A (endogenous FVIII level below 0.01IU/mL), the intron 22 inversion of the F8 gene and high-titer FVIII inhibitor. The patient was treated with on-demand replacement therapy with a single human plasma-derived FVIII concentrate rich in vWF (Fanhdi®, Grifols, Barcelona, Spain) from the age of 2 months. The © 2012 Kubisz et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.