Immunotolerance Induction Treatments in Hemophilia

Review Article

Immunotolerance Induction Treatments in Hemophilia

Saturnino Haya, Pilar Casaña, Andrés Moret, R Ana Cid, Noelia Cabrera, Lydia Abad and A José Aznar

Affiliations: Haemostasis and Thrombosis Unit, Hospital Universitario La Fe

Submission date: 1st July 2009, Revision date: 16th August 2009, Acceptance date: 24th August 2009


ABSTRACT

Hemophilia is the major congenital hemorrhagic disorder. The administration of the deficient factor can trigger the development of antibodies, also known as inhibitors, capable of neutralizing the infused protein function. This is considered the most serious complication in hemophilia and usually occurs in the first years of life after the first doses of factor concentrate are given; hence, the main objective in these patients is to permanently eradicate these inhibitors. Current treatments are based on immunotolerance induction (ITI) involving continued exposure to the deficient factor. The prognosis factors for success in ITI in severe hemophilia A have been obtained mainly from four registries and from several patient series. The strongest predictors of success are a low inhibitor titer at the beginning of the ITI and a maximum inhibitor titer. However, there are many other points to clarify: FVIII doses; the use of plasma‐derived or recombinant concentrates, especially whether the plasma‐derived concentrate contains large amounts of von Willebrand factor or not; concomitant infections during ITI; age at the start of ITI and delay in beginning it. Another controversial point is the use of immunosuppressants to help in the treatment of patients with a poor prognosis or in rescue treatments. In mild–moderate hemophilia, the incidence of inhibitors is lower and immunosuppressants can play an important role. Inhibitors in hemophilia B are rare. ITI usually leads to allergenic events and nephrotic syndrome, and the success rate is lower than in hemophilia A; therefore, ITI in hemophilia B must be carefully studied.

Keywords: hemophilia A, hemophilia B, inhibitors, immunotolerance induction, treatment
Correspondence: Saturnino Haya, Unidad de Hemostasia y Trombosis, Hospital Universitario La Fe, Avd. de Campanar 21, 46009 Valencia, Spain