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Introduction: The development of anti-factor VIII neutralizing antibodies in hemophilia A is the most severe com plication related to treatment. Immune tolerance induction (ITI) is the only known treatment for eradicating inhibitors. A successful ITI allows using factor VIII (FVIII) again for the treatment or prophylaxis of hemorrhagic events., Objective: To report the experience of pediatric patients who underwent ITI in the country's public health care network., Patients and Method: Retrospective and descriptive analysis of 13 pediatric patients with severe Hemophilia A and high-titer inhibitors persis tence who underwent ITI and complete follow-up. Plasma-derived FVIII concentrate was used at 70 180 IU/kg/day doses. The success of the treatment is defined by achieving a negative titer and a half life recovery of the FVIII. The results were expressed in median (range)., Results: In 13 patients, the inhibitor was identified at an average age of 17.6 months, after 35.2 days of exposure to the FVIII. 11 patients (84.6%) recovered the half-life of FVIII after 49.6 months of treatment. In the patients who responded to treatment, the inhibitor titer was negative at 6 months on average., Conclusions: ITI is the treatment of choice for patients with hemophilia A and inhibitors persistence. ITI must be perso nalized since the time response is variable in each patient.

A twenty seven year-old woman is reported with severe haemorrhagic symptoms caused by an acquired coagulant factor VIII inhibitor eleven months after delivery. The inhibitor was quantified as 77 units according to the Bethesda method. Steroids treatment and high-dose immunoglobulins failed to elicit any response. Combined chemotherapy will cyclophosphamide, vincristine and prednisone after intravenous factor VIII, every fourth week, succeeded in eradicating the acquired inhibitor and progressively restoring the rates of factor VIII in this patient with acquired haemophilia.

In the present report we describe a 66 year-old-woman, diagnosed of rheumatoid arthritis, who suffered a severe haemorrhagic syndrome caused by the presence of a circulating inhibitor to factor VIII. Inhibitor quantitation was measured with Bethesda test. After treatment with corticosteroids and high-dose immunoglobulin, a good clinical response was obtained; factor VIII:C activity increased with the disappearance of detectable inhibitor. This response was observed more effectively and rapidly than with prednisone treatment alone.

Three cases of postpartum acquired factor VIII inhibitors were seen in our hospital between 1981 and 1989. The clinical picture, which was mild in one patient and severe in two, began several months after delivery (four to nine). After treatment with methylprednisolone, good clinical response was obtained in the three cases. However, normal values of factor VIII:C were obtained more easily with the higher doses of steroids. A new pregnancy and delivery in one of our patients did not induce the reappearance of the inhibitor after several years of follow-up.

These studies were designed with the purpose of providing more information relevant about the new FVIII/VW circulating after administration intranasally DDAVP. One health subject was administered 260 microliter total dose of DDAVP. The newly released FVIII/VW could not be distinguished form circulating FVIII/VW on the basis of molecular size, electrophoretic mobility or "in vitro" stability of VIII:C and VIIIR:AG despite apparent differences in the duration of response of the procoagulant and antigenic components "in vivo". FVIII/VW cryoethanol-precipitations studies showed similar increase in the high molecular weight (HMW) and low molecular weight (LMW) after DDAVP administration. This suggest a immediately polymerization in the new VIIIR:AG circulating after DDAVP administration.

The frequent occurrence of peripheral cytopenias is a common clinical fact in patients with HIV-1 infection, and its pathogenetic mechanism is not clear, although several hypotheses have been proposed. Such cytopenias are frequently observed in haemophilic patients, in whom the immunologic alteration induced by continuous antigenic stimulants derived from plasma concentrate therapy has been postulated as an additional causative factor. One-hundred and forty five haemophiliacs treated with commercial antihaemophilic concentrates were studied. The patients were divided into three therapeutic groups according to the mean number of units of therapeutic factor VIII administered per Kg every year in the four years prior to the study (group I: less than 500 U; group II: between 501 and 1500 U; group III: more than 1500 U). The occurrence of cytopenias in the patients was co-ordinated with the presence or absence of HIV infection and the therapeutic group. The statistical studies showed clear correlation between peripheral cytopenias and presence of anti-HIV markers, regardless of the amount of concentrates perceived (except for the total neutrophil count).

We report a case of acute myelofibrosis. This is a rare myeloproliferative disorder characterized by pancytopenia, minimal or absent anisopoikilocytosis, bone marrow fibrosis with hyperplasia and immaturity of the three main cellular lines with megakaryocyte predominance, absence of splenomegaly and rapidly fatal course. We discuss its relationship with acute megakaryocytic leukemia, as its blast elements correspond to megakaryocytes when ultrastructural and antifactor VIII immunoperoxidase techniques are used; these techniques disclose alpha granules and cell demarcating membranes.