[Show abstract][Hide abstract] ABSTRACT: A young woman was examined for a mild thrombocytopenia which was present for some months. No signs of bleeding had so far occurred. Physical examination was normal except for a moderately enlarged spleen. Laboratory investigations showed a low platelet count. There was no evidence of an autoimmune or hematologic disease. Bone narrow aspirate indicated Gaucher's-like cells raising the suspicion of Gaucher's disease. This was further supported by electron microscopic demonstration of Gaucher's bodies in crista biopsy specimens. However, the definitive diagnosis was obtained by verifying deficient lysosomal glucosylceramide-beta-D-glucosidase activity in peripheral blood leukocytes. Upon the absence of neurologic involvement the patient was typical for the adult-onset or type 1 form of Gaucher's disease.
No preview · Article · Jul 2001 · Zeitschrift für Gastroenterologie
[Show abstract][Hide abstract] ABSTRACT: Immune tolerance induction (ITI) regimens with human factor VIII concentrates are rarely if ever implemented in adult patients with auto-inhibitors, in contrast to alloantibody suppression, which is used primarily in young children with congenital hemophilia. On the basis of some earlier experience with synchronization of plasma exchange therapy of various autoimmune disorders we have developed a new aggressive protocol for the treatment of patients with acquired factor VIII (FVIII) antibody. We have evaluated the outcome of 14 consecutive nonhemophilic FVIII inhibitor patients treated in a single center with our ITI protocol between 1992 and 1999, comparing them to 6 historical control patients, treated with traditional immunosuppression therapy (steroid +/- cyclophosphamide) between 1988 and 1992.
Our ITI protocol consists of three weeks of treatment with 1) human FVIII concentrates (30 U/kg/day for the 1st week, 20 U/kg/day for the 2nd, and 15 U/kg/day for the 3rd week), plus 2) iv. cyclophosphamide (200mg/day to a total dose of 2-3 grams), plus 3) methylprednisolone (100 mg/day iv. for one week and than tapering down the dose gradually over the next two weeks). The treatment of acute bleeding episodes in the two groups was not different. High purity and ultra-high purity factor VIII concentrates were used for the ITI. We performed aPTT and mixing tests before and after two hours of incubation, Bethesda inhibitor assay, porcine FVIII cross-reactivity, FVIII:C before and after FVIII administration (recovery), three times a week. The sex ratio and mean age (64 years for the ITI group versus 57 years for the controls), the initial and peak inhibitor titers, and residual FVIII: C values at the diagnosis were similar in the two groups.
Eradication of the inhibitor occurred in 13/14 patients in the ITI vs. 4/6 patients in the control group. The main difference between the two groups was in the time needed for the complete disappearance of the inhibitor (4.6 weeks for ITI vs. 28.3 weeks for controls). In the ITI group we have observed only two relapses during the relatively long follow-up period (26 months), and in both cases the same re-induction protocol was successful again. No bleeding-related mortality occurred in this group in contrast to that of 33% in the controls. Apart from the well-known adverse effects of glucocorticoid therapy, we have observed only one patient with transient cytopenia. We have not seen any adverse event which could be attributed to the use of FVIII concentrates.
We conclude that the ITI protocol described here is highly effective for the treatment of acquired hemophilia, induces quick therapeutic responses and favorably influences the underlying autoimmune disorder. We suggest that our ITI protocol is suitable for the eradication of idiopathic and autoimmune-associated FVIII autoantibodies in patients presenting with severe bleeding.
[Show abstract][Hide abstract] ABSTRACT: A young woman with no previous history of any diseases was admitted for further evaluation of a mild thrombocytopenia she has had for some months. No signs of bleeding have so far occurred. Physical examination was normal except for a moderately enlarged spleen. Routine investigations showed lower platelet count. There was no laboratory evidence of disease conditions with autoimmune/inflammatory or hematologic origin. Bone marrow aspirate indicated Gaucher's-like cells raising the suspicion of Gaucher's disease. This was further supported by electron microscopic demonstration of Gaucher's bodies (with the characteristic tubular structures) in crista biopsy specimens. However, definitive diagnosis was obtained by verifying deficient lysosomal glucosylceramide-beta-D-glucosidase activity in peripheral blood leukocytes. Upon the absence of neurologic involvement the patient was typical for the adult form or type-1 Gaucher's disease.