Disappearance of factor VIII:C antibodies in patients with haemophilia A upon frequent administration of factor VIII in intermediate or low dose

Abstract

In 18 haemophilia A patients with antibodies against factor VIII:C (F VIII:c) the effect of regular treatment with factor VIII (F VIII) in intermediate or low dose was studied. All patients with previous maximal F VIII:c antibody levels between 5 and 60 Bethesda Units per millilitre (BU/ml) showed a decrease of antibody level and normal F VIII recovery within 1-2 months. From nine patients with previous maximal antibody levels above 60 BU/ml four showed a decrease of antibody level within 2-26 months. In four young patients F VIII prophylactic therapy was started or continued as soon as there was evidence of F VIII:c antibody activity. In three of these patients F VIII recovery normalized within a few months.

Mortality and causes of death in Dutch haemophiliacs, 1973–86

“…In the last few years, inhibitor patients have received treatment with low dose Substitution therapy which leads to the disappearance of many inhibitors (Van Leeuwen et al, 1986). Therefore, it is likely that the prognosis for these patients is far better now than during the years of our study.…”

Optimizing management of immune tolerance induction in patients with severe haemophilia A and inhibitors: towards evidence‐based approaches

“…The high costs of the Bonn protocol and the complexity of the Malmö protocol, together with perplexities regarding the use of cyclophosphamide in children, led to the development of lower dose protocols. The original van Creveld Clinic protocol involved a neutralizing FVIII treatment during the first 1-2 weeks, followed by FVIII infusions on alternate days (van Leeuwen et al, 1986). In addition, a number of other low or intermediate FVIII dose regimens (£100 iu/kg/d) have been used (Ewing et al, 1988;Kucharski et al, 1996;Unuvar et al, 2000;Rocino et al, 2001) in the attempt to improve the costeffectiveness of ITI treatment (Table I).…”

Healthy subjects produce both anti-factor VIII and specific anti-idiotypic antibodies.

“…Nhydroxysuccinimidyl-LC biotin was purchased from Pierce (Rockford, IL), human serum albumin (HSA) was from Institut Merieux (Lyon, France), and PMSF was from Sigma Chemical Co. (St. Louis, MO). Buffers used were: phosphate-buffered saline, 8 mM, pH 7.4 (PBS); PBS containing 0.5% bovine serum albumin (PBS-BSA); PBS containing 0.1% Tween 20 (PBS-Tween) (Technicon, Tarrytown, NY); glycine-buffered saline, 270 mM, pH 9.2 (GBS); GBS containing 0.5% BSA (GBS-BSA); borate-buffered saline made of 20 mM boric acid in 150 mM NaCl, adjusted to pH 8.1 with NaOH (BBS); Tris, 10 Blood sample collection 10 healthy individuals (6 males and 4 females) volunteered to participate in the study. FVIII levels were assayed on citrated plasma and ranged from 64 to 128% of the normal value.…”

“…Therefore, much effort has been devoted both to improving our understanding of the reasons for the formation of anti-FVIII antibodies and to find alternative methods of treatment. Despite this effort, the mechanisms of production of anti-FVI antibodies are still largely unknown and treatment is limited nowadays to nonspecific measures such as cytostatic agents, infusions of pooled gammaglobulins (6), or infusions of large amounts of FVIII in an attempt to induce tolerance (7,8).…”