Effect of frequent factor VIII replacement on the level of factor VIII antibodies in haemophiliacs

Rizza, C. R.; Matthews, J. M.

doi:10.1111/j.1365-2141.1982.tb03857.x

Cited by 50 publications

(17 citation statements)

References 3 publications

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“…In the past, the treatment with F VIII would be stopped in most of the cases after inhibitor detection, even in patients with low titers; but F VIII replacement therapy will not be stopped in many cases now, because it may act as an immune tolerance regimen which may reduce the incidence of high-responders [37, 38, 39]. So we continued to administer F VIII therapy in patients with inhibitors, and an immune tolerance regimen has been planned whenever they needed.…”

Section: Discussionmentioning

confidence: 99%

Factor VIII Inhibitors in Patients with Hemophilia A

Ören¹,

Yaprak²,

İrken³

1999

Acta Haematol

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In 58 hemophilia A patients aged 1–18 years (mean 9.5 ± 4.7 years), the prevalence of inhibitors was found to be 27% by the Bethesda method in November 1995. Inhibitor activity was not detected in any of 14 patients with mild hemophilia while it was present in 9 of 27 (33%) patients with moderate, and 7 of 17 (41%) with severe disease. During follow-up, the inhibitors were transient in 10 of 16 patients (17%) and the prevalence of inhibitors was 10% at the end of the study. Our study has demonstrated that the patients’ age, factor VIII (F VIII) coagulant activity levels, type of F VIII replacement therapy, and frequency of F VIII administration affect inhibitor development, and these factors should be considered in the follow-up of hemophiliacs.

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Section: Discussionmentioning

confidence: 99%

Factor VIII Inhibitors in Patients with Hemophilia A

Ören¹,

Yaprak²,

İrken³

1999

Acta Haematol

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“…Recent prospective studies of inhibitor incidence among recipients of both plasma-derived [ I ] and recombinant factor VIII [21] have shown that inhibitors occurring under these circumstances can be transient in HIV-1 -uninfected patients. Furthermore, some HIV-1 -uninfected, high-responder patients exhibit disappearance of their inhibitors or significant titer reductions in response to frequent albeit irregular exposure to factor VIII [22,23]. Of the 13 patients described above, all had severe hemophilia, a peak inhibitor titer greater than 13 BU, and a history of treatment with products other than factor VIII for several years prior to its reinstitution.…”

Section: Discussionmentioning

confidence: 88%

Loss of high‐responder inhibitors in patients with severe hemophilia A and human immunodeficiency virus type 1 infection: A report from the multi‐center hemophilia cohort study

Kröner

Arkin³

et al. 1993

American J Hematol

114

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To evaluate the effects of human immunodeficiency virus type 1 (HIV-1) infection on the loss of factor VIII alloantibodies, we identified 77 patients with a history of inhibitors from among a large cohort of HIV-1-infected participants enrolled in a natural history study of HIV-1 infection in hemophilia. Fifty-six patients were high responders with inhibitors titers greater than 5 Bethesda Units (BU) measured on at least one occasion. From May 1985 to December 1989, 13 of the high-responder patients were rechallenged with factor VIII concentrates after several years of treatment with other plasma products. All exhibited excellent hemostasis upon reinstitution of factor VIII. Seven of the 13 patients (11.3-46.3 years of age) were in the advanced stages of HIV-1 infection at the time of rechallenge. Inhibitor titers measured subsequent to the reinstitution of factor VIII were consistently less than 1 BU in five of these seven patients. The remaining six patients (6.1-57.5 years of age) had mild to moderate CD4+ lymphocyte depletion (absolute CD4+ cells: 262-935/mm3) at the time of factor VIII rechallenge. Follow-up inhibitor titers were negative 7-42 months after consistent factor VIII use in these six patients. The lack of anamnestic response to factor VIII in all 13 patients who were rechallenged indicates that HIV-1-infected patients who have a history of high-responder inhibitors frequently benefit from the reintroduction of factor VIII use for the control of bleeding, regardless of their stage of HIV-1 disease.

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“…Wensley et al [38] re ported a successful outcome in treating patients with 250 units of FVIII every other day. There are also reports of hemorrhages treated with FVIII in patients with inhibitors regardless of FVIII recoveries with subsequent disappear ance of the inhibitors, such as in the experience reported by Rizza and Matthews [39], who claimed success in 26 pa tients over the years. More recently, Gruppo [40] predictors of success were assessed through multivariant lo gistic regression applied to subsets of patients who achieved success or failure.…”

Section: Management Options Inhibitors and Prevalencementioning

confidence: 99%

Induction of Immune Tolerance, the Future of the Registry

Ewing¹

1996

Vox Sanguinis

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Factor VIII (FVIII) inhibitors are IgG antibodies that neutralize the procoagulant activity of FVIII, rendering hemorrhages difficult to manage. There may exist a genetic predisposition with consequent imbalance of T and B cell function. Efforts at inhibitor eradication in the last 20 years have produced a multitude of immune tolerance induction (IIT) protocols with variable outcome. Data derived from the International Registry indicate that inhibitor titer at outset of IIT and dose of FVIII concentrate used are important predictors of success. Future Registry activities should identify optimally standardized IIT regimens designed on the basis of patient likelihood to achieve tolerance and should provide further understanding of T and B cell interaction in the treatment process.

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Effect of frequent factor VIII replacement on the level of factor VIII antibodies in haemophiliacs

Cited by 50 publications

References 3 publications

Factor VIII Inhibitors in Patients with Hemophilia A

Factor VIII Inhibitors in Patients with Hemophilia A

Loss of high‐responder inhibitors in patients with severe hemophilia A and human immunodeficiency virus type 1 infection: A report from the multi‐center hemophilia cohort study

Induction of Immune Tolerance, the Future of the Registry

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