Factor VIII inhibitors in haemophiliacs: a single‐centre experience over 34 years, 1964–97

Yee, T. T.; Pasi, K. J.; Lilley, P.; Lee, C. A.

doi:10.1046/j.1365-2141.1999.01268.x

Cited by 43 publications

(34 citation statements)

References 26 publications

(34 reference statements)

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“…The influence of ethnic origin of patients on inhibitor formation has been reported by several meta-analyses [23,24]. The prevalence of inhibitors in severe hemophilia patients of African-American and Latino origin has been found to be two times higher than that of Caucasians [25].…”

Section: Ethnicitymentioning

confidence: 96%

Immune Response to FVIII in Hemophilia A: An Overview of Risk Factors

Ghosh

Shetty

2009

Clinic Rev Allerg Immunol

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Development of inhibitors is perhaps the most serious complication of factor VIII (FVIII) replacement therapy, which can practically preclude efficient clinical management of patients with hemophilia A. Much effort therefore has been focused both in improving our understanding of the reasons for the formation of FVIII antibodies and to find alternative methods of treatment. Several patient-related factors have been related to the risk of inhibitor development such as ethnicity, FVIII gene mutation type, family history of inhibitors, HLA haplotype, polymorphisms in the promoter regions of IL 10 gene, single nucleotide polymorphisms of tumor necrosis factor alpha gene, and so on. In addition to the genetic determinants, there are several nongenetic factors which mainly include treatment characteristics like the type and purity of coagulation factor concentrates used for treatment, age at the time of initial treatment, initial doses of concentrate, mode of infusion, surgery, frequency of dosing prior to inhibitor development, and intensity of treatment or regular prophylaxis. Inflammatory processes in early childhood are under discussion as being an environmental factor that may modify the immune response to a foreign antigen. The genetic risks cannot be changed, while environmental factors may increase or decrease the inhibitor risk in an individual patient. In addition, there are other causes of inhibitor development against FVIII like stress, age, malignancy, infection, pregnancy, antibiotics, etc. Development of inhibitors in such cases happens in individuals who are not hemophilic and have normal plasma FVIII levels. Acquired inhibitors to FVIII in nonhemophiliacs (autoantibodies) pose a further challenge to treatment, as this is often associated with significant morbidity and mortality. Prognosis in case of autoantibodies is related to the underlying disease process and is associated with high mortality. Improved understanding of these complex interactions may lead to the development of preventive measures to minimize FVIII inhibitor formation. The modifiable risk factors for inhibitor formation may provide the key to predict and perhaps prevent the formation of inhibitors in hemophilia patients.

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Section: Ethnicitymentioning

confidence: 96%

Immune Response to FVIII in Hemophilia A: An Overview of Risk Factors

Ghosh

Shetty

2009

Clinic Rev Allerg Immunol

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“…[1][2][3][4][5][6][7][8][9] Although uncommon, these autoantibodies are associated with a high rate of morbidity and mortality as severe bleeds occur in up to 90% of affected patients and the mortality rate is high, ranging from 8% to 22%. [10][11][12] For these reasons, patients with acquired hemophilia A represent a demanding clinical challenge.…”

Section: Introductionmentioning

confidence: 99%

Acquired factor VIII inhibitors

Franchini

Lippi

2008

Blood

246

321

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Acquired hemophilia A is a rare bleeding diathesis caused by autoantibodies directed against clotting factor VIII and associated with an increased morbidity and mortality. This autoimmune disorder most commonly occurs in the elderly. Although it may be associated with several underlying pathologies, up to 50% of reported cases remain idiopathic. In contrast with congenital hemophilia, which is commonly characterized by hemarthroses, hemorrhages in patients with acquired hemophilia involve most frequently soft tissues. The 2 treatment priorities are to arrest the acute bleeding and to eradicate the factor VIII autoantibody. Acute bleeding episodes in patients with low-titer inhibitors can be treated using human factor VIII concentrates, whereas factor VIII bypassing agents, such as activated prothrombin complex concentrates or recombinant activated factor VII, are effective for the treatment of those with hightiter inhibitors. An analysis of the literature shows that the most effective first-line treatment for the eradication of factor VIII autoantibodies is the combination of steroids and cyclophosphamide. However, there is increasing evidence on the effectiveness of other treatment approaches, such as immune tolerance regimens and rituximab. If confirmed by large controlled studies, these innovative therapies might become a valid option for long-term eradication of factor VIII inhibitors. (Blood. 2008;112:250-255)

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“…The disease is commonly associated with other underlying medical conditions such as pregnancy and postpartum status, autoimmune disorders, malignancies, dermatological conditions, infections or drug interactions [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. However, up to 50% of cases have no identifiable underlying disorders.…”

Section: General Aspects Of Acquired Hemophilia Amentioning

confidence: 99%