A Public Health Approach to the Prevention of Inhibitors in Hemophilia

Soucie, J. Michael; Miller, Connie H.; Kelly, F. M.; Oakley, Meredith; Brown, Deborah L; Kucab, Phillip

doi:10.1016/j.amepre.2014.07.007

Cited by 10 publications

(12 citation statements)

References 27 publications

(41 reference statements)

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“…Because of the seriousness of such complication and its impact on patient management, CDC in collaboration with hemophilia organizations and other partners were involved in the development of public health agenda to prevent the development of inhibitors, through national surveillance, epidemiological studies and promoting research that is directed towards solving the puzzles and filling the knowledge gap in this issue. 4 The prevalence of inhibitors in severe hemophilia A is estimated to be 25-30%. Ethnicity plays a role in inhibitor development, reflecting the underlying prevalent factor VIII mutation, and polymorphism in different components of the immune system influencing reactivity to factor VIII concentrates.…”

Section: Discussionmentioning

confidence: 99%

Untitled

2018

HTIJ

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The aim of the current study was to assess the prevalence of factor VIII inhibitors among Omani haemophiliac children, and relationship of their development with different risk factors. AbstractIntroduction: A major challenging complication of factor VIII replacement therapy is the development of neutralizing antibodies, rendering therapy ineffective. There are recognized genetic and non-genetic risk factors for inhibitors development. This study aimed to screen for the prevalence of inhibitor development among Omani patients with severe haemophilia A and to define its non-genetic risk factors that might help to develop prevention protocols.Methods: A Retrospective cohort study that included all patients with haemophilia A registered in Oman. Data were collected using computerized hospital information system. Patients' demographic data: MRN, age at diagnosis, age at first treatment, date of the first documented inhibitor development, & data on non-genetic risk factors such as, mode of treatment (on demand versus prophylaxis), type and dose of the concentrate, time interval of exposure to factor VIII till inhibitor development, previous surgeries or major bleeding events/blood transfusion; were included. Missing data were collected through phone interviews whenever possible.Results: Out of the 156 patients registered in Oman, 78 patients had complete data. The age of inhibitor development ranged between 16 months and 21years (109.4+79.9 months). The prevalence of inhibitors among our patients was 35% and mainly of low titer 87%. There was a significant correlation between the intensity of prophylaxis and inhibitor development (p<0.05). Inhibitor development was not associated with type of the factor used, time interval of exposure to factor VIII, use of on-demand or prophylaxis regimen and history of major bleed or previous surgery. Discussion/Conclusion: Inhibitors development is a major complication in patients with hemophilia A in Oman. A larger scale study that includes all the registered patients and their genetic mutation is needed.

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Section: Discussionmentioning

confidence: 99%

Untitled

2018

HTIJ

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“…Haemophilia patients may have concurrent FVIII inhibitors and LA. 58,60 The protocol for the U.S. national inhibitor surveillance programme 81 treats positive inhibitor results below 2.0 NBU for FVIII and below 1.0 NBU for FIX as “grey zone” results, requiring repeating the test and performance of CBA for FVIII and antibody tests for FVIII and FIX for confirmation before reporting.…”

Section: | Recent Assay Modificationsmentioning

confidence: 99%

Laboratory testing for factor VIII and IX inhibitors in haemophilia: A review

Miller

2018

Haemophilia

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Inhibitors are antibodies directed against haemophilia treatment products which interfere with their function. Factor VIII (FVIII) inhibitors in haemophilia A and factor IX (FIX) inhibitors in haemophilia B are significant clinically when they require a change in a patient’s treatment regimen. Their persistence may increase morbidity and mortality. Multiple laboratory tests are now available for detecting and understanding inhibitors in haemophilia. Inhibitors are traditionally measured by their interference in clotting or chromogenic factor assays. They may also be detected using immunologic assays, such as enzyme-linked immunosorbent assay or fluorescence immunoassay. Anti-FVIII or anti-FIX antibodies of IgG4 subclass best correlate with the presence of functional inhibitors. Improvements in inhibitor measurement have been recently introduced. Preanalytical heat treatment of patient specimens allows testing of patients without delaying treatment. Use of chromogenic and immunologic assays may aid in identification of false-positive results, which are frequent among low-titre inhibitors. Validated reagent substitutions can be used to reduce assay cost. New methods for defining assay positivity and reporting low-titre inhibitors have been suggested. Challenges remain in the areas of quality control, assay standardization, monitoring of patients undergoing immune tolerance induction therapy and testing in the presence of modified and novel treatment products.

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“…Such rates would be useful when assessing whether local inhibitor rates exceed those expected, and therefore should be investigated. Such a surveillance system has been implemented as part of a public health approach to inhibitors in haemophilia [5]. Acquired haemophilia is a rare disorder and is almost universally mediated through autoantibodies, usually as acquired haemophilia A [1].…”

Section: Cluster Of Inhibitors Among Adult Inpatients With Haemophilimentioning

confidence: 99%

Cluster of inhibitors among adult inpatients with haemophilia in a single institution

Ishaku

Key²,

Miller

et al. 2015

Haemophilia

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FVIII replacement allowed him to remain bleed free; whilst on antiplatelet therapy. This situation may arise more frequently with increasing numbers of elderly PWH with the requirement for dedicated international guidelines for the TAVI procedure in PWH.To our knowledge, this is the first reported case of a PWH undergoing TAVI. Interestingly, this gentleman did not suffer bleeding complications despite a requirement for blood transfusion of nearly 20% in a large study of persons without haemophilia undergoing the same procedure [7]. The survival of this PWH into his 9th decade is likely due, not only to the improvements in the management of haemophilia but also the progression in general medical and surgical care over recent years. With increased longevity in PWH and advances in medical science, further consideration is required for dedicated guidelines for management of the elderly PWH. Author contributionsBM wrote the manuscript. GB directed and assisted with writing the manuscript. PW provided details on the results of genetic analysis and assisted with writing the manuscript.

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A Public Health Approach to the Prevention of Inhibitors in Hemophilia

Cited by 10 publications

References 27 publications

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Laboratory testing for factor VIII and IX inhibitors in haemophilia: A review

Cluster of inhibitors among adult inpatients with haemophilia in a single institution

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