The factor VIII treatment history of non‐severe hemophilia A

Abdi, Amal; Kloosterman, Fabienne R.; Eckhardt, Corien L.; Male, Christoph; Castaman, Giancarlo; Fischer, Kathelijn; Beckers, Erik A.M.; Kruip, Marieke J.H.A.; Peerlinck, Kathelijne; Mancuso, Maria Elisa; Santoro, Cristina; Hay, C. R. M.; Platokouki, Helen; Bom, Johanna G. van der; Gouw, Samantha C.; Fijnvandraat, Karin; Hart, Dan

doi:10.1111/jth.15076

Cited by 17 publications

(19 citation statements)

References 26 publications

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“…Non-severe hemophilia A patients (FVIII:C 1-40%), who account for 50-60% of all hemophilia A patients, suffer from prolonged bleeding episodes upon trauma or in a perioperative setting. 3,4 Based on disease severity, treatment approaches are different. 5 Although minor bleeds in non-severe hemophilia A patients are often successfully treated with 1-Deamino-8-D-ArgininVasoPressin (desmopressin; DDAVP), a substantial number of bleeding events demands exogenous FVIII supply or a combination of both.…”

Section: Introduction (787 Words)mentioning

confidence: 99%

Nonneutralizing FVIII-specific antibody signatures in patients with hemophilia A and in healthy donors

et al. 2022

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Previous studies identified nonneutralizing FVIII-specific antibodies in the circulation of severe and non-severe hemophilia A patients without FVIII inhibitors and also in some healthy individuals. To gain a better understanding of the nature of these nonneutralizing antibody responses, we analyzed and compared anti-FVIII antibody signatures in three study cohorts - previously treated severe as well as non-severe hemophilia A patients without FVIII inhibitors, and healthy donors. FVIII-binding IgM, IgG1-4 and IgA antibodies were differentiated, FVIII-specificity was assessed and associated apparent affinity constants were determined. Our results indicate that the nonneutralizing FVIII-specific antibody response in all study cohorts is dominated by IgG1 and IgA. Prevalences, titers and affinities of these nonneutralizing antibodies were higher in the hemophilia A cohorts than in healthy donors. Stratification for the anti-HCV antibody status demonstrated the presence of FVIII-specific IgA with elevated titers in severe hemophilia A patients with an active or past HCV infection when compared to HCV antibody positive non-severe patients or HCV antibody negative patients and healthy donors. Increased titers and affinities of FVIII-specific IgG1 antibodies were observed in a considerable number of hemophilia A patients as opposed to healthy subjects independently of the patients' anti-HCV antibody status. Overall, our findings support the hypothesis that the generation of nonneutralizing anti-FVIII antibodies in healthy individuals and in non-inhibitor hemophilia A patients might be based on similar immune mechanisms. However, differences in prevalences, titers and affinities of these antibodies indicate distinct differences in the antibody evolution between healthy individuals and patients.

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Section: Introduction (787 Words)mentioning

confidence: 99%

Nonneutralizing FVIII-specific antibody signatures in patients with hemophilia A and in healthy donors

et al. 2022

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“…Its use in people with severe HA effectively converts them to a non-severe bleeding phenotype and, in young patients, considerably postpones the age at which they receive their first FVIII replacement treatment. 22 However, this agent will only be used in the prophylactic setting and additional haemostatic treatment will be needed for major surgery and severe trauma/bleeds. It is not yet known what the potential impact of switching from FVIII replacement therapy to non-replacement therapy on the tolerant state towards FVIII in ageing patients might be, or the risk of inhibitor formation in association with severe trauma and surgical interventions in patients on non-replacement therapy requiring additional FVIII concentrate for appropriate haemostasis.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

New Inhibitors in the Ageing Population: A Retrospective, Observational, Cohort Study of New Inhibitors in Older People with Hemophilia

Astermark

Carvalho

et al. 2021

Thromb Haemost

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Introduction: A second peak of inhibitors has been reported in patients with severe haemophilia A (HA) aged >50 years in the UK.1 The reason for this suggested breakdown of tolerance in the ageing population is unclear, as is the potential impact of regular exposure to the deficient factor by prophylaxis at higher age. No data on haemophilia B (HB) has ever been reported. Aim: The ADVANCE Working Group investigated the incidence of late-onset inhibitors and the use of prophylaxis in patients with HA and HB aged ≥40 years. Methods: A retrospective, observational, cohort, survey-based study of all patients aged ≥40 years with HA or HB treated at an ADVANCE HTC. Results: Information on 3,095 people aged ≥40 years with HA or HB was collected. Of the 2,562 patients with severe HA, the majority (73% across all age groups) received prophylaxis. In patients with severe HA, the inhibitor incidence per 1,000 treatment years was 2.37 (age 40–49), 1.25 (age 50–59) and 1.45 (age 60+). Overall, the inhibitor incidence was greatest in those with moderate HA (5.77 (age 40–49), 6.59 (age 50–59) and 4.69 (age 60+) and the majority of inhibitor cases were preceded by a potential immune system challenge. No inhibitors in patients with haemophilia B were reported. Conclusion: Our data do not identify a second peak of inhibitor development in older patients with haemophilia. Prophylaxis may be beneficial in older patients with severe, and possibly moderate HA, to retain a tolerant state at higher age.

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“…It is clinically identified by prolonged clotting time, excessive bleeding in skin, mucous membranes, secondary joint complications, among others. In hemophilia, the factors in deficit are diminished in quantity, structure and function, resulting in an altered coagulation cascade and a significant increase in bleeding time [4] . The classification of hemophilia focuses on the plasma level of FVIII/FIX.…”

Section: Introductionmentioning

confidence: 99%

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2022

Int. J. Appl. Dent. Sci.

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Introduction: Hemophilia is an is an X-linked recessive inherited disorder. It belongs to the group of hereditary disorders caused by the deficiency of one or more coagulation factors. Objective:To analyze the literature on the considerations in the dental office in the management of the hemophiliac patient, particularly the etiology, clinical characteristics, diagnosis, treatment and dental management. Methodology: In order to carry out this literature review, an electronic search was necessary using PUBMED and Google Scholar with the words "Hemophilia AND dentistry" "etiology, clinical and dental characteristics, diagnosis and treatment" and "coagulation factors". Results: Hemophilia is due to an alteration in one of the genes that determine the way in which the organism produces coagulation factor VIII or IX. It occurs in 1 in 10,000 male births. It manifests as excessive bleeding in the joints, pain and edema, ecchymosis, urinary tract and digestive tract bleeding. It results in prolonged bleeding from wounds, dental extractions and surgery. The diagnosis of hemophilia is made by taking a blood sample and measuring the degree of factor activity. The main treatment for severe hemophilia is to receive specific clotting factor replacement. During the consultation, a detailed medical history should be taken and comprehensive clinical examinations should be ordered appropriately. The patient should provide the following information: type and severity of his hemophilia, medication ingest, whether he requires pre-treatment with factor concentrate, or an antifibrinolytic agent. Conclusion: Hemophilia is an X-linked recessive inherited disorder. It belongs to the group of inherited disorders caused by deficiency of one or more clotting factors. Practice guidelines are needed to improve the diagnostic process, improve the quality of dental care.

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The factor VIII treatment history of non‐severe hemophilia A

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 17 publications

References 26 publications

Nonneutralizing FVIII-specific antibody signatures in patients with hemophilia A and in healthy donors

Nonneutralizing FVIII-specific antibody signatures in patients with hemophilia A and in healthy donors

New Inhibitors in the Ageing Population: A Retrospective, Observational, Cohort Study of New Inhibitors in Older People with Hemophilia

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