Increased inhibitor incidence in severe haemophilia A since 1990 attributable to more low titre inhibitors

Berg, H. M. Van Den; Hashemi, Samaneh; Fischer, Kathelijn; Petrini, Pia; Ljung, Rolf; Rafowicz, Anne; Carção, Manuel; Auerswald, Günter; Kurnik, Karin; Kenet, Gili; Santagostino, Elena

doi:10.1160/th15-08-0692

Cited by 19 publications

(7 citation statements)

References 27 publications

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“…Table 4 denotes Patients showing Hemophilia A inhibitors. We sorted ten patients depending upon the clinical evidence of bleeding disorder, poor response to hemostatic therapy (Fischer et al, 2016) and patients experiencing more than 15 events /year to evaluate the ef icacy clotting capacity of Chromolena extract. Table 5 denotes FVIII assay in patients with inhibitors.…”

Section: Resultsmentioning

confidence: 99%

Assessment of Chromolena odorata potential ability of hemostasis in patients with and without Haemophilia A Inhibitors

P¹,

Ramesh²

2020

ijrps

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Haemophilia is a chronic bleeding illness that causes several difficulties in the patient's daily life in various aspects. Inhibitor development is presently the most important treatment complication observed in patients with hemophilia. Treatment modalities of Haemophilia A with either plasma or recombinant FVIII regimes results in the development of inhibitors and the risk of complications in patients. Hence, newer treatment strategies involving innovative hemostatic therapy are warranted for better management of hemophilia patients. The aim and objective of this study was to assess the efficacy of Chromolena odorata mediated hemostasis in patients with hemophilia A inhibitors. It was a cohort study constituting 147 clinically diagnosed hemophilic A patients. All the patients underwent treatment with FVIII A regimes (specific or multiple). The severity of hemophilia and clotting time was assessed by standard FVIII and aPTT assays, respectively. Modified Bethesda assay method was used to detect FVIII inhibitors. The hemostatic capacity of Chromolena odorata was evaluated by pooling the patient’s plasma with Chromolena extract concentrate. Younger age group (15-30) were more prevalent (56.4%) among hemophilia pathogenesis. Hemarthrosis was the significant co-morbidity observed in 58.5% of patients. Majority of the patients (72.7%) were diagnosed with severe hemophilia A. We identified 10 clinically evident patients to possess inhibitors for FVIII. Evaluation of Chromolena odorata hemostatic potential showed the improvement of clotting capacity with optimal concentrations of extract in patients with inhibitors. The findings of the study revealed the hemostatic properties of Chromolena odorata that can be recommended in the treatment strategies of Haemophilia patients.

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Section: Resultsmentioning

confidence: 99%

Assessment of Chromolena odorata potential ability of hemostasis in patients with and without Haemophilia A Inhibitors

P¹,

Ramesh²

2020

ijrps

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“…The definition of a clinical important inhibitor, excluding single positive laboratory tests, has been proven to be of great importance. Overall more low-titre inhibitors have been detected [ 8 , 32 ]. Interestingly, many of the on-going large prospective observational studies, despite not having performed central testing, still have found very similar results for high-titre inhibitor incidences [ 2 , 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…Nowadays it is recommended to test at least every 3 months for inhibitors during the first 50 EDs [ 31 ]. In a large study, the PedNet group divided all PUPs according to 5-year birth cohorts [ 32 ]. Over a 20-year period, inhibitor titres over a 20-year period where investigated in 926 PUPs with severe haemophilia.…”

Section: Reviewmentioning

confidence: 99%

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Different impact of factor VIII products on inhibitor development?

Berg

2016

Thrombosis J

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Inhibitors are the most serious side effect of haemophilia treatment; they occur in 25–30 % of all patients with severe haemophilia A. Over the last 2 decades, conflicting data on the impact of clotting products have been published.Due to small studies of selected cases, appreciation of the impact of any particular product has been difficult. Moreover, the emphasis on inhibitor testing has led to increased detection of low-titre inhibitors (to >10 %), while the percentage of high-titre inhibitors is still around 20 %.Other non-genetic risk factors, such as dosing and intensive treatment, are able to increase individual inhibitor risk. Early prophylaxis might reduce inhibitor risk. Well-defined large PUP studies including products should be considered. This can only be achieved in collaboration with all stakeholders.In conclusion, while the impact of FVIII products on inhibitor development is large, presently the actual impact of any specific product is unclear.

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“… 1 About 20% of children with SHA will have a high‐titer inhibitor and are in need of eradication treatment. 2 , 3 Inhibitors render FVIII replacement therapy ineffective, increasing the risk of morbidity and mortality. Immune tolerance induction (ITI) with repeated administration of FVIII is recommended as the only method for inhibitor eradication and would achieve 60% to 80% overall success rates.…”

Section: Introductionmentioning

confidence: 99%

Low‐dose immune tolerance induction alone or with immunosuppressants according to prognostic risk factors in Chinese children with hemophilia A inhibitors

Chen

Liu

et al. 2021

Research and Practice in Thrombosis and Haemostasis

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Background In developing countries, children with hemophilia A (HA) with high‐titer inhibitor and poor immune tolerance induction (ITI) prognostic risk(s) cannot afford the recommended high‐ or intermediate‐dose ITI. Objectives To determine the efficacy of low‐dose ITI (plasma‐derived factor VIII [FVIII]/von Willebrand factor at 50 FVIII IU/kg every other day) by itself (ITI‐alone) or combined with immunosuppressants rituximab and prednisone (ITI‐IS) in children with HA with high‐titer inhibitor. Methods All enrolled patients had pre‐ITI inhibitor ≥10 BU. We used ITI‐alone if inhibitor titer was <40 BU pre‐ITI and during ITI, and ITI‐IS if titer was ≥100 BU (historic) or ≥40 BU (pre‐ or during ITI) or if the patient was nonresponsive on ITI‐alone. Results Fifty‐six children were analyzable, with median historic peak inhibitor titer 48.0 BU and followed for median 31.4 months. Overall, 35 (62.5%) achieved phase 2 success with negative inhibitor and normal FVIII recovery. The phase 2 success rate was 95% for the 20 patients receiving ITI‐alone. For the 36 patients receiving ITI‐IS, the phase 2 success rate was 44.4%, but would increase to 63.6% if the 14 patients with historic peak inhibitor titer ≥100 BU (and having phase 2 success rate of only 14.3%) were excluded. One patient developed repeated infection after IS treatment. Relapse occurred in 11.4% (4/35) patients with phase 2 success associated with rapid ITI dose reduction or irregular post‐ITI FVIII prophylaxis. Our strategy reduced the cost from high‐dose ITI by 74% to 90%. Conclusion The use of low‐dose ITI with or without immunosuppressants according to ITI prognostic risk(s) is a clinically and economically feasible strategy for eradicating inhibitors in children with HA, particularly for those with historic peak inhibitor titer <100 BU.

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Increased inhibitor incidence in severe haemophilia A since 1990 attributable to more low titre inhibitors

Cited by 19 publications

References 27 publications

Assessment of Chromolena odorata potential ability of hemostasis in patients with and without Haemophilia A Inhibitors

Assessment of Chromolena odorata potential ability of hemostasis in patients with and without Haemophilia A Inhibitors

Different impact of factor VIII products on inhibitor development?

Low‐dose immune tolerance induction alone or with immunosuppressants according to prognostic risk factors in Chinese children with hemophilia A inhibitors

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