Prevention of inhibitor development in hemophilia A in 2016. A glimpse into the future?

Franchini, Massimo; Lippi, Giuseppe

doi:10.1016/j.thromres.2016.10.024

Cited by 10 publications

(6 citation statements)

References 47 publications

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“…21 The possible mechanisms underlying this phenomenon are still incompletely understood, and several hypotheses can be made. 25 The keystone probably resides in the close link between circulating FVIII and its carrier, VWF. 16 The lack of data about VWF levels in a relevant proportion of patients made it difficult to adequately investigate this issue in our cohort.…”

Section: Discussionmentioning

confidence: 99%

ABO Blood Group and Inhibitor Risk in Severe Hemophilia A Patients: A Study from the Italian Association of Hemophilia Centers

Franchini

Coppola

Santoro

et al. 2021

Semin Thromb Hemost

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Considering the profound influence exerted by the ABO blood group system on hemostasis, mainly through the von Willebrand factor and factor VIII (FVIII) complex, we have conducted a study evaluating the possible role of blood type on the risk of inhibitor development in hemophilia A. A total of 287 consecutive Caucasian patients with severe hemophilia A (202 without FVIII inhibitors and 85 with FVIII inhibitors) followed at seven Italian Hemophilia Treatment Centers belonging to the Italian Association of Hemophilia Centers (AICE) were included in the study. A higher prevalence of O blood group was detected in patients without inhibitors as compared in inhibitor patients (55 vs. 30.6%; p < 0.001). Among the other variables analyzed (age, F8 mutation, type and intensity of treatment and treatment regimen), F8 mutation class (high-risk vs. low-risk), and treatment regimen (on-demand vs. prophylaxis) were significantly correlated with inhibitor development. However, on a multivariate analysis, only the effects of F8 mutation and ABO blood type were independent of other covariates, being that non-O blood type is associated with a 2.89-fold increased risk of inhibitor development. In conclusion, our study supports the protective effect of O blood type on inhibitor risk in severely affected hemophilia A patients.

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Section: Discussionmentioning

confidence: 99%

ABO Blood Group and Inhibitor Risk in Severe Hemophilia A Patients: A Study from the Italian Association of Hemophilia Centers

Franchini

Coppola

Santoro

et al. 2021

Semin Thromb Hemost

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“…Prophylactic coagulation factor replacement therapy has become the standard of care for patients with severe haemophilia and quality of life has improved dramatically. Unfortunately, the development of neutralizing antibodies or ‘inhibitors’ against exogenously administered factors, particularly FVIII concentrates, has become the principal complication of haemophilia A therapy [32] and has become the main threat to haemophilia A patients [33].…”

Section: Discussionmentioning

confidence: 99%

Naive haemophilia mice displayed different pattern of cytokine profiles of cytokine profiles changes might be associated with subclinical bleeding

Zhang¹,

Zong

Zhou

et al. 2021

Blood Coagulation &Amp; Fibrinolysis

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Subclinical bleeding is a haemorrhage event not clinically detected in haemophilia, and no reliable method is available for predicting subclinical bleeding. We investigated whether haemophilia mice have subclinical haemorrhage and evaluated potential biomarkers including multiple cytokine changes to predict subclinical haemorrhage. Plasma from naïve FVIII−/− and FIX−/− mice and their wild-type counterparts (FVIII WT and FIX WT, respectively) were measured for prothrombin fragment 1 + 2 (F1 + 2) and multiple cytokines. Haemophilia mice with induced hemarthrosis were used as positive clinical bleeding controls. Naive haemophilia mice that displayed higher levels than positive bleeding control were counted. Univariate and multivariate analyses of cytokines were performed. Compared with wild-type mice (FVIII WT 1.1–6.2 vs. FIX WT 2.7–6.7 pmol/l), F1 + 2 widely varied in both haemophilia mouse strains (FVIII−/− 3.7–25.7 vs. FIX−/− 2.7–15.7 pmol/l). Each cytokine varied widely in both naive haemophilia A and B mice, but not significantly, for most cytokines. In comparison to haemophilia mice with hemarthrosis bleeding challenge, naive FVIII−/− mice had elevated pro-inflammatory cytokines and FIX−/− mice had elevated anti-inflammatory cytokines. In addition, interleukin (IL)-4, followed by IL-1, IL-6, TNF-α and MIP-1α in FVIII−/− mice and MIP-1α, followed by IL-1, IL-10 in FVIII−/− mice exhibited significant differences potentially associated with potential subclinical bleeding. Naive haemophilia mice showed elevated pro-inflammatory cytokines with different patterns, represented by pro-inflammatory cytokine elevation in more naïve FVIII−/− mice and more anti-inflammatory cytokines in FIX−/− mice.

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“…Development of inhibitors in hemophilia is a multifactorial process that dynamically comprises inherited factors (ABO blood group, 8 ethnicity, 9 human leukocyte antigen, 10 haplotype, 11 type of factor VIII or factor IX mutations, 12 , 13 and family history of developing inhibitors 14 ) and environmental factors (infection and vaccination, 15 – 17 type of infused coagulation factor, 18 and age at start of treatment). 8 , 4 , 19 About 30% of patients with severe hemophilia A, 0.9% to 7% of patients with moderate and mild hemophilia A, 20 and around 3% to 4% of individuals with severe hemophilia B develop inhibitors. 21 – 23 The development of inhibitors significantly complicates the control of hemorrhagic episodes in patients with hemophilia and makes challenges for hematologists because bleeds may not respond to conventional replacement therapy.…”

Section: Inhibitors In Hemophiliamentioning

confidence: 99%

Clinical Care of Bone Health in Patients on the Immune Tolerance Induction’s Protocols With an Immunosuppressive Agent for Inhibitor Eradication in Hemophilia

Rezaieyazdi

Mansouritorghabeh

2020

Clin Appl Thromb Hemost

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Nowadays, the development of factor VIII and IX inhibitors in patients with hemophilia is considered as the most challenging in the treatment of hemophilia. Immune tolerance induction (ITI) therapy is an approach for eradication of inhibitors. Some ITI protocols are routinely in use for the eradication of inhibitors in patients with hemophilia. Moreover, such a therapeutic regimen may facilitate the tendency to reduced bone density in patients with inhibitor. This study scheduled to investigate whether that predisposing role of ITI protocols with an immunosuppressive agent has considered or not. By a literature review, published ITI protocols in hemophilia with inhibitors were evaluated. Among them, 51 papers found and studied thoroughly. None of them had performed the bone mineral examination in patients with hemophilia and inhibitor under treatment. Since there are 2 coexisting facilitating factors in these protocols, considering the bone mineral density study for patients with inhibitor who are undergoing ITI protocols with an immunosuppressive agent is recommended.

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Prevention of inhibitor development in hemophilia A in 2016. A glimpse into the future?

Cited by 10 publications

References 47 publications

ABO Blood Group and Inhibitor Risk in Severe Hemophilia A Patients: A Study from the Italian Association of Hemophilia Centers

ABO Blood Group and Inhibitor Risk in Severe Hemophilia A Patients: A Study from the Italian Association of Hemophilia Centers

Naive haemophilia mice displayed different pattern of cytokine profiles of cytokine profiles changes might be associated with subclinical bleeding

Clinical Care of Bone Health in Patients on the Immune Tolerance Induction’s Protocols With an Immunosuppressive Agent for Inhibitor Eradication in Hemophilia

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