The need for speed in the management of haemophilia patients with inhibitors (original) (raw)
Related papers
European Journal of Haematology, 2018
The standard therapy for patients with haemophilia is prophylactic treatment with replacement factor VIII (FVIII) or factor IX (FIX). Patients who develop inhibitors against FVIII/FIX face an increased risk of bleeding, and the likelihood of early development of progressive arthropathy, alongside higher treatment-related costs. Bypassing agents can be used to prevent and control bleeding, as well as the recently licensed prophylaxis, emicizumab, but their efficacy is less predictable than that of factor replacement therapy. Antibody eradication, by way of immune tolerance induction (ITI), is still the preferred management strategy for treating patients with inhibitors. This approach is successful in most patients, but some are difficult to tolerise and/or are unresponsive to ITI, and they represent the most complicated patients to treat. However, there are limited clinical data and guidelines available to help guide physicians in formulating the next treatment steps in these patients. This review summarises currently available treatment options for patients with inhibitors, focussing The copyright line for this article was changed on 23 December 2019 after original online publication. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Blood Coagulation & Fibrinolysis, 2017
Haemophilia treatment guidelines advocate early homebased treatment of acute bleeds. In the ADEPT2 trial, data were collected on the home treatment of bleeds with recombinant activated factor VII (rFVIIa) in haemophilia patients with inhibitors and self-reported bleeding-related symptoms. A total of 93% of all bleeds, and 91.5% of joint bleeds, were treated successfully with one to three doses of 90 mg/kg rFVIIa. However, some patients self-administered additional haemostatic medication (AHM) up to 48 h after the first rFVIIa treatment. The aim of this trial was to investigate the relationship between patient-reported symptoms, time to treatment initiation, and the use of AHM. A post hoc analysis was conducted on 177 joint bleeds and the patient-reported categorical symptoms of pain, swelling, mobility, tingling, and warmth, and the pain visual analogue scale (VAS) score. Analyses were descriptive and used logistic regression modelling. Complete symptom data were available for 141, 136, and 129 joint bleeds at 0 or 1, 3, and 6 h, respectively. Pain and pain VAS assessments were the best predictors of AHM use. Patients who selfadministered AHM had higher mean pain VAS scores at each time point; both pain and pain VAS scores declined over time. Time to treatment initiation was an independent predictor for AHM use. Higher initial pain scores and longer time to treatment were the best predictors for administration of AHM. The observation that some patients chose to self-infuse in the face of declining levels of pain warrants further study to better understand the reasons behind patient decision-making. Blood Coagul Fibrinolysis
Haemophilia, 2007
Summary. The presence of inhibitory antibodies to clotting factors complicates the treatment of bleeding in haemophilia patients. For patients with high-titre inhibitors, bypassing agents are essential to haemostatic management. To determine optimal treatment practices, an international panel of physicians convened to develop a systematic treatment approach for problem bleeds (i.e. bleeds that are unresponsive to initial therapy with a single agent within a reasonable amount of time) in haemophilia patients with inhibitors. Aim: The goal of this panel was to develop a consensus algorithm that would aid physicians in considering a variety of treatment approaches to optimize patient care by preventing extensive therapy with inadequate treatments that may lead to suboptimal patient outcomes and unnecessary costs. Methods: Consensus opinions were analyzed for clinical preferences at different time periods, depending on patient response to treatment. Decision-making points were defined based on the type of bleed: every 8–12 h for the first 24 h, then every 24 h thereafter for limb-threatening bleeds; every 2–4 h for 2–7 days for life-threatening bleeds. Results: The resultant consensus guidelines provide a generalized methodology to guide the treatment of problem bleeds in patients with severe haemophilia A and inhibitors, and emphasize changing treatment at the first sign of an inadequate haemostatic response. The treatment algorithms apply to both paediatric and adult patients, although the differences between the two groups were reviewed. Conclusion: These guidelines are focused on optimising the timing of treatment decisions, which may lead to faster responses and improved outcomes.
Iranian Red Crescent Medical Journal, 2014
Context: Mild-to-moderate bleeding disorders in haemophilia are primarily treated via recombinant activated factor VII a (rFVIIa) or activated prothrombin complex concentrate (aPCC). However, the efficacy of each bypassing agents may vary and none of them is universally effective. Evidence Acquisition: After reviewing the databases of PubMed, Scopus, MD Consult, Ovid, Trip database, Google Scholar, ProQuest and the Cochrane Library, finally, 17 papers published from 2000 to 2013 were extracted. We used as a random effect model in meta-analysis. Comprehensive meta-analysis (CMA) software was used for calculating and estimating the mean of bleeding reduction and performing meta-analysis. Results: The mean of bleeding reduction in aPCC and rFVIIa were 71.2% with CI 95% (lower limit 86.8% and upper limit 82%) and 72.3% with CI 95% (lower limit 57.6% and upper limit 83.4%), respectively. Conclusions: Although differences between the two products were very close to each other, they reported similar effects on joint bleeds. Further clinical studies should be performed by incorporating a standardized measurement in comparative efficacy of aPCC and rFVIIa.
Haemophilia, 2009
Summary. The effect of bypassing agents is not as predictable as replacement therapy with the deficient factor in inhibitor patients. Consequently, these patients have more levels of arthropathy than patients without inhibitors. Prophylaxis for inhibitor patients has gained attention over the last decade and some papers have reported that bypassing agents could work in the prevention of arthropathy. However, there is a lack data to support any specific agent or regimen or even to recommend their use in different clinical conditions. We report ten patients with haemophilia A and inhibitors treated prophylacticaly with bypassing agents (5 with FEIBA and 5 with NovoSeven). The variable conditioning the choice of one agent or the other was the intention to initiate of immune tolerance induction therapy (ITI) in the future. In 8/10 patients (4 in FEIBA group and 4 in rFVIIa group) there was a decrease of bleeding episodes while 9/10 maintained or increased their joint range of motion (ROM). In the rFVIIa prophylaxis group, prophylaxis can be considered primary since all of them had had less than one joint bleed before prophylaxis. Economic analysis showed that prophylaxis is an expensive treatment. In our experience both agents seem to be safe and effective in reducing the number of bleeds in patients with inhibitors. The anamnestic response provoked by FEIBA could be an issue while awaiting a decline in titres before ITI can be initiated and so rFVIIa may be the best option for prophylaxis in patients with inhibitors who have not yet begun ITI.
European Study on Orthopaedic Status of haemophilia patients with inhibitors
Haemophilia, 2007
Summary. Development of inhibitors against factor VIII (FVIII) or factor IX (FIX) in haemophilia patients is one of the most serious complications of repeated exposure to replacement therapy and has major clinical and economic consequences. To evaluate the relationship between inhibitor status of haemophilia patients and their quality of life (QoL) and degree of arthropathy and to compare the orthopaedic status of patients with/without inhibitors. An observational, cross-sectional, case control study enrolling: group A (n = 38), males aged 14–35 years, with severe congenital haemophilia A or B who had inhibitors against FVIII/FIX >5 years; group B (n = 41), as group A, but aged 36–65 years and group C (n = 49), as group A, but without inhibitors. Socio-demographics: medical history, clinical characteristics and QoL were assessed. In groups A and B, 16% and 27% were hospitalized for orthopaedic procedures vs. 4% in group C. Patient mobility was also severely reduced in groups A and B, with 24% and 22% using wheelchairs vs. 4% in group C, and 50% and 51% needing a walking aid vs. 29% in group C. Significantly more joint pain was reported by patients in group A vs. those in group C; clinical/radiological orthopaedic scores were also worse in group A vs. group C. Significantly more joint abnormality was reported by patients in group A vs. group C. The burden of orthopaedic complications and the impact on QoL are more severe in haemophilia patients who have developed inhibitors than in those without inhibitors.
2014
Context: Mild-to-moderate bleeding disorders in haemophilia are primarily treated via recombinant activated factor VII a (rFVIIa) or activated prothrombin complex concentrate (aPCC). However, the efficacy of each bypassing agents may vary and none of them is universally effective. Evidence Acquisition: After reviewing the databases of PubMed, Scopus, MD Consult, Ovid, Trip database, Google Scholar, ProQuest and the Cochrane Library, finally, 17 papers published from 2000 to 2013 were extracted. We used as a random effect model in meta-analysis. Comprehensive meta-analysis (CMA) software was used for calculating and estimating the mean of bleeding reduction and performing meta-analysis. Results: The mean of bleeding reduction in aPCC and rFVIIa were 71.2% with CI 95% (lower limit 86.8% and upper limit 82%) and 72.3% with CI 95% (lower limit 57.6% and upper limit 83.4%), respectively. Conclusions: Although differences between the two products were very close to each other, they reported similar effects on joint bleeds. Further clinical studies should be performed by incorporating a standardized measurement in comparative efficacy of aPCC and rFVIIa.