Hemophilia A is characterized by a deficiency of clotting factor VIII (FVIII) requiring lifelong prophylactic treatment, typically with recombinant FVIII. In recent years, drugs with extended ...half-lives have become available, including damoctocog alfa pegol (Bayer S.p.A.). The clinical efficacy and safety of damoctocog alfa pegol were demonstrated in the PROTECT VIII phase II/III development program. To assess the physicians’ experience and to collect data on prophylactic treatment with damoctocog alfa pegol, a monitoring survey was carried out among 15 Italian hemophilia centers. A total of 149 patients on treatment with damoctocog alfa pegol for at least 6 months were considered. Zero bleeds were reported in 75% of patients treated with damoctocog alfa pegol in the last 6 months; zero hemarthroses were reported in 82% of the same patients. Overall, 86% of patients with damoctocog alfa pegol reduced their monthly infusions. The estimated average reduction in IU/kg during prophylaxis with damoctocog alfa pegol, both monthly and annually, was around 17.5%. All involved clinicians were satisfied with damoctocog alfa pegol. Survey results suggest that damoctocog alfa pegol reduced the number of weekly infusions, annual bleeding, and joint bleeding rate in the majority of patients, improving joint health and patients’ quality of life.
Acquired haemophilia A (AHA) is a rare bleeding disorder caused by inhibitory autoantibodies against coagulation factor VIII (FVIII). AHA is a disease that most commonly affects the elderly but has ...also been observed in children and in the postpartum period. AHA is idiopathic in 50% of cases and is associated with autoimmune diseases, malignancies, and infections in the remaining 50%. Recently, cases of association between AHA, COVID-19 vaccination, and infection have been reported in the literature. For diagnoses, determining FVIII levels is crucial to distinguish the different causes of aPTT prolongation. Treatment of AHA is based on bypassing agents (recombinant factor VIIa, activated prothrombin complex concentrate) and porcine FVIII to control the bleeding and immunosuppressive therapy (corticosteroids, rituximab, cyclophosphamide) to suppress autoantibody production. It is important to start a prophylactic regimen to prevent further bleeding episodes until the inhibitor is negative. Recently, the series of cases reported in the literature suggest that emicizumab may provide effective and safe haemorrhage prophylaxis in the outpatient setting.
AbstractBackgroundThe real goal on haemophilia treatment is to combine efficacy, safety, improvement in quality of life and cost-savings. Sometimes the choice for reaching this result is to switch ...the patients to an extended half-life (EHL) drug. In case of haemophilia A this goal is not always achieved due to the less pharmacokinetic (PK) differences among EHL and standard concentrates. A better and regular use of available tools, as MyPKfit®, can then optimize the treatment without distorting therapy or changing concentrate. MethodsWe now report our experience with a population of severe or moderate haemophilia A patients treated with octocog-alfa (Advate ® –Shire Takeda) and in which a tailored prophylaxis with MyPKfit® has been assessed. ResultsPK evaluations of 14 patients were carried out. A Bayesian curve and a tailored prophylaxis were assessed individually employing PK data. The weekly frequency of infusions was reduced in three severe patients, it was increased in four while it remained the same in the others five patients. The annual consumption of concentrate was reduced in 81.8% of patients. A subsequent economic evaluation carried out for each of the twelve severe haemophilia A patients included in this analysis, in which we have compared the standard and the PK-driven prophylaxis, showed that an optimized treatment can lead to an annual average saving of € 20,525 (−15.8%). ConclusionsThe use of MyPKfit® for a tailored prophylaxis may lead to a more rational use of available resources through an easy correction of the treatment strategies without distorting the individual patient therapy.
Hemostasis disorders require particular attention in dental treatment. Dental implants are a very widespread and valid method for total rehabilitation. Flapless dental implant surgery is a minimally ...invasive treatment that allows the implants to be placed in the jaw bones with minimal surgical trauma. The aim of this study is to report the bleeding incidence in a group of patients with bleeding disorders treated with flapless implants. A total of 52 patients with bleeding disorders (46 in anticoagulant therapy; 4 with hemophilia; 2 with von Willebrandt disease) were treated with 188 flapless implant surgeries Anticoagulants were not discontinued. Patients with hemophilia and VWD were treated following specific protocols. Four late, easy to treat bleeding complications were reported (three mild bleeding, one ecchymosis). No additional sutures or other hemostatic measures were taken, no further infusions or transfusions were reported, and no severe bleeding complications requiring more than easy on-chair treatment, were reported. In conclusion, with adequate knowledge of the procedure and the pathology, dental implantology can be safely performed in patients with bleeding disorders.
Opinions in the literature on the impact of cancer on patients with haemophilia are contradictory. There is a lack of data on the clinical presentation and management of cancer in patients with ...haemophilia (PWH).
Papers were found following a comprehensive search in PubMed, Google Scholar, and Scopus using the terms "cancer" and "haemophilia" without time limits and using the English language as a filter. The references from all the retrieved original articles and reviews were assessed for additional relevant articles.
The emergence of malignancies is one of the important causes of morbidity and mortality in PWH. In the past decade, the literature mainly focused on the epidemiology and outcome of blood-borne cancers in the haemophilia patient group, as the incidence of hepatitis B virus (HBV), hepatitis C (HCV), and HIV infection were high among them. However, with the introduction of recombinant clotting factor concentrates (CFCs), physicians now pay attention to non-virus-related malignancies. Bleeding and thrombotic complications are important causes of morbidity and mortality in critically ill patients with cancer; replacement therapy with factor VIII or IX or others should be maintained during antitumour treatment.
Overall, managing cancer in patients with haemophilia requires careful evaluation and individualised planning involving a multidisciplinary team of physicians experienced in haematology, oncology, and surgery.
Replacement therapy with clotting factor concentrates is the most appropriate and effective way to treat bleedings of Hemophilia A&B to prevent chronic arthropathy. Unfortunately, the short half-life ...(HL) of FVIII/IX concentrates obliges the patients to receive frequent infusions, a big concern for children. The development of inhibitors in about 30-45% of hemophilia A and in 3-5% of hemophilia B patient is the major adverse event of replacement therapy.
In the last few years, new rFIX have been developed with HL. New rFVIII concentrates are displaying small increase of PK characteristics. The new bio-engineering methods allowed the production of molecules fused with Fc fragment of IgG or Albumin or linked to PEG. A new approach to improve hemostasis is represented by Mab against TFPI and small RNA interfering with Antithrombin synthesis. Another innovative drug seems to be the new bi-specific antibody which mimics FVIII function in linking FXa and FX to tenase production.
The emerging drugs for hemophilia treatment seem to be very promising. The extended half-life will improve the adherence of patients to therapy. Accurate post-marketing surveillance studies will be necessary to check the efficacy, safety and immunogenicity of these new molecules.
The typical symptoms of COVID-19 mimic those of the common season flu. In addition, several changes in the coagulation processes have been observed. To date, it’s not fully clear how COVID-19 may ...affect patients with hereditary bleeding disorders. Anticoagulation in patients with haemophilia is still debated, but in this case could be needed. We are reporting a case of an elderly patient with mild haemophilia A hospitalized for Sars-Cov-2. On the 15th day of hospitalization, we observed an increase of all coagulation parameters. An antithrombotic prophylaxis at low dosage was immediately started, then increased at prophylactic dosage. Even if much more data are needed to ascertain the real thrombotic risk of haemophilia A in COVID-19 patients, it’s clear that the FVIII and vWF should be strictly monitored in order to promptly establish an adequate treatment and avoid the onset of thromboembolic events, even fatal, causing many deaths in COVID-19 patients.
Bleeding disorders can be divided into three categories: congenital coagulation disorders (CCDs), antiplatelet-induced bleeding disorders (APBDs) and anticoagulant-induced bleeding disorders (ACBDs). ...Implant placement can be challenging in these kinds of patients. The aim of this study is to provide evidence on implant surgery in patients with bleeding disorders and to generate some practical recommendations for clinicians.
Pubmed/MEDLINE, Scopus, Web of Science and Cochrane Library databases were screened. The latest search was performed in July 2022. Case reports, case series, cohort studies, cross-sectional studies, case control studies, reviews, consensus reports, surveys and animal studies were included in the analysis.
Seventeen articles on CCDs were found, fourteen on APBDs and twenty-six on ACBDs. Most of these articles were case reports or case series. Patients with CCDs can be treated after the infusion of the missing coagulation factor. Patients with APBDs can be treated without withdrawing the therapy. Patients with ACBDs should be treated depending on the anticoagulative medication.
Despite the low level of evidence, dental implants can be safely placed in patients with bleeding disorders. However, careful preoperative evaluation and the adoption of local and post-operative bleeding control measures are mandatory.
Background and Objectives: This study aimed to assess the effectiveness and costs associated with pharmacokinetics-driven (PK) prophylaxis based on the myPKFiT® device in patients affected by ...hemophilia A (HA) in Italy. Materials and Methods: An observational retrospective study was conducted in three Italian hemophilia centers. All patients with moderate or severe HA, aged ≥ 18 years, capable of having PK estimated using the myPKFiT device, and who had had a clinical visit between 1 November 2019 and 31 March 2022 were included. Differences in clinical, treatment, health resources, and cost data were assessed comparing post-PK prophylaxis with pre-PK. The incremental cost-effectiveness ratio (ICER) was estimated as cost (EUR) per bleed avoided. Results: The study enrolled 13 patients with HA. The mean annual bleeding rate decreased by −1.45 (−63.80%, p = 0.0055) after the use of myPKFiT®. Overall, the consumption of FVIII IU increased by 1.73% during follow-up compared to the period prior the use of the myPKFiT. Prophylaxis based on the myPKFiT resulted in an ICER of EUR 5099.89 per bleed avoided. Conclusions: The results of our study support the idea that the use of PK data in clinical practice can be associated with an improvement in the management of patients, as well as clinical outcomes, with a reasonable increase in costs.
Intracranial haemorrhage (ICH) is the most serious event in haemophiliacs, resulting in high rates of mortality and disability. Although the use of a prophylaxis regimen has improved outcomes, the ...mortality caused by ICH is still around 20%. ICH is more frequent at two different ages: in childhood (mostly in children aged ≤2 years) and in adulthood (with known risk factors such as hypertension and age ≥60 years). Our review shows how ICH remains one of the worst problems of patients with haemophilia. Greater attention to risk factors and early symptoms, together with an appropriate early prophylaxis, may reduce the risk of severe intracranial haemorrhagic events.
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