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Hemophilia is a rare X-linked congenital bleeding disorder due to a deficiency of factor VIII (hemophilia A [HA]) or factor IX (hemophilia B [HB]). Replacement and nonreplacement treatments are available but have limitations. Gene therapy (GT) provides an effective, long-term, single-dose treatment option, now approaching clinical practice. This study aimed to understand patient perspectives on GT for HA and HB in Italy using a qualitative questionnaire distributed through Italian patient associations, addressing patient views on daily life, treatments, unmet needs, quality of life (QoL), and GT for hemophilia. In total, 141 participants had HA, and 14 had HB (severe 78.6%). Daily life was most affected by pain and/or joint function limitations (57.5% of participants), high infusion frequency (42.5%), management of breakthrough bleeding episodes (40.3%), and anxiety/fear of severe or sudden bleeding (38.8%). Despite current treatments, about half of the participants experienced three or more annual bleeding episodes. Most participants knew of GT (87.2%) and expected improvements in QoL (60.5%), reduced frequency of current treatments (53.5%), and a permanent cure (49.1%); 46.4% were unaware of its once-off dosage and 46.4% were not concerned about the costs they anticipated to be associated with GT. Although several fears were reported, 25.0% of participants were willing to undergo GT with the support of a multidisciplinary team. This survey provided valuable insight into patient perspectives on hemophilia and GT in Italy. Overall, relevant proportions of patients still experience limitations affecting their daily life. Most were positive about GT and anticipated improvements in their clinical outcomes and QoL.
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BACKGROUND: Treatment options for people with haemophilia are evolving at a rapid pace and a range of prophylactic treatment options using various technologies are currently available, each with their own distinct safety and efficacy profile. TREATMENT GOALS: The access to replacement therapy and prophylaxis has driven a dramatic reduction in mortality and resultant increase in life expectancy. Beyond this, the abolition of bleeds and preservation of joint health represent the expected, but rarely attained, goals of haemophilia treatment and care. These outcomes also do not address the complexity of health-related quality of life impacted by haemophilia and its treatment. CONCLUSION: Capitalizing on the major potential of therapeutic innovations, 'Normalization' of haemostasis, as a concept, should include the aspiration of enabling individuals to live as normal a life as possible, free from haemophilia-imposed limitations. To achieve this-being supported by the data reviewed in this manuscript-the concept of haemostatic and life Normalization needs to be explored and debated within the wider multidisciplinary teams and haemophilia community.
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BACKGROUD: A huge amount of data about psychosocial issues of people with haemophilia (PwH) are available; however, these materials are fragmentary and largely outdated, failing to reflect the impact of current treatment strategies. AIM: Describing the influence of illness on psychosocial aspects of adult PwH (≥18 years) and caregivers of children with haemophilia (CPwH) without inhibitors, in Italy. METHODS: Surveys (for adult PwH, CPwH and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020. RESULTS: A total of 120 PwH without inhibitors and 79 CPwH completed the survey. Adult patients reported a significant impairment in many psychosocial aspects, including working activities, relations with family members and social relations. Caregivers generally reported better scores in all aspects of the survey. Mobility, Pain and Mental health domains of EQ-5D were the most frequently impaired in both patients and caregivers, reducing the perceived quality of life. Genetic counselling was an important issue, 53% of CPwH declaring unawareness of their carrier status, as well as the psychological support offered by the reference center, 67.0% of respondents reporting that no psychological support was provided at the time of diagnosis communication. CONCLUSION: This study provides information about PwH's and CPwH's point of view in the current scenario of continuous innovations in haemophilia treatment and management furthermore, updated insights on psychosocial problems faced by patients and caregivers are reported.
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Hemofilia A , Adulto , Niño , Humanos , Hemofilia A/terapia , Calidad de Vida , Cuidadores/psicología , Encuestas y Cuestionarios , ItaliaRESUMEN
INTRODUCTION: Considering the advances in haemophilia management and treatment observed in the last decades, a new set of value-based outcome indicators is needed to assess the quality of care and the impact of these medical innovations. AIM: The Value-Based Healthcare in Haemophilia project aimed to define a set of clinical outcome indicators (COIs) and patient-reported outcome indicators (PROIs) to assess quality of care in haemophilia in high-income countries with a value-based approach to inform and guide the decision-making process. METHODS: A Value-based healthcare approach based on the available literature, current guidelines and the involvement of a multidisciplinary group of experts was applied to generate a set of indicators to assess the quality of care of haemophilia. RESULTS: A final list of three COIs and five PROIs was created and validated. The identified COIs focus on two domains: musculoskeletal health and function, and safety. The identified PROIs cover five domains: bleeding frequency, pain, mobility and physical activities, Health-Related Quality of Life and satisfaction. Finally, two composite outcomes, one based on COIs, and one based on PROIs, were proposed as synthetic outcome indicators of quality of care. CONCLUSION: The presented standard set of health outcome indicators provides the basis for harmonised longitudinal and cross-sectional monitoring and comparison. The implementation of this value-based approach would enable a more robust assessment of quality of care in haemophilia, within a framework of continuous treatment improvements with potential added value for patients. Moreover, proposed COIs and PROIs should be reviewed and updated routinely.
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Hemofilia A , Humanos , Hemofilia A/tratamiento farmacológico , Calidad de Vida , Estudios Transversales , Atención Médica Basada en Valor , Evaluación de Resultado en la Atención de SaludRESUMEN
Soil water content (θ), matric potential (h) and hydraulic conductivity (K) are key parameters for hydrological and environmental processes. Several sensors have been developed for measuring soil θ-h-K relationships. The cost of such commercially available sensors may vary over several orders of magnitude. In recent years, some sensors have been designed in the framework of Internet of Things (i.e., IoT) systems to make remote real-time soil data acquisition more straightforward, enabling low-cost field-scale monitoring at high spatio-temporal scales. In this paper, we introduce a new multi-parameter sensor designed for the simultaneous estimation of θ and h at different soil depths and, due to the sensor's specific layout, the soil hydraulic conductivity function via the instantaneous profile method (IPM). Our findings indicate that a second-order polynomial function is the most suitable model (R2 = 0.99) for capturing the behavior of the capacitive-based sensor in estimating θ in the examined soil, which has a silty-loam texture. The effectiveness of low-cost capacitive sensors, coupled with the IPM method, was confirmed as a viable alternative to time domain reflectometry (TDR) probes. Notably, the layout of the sensor makes the IPM method less labor-intensive to implement. The proposed monitoring system consistently demonstrated robust performance throughout extended periods of data acquisition and is highly suitable for ongoing monitoring of soil water status.
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INTRODUCTION: Factor IX replacement therapy is used for treatment and prophylaxis of bleeding in haemophilia B. rIX-FP is an extended half-life albumin-fusion protein, which, in clinical studies, has demonstrated prolonged dosing intervals up to 21 days for routine prophylaxis, providing therapeutic benefit. AIMS: To describe dosing frequency and consumption (primary endpoint), efficacy and safety of rIX-FP treatment during routine clinical practice in Italy. METHODS: Patients with moderate/severe haemophilia B on prophylaxis with rIX-FP for ≥6 months, were enrolled in this observational study from October 2017 to February 2019 and followed-up for 2 years. Descriptive analysis included prospective and retrospective data (12 months prior to switching to rIX-FP). RESULTS: Data were collected from 59 male patients (median age 30.1 years) enrolled by 23 Italian centres. Of them, 50 were on prophylaxis during the entire observation period and completed the study. The infusion frequency changed from 2-3 times/week in 86.0% of patients with previous treatment, to less than once a week in 84.0% of patients treated with rIX-FP at the 2nd-year follow-up. The annual number of infusions decreased by about 70%, whereas the mean FIX activity trough level increased from 3.8% to 14.4% (mean > 10% in all the infusion regimens). Median Annualised Bleeding Rate of .0 was achieved across all prophylaxis regimens. Subjects with zero bleedings increased from 66.0% to 78.0% with rIX-FP. CONCLUSION: Treatment with rIX-FP reduced infusion frequency, while providing higher FIX trough levels with substantial benefit in terms of annualised bleeding rate and a good safety profile.
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Factor IX , Hemofilia B , Adulto , Humanos , Masculino , Albúminas , Factor IX/uso terapéutico , Hemofilia B/tratamiento farmacológico , Hemorragia/prevención & control , Hemorragia/tratamiento farmacológico , Italia , Estudios Prospectivos , Proteínas Recombinantes de Fusión/uso terapéutico , Estudios RetrospectivosRESUMEN
INTRODUCTION: Haemophilias are X-linked inherited bleeding disorders, due to de novo F8/F9 gene variants in 30-50% of cases. The identification of causative variant in index cases (IC) is crucial for genetic counselling in related women. Over the last 20 years the Emilia-Romagna Regional Haemophilia Registry documented high proportions of sporadic severe haemophilia. AIM: To clarify if carriers' reproductive choices influence the sporadic/familial ratio of severe haemophilia. METHODS: Genetic counselling and genotyping in 221 relatives of severe IC were retrospectively reviewed, retrieving reproductive choices and pregnancy history of childbearing-age carriers from familial and sporadic pedigrees and according to the IC degree of relationship (mothers, daughters, II/other). RESULTS: Carriers' identification rates were lower in sporadic women and in other-degree relatives. Among childbearing age women (n = 140), carriers were 37/48 (77%) and 57/92 (62%) of familial and sporadic relatives, respectively. Forty-five/57 sporadic carriers experienced 67 pregnancies, while 21/37 familial carriers had 39 pregnancies (four voluntary terminations), with a significantly higher number of affected sons in the former (40/67 vs. 12/35, P = .025). Prenatal diagnosis was chosen by 40% and 47% of sporadic and familial aware carriers, respectively. Sporadic mothers often avoided further pregnancies (17/38, 45%) after a firstborn affected child, while familial mothers tended to face pregnancies without prenatal approaches (6/10, 60%). CONCLUSION: In this cohort sporadic offspring account for more than 70% of severe haemophilia cases. This increasing proportion is likely to reflect the influence in reproductive choices of awareness of carriers' status, particularly in sporadic mothers, and of prenatal diagnosis options.
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Toma de Decisiones , Hemofilia A , Embarazo , Femenino , Hemofilia A/diagnóstico , Hemofilia A/epidemiología , Hemofilia A/genética , Heterocigoto , Humanos , Embarazo/psicología , Sistema de Registros , Historia Reproductiva , Estudios RetrospectivosRESUMEN
BACKGROUND: Immune tolerance induction (ITI) is the only proven strategy to eradicate factor VIII inhibitors in patients with haemophilia A (HA). AIM: To identify patients and treatment options with the highest chance of inhibitor eradication by primary ITI. PATIENTS AND METHODS: In the frame of the Italian ITI Registry, carried out from 1995 to 2015 (last follow-up 2018), 137 primary ITI courses in severe HA patients (90/137 with poor prognosis) were analysed for predictors of outcome (complete/partial response or failure). Sixty-six of them (48%) were prospectively evaluated. RESULTS: ITI was successful in 91/137 patients (66.4%) and 70 (51.1%) achieved complete response within 11 months (median). Historical peak titres ≤200 BU/ml (P = .033), inhibitor titres ≤5 BU/ml at ITI start (P = .001), peak titres ≤100 BU/ml during ITI (P < .001) and missense mutations and small insertions/deletions of FVIII gene (P = .027) predicted complete inhibitor eradication. A score that considers the cumulative number of these variables predicted complete response with positive predictive values up to .81 at ITI start and .91 during ITI, respectively. Patients who had no bleeding (OR, 3.45, 95% CI: 1.4-8.6) nor other adverse events (OR 2.6, 95%CI: 1.3-5.3) during ITI had higher chances of complete response. During the 120-month follow-up (median), 2/70 patients who had achieved complete response relapsed (2.9%). CONCLUSIONS: This Registry, with a centralized review of outcomes, homogeneous data collection (half of which prospective) and long-term follow-up, provides insights for optimizing ITI, with a rationale for further studies in the currently evolving scenario of inhibitor management in HA patients.
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Hemofilia A , Factor VIII , Hemofilia A/tratamiento farmacológico , Hemorragia , Humanos , Tolerancia Inmunológica , Estudios ProspectivosRESUMEN
INTRODUCTION: Haemophilia management and patients' quality of life significantly improved. However, data on current patients', caregivers' and clinicians' satisfaction and limitations of treatments and haemophilia management are limited. AIM: Assessing the management satisfaction and unmet needs from the perspective of Italian patients with haemophilia (PWH) without inhibitors (or caregivers if children) and of specialist physicians. METHODS: Surveys (for patients≥18 years, caregivers of children and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020. RESULTS: Among 275 participants, 120 (43.6%) were PWH without inhibitors, 79 (28.7%) caregivers and 37 (13.4%) clinicians. Patients and caregivers perceived a higher control of the disease compared to clinicians. However, more than 40% of patients and caregivers reported to feel significantly conditioned by the risk of bleeding during their daily life. PWH reported a 6-month mean/median (range) of bleeds 2.3/.0 (0-24) and caregivers 1.3/.0 (0-16) in children. The treatment burden (frequency of administration) was not satisfactory for more than half adults and caregivers of children treated with prophylaxis. A good access to treatment, haemophilia centres and medical service was reported, with issues associated to the multidisciplinary approach and treatment at emergency department. CONCLUSIONS: This large national study provides an updated overview of haemophilia care in Italy from different points of views, highlighting positive aspects and unmet needs. This information can guide future interventions to improve haemophilia management and the assessment of impact of new treatment options.
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Hemofilia A , Adulto , Cuidadores , Niño , Hemofilia A/tratamiento farmacológico , Humanos , Italia , Calidad de Vida , Encuestas y CuestionariosRESUMEN
OBJECTIVES: The present review aims to summarize the state-of-the-art von Willebrand disease (VWD) treatment focusing on specific clinical settings (obstetrics, surgery, long-term prophylaxis and comorbidities) as well as on the use of a Von Willebrand factor (VWF) concentrate with low FVIII content. METHODS: Literature research and case reports. RESULTS AND CONCLUSIONS: Considering that patients affected by VWD have an intact ability to synthesize FVIII, in order to avoid excessive levels of FVIII, a highly purified plasma VWF concentrate with low FVIII content could be particularly useful in those patients and clinical circumstances at high thrombotic risk as well as for long-term prophylaxis. When deciding the optimal therapeutic strategy, physicians should take into account both the patient's history and the differences among available concentrates according to the clinical situations requiring treatment.
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Trombosis , Enfermedades de von Willebrand , Testimonio de Experto , Factor VIII/uso terapéutico , Humanos , Trombosis/tratamiento farmacológico , Enfermedades de von Willebrand/terapia , Factor de von Willebrand/uso terapéuticoRESUMEN
Progress in the treatment of cancer has significantly improved survival of oncologic patients in recent decades. However, anticancer therapies, particularly some new, more potent and targeted agents, are potentially cardiotoxic. As a consequence, cardiovascular complications, including heart failure, arterial hypertension, coronary artery disease, venous thromboembolism, peripheral vascular disease, arrhythmias, pericardial disease, and pulmonary hypertension, as related to cancer itself or to anticancer treatments, are increasingly observed and may adversely affect prognosis in oncologic patients. Cardiovascular oncology is an emerging field in cardiology and internal medicine, which is rapidly growing, dealing with the prevention, the early detection, and the management of cardiovascular disease, in all stages of anticancer therapy and during the survivorship period, now crucial for reducing cardiovascular morbidity and mortality in cancer patients. In this narrative review, the existing literature regarding the epidemiology of cardiovascular oncology, the mechanisms of cardiovascular complications in cancer, and the pathophysiology of cardiotoxicity related to chemotherapeutic agents, targeted therapies, immunotherapies, and radiotherapy will be analyzed and summarized.
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Antineoplásicos , Enfermedades Cardiovasculares , Sistema Cardiovascular , Neoplasias , Antineoplásicos/efectos adversos , Cardiotoxicidad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Humanos , Oncología Médica , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiologíaRESUMEN
Cancer is associated with an increased incidence of both venous thromboembolism (VTE) and arterial thrombosis (cardiovascular events and ischemic stroke). Cancer-associated arterial thrombotic events are less well studied than VTE, but increasingly recognized, particularly in specific malignancies and in association with specific anticancer therapies. The pathogenesis of arterial thrombotic events in cancer is complex and involves generation of tumor-associated procoagulant factors and a variety of alterations in platelet function as well as in the coagulation and fibrinolytic systems, and endothelial injury and dysfunction, that combine to produce hypercoagulability. The multifactorial interaction between this prothrombotic state, the individual cardiovascular risk, advanced age and presence of comorbidities, and the specific neoplasm characteristics and therapy, may induce the vascular events. Recent studies based on population databases and prospective or retrospective analyses with prolonged follow-up highlight that cancer patients experience an increased (approximately 1.5-2-fold) risk of both cerebrovascular and cardiovascular events compared with noncancer individuals, which peaks in the time period of the diagnosis of cancer but may persist for years. Beyond the type of cancer, the risk reflects the tumor burden, being higher in advanced stages and metastatic cancers. The occurrence of arterial thromboembolic events is also associated with increased overall mortality. We here present an update of the pathophysiology, risk factors, clinical evidence, and treatment considerations on cancer-associated arterial thrombosis, in the light of the need for specific multidisciplinary prevention and surveillance strategies in this setting, in the frame of cardio-oncology approaches.
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Neoplasias , Trombosis , Tromboembolia Venosa , Humanos , Neoplasias/complicaciones , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Trombosis/epidemiología , Trombosis/etiología , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiologíaRESUMEN
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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Sistema del Grupo Sanguíneo ABO/genética , Hemofilia A/genética , Femenino , Hemofilia A/patología , Humanos , Italia , Masculino , Factores de RiesgoRESUMEN
INTRODUCTION: The factor VIII (FVIII)-mimetic bispecific monoclonal antibody, emicizumab, previously approved for prophylaxis in haemophilia A with inhibitors, has been recently licensed in several countries also in patients with severe haemophilia A (PWSHA) without inhibitors. The introduction of this innovative agent requires the development of specific pathways at Haemophilia Treatment Centres (HTC), particularly regarding laboratory testing and treatment of breakthrough bleeds and invasive procedures/surgeries, even more critical when patients are managed by non-specialist professionals. Limited literature data and clinical experience in PWSHA without inhibitors on emicizumab are currently available. AIM: To promote awareness and overcome these challenges, the Italian Association of Haemophilia Centres (AICE) issued a guidance on the management of PWSHA without inhibitors on emicizumab prophylaxis, focused on emergency and shared with other National Scientific Societies in the field. METHODS: The document, drafted by an AICE expert panel and approved through online consultation, was further revised by a multidisciplinary working group, including members of 5 haemostasis, laboratory and emergency scientific societies. The final version was approved by the Council of each society. RESULTS: General recommendations about use of FVIII concentrates for the treatment of bleeding or haemostatic coverage of invasive procedures/surgeries and laboratory monitoring in PWSHA without inhibitors on emicizumab are provided. Specific issues of the management in the emergency room are focused, highlighting the need for direct involvement or formalized supervision by specialist HTC physicians. CONCLUSIONS: This guidance provides a reference pathway to be implemented in the different healthcare organizations, especially for the challenging emergency management in this setting.
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Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Hemofilia A/tratamiento farmacológico , Anticuerpos Biespecíficos/farmacología , Anticuerpos Monoclonales Humanizados/farmacología , HumanosRESUMEN
BACKGROUND: The appearance of inhibitors is the most serious complication in haemophilia A (HA) patients. The primary objective is their eradication. Up to date, immune tolerance induction (ITI) was the only therapeutic option to achieve this. AIM: To assess the efficacy of moroctocog-alpha as an ITI regimen in a population of HA patients with high-titre inhibitors. METHODS: The REF.IT Registry is a retrospective-prospective study that collected data on all patients with HA and high-titre inhibitors treated with moroctocog-alpha as an ITI regimen at twelve Italian Haemophilia Centres. RESULTS: We enrolled 27 patients, 85.2% were children. All patients were high responders, 88.9% had severe HA. We found 69.3% of them had one or more risk factors for poor ITI prognosis, 14.8% were ITI rescue. Overall 59.3% achieved a complete/partial success (complete in 51.9%). ITI failed in 11 patients, 63.6% of them with poor-prognosis risk factors. Inhibitors appeared after a mean of 27 exposure days. Mean historical peak was 78.8 BU/mL. The primary ITIs started on average 20.2 months after the diagnosis. A partial or complete success after a mean of 15 months of treatment was achieved in 56.6% of the children while the same result was obtained by 75.0% adults after 22 months from ITI onset. Patients who were treated with high-dose moroctocog-alpha (200 UI/kg/day) were 63.0%. CONCLUSION: Our Registry showed that the use of moroctocog-alpha in the setting of ITI was effective and safe also in a population of patients with high-titre inhibitors, presenting one or more risk factors for poor ITI prognosis.
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Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia A/inmunología , Tolerancia Inmunológica/efectos de los fármacos , Sistema de Registros , Adulto , Niño , Preescolar , Femenino , Humanos , Italia , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
We describe the case of a childbearing-age woman presenting with spontaneous recurrent functional ovarian cysts and, more interestingly, chronic and asymptomatic elevation of cholestatic parameters. The patient showed no history of chronic viral infections, immunological and metabolic disorders, alcohol abuse and environmental toxins exposition. Hepatic ultrasonography and cholangio-pancreatography-magnetic-resonance excluded any morphological and structural abnormalities, while liver biopsy evidenced only minimal and not specific features of inflammation. Cholestasis indices obtained prompt recovery after each cycle of synthetic hormone therapy, implanted to treat functional ovarian cysts. She has continuously experienced the off-therapy asynchronous recurrence of liver laboratory abnormalities and functional ovarian cysts. The favorable effect of the synthetic hormone therapy to obtaining a stable recovery of this unexplained long-lasting cholestatic syndrome could be likely explained by downregulation of an endogenous ovarian overproduction, although estrogen-regulated local intracellular transduction pathways cannot be excluded.
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Antagonistas de Andrógenos/farmacología , Colestasis , Estradiol/farmacología , Quistes Ováricos , Adulto , Antagonistas de Andrógenos/administración & dosificación , Colestasis/tratamiento farmacológico , Colestasis/enzimología , Colestasis/etiología , Quimioterapia Combinada , Estradiol/administración & dosificación , Femenino , Humanos , Quistes Ováricos/complicaciones , Quistes Ováricos/tratamiento farmacológico , Quistes Ováricos/enzimologíaRESUMEN
The development of neutralizing antibodies (inhibitors) against infused factor VIII currently represents the main complication of replacement therapy in patients with severe hemophilia A. Inhibitors, indeed, particularly high-titer inhibitors (>5 BU/mL), greatly complicate the management of bleeding, exposing patients to an increased morbidity and mortality risk, thus representing a significant burden for physicians of Hemophilia Treatment Centers (HTCs). Although bypassing agents (i.e., activated prothrombin complex concentrate [APCC] and recombinant activated factor VII [rFVIIa]) are available for the treatment and prevention of bleeding in inhibitor patients, their efficacy, safety, and cost-benefit outcomes are poorly known in the long term and should be further improved. In the frame of the update of recommendations for the management of inhibitor patients by the Italian Association of Hemophilia Centers (AICE), to collect more information on real-life therapeutic approaches with bypassing agents in this setting, a survey was conducted among the Directors of the Italian HTCs. From questionnaires returned by 55% of them, data on the use of rFVIIa and APCC in children, adolescent, and adult patients with hemophilia A and inhibitors were obtained and are summarized in this article, including information about the implementation of prophylaxis with both bypassing agents, the adopted regimens, and reasons for starting, adjusting, and interrupting such a therapeutic approach.
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Factor VIII/uso terapéutico , Hemofilia A/terapia , Factor VIII/farmacología , Hemofilia A/patología , Humanos , Italia , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Persons with haemophilia (PWH) experience recurrent joint bleeding which leads from early synovitis to irreversible joint damage. Pain strongly affects patients' quality of life, as PWH suffer from acute pain associated with haemarthroses and chronic pain due to arthritic and degenerative complications. AIM: To investigate pain issues among PWH and their treaters in Italy. METHODS: Persons with haemophilia and specialist physicians responded to a survey focused on pain characteristics, assessment, and management by phone call and online, respectively. RESULTS: One hundred and nineteen patients (76% severe haemophilia, 61% ≥18 years) and 44 physicians were involved. Pain was reported by 61% of PWH; among those who did not experience pain, 70% were children on prophylaxis. Patients described pain as chronic (71%), acute (69%) or postoperative (8%), and rated it as severe in 65% of cases. Clinicians reported lower percentages of patients with pain (46%), classified as chronic (58%), acute (33%) or postoperative (21%), half using specific scales. Pain was systematically investigated by treaters according to 36% of patients. Paracetamol was largely the most prescribed first-line pain therapy (89%), as well the most employed analgesic by PWH (51%), who also used non-steroidal anti-inflammatory drugs (24%), cyclo-oxygenase-2 inhibitors (21%) or opioids (26%). To manage pain, 61% of clinicians stated to collaborate with other specialists. Physiotherapy was often suggested but less frequently used by PWH. CONCLUSIONS: Pain is under-recognized and unsatisfactorily addressed by haemophilia treatment centre (HTC) clinicians, with discrepant management compared to PWH responses. Education in systematic pain assessment and multidisciplinary treatment and development of management guidelines are highly needed.
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Dolor Crónico/etiología , Hemofilia A/complicaciones , Manejo del Dolor/métodos , Dimensión del Dolor/métodos , Adolescente , Adulto , Anciano , Niño , Femenino , Hemofilia A/patología , Humanos , Italia , Masculino , Persona de Mediana Edad , Médicos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: In older people, multiple chronic ailments lead to the intake of multiple medications (polypharmacy) that carry a number of negative consequences (adverse events, prescription and intake errors, poor adherence, higher mortality). Because ageing patients with haemophilia (PWHs) may be particularly at risk due to their pre-existing multiple comorbidities (arthropathy, liver disease), we chose to analyse the pattern of chronic drug intake in a cohort of PWHs aged 60 years or more. PATIENTS AND METHODS: S + PHERA is a multicentre observational study, with the broad goal to evaluate prospectively the health status and medication intake in 102 older patients with severe haemophilia A or B compared with 204 age- and residence-matched controls chosen randomly from the same general practices of PWHs. The rate of potential drug-drug interactions (PDDI) was evaluated as a proxy of prescription appropriateness. RESULTS: After excluding replacement therapies and antiviral drugs, PWHs took in average less daily drugs than controls (2.4 ± 2.5 vs 3.0 ± 2.4) and had a lower rate of polypharmacy. Moreover, their prevalence of PDDI was lower (16.7% vs 27%). CONCLUSIONS: The rate of polypharmacy and the appropriateness of medications other than those for haemophilia and related comorbidities are acceptable in Italian PWHs, and better than those in their age peers without haemophilia, perhaps owing to drug tailoring and deprescribing by the specialized haemophilia centres at the time of regular visits. However, the PWHs investigated herewith were relatively young and the rate of polypharmacy and related PDDIs may become more prominent and crucial when older ages are reached, suggesting the need of continuous surveillance on prescribed drugs and the risk of drug-drug interactions.