Real-world cost estimates of initiating emicizumab in US patients with haemophilia A.

INTRODUCTION: Emicizumab is the first approved non-factor therapy for haemophilia A. It provides superior prophylactic bleeding control compared to other products in both patients with and patients without inhibitors. However, there is no real-world data about the monetary consequences of starting emicizumab. AIM: To examine the estimated costs of starting emicizumab in a cohort of real-world haemophilia A patients with and without inhibitors. METHODS: The cost of haemostatic therapy for 6 months before and after initiating emicizumab for participants in a multicentre observational study was calculated based on the type of product and dosing that was used for prophylaxis and treating breakthrough bleeds, the number of treated bleeds and the participant weight. RESULTS: Ninety-two patients were included, 18 with an active inhibitor. The median age was 8.7 years. The median total cost for all patients decreased from $176,720 to $128,099 (p = .04) after initiating emicizumab, largely because of decrease in the total cost of high-cost outliers. The cost of prophylaxis and the total cost of bleeds also significantly decreased after starting emicizumab, both for patient with and patients without inhibitors. CONCLUSIONS: Starting or switching to prophylaxis with emicizumab results in decreased costs for the treatment of patients with haemophilia A. This real-world data could inform on payer decisions as well as future cost-effective analysis.

Real-world use of emicizumab in patients with haemophilia A: Bleeding outcomes and surgical procedures.

INTRODUCTION: Emicizumab is a recombinant humanized bispecific antibody that bridges factor IXa and factor X to mimic the cofactor function of factor VIII. It is approved to prevent bleeding in patients with haemophilia A (HA). Outside of clinical trials, there is limited data on outcomes of patients treated with emicizumab, particularly in children without inhibitors. AIM: To report our experience treating patients with emicizumab, including (a) bleeding rates pre and postemicizumab, (b) peri-procedural management and outcomes and (c) serious drug-related adverse events. METHODS: Multicentre observational study in patients with HA who started emicizumab prior to 15 May 2019. Data collection continued until 15 October 2019 and included demographics, disease history, bleeding events, invasive procedures, thrombotic events and death. Annualized bleeding rates (ABR) prior to emicizumab were compared to postemicizumab. RESULTS: Ninety-three patients (including three females) met inclusion criteria, 19 with an active inhibitor. Median age was 8.6 years; patients <12 years without inhibitors (n = 49) accounted for the majority. ABR dropped from 4.4 (inhibitors) and 1.6 (non-inhibitors) to 0.4 (both groups) on emicizumab, P = .0012 and .0025, respectively. There were 28 minor (21 port removals) and two major procedures. Three patients received 1-2 doses of unplanned factor postoperatively to treat minor bleeding events. No patient discontinued therapy, and there were no thrombotic events or deaths. DISCUSSION: Our favourable clinical experience with emicizumab is similar to that reported in the clinical trials. Notably, this is the largest cohort of patients <12 years without inhibitors treated with emicizumab.

Integrated Hemophilia Patient Care via a National Network of Care Centers in the United States: A Model for Rare Coagulation Disorders.

Rare, chronic diseases such as hemophilia and other congenital coagulation disorders require coordinated delivery of services for optimal outcomes. Hemophilia Treatment Centers (HTCs) are specialized, multidisciplinary health-care centers providing team-based care to meet the physical, psychosocial, and emotional needs of people with hemophilia (PWH) and may serve as a model for other rare coagulation disorders. Health-care purchasers, as well as the general medical community, may not appreciate the breadth and quality of services provided by HTCs. They exemplify the acculturalization and actualization of integrated care by providing comprehensive diagnostic and treatment services that reduce morbidity, mortality, avoidable emergency room visits, hospitalizations, and overall costs, while promoting a longer lifespan and improved patient functioning and outcomes. This is accomplished by a team-based approach relying upon a shared decision-making model to effectively prevent complications and manage symptoms in PWH, who are dependent on high-cost treatments. This article provides a concise yet comprehensive description of the core components of an HTC and the regional and national networks in the United States, which together achieve their incomparable value for all stakeholders.

Incidence of bleeding complications in pediatric patients with type 1 von Willebrand disease undergoing adenotonsillar procedures.

OBJECTIVE: To review the incidence of postoperative bleeding in children with type 1 von Willebrand disease (VWD) who were treated with a single institution protocol. STUDY DESIGN: We performed a retrospective study to determine the postoperative hemorrhage rate in pediatric patients with type 1 VWD who were treated via the Children's Hospital of Philadelphia institutional protocol. This protocol utilizes intravenous desmopressin (DDAVP), oral aminocaproic acid, and overnight observation. RESULTS: Between the years of 2000 to 2006, 41 children with type 1 VWD underwent an adenotonsillar procedure and were treated with this protocol. Seven patients (17%) experienced delayed (>24 hours after surgery) postoperative hemorrhage requiring intervention. Five of the 7 patients required cautery to control the bleeding, and the remaining 2 patients responded to DDAVP and aminocaproic acid alone. Older age and lower VW antigen levels were associated with postoperative hemorrhage (P = .05). CONCLUSIONS: Despite therapeutic intervention to decrease the risk of postoperative hemorrhage, the incidence of hemorrhage was higher in pretreated patients with type 1 VWD than in children without bleeding disorders. Further prospective studies are necessary to determine the optimal treatment to reduce bleeding complications in these patients.

The clinical management of hemophilia and head trauma: a survey of current clinical practice among pediatric hematology/oncology physicians.

BACKGROUND: Determining the appropriate evaluation for a pediatric patient with hemophilia and head trauma is a diagnostic challenge with no neuroimaging guidelines and limited clinical evidence to direct care. PROCEDURE: A questionnaire, with two case scenarios, was emailed to members of the American Society of Pediatric Hematology/Oncology. The case scenarios involved asymptomatic toddlers with severe hemophilia who had either fallen from a height (case 1) or from standing (case 2). Respondents were asked to select from six management options. The case scenarios were then altered to include: a large palpable hematoma, prophylactic factor infusion 24 hr prior, the trauma occurred 48 hr prior, wearing a soft helmet, or emesis. RESULTS: The completed response rate was 23% (252/1,077). Computed tomography (CT) was selected by 68.9% (#1) and 56.4% (#2) of respondents. In both case scenarios the presence of a palpable bruise resulted in a statistically significant increase in CT usage to 83.7% and 82.8% (P < 0.001). The use of prophylaxis did not result in a statistically significant decrease in CT usage. Duration of factor replacement was variable ranging from 1 to 4 days. CONCLUSION: Physician self reported management of pediatric patients with hemophilia and head trauma is diverse. The use of CT imaging for mild head trauma in patients without signs or symptoms of intracranial hemorrhage was very common. The use of prophylaxis did not reduce the use of head CT imaging. This variation in clinical practice demonstrates the lack of evidence regarding the management of head trauma in patients with hemophilia.

Education needs of nurses in thrombosis and hemostasis: An international, mixed-methods study.

BACKGROUND: The need for a more integrated, multidisciplinary approach to care for individuals with bleeding or clotting disorders has been highlighted in recent years. Evidence-based education adapted to nurses' needs is essential for a successful evolution. However, limited data currently exist on the clinical challenges nurses face in this specialty area. OBJECTIVES: Identify barriers and challenges faced by specialty nurses, and determine possible causes, to develop appropriate educational interventions. METHODS: A mixed-methods study, combining qualitative (semi-structured interviews) and quantitative (online survey) data was conducted on the challenges experienced by hemostasis nurses in nine countries (Argentina, Australia, Canada, China, France, Germany, Spain, the UK, and the US), and deployed in five languages (English, French, German, Mandarin, and Spanish). Qualitative data were analyzed using thematic analysis. Quantitative data were analyzed using frequency tables, chi-squares and standard deviations. RESULTS: Participants (n = 234) included nurses (n = 212; n = 22 qualitative; n = 190 quantitative); and patients receiving care for bleeding or clotting conditions or their caretakers (n = 22 qualitative phase only). Through triangulated data analysis, six challenging areas emerged: (a) Understanding of von Willebrand disease (VWD); (b) Anticoagulant safety profile in specific patients; (c) Understanding the treatment of patients with inhibitors; (d) Patient risk assessments; (e) Individualization of care and communication with patients; and (f) Accessing and implementing relevant professional education. CONCLUSIONS: This needs assessment provides a comprehensive illustration of the current challenges faced by nurses in the field of bleeding and clotting disorders, and indicates where gaps in skills, knowledge or confidence would benefit from nurse-specific educational programming.

Utility of repeat testing in the evaluation for von Willebrand disease in pediatric patients.

BACKGROUND: Von Willebrand disease (VWD) is the most common inherited bleeding disorder and is caused by quantitative and qualitative defects in von Willebrand factor (VWF). The laboratory diagnosis of VWD in pediatric patients is complicated by VWF interassay and intra-assay variability, stress-induced elevations in VWF levels, and a lack of significant bleeding history with which to correlate test results. OBJECTIVE: Guidelines recommend repeat testing in patients with a high suspicion of VWD and unclear laboratory assay results; however, no studies have evaluated the utility of repeat VWF testing in pediatric patients. METHODS: This retrospective single-center cohort study aimed to determine clinical variables associated with requiring more than one test to diagnose VWD and to establish a cutoff VWF value above which further testing is not informative. RESULTS: Of 811 patients evaluated for a suspected bleeding disorder, 22.2% were diagnosed with VWD, with ~70% diagnosed on the first test. Patients with VWD were younger (5.8 vs. 8.5 years, P = .002) and more likely to have a family history of VWD (38% vs. 22%, P < .001) than those without VWD. Univariate analysis failed to identify any clinical variables that correlated with needing multiple tests for a VWD diagnosis. A cutoff of 100 IU/dL for VWF antigen or activity on the first test yielded negative predictive values >95%. CONCLUSIONS: We demonstrate that the majority of pediatric patients had diagnostic VWF values on the first set of testing. Pediatric patients without a family history of VWD and VWF levels >100 IU/dL may not need further testing to rule out the diagnosis of VWD.

Assessment of treatment practice patterns for severe hemophilia A: a global nurse perspective.

This paper reports findings from a global survey of practice patterns for severe hemophilia A. Nurses from 105 hemophilia treatment centers in the US, the UK, Canada and Sweden responded to a questionnaire and provided data for more than 10,100 children and adults. Forty-eight percent of the US patients and 38 and 37% of the British and Swedish patients, respectively, were reported to have severe hemophilia A. The survey found that 28% of US patients and 38% of UK patients with severe hemophilia A were on primary prophylaxis in 2005. These rates were significantly higher than those reported in a 2003 survey. Sweden continues to lead the world in prophylaxis utilization, with virtually 100% of patients aged 3-18 on primary prophylactic regimens. Bleeding history and target joint development were major reasons for initiating prophylaxis; poor adherence, inadequate family commitment and venous access problems were cited as the top causes for discontinuing treatment. Nurses in all 4 reporting countries agreed that prophylaxis is the optimal therapy for patients with severe hemophilia A because it prevents joint and muscle damage and improves quality of life. They cited patient/family education as the most appropriate strategy for overcoming the barriers to prophylaxis.

Predictors of retention among HIV/hemophilia health care professionals.

Health care professionals working with individuals with chronic medical illness, especially those infected with the Human Immunodeficiency Virus (HIV), may be at risk for burnout and departure due to various job stresses such as the death of patients and social stigma. Factors that prevent burnout and employee attrition are seldom studied. Two hundred thirteen staff (doctors, nurses and mental health workers) at a representative sample of Hemophilia Treatment Centers (HTC) completed instruments to measure Burnout (Maslach Burnout Inventory), and perceived job stresses and satisfaction (job tasks, interactions with colleagues and patient care). The staff were surveyed again after two years and their job status determined after 4 years. After 4 years, 35% of the staff had left the field of Hemophilia/HIV care. Univariate tests found that retention was significantly associated with initial job satisfaction, being married and low levels of stress with colleagues. Burnout, as measured by the Maslach Burnout Inventory, at baseline, was unrelated to job retention over 4 years. An adjusted multiple logistic regression of all significant variables found that colleague support was most related to retention (OR=2.8, CI=1.49,5.1). We conclude that attrition of highly trained staff is a significant issue for patients and HTCs. These data suggest the important role that a well-functioning team can have in buffering the inevitable stresses associated with HIV care. Mental Health professionals have considerable expertise in addressing these issues.

Practice patterns in haemophilia A therapy--a survey of treatment centres in the United States.

A survey was conducted to ascertain practice patterns for haemophilia A therapy in the United States. Questionnaire data were supplied by 52 haemophilia centres with a total of 4129 patients under treatment. Most participating centres were affiliated with academic/teaching hospitals or institutions. Patients below 5 years comprised 17% of the study population, 6-18 years 41% and >18 years 42%, and the apportionment across severity categories was 53% severe, 17% moderate and 30% mild. Among patients with severe haemophilia, 49% were receiving on-demand treatment, while 44% were receiving some form of prophylaxis (13% primary, 20% secondary and 11% tertiary). Primary prophylaxis was the most common type in children below 5 years of age, accounting for 25% of this age group. In children 6-18 years old, 58% were on some type of prophylactic regimen, while on-demand treatment was most frequent among adults. Difficulties of venous access were the most frequently cited barrier to instituting prophylaxis. Catheters were in use among 37% of the patients under primary prophylaxis and 14% of those on secondary prophylaxis. No major differences were observed in forms of therapy used between larger and smaller centres. These observations provide an extensive characterization of haemophilia A practice patterns in the United States.