Research Studies

Objective:

Knowledge gaps among clinicians regarding diagnosis, classification, and/or management in hemophilia can potentially delay diagnosis/referral and lead to adverse clinical outcomes. A study was undertaken to identify hemophilia clinical practice gaps among pediatricians.

Methods:

A global, hemophilia-specific continuing medical education-accredited clinical practice assessment survey was developed based on current evidence-based consensus guidelines and best practices, including guidelines from the National Hemophilia Foundation and the World Federation of Hemophilia. The assessment included both knowledge- and case -based, multiple-choice questions that healthcare providers completed confidentially on-line between March 21, 2014 and April 16, 2014. Areas such as appropriate triggers for initiating prophylaxis and use of physical therapy were assessed. Responses from pediatric providers were de-identified and aggregated prior to analyses.

Summary:

817 pediatricians (42% of total respondents) completed the survey, from the following locales: North America (29%), Asia (23%), Europe (16%), Middle East (13%), Africa (9%), Central/South America (6%), and Australia (3%). Academic (36%), private practice (26%), community hospital (24%), community clinic (9%), and hemophilia treatment center (1%) practice settings were identified. For most responses, the proportion of incorrect responses appeared to be consistent regardless of whether pediatricians indicated professional interaction with hemophilia patients (Group A: 60%) or not (Group B: 40%). Pediatrician knowledge gaps included (% incorrect responses): classification of severity of hemophilia (28% A v. 39% B; P=.0030); optimal use of prophylactic therapy, e.g., when to initiate (29% A v. 30% B; P=.83), at what dose (16% A v. 17% B; P=.93); likelihood of inhibitors (51% A v. 55% B; P=.14); and adolescent care, e.g., adherence (25% A v. 22% B; P=.33), transitioning (14% A v. 14% B; P=.36), and long-term prophylaxis (76% A v. 76% B; P=.68). Differences in correct responses were observed when comparing Australia, Europe, and North America versus Africa, Asia, Central/South America, and the Middle East on topics such as classification of severity of hemophilia (P<.0001) and when to initiate prophylaxis (P=.04), although knowledge gaps existed in both groups. A low level of confidence in ability to identify when to use prophylaxis was reported among 42% [95% CI: 40%-46%] of pediatricians. The top barriers to the administration of prophylaxis included cost and lack of availability of FVIII or FIX (41% and 26% for all respondents, respectively).

Conclusions:

Substantial knowledge gaps permeate pediatric clinical practice in the diagnosis and optimal care of hemophilia. Educational efforts tailored to the practice setting and geographic locales are warranted.

Objective:

Joint status was assessed in the 3-year SPINART study, which compared routine prophylaxis versus on-demand treatment in adults with severe hemophilia A. We report joint outcomes at year 3 obtained using magnetic resonance imaging (MRI).

Methods:

The open-label, randomized, controlled, parallel-group, multinational SPINART study enrolled males aged 12–50 years with severe hemophilia A who had ≥150 exposure days with any factor VIII (FVIII) product, no inhibitors, no prophylaxis for >12 consecutive months in the past 5 years, and 6–24 documented bleeding events or treatments in the previous 6 months. Patients were treated with Bayer’s sucrose-formulated recombinant FVIII (rFVIII-FS), either on demand or as prophylaxis (25 IU/kg 3 times weekly, with dose escalation by 5 IU/kg permitted once per year). MRI was performed at baseline and year 3 to evaluate the structure of 6 index joints. Each MRI was read by 3 radiologists blinded to treatment assignment who independently completed the extended MRI (eMRI) scale; higher eMRI scores indicate greater joint structure damage. The score for each joint was based on the readers’ median change score for each of the 45 eMRI scale items when comparing MRIs from different timepoints. Total patient score was derived; change from baseline in total patient score was prespecified as the first in a hierarchy of 2 secondary endpoints. Between- group comparison was made using constrained longitudinal data analysis. Data are presented for the intent-to-treat population.

Summary:

Of 84 patients enrolled (42 per treatment group), MRI data were available for 38 on-demand and 41 prophylaxis patients. Least squares (LS) mean change from baseline to year 3 on the eMRI scale total score was 0.96 for on demand and 0.79 for prophylaxis (LS mean difference, –0.17; 95% CI, –0.92 to 0.59; P=0.66). LS mean change from baseline to year 3 for on demand and prophylaxis was 0.06 and 0.01 for the eMRI soft-tissue domain (LS mean difference, –0.04; 95% CI, –0.18 to 0.10; P=0.53) and 0.90 and 0.78 for the eMRI osteochondral domain (LS mean difference, –0.12; 95% CI, –0.82 to 0.58; P=0.74).

Conclusions:

In adults with severe hemophilia A, progression of structural joint damage was not significantly different between patients using rFVIII prophylactically or on demand over a 3-year follow-up period, although less progression was seen with prophylaxis.

Dr. Tammuella Chrisentery-Singleton is an Assistant Professor of Clinical Pediatrics at Tulane University and is board certified in pediatric hematology/oncology. She will receive training under the mentorship of Cindy Leissinger, MD, Chief, Section of Hematology & Medical Oncology at Tulane University School of Medicine and Director of the Louisiana Center for Bleeding and Clotting Disorders. Chrisentery-Singleton graduated with honors from Xavier University, received her MD from Louisiana State University and then completed her pediatric residency at the University of Miami. Following residency, she completed pediatric hematology/oncology fellowship training at Johns Hopkins University, where she worked with Dr. Jim Cassella and developed a serious interest in disorders of coagulation, particularly hemophilia. After her fellowship training, she was recruited to join the pediatric hematology/oncology faculty at LSU and Children's Hospital of New Orleans. In 2010, Chrisentery-Singleton accepted a position at Tulane University because of her desire to receive more training and spend more time in the specialized coagulation medicine program. As an NHF-Baxter Clinical Fellow, she will receive dedicated training in bleeding and clotting disorders for both children and adult patients, along with mentoring in clinical research related to bleeding disorders. She will also continue her work on several ongoing clinical trials, and pursue her project in developing models to better determine pharmacokinetic parameters with a minimal number of needle sticks in pediatric patients with hemophilia. Her goals are to steadily improve her knowledge and skills in caring for patients with coagulation disorders, and continue building her academic career in coagulation medicine.

Dr. Jonathan Roberts is currently a pediatric hematology and oncology fellow with the Medical College of Wisconsin and the Children's Hospital of Wisconsin. His fellowship mentor will be Joan Gill, MD, Professor of Pediatrics at the Medical College of Wisconsin and Director of the Comprehensive Center for Bleeding Disorders (CCBD) at the BloodCenter of Wisconsin. Roberts graduated with honors from Greenville College, Illinois, and received his MD from Southern Illinois University School of Medicine. He did his residency in Pediatrics at the University of Illinois at Peoria and Children's Hospital of Illinois, where he also distinguished himself, receiving awards of excellence for critical care and research. During his pediatric residency, Roberts worked with Dr. Michael Tarantino to initiate a clinical research trial to assess the role of FXIII on intraventricular hemorrhage in premature, low birth weight infants. As a NHF-Baxter Clinical Fellow, Roberts will receive focused training and gain clinical experience through the hemostasis clinics at CCBD and further develop his research skills in a project to develop a new ELISA-based assay for assigning VWF phenotype. Roberts has plans to pursue a Master's Degree in Clinical and Translational Science. His goal is to become an expert physician/scientist with a long-term career focus on hemophilia, and other bleeding and clotting disorders.

As technology advances and provides electronic tools for enhancing communication by phone and computer, health care providers are finding ways to adapt these tools into patient care. Telehealth is the use of electronic information and telecommunications technologies to support long-distance clinical health care. For patients with hemophilia who experience a bleed in the home setting, telehealth has the potential to help the patient, family, and health care provider assess what is going on and develop the best plan of care, all while the patient stays in the home setting. In this clinical project, we will use the telehealth resources available at our institution to partner with patients and families with severe hemophilia with a high risk of bleeding episode who also have a home computer with a camera and internet access. We want to find out more about how many patients have these home resources, how to use video-conferencing when managing a bleed and what patients, families, and health care staff think about using video conferencing. This will help us plan future research using telehealth video-conferencing for a larger group of hemophilia patients.