Social workers have been active members of the multidisciplinary teams of hemophilia treatment centers for many years, but the roles of these social workers may differ greatly from center to center. Social workers are often the advocate for patients and a primary source of assistance, information and referral. In many HTCs, they also provide counseling and therapy services to patients and consultation to staff. Indeed, these social workers appear to provide a wide variety of psychosocial and case management services to patients with bleeding disorders and their families. This research project will attempt to describe the various role tasks of hemophilia treatment center social workers, describe these tasks and identify the influences of the role in each HTC. An online survey will be developed and emailed to the approximately 135 HTC social workers across the nation. Data will be analyzed and shared with the social worker community through sessions and posters and the NHF annual meeting.
Background:
BAY 1093884 is a fully human monoclonal antibody against tissue factor pathway inhibitor (TFPI) developed as a bypass agent for hemophilia patients with inhibitors. It restores thrombin burst for stable clot formation in hemophilic conditions in vitro.
Aims:
The goal of this study was to elucidate the in vivo prophylactic hemostatic potency of BAY 1093884.
Methods:
The hemophilia A mouse tail vein transection model was used for this study to mimic the venous bleeding characteristics of severe hemophilia. Male hemophilia A mice (n=12/group) were treated prophylactically with escalating doses of BAY 1093884. All treatments were administered as single intravenous (IV) bolus at 4 different time courses prior to injury (1, 3, 5, and 7 days). Bleeding was induced by a 1.2-mm deep incision across the left lateral vein. Following injury, the animals were monitored hourly for moribundity for up to 9 hours and after 24 hours followed by euthanasia.
Results:
Efficacious doses of BAY 1093884 providing 50% protection for survival (ED50) for up to 6 days after IV bolus ranged from 0.6–2 mg/kg. In comparison, only 25% protection was achieved 6 days after the treatment with a very high dose of 1000 IU/kg of recombinant factor VIII (rFVIII). The effect of a single IV dose of 18 mg/kg BAY 1093884 providing 80%–90% survival was maintained over 8 days (ED50 6 mg/kg), whereas a single IV dose of rFVIII failed to provide protection over an 8-day period.
Conclusions:
These studies demonstrate that BAY1093884 prevents bleeding and increases long-term survival to a greater degree than rFVIII in hemophilia A mice and may offer a convenient prophylactic treatment option for hemophilia patients with inhibitors.
Background:
Activity limiting joint disease has greatly decreased with the introduction of prophylactic treatment for people with severe bleeding disorders. Previous research using the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition (BOT-2TM), a standardized, normative, age and sex matched test of motor development, suggested motor development of males aged 4-21 years with bleeding disorders may be lower than age-matched peers.
Objective:
The primary purpose of this study was to compare the gross motor proficiency of boys with hemophilia ages 4-21 years followed at the Hemophilia Center at Oregon Health & Science University utilizing the BOT-2. Secondarily, we examined the relationship between joint health and gross motor proficiency.
Methods:
a) Participants and setting: Thirty-four subjects with either hemophilia A or B were recruited
from our center. Data collection occurred during clinic visits or at the patients’ homes.
b) Design and Procedures: A prospective, cross-sectional study design was used. The Upper Limb Coordination, Bilateral Coordination, Balance, Running Speed and Agility, and Strength subtests of the BOT-2 were administered. Body composition, range of motion, presence of an inhibitor, and use of prophylaxis were collected at the time of testing or from chart review.
c) Analyses: Analysis of variance (ANOVA) modeling was used to compare BOT-2 scores of PWH with baseline BOT-2 scores estimated from the general population of comparable age.
Summary:
Mean Running Speed & Agility scores were greater among boys with hemophilia compared to the control population (p=0.0026). Agility scores were similar between boys with hemophilia A and B (p>0.60), and significantly greater compared to the control group (p=0.0153). No other significant differences were found comparing boys with hemophilia to the control group. Within the boys with hemophilia cohort, age-adjusted ANOVA found no significant differences in BOT-2 scores between subjects of different severities, treatment regimen (prophylaxis or episodic), or diagnoses (Hemophilia A or B).
Conclusion:
Boys with hemophilia have the same or better gross motor proficiency as age matched peers.
Objective:
Kids B-LONG was an open-label phase 3 study that evaluated the safety, efficacy, and pharmacokinetics (PK) of rFIXFc in previously treated children (aged <12 years; ≥50 prior exposure days [EDs] to FIX) with severe hemophilia B (≤2 IU/dL endogenous FIX) and no history of FIX inhibitors.
Methods:
Participants initiated prophylactic treatment with 50–60 IU/kg rFIXFc once-weekly; dose and interval adjustments were based upon PK data and bleeding frequency. The primary endpoint was development of inhibitors (neutralizing antibodies). Key secondary outcomes included PK and annualized bleeding rate (ABR).
Summary:
The study enrolled 30 participants (<6 years of age, n=15; 6 to <12 years of age, n=15); 90% completed the study. Prestudy, all participants received FIX prophylaxis (23/30 were dosing ≥2x/week). The median time on study was 49.4 weeks; 24 participants had ≥50 rFIXFc EDs. No participant developed inhibitors to rFIXFc. The pattern of adverse events reported was typical of the population studied. There were no serious allergic reactions and no thrombotic events. No serious adverse events were assessed by the investigator as related to rFIXFc. The terminal half-life (geometric mean [95% CI]) of rFIXFc was 66.5 (55.9, 79.1) hours in the <6 years cohort (n=11) and 70.3 (61.0, 81.2) hours in the 6 to <12 years cohort (n=13). The geometric mean (95% CI) half-life of prestudy BeneFIX was 18.2 (15.5– 21.3) hours in the <6 years cohort (n=11) and 19.2 (17.6–20.9) hours in the 6 to <12 years cohort (n=9). Median (IQR) ABR was 1.97 (0.00, 3.13) overall, and 0.00 (0.00, 1.16) for spontaneous bleeds; 33.3% of participants reported no bleeds on study. At study end, 97% of participants were dosing once weekly. The median (IQR) total weekly prophylactic dose with rFIXFc was 59.4 (53.0, 64.8) IU/kg and 57.8 (51. 7, 65.0) IU/kg, in the <6 years and 6 to <12 years cohorts, respectively. The prestudy FIX median (IQR) total weekly prophylactic dose was 110.0 (58.0, 188.0) IU/kg and 100.0 (58.0, 120.0) IU/kg in the <6 years and 6 to <12 years cohorts, respectively. 75.0% of bleeding episodes were controlled with 1 infusion; 91.7% with 1 or 2 infusions (median average dose per infusion: 68.22 IU/kg).
Conclusions:
rFIXFc was safe and effective for the prevention and treatment of bleeding in children with severe hemophilia B. Study participants achieved low bleeding rates with extended-interval rFIXFc prophylaxis, while reducing their weekly prophylactic factor consumption compared with their prior FIX regimen.
Background:
Arthropathy is one of the major complications in hemophilia, leading to functional limitations and poor quality of life. Exercise is recommended as being beneficial for people with hemophilia, yet a lack of exercise-related evidence using exercise and control groups exists in this population, compared to other joint pathologies (i.e. osteoarthritis).
Objective:
To evaluate effects of post-hemarthrosis exercise on: pain; swelling; bone density and joint damage, using an animal model.
Methods:
Twelve Wistar rats were divided into an Exercise Group (EG; n=6) and Control Group (CG; n=6). All rats received eight weekly intraarticular injections in their right knees with 0.1 mL autologous blood, and left knees with 0.1 mL saline solution. The EG performed an 8 wk swimming protocol (during the period of intraarticular injections) of 60 min (5x week) with 5% body weight attached on their tails. Pain status was assessed weekly with a static weight-bearing incapacitance test (SWIT). Joint diameters were measured post-protocol with a digital microcaliper. Bone mineral density was assessed using dual-energy X-ray absorptiometry (whole-body, tibia, femur and knee joint) pre and post-study. Following sacrifice, bilateral knee X-rays were taken and scored with Pettersson’s score. Resting heart rate and heart weight were registered post-study, as markers of physical training.
Results:
CG manifested decreased weight-bearing with SWIT, compared to EG (p<0.001). EG presented reduced joint swelling, compared to CG (p=0.034). Significant increase in bone mineral density variation (BMD∆) was observed at the tibia (p=0.016), and knee (p=0.018) of the EF compared to CG. The EG also showed a tendency of an increase in femoral BMD∆ compared to CG (p=0.09). Pettersson scores demonstrated increased bone destruction in the CG compared to EG (p=0.05).
Conclusion:
This is the first time that beneficial effects of a swimming exercise protocol on pain, swelling, bone density and radiologic changes have been shown in a blood-induced, joint damage animal model. Hopefully this data will provide clues for future study designs in this area.
Objective:
To evaluate efficacy of IB1001 with respect to breakthrough bleeding during prophylaxis and with respect to control of hemorrhaging in prophylaxis and on-demand treatment regimens in previously treated patients (PTPs) with hemophilia B.
Methods:
The efficacy of IB1001 has been evaluated in a prospective, open-label, uncontrolled multicenter international study in which a total of 68 male PTPs between 7 and 64 years of age received IB1001 either as prophylaxis or on-demand treatment. All subjects had severe or moderately severe (factor IX level ≤ 2 IU/dL) hemophilia B without inhibitors. There were 61 subjects who received prophylaxis [predominantly secondary or tertiary prophylaxis as defined by World Federation of Hemophilia (WFH) guidelines] and 12 were treated on-demand during the study conduct. Both, the subjects and the study investigators rated the efficacy of IB1001 in management of bleeding episodes.
Summary:
The mean number of exposure days (ED) was 138.2 (median: 127.5 ED), including 55 subjects with ≥ 50 ED and 45 subjects with ≥ 100 ED. Subjects on prophylaxis received a mean intravenous dose of 55.0 ± 12.8 IU/kg IB1001 twice weekly, while subjects in the on- demand regimen received a mean dose of 60.0 ± 18.2 IU/kg IB1001. In the prophylaxis group, median annualized bleed rate (ABR) was 1.52, and in the on-demand group, median ABR was 16.39. There were 19/61 (31.1%) subjects on IB1001 prophylaxis who reported no bleeding episodes. A total of 508 bleeding episodes were treated with IB1001; 286 bleeds were recorded for patients on prophylaxis and 222 in the on-demand regimen. Majority of the bleeds (70.9%) resolved after a single IB1001 infusion, while 13% of the bleeds required two infusions. A minority of the bleeds (4.7%) required 5 or more infusions; these bleeds were predominantly related to trauma, target joints and/or muscle bleeds. Subjects rated efficacy of IB1001 as ‘excellent’ or ‘good’ in 84% of all treated bleeding episodes. Of 414 subject visits where the efficacy of IB1001 was evaluated by the study investigators, 92% were rated as ‘effective’ in prevention and treatment of bleeding by IB1001.
Conclusions:
IB1001 is effective for the treatment of hemophilia B either as secondary or tertiary prophylaxis or on an episodic (on-demand) basis. Based on clinical trial data, IB1001 is effective in controlling breakthrough or episodic bleeding episodes.
