Objective:
To evaluate efficacy of IB1001 for perioperative management of bleeding under surgical circumstances in hemophilia B patients.
Methods:
The efficacy of IB1001 for perioperative management has been evaluated in a prospective, open-label, multicenter international study where 17 subjects (16 male PTPs and one female hemophilia B carrier) underwent 20 major surgical procedures. The PTPs were defined as patients with a minimum of 150 exposures to another factor IX preparation. The subjects had severe or moderately severe (factor IX level ≤ 2 IU/dL) hemophilia B without inhibitors, with exception of one mild hemophilia B female carrier. Efficacy of IB1001 was based on the surgeon’s assessment including estimation of blood loss as ‘less than expected’, ‘expected’, or ‘more than expected’ at the time of surgery and assessment of hemostasis at 12 and 24 hours post-surgery as ‘superior’, ‘adequate’, or ‘poorly controlled’. Transfusion requirements were also monitored.
Summary:
Thirteen major procedures in 12 male subjects were managed by bolus regimen, and 6 major procedures in 4 male subjects were managed by continuous infusion regimen. Mean loading dose for 13 major procedures managed by bolus regimen was 120 ± 11.4 IU/kg and mean maintenance bolus dose (given every 12 hours) was 59.7 ± 12.2 IU/kg. During the 24 hours following surgery, factor IX levels were successfully maintained over 60%, as intended. Factor IX levels at pre-infusion were 59.7% ± 15.9% at 12 hours after surgery and 54.4% ± 16.5% at 24 hours after surgery. For a major procedure in one female carrier, the bolus dose was 110 IU/kg, while the mean maintenance dose was 44.9 ± 7.0 IU/kg. Mean loading dose for 6 major procedures managed by continuous infusion regimen was 95.4 ± 14.5 IU/kg and the mean maintenance infusions were 7.1 ± 4.0 IU/kg/hr. In all major procedures, blood loss at the time of surgery was ‘expected’ or ‘less than expected’ as assessed by the surgeon. IB1001 was rated by the surgeon as ‘superior’ or ‘adequate’ in controlling hemostasis post-surgery, including 8 knee arthroplasties, two elbow arthroplasties, one knee amputation, one percutaneous Achilles tendon lengthening, one open inguinal hernia repair, one tibiotalar fusion, two arthroscopic synovectomies, three debridements and one total hysterectomy/bilateral oopherectomy. There were no transfusions required perioperatively.
Conclusions:
At the time of surgery, blood loss was expected or less than expected after IB1001 treatment, while post-surgery effective hemostasis control was achieved following IB1001 treatment in hemophilia B patients.
Pediatric pain, especially in the hemophilia population, is under-recognized and under-treated. Barriers to adequate treatment include lack of knowledge, variability of practice, and outmoded beliefs. All of these factors lead to a culture of slow to no change in practice patterns. Health care providers need current, state-ofthe- art education and tools to assist them in developing the skills required to assess and manage pain in children. Children are often given minimal or no analgesia for procedures that would be treated aggressively in adults. Although more is now known about pain management in children, this knowledge has not been widely or effectively translated into routine pediatric clinical practice, including the practice of most HTCs. In the bleeding disorders community, especially for those with hemophilia, children begin to experience frequent pokes secondary to frequent factor infusions and blood draws at an early age. Depending on the severity of their disorder, they may experience a poke daily or more frequently. This gives rise to anxiety for the child as well as their parents and other family members. Anticipatory anxiety is not uncommon in this setting. The child and their family often feel as though they have no control over the situation. A distraction box is filled with tools for providers to implement during any procedure involving children. The simple act of distraction (in whatever form) can significantly decrease pain and anxiety for both the child as well as their parent. This box offers multiple methods of distraction and informational videos on techniques. The focus of the Poke Plan is to give control over a painful or anxiety provoking situation back to the parent/child. The simple wallet card quickly educates any provider on how the child best handles the discomfort and anxiety associated with a poke/needlestick. Filling out the card educates the parents on distraction techniques that may be helpful for their child in painful and anxiety provoking situations. To date there have not been any studies done in this population. However centers in Michigan using similar Poke Plans in the general pediatric population include but not necessarily limited too are: Sparrow Hospital in Lansing Michigan, Munson Medical Center in Traverse City, Michigan as well as the University of Michigan Children and Women’s Hospital in Ann Arbor, Michigan.
Objective:
In the 3-year SPINART study, routine prophylaxis and on-demand treatment were compared in adults with severe hemophilia A. We report final SPINART efficacy and safety results after 3 study years.
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. All 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). The primary efficacy endpoint, bleeding frequency (number of all bleeding episodes at 1 year), has been previously reported. Endpoints reported here are total and annualized numbers of all bleeding episodes, joint bleeding episodes, spontaneous bleeding episodes, and trauma-related bleeding episodes. Between-group comparisons of bleeding frequency were made within the framework of a negative binomial regression model to account for different follow-up times of patients who discontinued prematurely, with stratification variables (presence of target joints at baseline, number of previous bleeding episodes at baseline) included in the model. Safety variables included adverse events (AEs), serious AEs, and inhibitor development.
Summary:
84 patients (42 prophylaxis, 42 on demand) comprised the intent-to-treat population. The total number of all bleeding episodes during the 3-year study was significantly lower with prophylaxis versus on demand (median, 2.0 vs 96.5, respectively; P<0.0001). Annualized number of all bleeding episodes (median [quartile 1; quartile 3], 0.7 [0; 1.6] vs 37.4 [24.1; 52.6]), total joint bleeding episodes (median, 1.0 vs 67.0), and joint bleeding episodes per year (median, 0.3 vs 27.3) were all lower with prophylaxis versus on demand. The numbers of spontaneous and trauma-related bleeding episodes were also lower with prophylaxis versus on demand. Observed AEs were consistent with the established rFVIII-FS safety profile. No patient developed inhibitors.
Conclusions:
Long-term prophylaxis with Bayer’s rFVIII-FS is efficacious in decreasing bleeding episodes, including joint bleeding episodes, in adults with severe hemophilia A. 75% of prophylaxis patients had <2 bleeding episodes per year during the 3-year study. No inhibitors were reported.
Objective:
To describe the rates of falls, injurious falls, and activity restriction due to fear of falling in a population of patients with hemophilia.
Methods:
As part of a study on identifying fall risk in patients with hemophilia, subjects completed a self-administered questionnaire inquiring about fall history over the previous 12 months.
Summary:
75 patients with hemophilia between the ages of 18 and 85 completed the questionnaire. 59 (79%) of these patients had hemophilia A, and 16 (21%) had hemophilia B. 34 (45%) had severe disease, 17 (23%) had moderate disease, and 24 (32%) had mild disease.
25 (33%) of the subjects reported a fall within the last 12 months. The average and median ages of the subjects who fell were 46 and 45 respectively, while the average and median ages of the non-fallers were 41 and 39.5 respectively. Of the 25 patients who fell, 11 (44% of fallers or 15% of total sample) reported an injury caused by the fall. 12 patients (16%) reported restricting activity due to fear of falling. The majority of subjects who reported a fall or injurious fall had mild disease (55 %.), with an average age of 45 and median age of 46.5. The majority of subjects who restricted activity due to fear of falling had mild disease (50%), with most subjects who restricted activity reporting a fall in the previous 12 months (58%)
Conclusions:
Fall rates in hemophilia patients in this study (33%) are similar to or higher than the fall rates found in community dwelling adults 65 years and older (22-33%), although the subjects in this study were younger. Injurious fall rates found in the study (15%) are higher than non-fatal injurious fall rates described in adults age 65 and up (5-11.5%), and similar to those found in adults with arthritis age 45 and up (16.2%). Subjects in this study with mild disease were more likely to fall and to be injured. Activity restriction due to fear of falling (16%) was lower than that found in older adults in other populations (20-60%).
This study suggests that fall risk screening may be an important component of the comprehensive evaluation of patients with hemophilia, including those with mild disease. These results should be confirmed in a larger population of patients and across different treatment centres. Further research into optimal fall risk screening, in-depth assessment and treatment in this population is warranted.
The purpose of this project is to determine if children with hemophilia have gross motor delays. Gross motor skills include, but are not limited to walking, running, jumping, climbing, crawling, balancing, kicking, catching and throwing activities. The large muscles of the body are responsible for performing these types of activities. Strength, balance and coordination are needed to demonstrate and improve these skills. Children with hemophilia may experience internal bleeding in their joints or muscles, which limits their activity. Some children with hemophilia may be restricted from active play or sports for fear of getting an injury that could cause internal bleeding. When activity is restricted, there can be decrease in strength, balance and endurance. If a child has gross motor delays, it puts him at risk for injury when playing with his peers. Physical Therapy evaluations in the Hemophilia Treatment Center help determine changes caused by bleeding episodes. There are specific motor skills children master as they grow, which represent strength, balance and coordination. The comprehensive clinic visits do not allow time to complete an intensive gross motor assessment. Physical Therapists use Manual Muscle Testing, MMT, to grade the strength of each muscle group. MMT strength testing is not appropriate for young children and does not represent strength during functional activities. To accurately determine children's muscle strengths, a standardized gross motor test should be used. The PT at the Comprehensive Care Center for Inherited Blood Disorders will conduct gross motor evaluations in conjunction with the annual visit. The scores will be evaluated to determine which patients have gross motor delays, so they can be referred for therapy services. The BOT 2 is the standardized gross motor test that will be used to determine gross motor levels. The gross motor skills that will be evaluated include bilateral coordination, balance, running speed and agility, upper limb coordination and strength. All patients with hemophilia between the ages of 4 and 12 years will be eligible to be evaluated in the upcoming year with additional PT testing with their annual visit. Patients may be referred to therapy or given a home exercise program depending on the deficits noted during the assessments. The goal is to improve our standard of care at the HTC, by adding gross motor screening for our patients to ensure appropriate referrals are made for therapy services.
