Research Studies

Hemophilia is a rare bleeding disorder in which the blood doesn't clot normally. (National Heart, Lung, and Blood Institute, 2013). It mostly affects males.(Raabe, 2008).

For parents hearing that their new baby has hemophilia can be stressful and worrying. Babies do not realize what is happening around therefore parents often tend to be overprotective. As the boys grow up, they are capable of seeing the cause and effect of situations on their own and they realize that they cannot do the same things like their friends. When the adolescence come, teenagers worry about what society thinks, so having hemophilia may make them feel different. (Hemophilia Federation of America, 2015). Hemophilia is not an illness, it ́s just a “life style” which people have to live with.

Within psychological intervention is important to address the emotional aspect of patients and family ́s support patient handling of his illness, personal life and surroundings.

Objective:

Describe intervention strategies in the summer camp “Ceiba” of “Tabasqueña de Hemofilia A.C.” in order to promote the social integration in patients with hemophilia.

Materials:

Intervention programs carried out in the camp were used to realize an analysis of the strategies, which were provided by "Tabasqueña de Hemofilia A.C."

During the last eight years, eight camps were realized, the average of assistants every year was 80, 60 patients (between 6 and 24 years old) and 20 additional people in medical field. The objective of the camps is to learn, enjoy, bring all their everyday life experiences and have a better quality of life. (Tabasqueña de Hemofilia, 2007).

The interventions were directed to: accept and make awareness of patient ́s life ́style, learn about hemophilia, live in cooperation, socialize and integrate, improve communication, express himself, team work, experience the freedom, become independent, self-esteem and have a better quality of life.

Each intervention was related to a specific activity; 3 workshops (Psychologist, hematology and nursing), parents and relatives letters, hydrokinesitherapy, talent show, treasure hunt and visits to entertainment and cultural places.

Camps have a great significant learning in their lives and teach children and teenagers valuable life skills through education, activities and games; socialization is achieved, independence, and sense of individual responsibility and group.

Having this camps around the world and taking this interventions will be excellent, because its an interactive way to achieve self- realization and learn to live with the disease, knowing others with the same "life ́s style".

Objective:

People with hemophilia (PWH) commonly self-infuse at home, and can provide valuable insights into device attributes. While Novo Nordisk initially launched recombinant activated FVII (NovoSeven® RT) with vial adaptors, these were replaced with prefilled diluent syringe (MixPro®) in 2013; rFVIII (NovoEight®) launched with MixPro® in the US in 2015. This market research study assessed PWH and caregiver perceptions and preferences between MixPro® and vial adaptors (original device).

Methods:

A market research study was conducted in Fall 2014, comprising 30-minute face- to-face interviews. In total, 38 PWH (≥18 years) and 29 caregivers of children with hemophilia participated in the study, from Italy (n=20), Spain (n=20) and the US (n=27). Participants were eligible if they regularly home-infused replacement factor, and were excluded if they had ever used rFVIIa or were already familiar with MixPro®.

Summary:

The mean age of participants was 27 years. Most had hemophilia A (84%) with the remainder having hemophilia B (16%), more received prophylaxis (73%) than on demand (27%), and most received rFVIII (73%). Other participants were treated with FIX or plasma- derived FVIII. One PWH had inhibitors and was treated with activated prothrombin complex concentrate. MixPro® was clearly and consistently preferred over vial adaptors, both overall and based on key criteria. Overall, 96% were confident that they could use the system correctly, 73% thought it was intuitive to use, and 93% thought it was easy to learn. When asked to rank 18 defined benefits in order of importance, ‘low contamination risk’ was deemed the most important; the only criteria where MixPro® was not superior were related to verifying mixed factor had been drawn into the syringe. MixPro® was most associated with being: quick, easy, and convenient to use; portable; and overall user friendly. Caregivers placed more emphasis on a device being suitable for a person with less strength, while PWH were more interested in portability and convenience. Results were generally consistent across sub- populations: PWH vs caregivers, and those treated on demand vs prophylaxis.

Conclusions:

MixPro® demonstrated clear advantages over vial adaptors, based on feedback from PWH and caregivers, with respondents reporting it easy to learn and use, and confident they could use it correctly. The results affirm the importance of continuing to innovate on devices in collaboration with the hemophilia community.

Objective:

Highlight the importance of collaboration in addition to dose, frequency, and PK data to personalize regimens in order to minimize bleed rates in Hemophilia A patients on prophylaxis.

Methods:

Dose and bleed data was collected and reviewed from January 1, 2015 through March 31, 2015 for all moderate to severe hemophilia A patients on prophylaxis regimens with traditional acting products in 2 regional bleeding disorder hubs. Units per kilogram per dose, units per kilogram per week, and spontaneous bleed rate were calculated from data. If reporter was unsure of bleed origin, it was counted as a spontaneous bleed.

Results:

Region X had 34 and Region Y had 40 patients that met the inclusion criteria for review. The average dispensed dose for Region X was 43.89 units per kg per dose. For Region Y, it was 35.47 units per kg per dose; a difference of 8.42 units per kg per dose. Due to varying frequency orders, regimens were further calculated in units per kg per week. Region X’s average was 121.38 units per kg per week and Region Y’s was 96.98; a difference of 24.4 units per kg per week. Patients in Region X reported zero spontaneous bleeds during the study period. Patients in Region Y reported 16 spontaneous bleeds from 12 unique patients. Of these patients, target joints were cited as contributing factors with 8 of the 16 bleeds. When appropriate, prescribers were notified and collaboration on regimen adjustments was made. Pharmacokinetic data was inconsistently available.

Conclusion:

Zero spontaneous bleeds should be the goal for hemophilia A patients on prophylaxis. Small changes in dose or frequency can make significant changes in outcomes. Many variables impact bleed rates and doses vary widely. There is the potential for refining dosing algorithms based on a more personalized approach that includes close and careful monitoring of trough levels, patients activity level, bleed pattern and response to changes in treatment plans. This individualized approach would require collaboration between patients, prescribers, and pharmacies. Such an approach can have huge and long-term beneficial effects on pharmacoeconomic, clinical, and quality of life outcomes. Data collected from this study may further assist pharmacists with influencing prescribers to consider pharmacist obtained bleed data and/or obtain and provide PK data so they can assist with regimen adjustment recommendations based on their assessments. With increasing payer pressure and the introduction of longer acting products, this collaboration will become even more imperative.

Background:

Current available factor replacement therapy (FRT) for von Willebrand Disease (vWD) contains FVIII. Thromboembolic events (TEE) are a small but serious risk in patients with elevated FVIII levels as a result of accumulation from repeated doses of FRT (Manucci, 2004).

Aim:

To assess the total medical cost incurred in one year of treating TEEs in vWD.

Methods:

This retrospective database analysis utilized the Marketscan®Database, a US medical claims database, from Jan 2006 to Mar 2014. Patients with inpatient diagnosis for a TEE (ICD-9 code for venous thromboembolism [VTE], myocardial infarction [MI], ischemic stroke [IS], etc.) were identified, with the first inpatient TEE visit defined as the index date (ID). VWD diagnosis (286.4) was required prior to ID and ≥12 month continuous enrollment both prior and post ID. Direct medical costs of TEE management in the first year were estimated for inpatient and outpatient settings. The subset of VWD patients prescribed FRT prior to ID was also described. Costs were adjusted to 2013USD using the medical consumer price index.

Results:

One hundred fifty-three vWD subjects were identified with an inpatient TEE. Mean age at the ID was 56 years (2–94 yrs) and 69.9% were female. Median annual cost and range associated with treatment of TEEs was $21,166 ($1,300–$867,710). VTE and IS were the most common TEEs (36.0% ≥1 VTE, $24,338 ($1,063–$235,090) and 32.7% ≥1 IS, $11,326 ($1,300–$368,550), respectively). Patients prescribed FRT (n=12) had a median annual cost of $64,648 ($4,690–$137,705) for TEE treatment.

Conclusion:

This is the first study to estimate the total cost associated with management of TEEs in vWD. TEEs are a burden to the healthcare system and are potentially life- threatening. A vWD treatment option that can avoid the risk of FVIII accumulation may benefit vWD patients at risk for TEEs.

Dr. Chappell's research project will develop a model for characterizing bleeding in hemophilia and particularly in joints. Using mouse models of hematoma formation and knee joint bleeding, Dr. Chappell will use 3D fluorescent imaging technology in "living" hemophilia B mice to better trace bleeding over time- from induction of a bleed to its resolution. This project will provide additional insights on the basic science underlying hemophilic bleeds, not to mention the optimal interventions and timing of treatment to potentially prevent damage caused by bleeds. Dr. Chappell earned her Ph.D. in Pharmaceutical Sciences from UNC Chapel Hill in 2013. She will pursue her research under the mentorship of Dr. Dougald Monroe, Professor in the Division of Hematology/Oncology, UNC School of Medicine and the UNC McAllister Heart Institute.

 Objective:

The ongoing rFIXFc extension study, B-YOND (clinicaltrials.gov #NCT01425723) , evaluates the long-term safety and efficacy of rFIXFc for the treatment of severe hemophilia B. Here we report interim safety and efficacy data for children aged <12 yrs enrolled in B- YOND.

Methods:

Upon completing Kids B-LONG, eligible subjects could enroll in one of the 3 prophylactic treatment groups in B-YOND: weekly (20 to 100 IU/kg every 7 days), individualized (100 IU/kg every 8 to 16 days, or twice monthly), or modified (a prophylaxis regimen different from weekly or individualized prophylaxis). Subjects could change treatment groups at any point in the study. The primary endpoint was development of inhibitors. Secondary outcomes included annualized bleeding rate (ABR) and rFIXFc exposure days (EDs).

Summary:

At the time of the interim data cut (17 October 2014), 23 subjects had completed Kids B-LONG; all enrolled in B-YOND (<6 yrs of age cohort, n=9; 6 to <12 yrs of age cohort, n=14). As of the interim data cut, 2 subjects had completed and 21 subjects continued in B-YOND (median time on study: 47.7 weeks). From the start of Kids B-LONG to the B-YOND interim data cut, the median time on rFIXFc was 95.3 weeks, with a median of 94 cumulative rFIXFc EDs. All subjects were on weekly prophylaxis in Kids B-LONG; 5 subjects changed treatment groups at the start of or during B-YOND. In the weekly prophylaxis group, the median (IQR) average weekly prophylactic dose was 64 (52, 66) IU/kg and 63 (59, 64) IU/kg in the <6 yrs and 6 to <12 yrs of age cohorts, respectively. The median (IQR) dosing interval among subjects on individualized prophylaxis was 10 (10, 11) days. As of the interim data cut, no inhibitors were observed, there were no reports of anaphylaxis or serious hypersensitivity reactions associated with rFIXFc, and no thrombotic events. Adverse events were typical of the pediatric hemophilia B population; no subject discontinued the study due to an adverse event. Median ABRs were low in both age cohorts (Table). Overall, 95% of bleeding episodes were controlled with 1 or 2 infusions.

Conclusions:

Interim data in children with severe hemophilia B participating in B-YOND confirm the long-term safety of rFIXFc and the maintenance of a low ABR with extended-interval prophylactic dosing.

Introduction:

Efficacy and safety of routine prophylaxis vs on-demand treatment with Bayer’s sucrose-formulated recombinant factor VIII (rFVIII-FS) in patients with severe hemophilia A were evaluated in the randomized, controlled SPINART study.

Aim:

Patient- and joint-level changes at year 3 in magnetic resonance imaging (MRI) and Colorado Adult Joint Assessment Scale (CAJAS) scores were compared to investigate if individual joint data revealed results that may have been obscured in previously reported patient-level analyses.

Methods:

SPINART included males aged 12–50 years with severe hemophilia A, ≥150 exposure days to FVIII, no inhibitors, and no prophylaxis for >12 months in the past 5 years. Patients were randomized 1:1 to rFVIII-FS on demand or prophylaxis (25 IU/kg 3x/wk). Changes from baseline to year 3 were evaluated for 6 index joints (knees, ankles, elbows) using the Extended MRI (eMRI) scale and CAJAS. Percentages of patients or joints with improved, unchanged, or worsened scores were evaluated.

Summary:

Of the 84 patients in SPINART, eMRI and CAJAS change from baseline data were available for 62 (prophylaxis, n=32; on demand, n=30) and 76 patients (n=39; n=37) and for 386 (n=197; n=189) and 446 joints (n=224; n=222), respectively. Categoric analysis of CAJAS data at year 3 showed a higher percentage of patients treated prophylactically vs on demand with improved scores (64.1% vs 43.2%) and a lower percentage with worsened scores (28.2% vs 51.4%); with eMRI, the percentage improved was smaller (12.5% vs 6.7% improved; 75.0% vs 73.3% worsened). At individual joints, improved, unchanged, and worsened CAJAS scores in patients treated with prophylaxis vs on demand were 46.0% vs 33.3%, 22.3% vs 24.3%, and 31.7% vs 42.3%; eMRI values were 8.1% vs 3.7%, 61.9% vs 69.8%, and 29.9% vs 26.5%.

Conclusions:

These data suggest that in adults and adolescents with severe hemophilia A, joint function as measured by CAJAS is more likely to improve after 3 years of routine prophylaxis with rFVIII-FS than joint structure as measured by MRI.

Objective:

TFPI is a potent inhibitor of the tissue factor (TF)-induced extrinsic pathway of coagulation. Inhibition of TFPI with antibodies, aptamers, or peptide inhibitors improves hemostasis and may become an option for non-i.v. treatment of patients with hemophilia including those with inhibitors.

Method:

We developed a TFPI inhibitory fusion peptide (FP) consisting of a linear and a cyclic peptide connected by an optimized linker. The two peptides bind to different epitopes on TFPI and synergistically inhibit TFPI. The FP was further improved by half-life extending (HL) non-covalent albumin binding. HL-FP was characterized for in vitro inhibition of TFPI, pharmacokinetics, and improvement of coagulation in animal models of hemophilia.

Results:

HL-FP bound to and efficiently inhibited TFPI in several in vitro test systems. The binding affinity of < 1nM correlated well with inhibition of TFPI in model assays, resulting in IC50s of ~0.7nM. HL-FP efficiently inhibited plasma TFPI, which improved all thrombin generation (TG) parameters in hemophilia A and B patient plasma (EC50s of 6 to 20nM). HL-FP increased peak thrombin levels of hemophilia plasma to a range established for individual normal plasma. Assays were also carried out at flTFPI concentrations up to 10nM, which is 40- to 50- fold above normal. Increased TFPI levels may occur locally upon platelet activation. HL-FP efficiently neutralized elevated TFPI, raising TG to levels observed for inhibition of physiologic TFPI concentrations. Non-covalent binding to albumin substantially increased the half-life to ~4 h with ~50% s.c. bioavailability in mice. The ex vivo procoagulant activity determined by TG correlated well with HL-FP plasma concentrations. In a repeated dose study, the HL-FP was well tolerated and did not accumulate TFPI, indicating that HL-FP did not interfere with TFPI clearance. HL-FP significantly reduced bleeding in the hemophilia mouse tail cut model at a dose as low as 40 nmol/kg. In marmoset monkeys, HL-FP efficiently improved ex vivo plasma TG, even at low peptide plasma concentrations (25-55nM).

Conclusion:

To summarize, we developed a TFPI inhibitor composed of two TFPI antagonistic peptides that completely inhibits TFPI. Introduction of an entity non-covalently binding to albumin provides intermediate half-life extension and s.c. bioavailability. This HL-FP improved coagulation and hemostasis in animal models of hemophilia, did not interfere with TFPI clearance receptor interactions, and efficiently neutralized elevated TFPI. Our HL-FP appears to be useful in preventing bleeding in hemophilia, and provides a FVIII and FIX independent approach for non-i.v. treatment.

Objective:

To assess the pharmacokinetics (PK), safety, and efficacy of the first high- purity, plasma-derived factor X concentrate (pdFX) for on-demand treatment of bleeding episodes in a prospective, open-label, multicenter, nonrandomized phase 3 study in subjects with hereditary moderate or severe factor X (FX) deficiency (basal plasma FX activity <5 IU/dL).

Methods:

Included subjects were aged ≥12 years who required treatment with replacement therapy for ≥1 spontaneous or menorrhagic bleed in the past 12 months. Subjects received 25 IU/kg of pdFX on-demand for specific bleeds or as preventative use for 6 months to 2 years. PK was assessed following a single dose at baseline and after ≥6 months. Each bleed was categorized as major or minor, and subjects assessed efficacy for each bleed as “excellent,” “good,” “poor,” or “unassessable”; hospital- treated bleeds were also assessed by investigators. At study end, each investigator assessed the overall efficacy of pdFX. Safety assessments were adverse events (AEs), inhibitor development, viral seroconversions, and changes in laboratory parameters.

Summary:

The study enrolled 16 subjects (aged 12-58 years [mean 27.1 years], 62.5% female) with moderate (n=2) and severe (n=14) FX deficiency. PK parameters did not differ between baseline and repeat assessment visits, with overall mean (median, interquartile range [IQR]) incremental recovery of 2.00 (2.12, 1.79-2.37) IU/dL per IU/kg and half-life of 29.4 (28.6, 25.8-33.1) hours. In total, 468 pdFX infusions were administered; 187 bleeds treated with pdFX were analyzed for efficacy (98 major and 88 minor), of which 155 (82.9%) were treated with one pdFX infusion. A mean (standard deviation) of 1.2 (0.5) infusions per bleed were administered, with a median (IQR) dose of 25.0 (24.4-26.7) IU/kg. Efficacy of pdFX was rated as excellent in 90.9% of bleeds, good in 7.5%, and poor in 1.1%. For the 15 subjects who completed the study, investigators rated overall pdFX efficacy as excellent in 12 (80%) and good in 3 subjects (20%). Six mild/moderate AEs were observed, no serious AEs were considered by investigators to be possibly related to study drug, and no hypersensitivity reactions or clinically significant trends in any laboratory safety parameters were observed.

Conclusions:

In this study, pdFX was safe and efficacious in on-demand treatment of bleeds and short-term preventative therapy in subjects with moderate or severe FX deficiency at a nominal dose of 25 IU/kg. PK results supported these observed hemostatic effects.

Objective:

Patient satisfaction with healthcare services enhances patient experience, improves outcomes, and is increasingly mandated by public and private payers. While many US Hemophilia Treatment Centers (HTC) periodically assess patient satisfaction, the lack of a uniform survey hampered national measurement. To remedy this knowledge gap, the US HTC Network implemented a national patient satisfaction survey in 2015.

Methods:

A Regional HTC Coordinator workgroup devised, piloted, and finalized a two-page survey for self-administration online, at clinic, or at home, in English or Spanish and mailed to households. Survey content and format were based on national health surveys to enhance comparability and scientific robustness, informed by legacy regional HTC surveys. Questions assessed patient demographics; satisfaction with services, team members, and care processes; and Healthy People 2020 adolescent transition objectives. Surveys included open ended questions to obtain qualitative data. Respondents were anonymous but identified with their respective HTCs. Participation was voluntary. Persons with genetic bleeding disorders who had HTC contact in 2014 were eligible. During February 2015, 124/130 HTCs sent surveys to 27,563 households. Parents completed surveys for children under age 15. No reminders were sent. Data were entered and analyzed at a central site and aggregated at national, regional and HTC levels.

Results:

Over 4800 households (17.4%) returned surveys by April 30, 2015. National analyses on 4332 surveys reveal that 96.6% were ‘always’ or ‘usually’ satisfied with HTC care. Over 80% were ‘always’ satisfied with the core HTC team members. Three quarters of 12-17 year olds were ‘always’ satisfied with HTC encouragement regarding becoming more independent, and how the HTC discussed caring for a bleeding disorder upon reaching adulthood. Eighty– 90% were ‘always’ or ‘usually’ satisfied with care processes, e.g. shared decision making, care coordination, ease of obtaining timely information and services, and being treated respectfully. Insurance and language were ‘always’ a problem for 20%. 29.0% of respondents were female and 10.3% Hispanic. 83.4% were Caucasian, 5.8 African- American, 3.1% Asian/Pacific Islander or Native Hawaiian, 4.3% Multiple races, and 4% Other. Over half had severe or moderate FVIII or FIX deficiency or VWD Type 3. Ages ranged from newborns to 96 years: 38% under 18, 20% age 18 – 34, and 42% over age 35.

Conclusions:

Implementing a National Patient Satisfaction Survey for the US HTCN is feasible, and provides valuable information. Satisfaction with HTC services is high, but insurance and language ‘always’ pose problems for one fifth. Further analyses will examine regional differences.

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.

Objective:

The ongoing rFVIIIFc extension study, ASPIRE (clinicaltrials.gov #NCT01454739), evaluates the long-term safety and efficacy of rFVIIIFc in adults, adolescents, and children with severe hemophilia A. Here we report interim outcomes for United States (US) subjects in ASPIRE.

Methods:

Eligible subjects could enroll in ASPIRE upon completing A-LONG or Kids A-LONG. There were 4 treatment groups: individualized prophylaxis (25-65 IU/kg every 3-5 days, or 20-65 IU/kg on D1, 40-65 IU/kg on D4 if twice weekly); weekly prophylaxis (65 IU/kg every 7 days); modified prophylaxis (to further personalize and optimize treatment when needed); or episodic treatment. Subjects could change treatment groups at any time. Subjects <12 yrs participated only in individualized and modified prophylaxis groups. Primary endpoint: development of inhibitors. Secondary outcomes included annualized bleeding rate (ABR) and rFVIIIFc exposure days (EDs).

Summary:

Sixty subjects (49 from A-LONG; 11 from Kids A-LONG) enrolled. As of the interim data cut (6 Jan 2014), the median time on ASPIRE was 80.37 (A-LONG) and 15.94 (Kids A-LONG) wks; 82% (A-LONG) and 27% (Kids A-LONG) of subjects had ≥100 cumulative rFVIIIFc EDs. 7/49 A-LONG subjects changed treatment groups upon enrollment into or during ASPIRE; 2 Kids A-LONG subjects switched from individualized to modified prophylaxis upon enrollment into ASPIRE. Median ABRs were low with rFVIIIFc prophylaxis (Table). Overall, most subjects treated prophylactically during the parent study did not experience changes to their total weekly prophylactic dose or dosing interval during ASPIRE. For subjects who enrolled from A-LONG and Kids A-LONG, 94% and 100% of all bleeding episodes during ASPIRE, respectively, were controlled with 1 infusion. In the overall study population, no inhibitors were observed during ASPIRE; adverse events were typical of the general adult and pediatric hemophilia A populations.

Conclusion:

Interim data from US subjects in ASPIRE are consistent with those of the phase 3 parent studies and the overall ASPIRE interim analysis. Results from ASPIRE confirm the longer-term safety of rFVIIIFc and the maintenance of a low ABR with extended interval prophylactic dosing in individuals with severe hemophilia A.

Objective:

Personalizing treatment to a patient’s lifestyle and promoting overall health and wellness in persons with hemophilia (PWH) is essential to optimizing outcomes. There is limited evidence that correlates how activity and infusions impact bleeding episodes and further data on this relationship is needed. The research objective of SPACE is to prospectively explore the association between activity level, timing of infusion, and occurrence of a bleeding episode in PWH using novel technology.

Methods:

This six-month prospective, observational study includes PWH A or B in the United States currently receiving ADVATE or RIXUBIS between the ages of 13 and 65 years. Enrolled PWH use a smartphone eDiary application to log information on activities, infusions, and bleeding episodes. As an additional measurement of activity, enrollees are given a FitBit, a consumer-based activity tracker that measures steps taken and calories burned. Activity types are assessed based on their level of perceived risk for collision, according to the NHF “Playing It Safe” brochure. We report here current study status and descriptive analysis of baseline data.

Results:

The interim analysis included 15 patients with a median age of 19 (Range: 13 to 47). At baseline, 87% of patients were on prophylaxis and 13% treated on-demand treatment. Fifty-three percent of patients had 0 target joints at baseline. Eighty-seven percent of patients indicated that they had discussed activity participation with their physician. Sixty-seven percent of patients considered themselves ‘very satisfied’ or ‘satisfied’ with their level of activity. Data collected from the FitBit indicated that patients in SPACE walked on average 7,367 (SD: 3250) steps per day and burned 979 (SD: 398) calories from their activity. For patients on prophylaxis, the mean number of days per week doing mild, moderate and strenuous activity were 3.57, 2.64, and 1.5 respectively. Of the data reported on bleeding episodes, 40% of patients reported no bleeds at the time of the interim analysis. Forty percent of patients did not report having a bleed at the time of the interim analysis. Of all bleeds reported, 34% were associated with physical activity.

Conclusions:

Current data from SPACE demonstrates that subjects are active and participating in various activities. Continued data will provide better understanding of the types of activities and infusion schedules that may be associated with risk as well as protective effects on bleeding episodes by infusing prior to activity. A personalized approach to treatment based on physical activity levels may minimize bleeding risk in PWH.

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.