Clinical Research

Objective:

My Life, Our Future (MLOF) is a national project directed by a partnership formed to: 1) conduct wide-scale genetic testing of the U.S. hemophilia community, thereby increasing the rate of patient testing above the currently estimated 20% and allowing carrier detection; 2) establish a repository of associated samples and data to support scientific discovery and treatment advances including informing inhibitor risk and disease severity.

Methods:

A multi-sector partnership was formed to make hemophilia genotype analysis available to the U.S. community. The National Hemophilia Foundation (NHF) educates consumers and supports recruitment. The American Thrombosis and Hemostasis Network (ATHN) provides hemophilia treatment center (HTC) provider education, a secure infrastructure for data collection, and point of access for research proposals. HTCs enroll patients, obtain samples and provide clinical results to patients. Puget Sound Blood Center (PSBC) serves as the central genotyping laboratory and sample repository. Biogen Idec provides scientific collaboration and initiative support.

A pilot study involving 11 HTCs was successfully completed in 2013, and patients continue to be enrolled at those and additional sites. Genotyping is performed through an initial screen by Next Generation sequencing of extracted DNA using a molecular inversion probe-based capture strategy. FVIII and FIX mutations are confirmed in the CLIA-certified PSBC hemophilia genomics laboratory using a separate DNA sample. A clinical laboratory report is returned to the HTC and results transmitted into the ATHN Clinical Manager database accessible only to the patient’s HTC providers. For patients who give informed consent, coded data and samples are stored in a research repository, which can be linked to coded clinical data from the ATHNdataset for future research applications. NHF’s national and local chapter educational programs increased awareness and educated families about MLOF.

Summary:

As of June 13, 2014, 25 HTCs were enrolling patients and 865 patients were enrolled. Of those patients, 168 opted for clinical genotyping only and 697 also gave informed consent to have data and samples entered into the research repository. Mutation analysis has been completed in 707 patients, including 354, 151 and 202 with severe, moderate and mild haemophilia respectively. By comparison to available hemophilia A and B databases, 61 novel mutations have been identified in 68 patients. Lessons learned from the initial stages of the program’s rollout helped us to improve our approach to recruitment and education about the importance of genotyping and research in hemophilia.

Conclusions:

My Life, Our Future is a novel partnership to address unmet needs for hemophilia genotyping services and research. Expanding participation in the program will increase clinical genotyping for patients with hemophilia, increase knowledge of FVIII and FIX mutations present in the U.S. hemophilia population, and provide a robust research repository for future scientific discovery.

Objective:

To investigate the prevalence of comorbidities among adults with hemophilia in the Hemophilia Utilization Group Studies (HUGS)

Methods:

Standardized interviews were conducted for two prospective cohort studies HUGS- Va (hemophilia A) and HUGS-Vb (hemophilia B) at six and ten US Hemophilia Treatment Centers, respectively, between 2005 and 2011. Clinical records were reviewed. Information captured included self-reported comorbidities, sociodemographics, treatment patterns and other clinical characteristics. Overweight and obesity were defined as body mass index (BMI) 25-29 kg/m2 and BMI ≥30 kg/m2, respectively. The prevalence of comorbidities was calculated. The association of comorbidities with hemophilic severity, age and type of hemophilia were assessed using appropriate statistical methods for categorical or continuous variables.

Summary:

The analyses included a total of 213 adults (HUGS-Va: n=147, HUGS-Vb: n=66) aged 20 to 65 years (mean±standard deviation: 36.6±12.9). Approximately, 64% of hemophilia A and 44% of hemophilia B individuals had severe hemophilia. The five most prevalent self-reported comorbidities were liver disease/hepatitis (66%), overweight/obesity (60%), arthritis (51%), human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) (24%), and hypertension (23%). The individuals in the hemophilia A sample were more likely to report liver disease/hepatitis (71% vs. 53%) and HIV/AIDS (30% vs. 9%) than those in the hemophilia B sample (all p<0.009). The prevalence of overweight/obesity (59% vs. 60%), arthritis (55% vs. 42%), and hypertension (22% vs. 24%) were not significantly different between hemophilia A and hemophilia B samples (all p>0.05). Prevalence of comorbidities was greater among individuals with severe than mild/moderate hemophilia for most conditions: liver disease/hepatitis (79% vs. 48%), arthritis (61% vs. 38%), HIV/AIDS (37% vs. 6%), and stroke/brain haemorrhage (11% vs. 2%) (all p<0.02), the exception being overweight/obesity (52% vs. 70%, p=0.007). The individuals with hemophilia A had a significantly greater number of comorbidities than those with hemophilia B (mean±standard deviation: 2.5±1.9 vs. 1.0±1.1; p<0.0001); 85% of the hemophilia A sample reported having more than one comorbidity compared to 61% of those with hemophilia B (p<0.0001). The number of comorbidities increased significantly with advancing age (p<0.0001).

Conclusions:

As one of the largest prospective studies of persons with hemophilia, the HUGS sample is representative of the US hemophilia A and B populations. Except for overweight/obesity, the most prevalent comorbidities reported in HUGS related to their hemophilia complications, and were significantly associated with hemophilic severity. As the life expectancy of persons with hemophilia increases, the need for studies focusing on the health care needs of individuals with hemophilia and comorbid conditions will increase.

Objectives:

PAIR is an ongoing, global, non-interventional, post-authorization safety surveillance designed to collect information on ADVATE safety and effectiveness in immune tolerance induction (ITI) therapy in routine practice.

Methods:

From July, 2007 to April, 2011, individuals with hemophilia A and inhibitors were enrolled in 10 countries. The primary objective is to assess the incidence of adverse events (AEs) related to ADVATE during ITI therapy. Secondary objectives are incidence of central venous access device (CVAD)-related complications, and success rates of ITI therapy. Maximum observation period for ITI is 33 months plus a 12 month follow-up.

Summary:

As of April 1, 2014, 36 of 44 subjects (81.8%) completed ITI therapy, 28 (63.6%) of which completed the 12 month follow-up. Six subjects withdrew prior to completing ITI therapy. Dosing regimens were: ≥200 IU/kg/day (n=4, 9.1%); 131-199 IU/kg/day (n=3, 6.8%); 90-130 IU/kg/day (n=26, 59.1%) and <90 IU/kg/day (n= 11, 25.0%). During the observation period, 337 bleeding episodes and 273 AEs were reported for all enrolled subjects (N=44). Of these AEs, 52 (19.0%) were serious and none were considered related, while 15 (5.5%) were non-serious and related. CVAD complications were common; 32 subjects experienced one or more CVAD-related AE such as hospitalization, line infection, line malfunction, line removal, and pain following port-a-cath bleed. Of the subjects that completed ITI, 21 achieved negative titer levels, two experienced a high to low titer conversion, seven failed to achieve negative titer, and six were un-assessable per protocol. After 18 months therapy, Kaplan Meier estimates of success for achievement of first negative titer was 65.4% (asymptotic 95% CI: 48.7-81.5%, n=36) for the completer group. Rates were higher for the per protocol analysis set (72.2%, CI: 54.6-87.5%, n=30), and slightly lower for the full analysis set (63.5%, CI: 48.0- 78.7%, n=44).

Conclusions:

These interim outcome results are consistent with previous reports from PAIR and other published data on ADVATE in ITI. No new ADVATE related safety issues have been seen. The last two participating subjects will end observation within the next year.

Objective:

Joint status and health-related quality of life (HRQoL) were assessed as part of the 3-year SPINART study, which compared routine prophylaxis versus on-demand treatment in adults with severe hemophilia A. We report SPINART joint outcome results obtained using the Colorado Adult Joint Assessment Scale (CAJAS) and HRQoL data from Haemo-QoL-A assessments.

Methods:

The open-label, randomized, controlled, parallel-group, multinational SPINART study enrolled male patients aged 12–50 years with severe hemophilia A who had ≥150 exposure days to 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 of 5 IU/kg permitted once per year). CAJAS assessments were performed at baseline and years 1, 2, and 3. The physiotherapists performing CAJAS assessments were blinded to patient treatment assignment, bleeding history, and previous joint assessment data. Change from baseline to year 3 in CAJAS total score was prespecified as the second of 2 secondary endpoints; higher CAJAS scores indicate worse joint function. Haemo-QoL-A was completed at baseline, month 6, and years 1, 2, and 3; higher Haemo- QoL-A scores indicate better HRQoL. Between-group comparison was made using constrained longitudinal data analysis. Data are presented for the intent-to-treat (ITT) population.

Summary:

84 patients (42 prophylaxis, 42 on demand) comprised the ITT population; Haemo-QoL-A data were available for 41 and 42 patients, respectively. For CAJAS total score, least squares (LS) mean change from baseline to year 3 was 0.63 for on demand and –0.31 for prophylaxis (LS mean difference, –0.94; 95% CI, –1.61 to –0.26; P=0.0072). LS mean change in CAJAS total score for the on-demand and prophylaxis groups was 0.19 and –0.46 at year 1 and 0.34 and –0.57 at year 2, respectively. For Haemo-QoL-A total score, LS mean change from baseline to year 3 was –6.00 for on demand and 3.98 for prophylaxis (LS mean difference, 9.98; 95% CI, 3.42 to 16.54).

Conclusions:

In adults with severe hemophilia A, joint function and HRQoL improved continuously over 3 years with prophylaxis compared with on-demand use.

Objectives:

Factor VIII (FVIII) prophylaxis regimens for severe hemophilia A that allow more flexible dosing than the standard 3-times-weekly regimen while maintaining efficacy may improve adherence. This analysis compared the clinical efficacy of once- or twice-weekly versus ≥3-times-weekly prophylaxis dosing of Bayer’s sucrose-formulated recombinant FVIII (rFVIII-FS) in patients with severe hemophilia A.

Methods:

Data from 3 postmarketing studies were pooled. Patients with severe hemophilia A and no history of inhibitors who were receiving ≥1 prophylaxis infusion/wk of rFVIII-FS for ≥80% of a prophylaxis observation period (≥5 months) were included. Patients were categorized based on age (<18 and ≥18 years) and physician-assigned treatment regimens of 1–2 prophylaxis injections/wk (n=63) or ≥3 prophylaxis injections/wk (n=76). Descriptive statistics were determined for annualized bleeding rates (ABRs) by dosing group and age subgroups.

Summary:

Median (quartile 1; quartile 3) ABR for all bleeds was 2.0 (0; 4.0) in the group receiving 1–2 prophylaxis injections/wk and 3.9 (1.5; 9.3) in the group with ≥3 prophylaxis injections/wk. Similarly, median ABRs for joint, spontaneous, and trauma-related bleeds were numerically lower in the group receiving 1–2 prophylaxis injections/wk. The trend toward lower ABRs in the group with 1–2 prophylaxis injections/wk was observed in both age subgroups, although ABRs were somewhat higher in patients ≥18 vs <18 years. Zero annualized bleeds were reported by 30% and 7% of patients in the groups with 1–2 prophylaxis injections/wk and ≥3 prophylaxis injections/wk, respectively.

Conclusions:

These data demonstrate that bleeding control can be achieved in some patients with severe hemophilia A using a <3-times-weekly prophylaxis dosing regimen and that physicians’ judgment based on bleeding phenotype can successfully direct the frequency of prophylactic dosing.

Objective:

A previous retrospective study of the MarketScan® claims database reported increased prevalence and earlier onset of cardiovascular (CV) comorbidities in patients with hemophilia A compared with patients without hemophilia. Our study was designed to confirm these findings in a second population of male patients with hemophilia A in the United States.

Methods:

Male patients with hemophilia A and continuous insurance coverage were identified by ICD-9-CM code 286.0 using the PharMetrics LifeLink claims database (IMS Health) of patient records from January 1, 2008 to December 31, 2011. Patients with hemophilia A were matched 1:3 with controls for sex, age, plan type, geographic region, and eligibility months in the study period. The prevalence of CV comorbidities (identified by ICD-9- CM codes) was compared between matched cohorts. Statistical significance was calculated using Fisher’s exact test.

Summary:

Overall, 1050 patients were included in the hemophilia A cohort and 3150 in the control cohort (Table). Prevalence of hemorrhagic stroke, ischemic stroke, coronary artery disease, myocardial infarction, hypertension, hyperlipidemia, arterial thrombosis, and venous thrombosis was significantly higher in the hemophilia A cohort (all P≤0.016). Increased prevalence of CV comorbidities was consistent across most age groups, and patients with hemophilia A experienced CV comorbidities at an earlier age than those without hemophilia.

Table: Cardiovascular comorbidities in patients with hemophilia A

Conclusions:

This second retrospective study of claims databases confirmed an increased prevalence and earlier onset of CV comorbidities in patients with hemophilia A. These findings support increased screening in patients with hemophilia for CV comorbidities at an earlier age than recommended for the general population.

Objective:

To analyse real-world FIX dosing and treatment interval patterns. A secondary objective was to compare the observed dosing patterns with the dosing regimens for FIX products evaluated in clinical studies.

Methods:

A retrospective analysis was conducted using aggregate Specialty Pharmacy Provider (SPP) records from 2012 through Q12014. SPP data included 63 different attributes for each prescription, including trade name, NDC, quantity shipped, prescribed infusion dose, days supplied, and dose frequency. Patients were considered eligible for the analysis if they received a shipment of any FIX product. Patients were excluded from the analysis if they were being treated episodically, for immune tolerance induction, or their pharmacy records did not specify a prescribed infusion dose. Patients with missing or extremely abnormal weights were also excluded. The patient’s weekly consumption was calculated for each shipment record by multiplying the prescribed infusion dose by the dose frequency and dividing the product by the patient’s weight, resulting in the patient’s average weekly prescribed dose (IU/kg/week). Patients were also categorized according to dosing interval.

Summary:

The analysis included 118 hemophilia B patients with a median age of 20 (range: 2-63) and median weight of 55.4 kg (range: 9.5-129 kg). Pharmacy dispensing records represented 78 distinct prescribers across 29 states. FIX therapies evaluated included Benefix®, Alphanine®, Mononine®, and Rixubis®. The average weekly consumption across all therapies was 139.0 IU/kg/week (95% CI, 128.7-150.3). Dosing frequency ranged from every other day to once weekly. Twice weekly was the most common dosing interval, representing 56.8% of patient records. According to clinical trial data and FDA labelled dosing for FIX therapies, lower weekly consumption may be expected. For BeneFIX the mean weekly consumption was 80.6 IU/kg, 40.3 IU/kg administered twice-weekly. For Rixubis the mean weekly consumption was 88.9 IU/kg, 49.4 IU/kg administered 1.8 times/week and a US dosing recommendation of 40-60 IU/kg dosed twice-weekly. Two prophylactic regimens have been evaluated for AlprolixTM. In the last 3 months of B-LONG, in the weekly prophylaxis arm, the overall median dose on study was 40.5 IU/kg. The individualized interval prophylaxis arm had a median weekly dose of 50.0 IU/kg, 100 IU/kg administered every 14 days. No real world dosing is available for Alprolix due to its recent approval.

Conclusions:

Dosing regimens evaluated in the real world for conventional FIX products indicate greater consumption than reported in clinical trials. This may result in unpredictability for payers who are responsible for healthcare budgets.

Objective:

To analyse real world FVIII dosing and treatment interval patterns in patients with haemophilia A. A secondary objective was to compare the observed dosing patterns with the dosing regimens for rFVIII and rFVIIIFc evaluated in clinical studies.

Methods:

A retrospective analysis was conducted using aggregate Specialty Pharmacy Provider (SPP) records from Nov 2013 through Mar 2014. SPP data included 63 different attributes for each prescription, including trade name, National Drug Code (NDC), drug quantity shipped, prescribed infusion dose, days supplied, and dose frequency. Patients were considered eligible for the analysis if they received a shipment of any FVIII product. Patients were excluded from the analysis if they were being treated episodically, for immune tolerance induction, or their pharmacy records did not specify a prescribed infusion dose. Patients with missing or extremely abnormal weights were also excluded. The patient’s weekly consumption was calculated for each shipment record by multiplying the prescribed infusion dose by the dose frequency and dividing the product by the patient’s weight, resulting in the patient’s average weekly prescribed dose (IU/kg/week). Patients were also categorized according to their dosing interval.

Summary:

The analysis included 520 hemophilia A patients with a median age of 18 (range: 1-77) and median weight of 63.5 kg (range: 8-161 kg). Pharmacy dispensing records represented 227 distinct prescribers across 43 states. FVIII therapies evaluated included Advate®, Recombinate®, Helixate® FS, Kogenate®, Hemofil and Xyntha®. The average weekly consumption across all therapies was 108.0 IU/kg/week (95% CI, 104.6-111.5). Dosing frequency ranged from once-daily to once-weekly with three times/week and every other day as the most common dosing intervals, representing 81.3% of patient records. For patients infusing thrice-weekly, the average infusion dose was 35.1 IU/Kg. Only 15.4% of the population was infusing ≤ two times per week. Clinical trials for Advate report weekly consumption of 110.3 IU/kg (31.4 IU/kg administered QOD). Two prophylactic regimens were evaluated for rFVIIIFc in A-LONG. In the last 3 months of this study, the median weekly consumption was 77.7 IU/kg for the individualized prophylaxis and the median weekly dose of 65.5 IU/kg for the weekly prophylaxis regimen.

Conclusions:

Pharmacy dispensing records support the clinical trial dosing intervals of rFVIII products currently requiring every other day or thrice-weekly dosing; however, real-world dosing (IU/kg/week) may be greater. This may result in unpredictability for payers who are responsible for healthcare budgets.

Objective:

Hemophilia A and B are X-linked bleeding disorders caused by the deficiency of clotting factor VIII or IX, respectively. Mutations in the F8 gene can result in hemophilia A while mutations in the F9 gene can lead to hemophilia B. The objective of this analysis was to evaluate the F8 and F9 genotypes of subjects screened for enrollment in the phase III clinical trials of rFVIIIFc in hemophilia A (A-LONG) and of rFIXFc in hemophilia B (B-LONG).

Methods:

The F8 and F9 genotypes of 170 subjects with severe hemophilia A and 114 subjects with severe hemophilia B, respectively, were compared with several genotype databases (HAMSTeRS, [Hemophilia A Mutation, Structure, Test and Resource Site], CHAMP [CDC Hemophilia A Mutation Project], and King’s College London Hemophilia B database), as well as with the NCBI human F8 and F9 sequences.

Summary:

Among 170 subjects with hemophilia A, inversions in intron 22 (Int22inv) were identified in 36%, nucleotide substitutions in 39%, frameshift mutations in 21%, Int1inv in 3%, and an in-frame duplication in 1 subject. Previously unreported mutations (frameshift, missense, nonsense, and splice site changes) were found in 24 subjects, with 2 unrelated subjects having the same mutation, resulting in 23 novel mutations being identified. Among 114 subjects with hemophilia B, the majority (86%) had some form of substitution mutation (missense, nonsense, splice-site change), consistent with previous reports. Thirteen previously unreported mutations were identified, including 10 substitutions (7 missense, 2 nonsense and 1 splice-site change), 1 deletion, and 2 insertions.

Conclusions:

In this analysis, 23 previously unreported mutations in the F8 gene of subjects with severe hemophilia A and 13 in the F9 gene of subjects with severe hemophilia B were identified. Identifying mutations allows for prenatal diagnosis and identification of carrier status. These results will lead to further enhancement of databases for hemophilia A and B mutations and may assist in clarifying the relationship between genotype, phenotype, and pathophysiology in individuals with hemophilia.

Objectives:

This prospective clinical trial was conducted to assess the safety, hemostatic efficacy and pharmacokinetic (PK) profile of a recently developed recombinant factor IX (BAX326*) in pediatric previously-treated patients (PTPs) with severe or moderately severe hemophilia B.

Methods:

PTPs aged <12 years with severe (FIX level < 1%) or moderately severe (FIX level ≤ 2%) hemophilia B were eligible for enrollment. BAX326 was administered as prophylaxis twice a week over 6-months, and on demand for treatment of bleeds. Efficacy was evaluated by treatment response rating (excellent, good, fair, none) and annualized bleeding rate (ABR). PK assessments after one 75 ± 5 IU/kg infusion of BAX326 were assessed using a non-linear mixed model (population PK) approach. IR was measured as part of the PK evaluation 30 minutes after the initial PK infusion and at 5, 13 and 26 weeks after the initial infusion.

Summary:

Nine subjects (39.1%) had no bleeds during the study. A total of 26 bleeds occurred (mean ABR 2.7 ±3.14, median 2.0), of which 2 were spontaneous. Fewer bleeds occurred in joints than in non-joint sites (19 non joint vs. 7 joint bleeds). Hemostatic efficacy was excellent or good in >96% of bleeds, and the majority (88.5%) resolved after 1-2 infusions. The median IR (IU/dl)/(IU/kg) at the initial PK assessment was 0.685 (range: 0.31- 1.00). As expected, a higher IR was observed in association with increased patient age; IR was slightly lower in subjects < 6 years (median 0.591; range: 0.31-0.75), than in subjects aged 6 to <12 years (median 0.714; range: 0.51-1.00). IR was consistent over time. There were no adverse reactions, no thrombotic events and no hypersensitivity reactions. None of the subjects treated (N=23) developed inhibitory or specific binding antibodies against FIX.

Conclusions:

BAX326 is efficacious and safe as prophylactic treatment as well as for bleed control in pediatric hemophilia B patients.

*Licensed in the USA and Australia (Rixubis®; Baxter Healthcare Corp., USA).

Objective:

Kids A-LONG was a global, multi-center, open-label phase 3 study that evaluated the safety, efficacy, and pharmacokinetics (PK) of rFVIIIFc in previously treated patients aged <12 years with severe hemophilia A (<1 IU/dL FVIII activity).

Methods:

All participants had ≥50 prior exposure days (EDs) to FVIII, and no history of FVIII inhibitors. Participants were to be treated with twice-weekly rFVIIIFc prophylactic infusions (Day 1, 25 IU/kg; Day 4, 50 IU/kg), with adjustments to dose (≤80 IU/kg) and dosing interval (≥ every 2 days) as needed by the investigator. A subset of participants (<6 years of age, n=25; 6 to <12 years of age, n=35) underwent sequential PK evaluations with FVIII (50 IU/kg), followed by rFVIIIFc (50 IU/kg). The primary endpoint was development of inhibitors (neutralizing antibodies). Secondary endpoints included PK, annualized bleeding rate (ABR) and number of infusions required to control a bleed.

Summary:

The study enrolled 71 participants from 23 centers (<6 years, n=36; 6 to <12 years, n=35); 94.4% of participants completed the study. Prestudy, 89% of participants received FVIII prophylaxis, the majority (74.6%) of whom required ≥3 infusions per week. The median time on study for treated subjects (n=69) was 26 weeks; 61 participants had ≥50 EDs to rFVIIIFc. No participant developed inhibitors to rFVIIIFc. Overall, the pattern of adverse events reported on rFVIIIFc treatment was typical of the population studied; no serious adverse events were assessed as treatment-related by the investigator. The terminal half-life (arithmetic mean [95% CI]) in participants aged <6 years and 6 to <12 years was 12.67 (11.23, 14.11) hours and 14.88 (11.98, 17.77) hours, respectively. The relative increase in half-life over prior FVIII therapy was ~1.5-fold, consistent with the increase in half-life seen in the A-LONG study of adults and adolescents. Median (IQR) ABR was 1.96 (0.00, 3.96) overall, and 0.00 (0.00, 0.00) for spontaneous bleeds. Median total weekly dose and dosing interval were 88.1 IU/kg and 3.5 days, respectively. 83.7% and 93.0% of bleeding episodes were controlled with 1 or 1–2 infusions, respectively (median dose per bleeding episode: 54.9 IU/kg).

Conclusions:

rFVIIIFc was well-tolerated, efficacious for prophylaxis and treatment of bleeding, and resulted in low bleeding rates. The extended half-life compared to FVIII and the safety profile were generally consistent with that observed in the Phase 3 study in adults and adolescents. rFVIIIFc offers the potential of prolonged dosing intervals and fewer infusions for children with severe hemophilia A.

Objective:

Describe the role of H. pylori as a cause of chronic iron deficiency in children with congenital bleeding disorders.

Methods:

As part of their routine comprehensive care children at our haemophilia treatment center have a CBC done. Over the past year 4 children who underwent diagnostic workup for microcytic anemia were found to have iron deficiency associated with H. pylori infection. We describe the clinical findings in these children and their outcomes after appropriate therapy.

Summary:

From March 2012 to March 2013, 4 children were identified with iron deficiency anemia due to H. pylori. None of the 4 patients gave a history of excessive blood loss and none had GI symptoms such as weight loss, abdominal pain, vomiting or diarrhea. Clinical and laboratory findings at presentation are summarized below. No patients had thrombocytopenia.

Only one patient had positive occult blood in stool (RG) and underwent endoscopy. Diagnosis of H. pylori was made on gastric biopsy. RG also had 4 weeks of IV iron sucrose therapy. All patients were seen by gastroenterology and successfully treated with triple therapy consisting of amoxicillin, Biaxin, and omeprazole. RG had a recurrence and was retreated with quadruple therapy consisting of amoxicillin, metronidazole, omeprazole, and bismuth subsalicylate. All 3 patients with FVIII deficiency were also on secondary prohylaxis.

Conclusions:

H. pylori is a common cause of gastritis and often presents with upper gastrointestinal symptoms. It is also associated with idiopathic thrombocytopenic purpura. However, in children with congenital bleeding disorders, it may present with few symptoms and an incidental finding of iron deficiency anemia. We suggest that children with bleeding disorders should be screened for H. pylori as a cause of iron deficiency.

Objective:

Treatment of bleeding disorders consists of factor replacement on-demand in response to acute bleeding or prophylactically to prevent bleeding. Venous access is a critical aspect of hemophilia care. Placement of Arteriovenous Fistulae (AVF) has previously been reported (Urgo, J et al 2008). We are reporting the long-term use of the AVF and an additional 3 patients.

Methods:

All patients who received an AVF had their records reviewed and they were evaluated for their AVF usage patterns, perceived appearance, longevity of use, and overall satisfaction. The insertion protocol has been previously reported. Each patient’s AVF was assessed routinely at each clinic visit.

Summary:

There were 17 AVF insertions in 16 patients: two von Willebrand disease, 12 Hemophilia A (3 inhibitor), and 3 Hemophilia B (1 inhibitor). Mean follow-up was 5 years (1- 13 years). 15 patients had excellent results with adequate flow and patients/caregivers were able to easily access the AVF for treatment. 1 patient, who underwent 2 procedures, had a poor surgical result with inadequate blood flow to the AVF. No patients had bleeding complications from AVF creation. No patients have an AVF related infection over 5 years. Patients have not experienced any difficulty accessing the AVF for administration of factor. Four patients have reported dissatisfaction with the appearance of the AVF. All report embarrassment over appearance, self-consciousness, wear clothing to hide the AVF, and limited participation in activities where others may question the AVF. All report the AVF works well, no issues with access, and increased confidence in self-infusion. These patients all had enlarged AVF with increased blood flow as demonstrated by fistulogram. 1 patient had revision with banding that had excellent results as well as improved appearance and continued excellent intravenous (IV) access. Two more patients are scheduled for revision. The 4th patient had removal of the AVF due to increased availability of peripheral access.

Conclusion:

AVF continues to be a viable option in patients who do not have IV access and have had repeated complications with other methods of IV access. The complication rate for insertion is 3/17 (18%). Excellent IV access was achieved in 15/16 (94%) patients. Overall satisfaction is good with 9/13 (69%) patients reporting excellent function, ease of access, and satisfaction of the cosmetic appearance of the AVF.