Research Studies

Objective:

Our hypothesis was that females with FVIII deficiency enrolled in the Universal Data Collection (UDC) project have reduced mean joint range of motion (ROM) compared to historic controls from the Normal Joint Study.

Methods:

We employed a cross-sectional study design utilizing the UDC dataset. The overall joint ROM was the sum of the ROM measurements of the five joints for the females with FVIII deficiency and the normal females. Results were displayed as mean overall joint ROM by age group and factor deficiency with differences between groups assessed using the Wilcoxon- rank-sum test.

Summary:

A total of 513 females were identified with FVIII deficiency; 144 females were removed because of a lack of verification for factor deficiency, one female lacking recorded range of motion data. Of the 368 females, the median age was 26 years (range 0-78). Final analysis was performed on 247 females with FVIII deficiency between the ages of 2-69 (excluding very obese females) for comparison to the control group. The mean overall joint ROM worsened with decreasing FVIII activity and in most cases was lower than that of the controls (see table 1).

Conclusions:

Females with FVIII deficiency enrolled in the UDC project had reduced mean ROM compared to normal females without deficiency.

Table 1. Mean overall joint ROM in females with FVIII deficiency by age and factor activity.

Objective:

Hemophilia A patients in the US benefit from safe, efficacious, and reliable factor VIII (FVIII) treatments. Novo Nordisk (Bagsværd, Denmark) has developed turoctocog alfa, the first new recombinant (r) FVIII in over a decade.

Methods & Summary:

Turoctocog alfa is a state-of-the-art, B-domain truncated rFVIII product manufactured without the use of human or animal proteins. Truncation of the B- domain was chosen as this domain does not have any function with respect to FVIII clotting activity. Once activated by thrombin, the turoctocog alfa truncated B-domain is cleaved, leaving an active FVIII molecule similar to the endogenous form. Turoctocog alfa is produced in Chinese hamster ovary cells, a reliable, well-established cell line used for the production of recombinant proteins for medicinal purposes. To ensure a homogenous product, isolation of turoctocog alfa uses a five-step purification process; detergent inactivation and concentration, immunoaffinity chromatography, anionic exchange chromatography, nanofiltration (20 nM filter), and gel filtration. The turoctocog alfa production method, together with its molecular structure ensures that all six FVIII tyrosines are fully sulfated. Tyrosine sulfation is important for physiologic binding of FVIII to its co-factor von Willebrand Factor, essential for FVIII stability when in circulation. Turoctocog alfa plasma concentration can be measured using standard one-stage clotting or chromogenic assays without the need for an external standard. Turoctocog alfa has been clinically tested in the guardianTM trials, one of the largest pivotal trial programs undertaken in hemophilia A with over 200 previously treated patients (PTPs) dosed. The safety and efficacy of turoctocog alfa was tested in adults and adolescents (guardianTM1) and children (guardianTM3). For adults and adolescents, turoctocog alfa had a success rate of 85% in management of bleeding episodes, and 89% of bleeds were successfully treated with 1-2 doses. For children, the success rate was 94%, and 95% of bleeds were treated with 1-2 doses. When used for prophylaxis, the median annualized bleeding rate for adults and adolescents was 3.7, while for children it was 3.0. In all surgical procedures performed in guardianTM1 and 3, the success rate was 100% with no safety concern. For both trials, no turoctocog alfa inhibitors were reported, and no safety concerns were observed. A clinical trial in pediatric previously untreated patients (guardianTM4) is ongoing.

Conclusions:

Turoctocog alfa is the new rFVIII treatment from Novo Nordisk, offering an alternative treatment option for patients with hemophilia A.

Objective:

Examine potential relationships between health-related quality of life (QoL), pain interference and self-reported arthritis and age, employment, activity, bleed frequency, and hemophilia treatment center (HTC) and healthcare professional utilization within the HERO psychosocial assessment study.

Methods:

In HERO, adults with hemophilia (≥18 years) from 10 countries completed a 5-point Likert scale on pain interference over the prior 4 weeks, EQ-5D-3L (mobility, usual activities, self-care, pain/discomfort, anxiety/depression) and EQ-5D health-related visual analog scale (VAS, 0-100, coded as an 11-point categorical response). US responses are considered below.

Summary:

Of 675 adults, 189 (90 with self-reported arthritis) respondents were from the US. Adults with arthritis were older; median age also increased with progressive disability and worsening pain. The percentages reporting full-time, part-time, or self-employment and the percentage reporting “good” EQ-5D VAS scores of 80-90-100 declined with increasing disability and pain interference. Median number of annual bleeds increased with increasing disability, pain interference, and arthritis. There was little difference in the median number of HTC visits per year in those reporting pain or arthritis. The percentage of adults reporting a lot/extreme pain interference was higher in those with more disability and with arthritis. Adults with increasing pain interference and arthritis were more likely to report social worker and nurse involvement. Physiotherapist utilization decreased with increasing disability and arthritis.

Conclusions:

In the US, increased disability and pain were associated with increased age, lower employment, higher reported bleed frequency, and lower QoL. Adults who reported experiencing more pain were more likely to report suffering from arthritis and more issues with mobility.

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.

This research project will examine fall history and fall risk in patients with hemophilia. Multiple risk factors for falls identified in the general population are prevalent in the hemophilia population. Existing data suggest that fall rates may be higher and that fall risk may begin at an earlier age in patients with hemophilia. Identification of fall risk enables early intervention, thereby preventing injury and fear of physical activity, both of which have been associated with falling and may carry an increased risk in patients with bleeding disorders.