Background:
Octanate is a highly purified, double virus inactivated, human plasma-derived factor VIII (FVIII) concentrate with all coagulation FVIII bound to its natural stabilizer VWF in a VWF:RCo/FVIII:C ratio of approximately 0.4. Five prospective GCP studies with octanate were conducted in 77 previously treated patients (PTPs) with severe haemophilia A. None of these 77 PTPs developed an inhibitor.
Aim:
To assess the immunogenicity in previously untreated patients (PUPs), a prospective clinical trial has been initiated in 2000. This included 48 PUPs with severe hemophilia A after treatment with octanate for an observational period of 100 exposure days and at least 6 months.
Methods:
Patients with severe haemophilia A without previous exposure to FVIII or FVIII containing products were enrolled. Efficacy and tolerability are assessed by a 4-point verbal rating scale. Inhibitor assay, according to modified Bethesda method is tested pre-treatment, every 3-4 exposure days (ED 1-20) and every 10 EDs (ED 21-100) but at minimum every three months.
Results:
Two of 48 (4.2%) subjects receiving treatment developed clinically relevant inhibitor titers over the course of the study. Another two displayed inhibitors that disappeared spontaneously without change of dose or dosing interval. All inhibitors developed under on- demand treatment and before ED 50. From the 48 subjects, 42 had exceeded 50 EDs at the time of this analysis. octanate was well-tolerated and the adverse event profile was consistent with the population studied. The haemostatic efficacy in prophylaxis and treatment of bleeding were generally rated as “excellent” and no complication was reported for any surgical treatment.
Conclusion:
Despite frequent inhibitor testing and predominant on-demand treatment, octanate showed a low rate of clinically relevant inhibitor formation (4.2%) in this cohort of patients.
Objective:
Describe social worker and nurse perspectives on the Hemophilia Experiences, Results and Opportunities (HERO) results from Canada.
Methods:
Adults with hemophilia (“adults,” ≥18 years) and parents of children (<18 years) with hemophilia (“parents”) were recruited through local hemophilia organizations and completed an online psychosocial assessment. Advisory board meetings with Canadian social workers and nurses were held to discuss the HERO results in January and April 2013, respectively.
Summary:
Key psychosocial issues identified by social workers and nurses included issues with sex life, pain, and employment. One-half (9/18) of adults with hemophilia in Canada reported that hemophilia had affected the quality of their sex life. Social workers noted that there is a need for more discussions and professional support regarding sexual intimacy, in addition to a need for more training for healthcare professionals (HCPs) on how to engage in conversations about sexual intimacy. Possible solutions to this issue provided by nurses include handouts to start conversations, education on strategies for HCP seminars, websites with patient testimonials, and information nights through local hemophilia chapters. Overall, 9/30 adults with hemophilia reported that pain had interfered with their daily life extremely or quite a lot. Of 27 adults, 9 reported pain all the time and 13 reported pain all the time that gets worse when they have a bleed. Social workers noted that there is a lack of chronic pain care and there needs to be an increase in sensitivity toward pain issues. Solutions proposed by nurses included a literature review about pain-assessment tools for hemophilia, developing tools to teach parents how to assess pain, developing an application for assessing and managing hemophilia-specific pain, offering pain intervention, developing distraction tool kits, and teaching alternative ways to cope with pain. Only 15/29 Canadian adults with hemophilia were employed; 35/39 parents were employed. Social workers noted that there is discrimination at work and school. To improve career guidance, nurses suggested the following: explore vocational issues, increase hemophilia treatment center (HTC) awareness, capture facts around what is or is not possible with respect to jobs, vocational support programs to start earlier, and clarify the HTC’s role in advocacy.
Conclusions:
HERO provided key insights into psychosocial issues facing Canadian adults with hemophilia and Canadian parents of children with hemophilia. Nurses and social workers provided strategies that could help improve the lives of both patients and parents.
Objective:
Caregivers of hemophilia patients may experience physical, social, emotional and financial problems as a result of their care tasks. Measurement of the caregiver experience is important in hemophilia as the majority are informal caregivers; typically unpaid family or friends. In order to carry out studies within the United States, a need exists for a translated and validated instrument to measure informal caregivers’ care-related quality of life in English for the U.S.
Methods:
The CarerQol instrument, covering 7 domains measuring the care-related quality of life of informal caregivers, including fulfillment, relational, mental and physical health problems, social impact, receipt of family support and financial impact, was selected on which to base an English U.S. version. The Dutch (Netherlands) source was translated into English (U.S.) by two forward linguists, working independently, who then collaborated to create a harmonized version. The project team, consisting of the forward translators, project manager, survey research analyst and independent Dutch (Netherlands) reviewer, discussed the harmonized English (U.S.) version to make necessary revisions. The English (U.S.) harmonization was then back-translated into Dutch (Netherlands), and a second Dutch linguist compared the back-translation to the source Dutch to ensure conceptual equivalence of the English forward translation and Dutch source. A client representative, who is a native English (U.S.) speaker, reviewed the English translation against the Dutch as an additional quality measure. After the English (U.S.) harmonization was finalized, it was debriefed via telephone interviews with 5 volunteers using screenshots of the questionnaire’s web version.
Summary:
A total of 5 subjects from the U.S. participated in debriefing interviews. Subjects ranged in age from 24 to 59 years, with educational levels ranging from 11 to 16 years. Sixty percent (60%) of the sample was female. Interview data confirmed that the English (U.S.) harmonized translation is conceptually equivalent to the source Dutch, and is understood by subjects in the United States.
Conclusion:
Per the cognitive debriefing results, the English (U.S.) harmonized translation based on the Dutch CarerQol instrument adequately captures the concepts in the original Dutch and, overall, is easily understood and confirmed as culturally appropriate by subjects in the United States. The resulting instrument is validated for use by English speakers in the United States, and captures the 7 quality of life domains as included in the source instrument.
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.
Background/Aim:
Little data exist, especially for adolescents and young adults (AYAs), about the relationship between adherence to prescribed hemophilia treatment regimens and chronic pain (CP).
Methods:
A convenience sample of hemophiliacs aged 13-25 completed an IRB-approved, online survey addressing regimen-specific adherence and CP between April through December of 2012. Adherence was assessed for prophylactic (VERITAS-Pro) and on- demand (VERITAS-PRN) participants. VERITAS scores range from 24 (most adherent) to 120 (least adherent). CP was measured using the revised Faces Pain Scale (FPS-R). CP was dichotomized as high (‘moderate’ to ‘worst pain possible,’ i.e., ≥4) or low (‘mild’ or ‘no pain,’ (i.e., <4). Multivariable, parsimonious logistic regression models assessed factors associated with high vs low CP levels. Separate models were constructed to evaluate a combined VERITAS score among prophylactic and on-demand patients and the VERITAS- Pro score among prophylactic patients only. Small sample size precluded analysis of on- demand (only) participants.
Results:
Ninety-three AYAs participated. Mild patients (n=13) were excluded. Of the remaining 80 participants (79 male), 91% had severe disease, 86% infused prophylactically, and 91% had Hemophilia A. Fifty-one percent were aged 13-17, most were white (76%), non- Hispanic (88%), and never married (93%). The majority (94%) had some type of health insurance.
Mean VERITAS-Pro (n=69) and PRN (n=11) scores were 49.6 ±12.9 (range 25-78) and 51.0 ±11.6 (range 35-74), respectively. CP was reported as high for 35% of respondents (36% for prophylactic vs 27% for on-demand, p=.74). Mean VERITAS-Pro scores for those with high and low CP were 53.6 ±12.3 vs 47.4 ±12.9, p=.05. VERITAS-PRN scores were similar across CP status. Logistic regression analysis revealed that for each 10-point reduction (increase in adherence) in the combined VERITAS score (Pro and PRN) there was a 35% (OR=0.65; 95%CI=0.44, 0.96; p=.03) reduction in the odds of having high CP. Among prophylactic respondents: for each 10-point reduction in the VERITAS-Pro score there was a 39% (OR=0.61; 95%CI=0.39, 0.96; p=.03) reduction in the odds of having high CP and compared to whites, non-whites were 4.42 (95%CI: 1.21, 16.1; p=.02) times as likely to report high CP.
The goal of Dr. Chen's research is to examine a method for selectively expanding hematopoietic stem cells expressing the factor VIII transgene. She will also examine the immune consequences of this approach, based on the idea that gene transfer in platelets evades immune recognition. This research has the potential to elicit important clues to developing an approach for gene therapy of hemophilia A and hemophilia A with inhibitors.
Dr. Chen earned a PhD in hematology from Fujian Medical University in China. She already has more than 27 papers published in the Chinese medical literature. Her research in hemophilia and gene therapy will be under the mentorship of Dr. Qizhen Shi, MD, PhD, Associate Investigator at the Blood Research Institute and Assistant Professor of Pediatric Hematology at the Medical College of Wisconsin.
