Objective:
Report results of an open-label international study that collected retrospective data on compassionate use of high-purity plasma-derived FX concentrate (pdFX) in subjects with hereditary factor X (FX) deficiency (FXD).
Methods:
This study included subjects with hereditary FXD (irrespective of severity) who received compassionate use pdFX as routine prophylaxis (RP), on-demand (OD) treatment, short-term prevention, and/or perisurgical hemostatic cover. Dosing was at the investigator’s discretion and tailored to each patient. Data from date of first compassionate use dose until data cutoff (31 December 2015) were collected retrospectively.
Summary:
All 15 enrolled subjects from 12 study centers received ≥1 pdFX dose for compassionate use. Of these, 13 subjects were aged ≥12 years (mean, 22.8 years) and 2 were aged <12 years, 8 (53.3%) were female, 12 (80.0%) were white, 3 (20.0%) were Asian. All subjects had moderate or severe FXD (FX activity [FX:C] <5 IU/dL).Of the 15 patients, 7 received only RP, 7 received only OD, and 1 alternated between OD and RP. The 8 subjects on RP received a total of 1239 RP infusions (mean, 154.9 infusions/subject, range 39–492), with a mean dose/infusion/subject of 32.5 IU/kg. The 2 subjects aged <12 years received larger RP doses than the 6 older subjects (mean doses/infusion/subject of 51.1 vs 26.3 IU/kg).Twelve subjects (8 OD, 4 RP; all aged ≥12 years) reported 88 bleeds (34 minor, 7 major, and 47 not rated); 37 bleeds were menorrhagic, 28 were traumatic, 17 were spontaneous, 4 were other, and 2 had unknown cause. pdFX efficacy was rated as effective for the 79 bleeds (including 1 subdural hematoma) treated with OD pdFX. Mean pdFX dose was 22.2 IU/kg/infusion/subject, with a mean of 9.5 infusions/subject to treat a bleed. More bleeds occurred in the OD than in the RP population.Two subjects underwent 1 dental procedure each, with only 1 presurgical pdFX dose required per patient; a third surgery, a portacath insertion, required 6 infusions to prevent postoperative bleeding. Two successful pregnancies/childbirths were also reported, with no abnormal bleeding complications or efficacy/safety concerns reported.The mean duration of compassionate use was 87.6 weeks for the 15 subjects, with a range of 15–211 weeks (0.3–4.0 years). Over the 1373 infusions administered across 25.2 subject-years, investigators rated overall pdFX efficacy as excellent in 14 (93.3%) subjects and good in 1 (6.7%) subject. No adverse drug reactions, safety concerns, infusion site reactions, tolerability issues, or inhibitor development were reported during pdFX compassionate use.
Conclusions:
The higher bleed rate in OD versus RP use and the treatment duration (up to 4 years) support the efficacy and safety of pdFX demonstrated in prospective clinical studies and its continued use in the treatment of subjects with hereditary FXD.
Objective:
The NHF Ethics Working Group’s (EWG) mission is to promote integrity and ethical behavior in the bleedings community. The EWG wants to determine if our Hemophilia Treatment Centers (HTCs) want or need a regional ethics committee to help work through ethical dilemmas.
Method:
A 16 question needs assessment survey was written and distributed to all 12 regional HTC’s healthcare providers within NHF’s database. The data was collected from January 25, 2018 thru March 6, 2018 and analyzed via Monkey Survey.
Summary of Results:
The survey was distributed to 1322 HTC staff members, 192 responded to the survey, with a response rate of 14.4%. All 12 HTC regions had participants.
A variety of professionals participated in the survey: nurses (26%), social workers (23%), physicians (16%), physical therapist (12%) advanced practice providers (9%) & non-clinical staff (3%).
Ethical dilemmas were difficult to resolve according to 61% of participants while 9% thought they were easy to resolve. Ethical dilemmas were also described by 32% as confusing, 45% as frustrating and 60% as interesting.
The frequency of ethical dilemmas varied; 43% monthly, 25% yearly, 23% weekly and 5% daily.
When resolving an ethical dilemma 22% resolved them on their own. Others liked to collaborate with colleagues (96%), consult with their institution’s ethics committee (36%), consult the NHF EWG (4%) and 2% avoided them. When dealing with an ethical dilemma, most people were sometimes comfortable (42%), usually comfortable (41%,), always comfortable (9%) and never comfortable (6 %).
When our respondents consulted their colleagues, 13% responded that their concerns were always adequately addressed, 53% usually, 28% sometimes, 2% never and 3% n/a.
Over 50% of our respondents have never consulted their institution’s ethics committee.
When asked if a confidential regional ethics committee would be a valuable HTC resource only 8% responded no.
If there was a regional ethics committee, 27% said they would like to be involved and 40% responded maybe.
Only 45% of our participants knew of NHF Ethics Working Group and 70% were interested in a case based ethical presentation by the NHF Ethics Working Group.
Conclusion:
Ethical dilemmas occur frequently are are difficult to resolve. Most people did not consult their institution’s ethics committees and the majority of participants didn’t know that NHF had an ethics working group. There is interested in ethical educational presentations/discussions with the EWG. Participants thought that a regional ethics committee would be a valuable HTC resource and greater than a quarter of the participants showed interested in being involved with the regional ethics committee.
This study will evaluate hemophilia treatment center (HTC) services provided to women with hemophilia A or B (Factor VIII or Factor IX level [ 50%). The American Thrombosis and Hemostasis Network (ATHN) maintains a confidential national database for patients with bleeding and clotting disorders. Utilizing this existing ATHNdataset, the study will analyze the effect of gender on the delivery of comprehensive care in patients with hemophilia A and B. The project will focus on how gender impacts three specific components of care: identification of patients with factor VIII or IX deficiency, inclusion of patients in the comprehensive care model, and monitoring of joint bleeding as a key component of comprehensive care provided by HTCs. Demonstrating gender-based disparities in comprehensive care would provide evidence for making changes to improve the clinical care provided to women with hemophilia. This study will add to the knowledge regarding the care of women with hemophilia, helping to inform future studies of this under-researched population.
Objective:
BAY 81-8973 (Kovaltry®) is a full-length, unmodified recombinant human factor VIII (FVIII) for prophylaxis and treatment of bleeds in patients with hemophilia A. Safety and efficacy of BAY 81-8973 in children, adolescents, and adults were established in the LEOPOLD clinical trials. This analysis reports interim data from the LEOPOLD Kids extension study for patients with ≥100 exposure days (EDs) to BAY 81-8973 in the main study plus extension study.
Methods:
In LEOPOLD Kids, boys aged ≤12 years with severe hemophilia A and ≥50 EDs to FVIII received BAY 81-8973 (25–50 IU/kg) ≥2 times/wk for ≥50 EDs. Patients completing the main study could enroll in an ongoing extension study for ≥100 EDs.
Summary:
Of 51 patients who completed the main study, 46 (90.2%) entered the extension study (aged <6 years, n=22; aged 6–12 years, n=24). Patients were treated for a median (range) of 1494 (175–1989) days and accumulated 546 (67–1011) EDs in the extension study. Median (quartile [Q]1; Q3) dose per prophylaxis infusion was 37.7 (33.1; 41.8) and 30.9 (29.1; 34.9) IU/kg for younger and older patients, respectively; annual prophylaxis dose was 4984 (3679; 6529) and 4089 (3283; 5555) IU/kg. Median (Q1; Q3) annualized number of total bleeds was 2.0 (0.2; 4.2) and 1.8 (0.5; 3.0) for younger and older patients, respectively; annualized total bleed rate was 3.0 (0; 6.0) and 0 (0; 6.4) for these patients in the main study. Median (Q1; Q3) annualized total bleeds within 48 hours of prophylaxis infusion was 0.8 (0; 1.7) and 1.0 (0.1; 1.6) in younger and older patients in the extension study. Response was excellent/good in 337/405 bleeds (83.2%); data were missing for 22 (5.4%) bleeds. Most bleeds (93.5%) were mild/moderate and were spontaneous (42.4%) or trauma related (53.6%). One patient experienced a mild treatment-related serious adverse event (transient very low FVIII inhibitor titer concurrent with acute infection and positive immunoglobulin G anticardiolipin) and remained in the extension study. No change in treatment was required, and the patient was clinically well.
Conclusions:
Data from the LEOPOLD Kids extension study show that BAY 81-8973 provides safe and effective long-term prophylaxis in children with severe hemophilia A treated for a median of 4.1 years, confirming safety results observed in the main study.
Background:
Congenital afibrinogenemia is an autosomal recessive bleeding disorder referring to the total absence of fibrinogen measured by an antigenic assay. The commonest manifestation of the disease is bleeding from mucosal surfaces, however musculoskeletal bleeding, gynecologic and obstetric complications, spontaneous bleeding, bleeding after minor trauma and during interventional procedures or thromboembolic episodes.
Objective:
We hereby report the only case of this disorder in Slovakia with a successful perioperative management of hemostasis during revision total hip arthroplasty.Method and results: Preoperatively, the patient received fibrinogen concentrate in the dose of 75mg/kg, this dose increased the level of fibrinogen after 2 hours to corresponding 170mg/dL. During surgery, the patient received fibrinogen concentrate in the dose of 25mg/kg. The patient was administered an intraoperative transfusions because of blood loss. Twenty-four hours after surgery, the fibrinogen concentrate was applied in the patient at the dose 37.5 mg/kg every 8 hours. One day after surgery, we administered fibrinogen concentrate at the dose of 37.5 mg/kg every 12 hours with a targeted level of fibrinogen in the interval of 130-150mg/dL. We continued to reduce the dose of fibrinogen concentrate. The patient was discharged safely at 12th day after surgery with level of fibrinogen above 50mg/dL. The administration of fibrinogen concentrate was combined with low molecular weight heparin.
Conclusion:
Our results in this patient with congenital afibrinogenemia who underwent the successful repeated total left hip arthroplasty reaffirm the recommendation to tailor treatment to ensure a hemostasis balance between the replacement of clotting factor (fibrinogen concentrate) and thromboprophylaxis.
Background:
Many hemophilia treatment centers (HTCs) have a comprehensive care clinic in which a variety of providers see patients with bleeding disorders. Registered dental hygienists (RDHs) are, in some cases, a part of the comprehensive care clinic due to an access to dental care issue for those with bleeding disorders. The RDH may educate patients with bleeding disorders about oral health and act as a liaison between the patients’ hematologist and dentist.
Objective:
To determine if HTC nurses who work with RDHs are more confident in addressing patients’ oral health than nurses who do not. Methods: HTC nurses in the United States were sent a 10-item survey to evaluate presence of a RDH within the HTC, oral health related services provided to patients, and level of confidence and knowledge in discussing oral health with patients. IRB approval was obtained prior to data collection.
Results:
Response rate=49.7%. 45% of nurses that responded stated their HTC employs a RDH (n=31). There were not statistically significant differences in confidence levels between nurses working with a RDH versus those that do not. Data revealed that RDHs help patients find access to dental care, educate patients on oral health, and act as a liaison between the hematologist and the patient’s dentist. 19.4% of nurses that do not have a RDH do not help patients find access to dental care. Nurses that worked more often were more likely to help patients find access to dental care (p=0.01) and more confident in the relationship between oral health and bleeding disorders (p=0.001) and in discussing oral health with patients (p=0.002).
Conclusions:
Although there were no statistically significant differences in the two groups of nurses when measuring confidence, knowledge, and services provided, the study shed light into what services RDHs are providing within the comprehensive care setting. Due to the many complications patients with bleeding disorders can face during treatment, it would be beneficial to have a specialized oral health care provider incorporated into the HTC team to educate patients on preventing oral disease. This model of an RDH as a part of the comprehensive care clinic could translate into additional career opportunities for the RDH.
Background:
Inherited factor X deficiency is an autosomal recessive bleeding disorder with an estimated occurrence rate of 1:1,000,000¹. Historically, bleeding symptoms have been treated with topical therapies, antifibrinolytic agents, fresh frozen plasma (FFP) or plasma-derived FIX concentrates (PCCs). In 2015, the first factor X (FX) concentrate was approved in the U.S.
Objective:
This organization was interested in reviewing clinical outcomes such as perceived pain and unplanned hospitalizations of adults and children with FX disease currently being treated in the home with Coagadex®. METHODS: This organization conducted a retrospective review of a population of seven adult and pediatric patients. Patients were surveyed for pain, bleeding episodes, hospitalizations/ ER visits, dosing parameters and administration methods pre/post initiation of FX therapy. There were 3 children, 12 years old and under and four adults. Ages ranged from 5-60 years old with the average age of 27.9. There were five males and two females. The average length of treatment was 6.4 months. One patient was naïve, six converted from other therapies. Dose ranges administered by caregivers or self-infusion were 750 -2800 IU (26-61 IU/Kg). One patient was on-demand and six were administering prophylaxis therapy.
Results:
There were two converted prophylaxis patients reported pain with PCC’s and none with FX; one on-demand naïve patient stated his pain was markedly improved with prn administration of FX; four converted prophylaxis patients with no prior pain history reported no changes in pain on FX therapy. For on-demand patients treating bleeding episodes, three reported a decrease in the number of bleeding episodes, three were unchanged and one reported one additional bleeding episode. A total of ten hospitalizations or emergency room visits were reported during the six months prior to initiation of FX treatment and only one in the six months following initiation of treatment.
Conclusion:
Early recognition and home treatment with FX concentrate allows for prompt resolution of bleeding symptoms, decreased pain and decreased hospitalization or emergency room visits. Further investigation is needed to determine cost-savings for decreased hospitalization/ ER visits.References:Brown, D.L. & Kouides, P.A. (2008). Diagnosis and treatment of Inherited Factor X deficiency. Haemophilia. (14). 1176-1182. Retrieved from: https://www.hemophilia.org/sites/default/files/document/files/DiagnosisAndTreatmentOfInheritedFact…
Klaus Bonazza received his Ph.D. in chemistry from Vienna University of Technology. He is currently a postdoctoral researcher at Boston Children's Hospital and appointed at Harvard Medical School, mentored by Dr. Timothy Springer. His field of interest is the ultra-large concatemeric protein von Willebrand factor (VWF), which accounts for the adaptability of hemostasis to different flow conditions in the blood vessels.
At moderate, physiological flow VWF has a packed, "bird nest's" shape whereas strong elongational flow conditions, occurring downstream of vascular restrictions or injuries, induce a transition to a threat-like, elongated state. On top of this overall unpacking, tensile forces, which are exerted on the chain and transmitted by its A1 domain, cause local conformational changes which activate binding of thrombocyte receptor Glycoprotein Ib (GPIbα) to initiate coagulation. With his JGP fellowship award, Dr. Bonazza will pioneer a new method to obtain structural insights into force dependent VWF unpacking, A1 deformation and GPIbα binding based on hydrogendeuterium exchange under elongational flow conditions.
Objective:
The purpose of this study is to explore the bivariate and linear relationships between and among self-compassion, hope, and quality of life (QOL) among individuals with bleeding disorders. It is expected that these findings will guide the development of positive psychological interventions for this population.
Methods:
The final sample included 86 participants (61.6% male) with a mean age of 29.7 years (SD = 14.42). The majority of participants were diagnosed with hemophilia A (44.2%) or von Willebrand disease (44.2%). Participants completed a demographic questionnaire, and 3 self-report measures: the Self-Compassion Scale (SCS; Neff, 2003), the Adult Hope Scale (AHS; Snyder et al., 1991), and the PedsQL Inventory – Core Generic (Varni et al., 1999). The SCS is a 26-item scale with 6 subscales. Three subscales assess positive components (self-kindness, common humanity, and mindfulness) and three subscales assess negative components (self-judgment, isolation, and over-identification). The AHS is a 12 item instrument comprised of two scales: agency (the ability to identify goals for the future) and pathways (the ability to identify means to achieve those identified goals). The PedsQL assesses physical, mental, social, and school/work domains of QOL, in addition to total QOL, assessing all subscales.
Summary:
There was a significant and positive relationship between overall Quality of Life (QOL) and Overall Self-Compassion (r = .39, p < .001). There were significant and inverse bivariate relationships between Overall Quality of Life and each of the negative Self-Compassion components including Self-Judgement (r = -.44, p < .001), Isolation (r = -.35, p < .001), and Over-Identification (r = -.45, p < .001). A multiple regression analysis was conducted to explore the linear relationship of self-compassion and hope with QOL. Self-Compassion and hope were found to be significant concurrent predictors of QOL, F (2, 83) = 11.45, p < .001. Examination of the standardized beta weights revealed that hope (β = .31, t = 2.54, p < .05) was the only significant individual contributor to QOL.
Conclusions:
Hope and self-compassion were identified as variables that contribute to QOL among individuals with bleeding disorders. Hope, defined as the ability to identify and work toward identified goals, was the strongest predictor of QOL in the model. These findings provide implications for the use of hope-increasing interventions as a means to improve QOL. These findings provide further evidence for the use of strengths-based strategies to enhance well-being within the bleeding disorder population. Future studies could evaluate the effectiveness of specific interventions to improve hope and QOL among various subsets of the bleeding disorder community.
