Research Studies

Bleeding disorders are a group of conditions that result when the blood cannot clot properly (American Society of Hematology, 2017). The most frequently occurring bleeding disorders include von Willebrand Disease (VWD), Hemophilia A, and Hemophilia B (FDA ́s, 2016).Some studies shows that is important to considered the depression in the psychological approach of patients with a bleeding disorder (Recht, Batt, Witkop, Gut, Cooper, Kempton, 2016 and Osorio, Bazán, Izquierdo, 2016). Beck ́s theory defined depression in cognitive terms. He saw the essential elements of the disorder as the “cognitive triad”: (a) negative view of self, (b) a negative view of the world, and (c) a negative view of the future. The depressed person views the world through an organized set of depressive schemata that distort experience about self, the world, and the future in a negative direction (Beck, A. 1972 in Lynn, P. 2015).

Objective:

Compare depression levels in groups of patients with haemophilia, Von Willebrand (VWD) and apparently healthy people.

Methods:

The study design was quantitative, non-experimental, transactional and correlational in which the difference between three groups of participants was analyzed: 41 patients with hemophilia A or B, 10 patients with VW and 20 apparently healthy people. The sample was obtained from Tabasqueña de Hemofilia A.C. through a non - random sampling of subjects - type. Depression symptoms were obtained by Beck ́s inventory and for control variables a questionnaire was applied. All of the findings were assessed by SPSS 21 for Windows program. Data were analysed using descriptive statistics, comparisons between groups were evaluated with Games-Howell coefficient and post hoc test.

Summary:

71 participants with a mean age of 28.24. Considering the patients who have a bleeding disorder, 74.50% of the sample was deficient of factor VIII, 11.76% of factor von Willebrand, 11.76% of factor VII and 1.96% of factor IX; 82.35% of them have access to treatment while 17.64 have not access. Statistically significant differences were found only in apparently healthy people compared to haemophilia patients (p=0.031). A marginal difference was detected between the group of apparently healthy people and von Willebrand patients (p=0.081).

Conclusions:

The presence of a coagulation disease increase the levels of depression and the severity of the symptoms.

Key Words: Hemophilia, Von Willebrand, Depression.

Camping programs for individuals with chronic illness are increasingly common. Unfortunately, few studies have been conducted to empirically evaluate whether camping programs are meeting their intended goals or having the positive outcomes that are expected of them. The current study was conducted as an evaluation of a bleeding disorder camp for patients with bleeding disorders and their siblings.

Participants in the current study included 77 participants, ages 7-20 (mean 11.58, SD = 3.21). The sample was 62.3% male and 63.6% patients (36.4% siblings). Most of the patients (52.6%) had severe bleeding disorders. Participants were administered the Children’s Hope Scale (CHS; Snyder et al., 1991), which evaluates two dimensions of hope (1. Agency, the ability to identify positive goals and 2. Pathways, the ability to find ways to meet identified goals) and overall hope. Participants demonstrated a significant improvement on the agency subscale of the CHS, t(35) = -2.16, p < .05. Participants reported qualitative aspects of living with bleeding disorders, including differences in their lives, aspects of their lives that are better, aspects about bleeding disorders that are often misunderstood, and advice for others with bleeding disorders. Responses to qualitative were analysed across groups (patients and siblings; severe and mild patients) and were found to be very consistent across these groups. This information has helped to provide information about experiences of youth affected by bleeding disorders and will be used to help inform upcoming camp programming. These findings have also demonstrated positive psychosocial outcomes associated with camp attendance.

Background:

A high-purity plasma-derived FX concentrate (pdFX) has been developed for treatment of hereditary FX deficiency, an autosomal recessive disorder.

Aim:

This post hoc analysis describes the pharmacokinetics, safety, and efficacy of pdFX in 10 women and girls with hereditary FX deficiency.

Methods:

In this open-label study, subjects (10 women/girls, 6 men/boys) aged ≥12 years with moderate or severe FX deficiency (basal plasma FX activity ≤5 IU/dL) were enrolled and received 25 IU/kg pdFX for on-demand treatment of bleeding episodes or preventative use for up to 2 years. All subjects provided informed consent and the protocol was approved by appropriate independent ethics committees.

Results:

Nine women and girls had severe and 1 had moderate FX deficiency, were aged 25.5 (median; range 14–58) y, and received a total of 267 pdFX infusions (178 for on-demand and 89 for preventative treatment). Men and boys (5 severe and 1 moderate FX deficiency) received a total of 159 pdFX infusions (64 on-demand; 95 preventative). The mean number of infusions per subject per month was higher among women and girls (2.48) than males (1.62). The mean pdFX incremental recovery was similar between women/girls and men/boys (2.05 vs 1.91 IU/dL per IU/kg, respectively), as was mean half-life (29.3 and 29.5 h, respectively). Among women and girls, 132 assessable bleeding episodes (61 heavy menstrual bleeding, 47 joint, 15 muscle, and 9 other) were treated with pdFX. Women and girls reported a treatment success rate (ie, subject rating of “excellent” or “good” response to pdFX) of 98%, comparable to the 100% treatment success rate among men and boys. After study completion, 2 subjects received pdFX for hemostatic cover during obstetric delivery. Additional infusion, bleed, and safety data will be presented.

Conclusion:

These results show that, in women and girls with moderate or severe hereditary FX deficiency, who experience reproductive tract and other bleeding events, pdFX was safe and effective. The pharmacokinetic profile of pdFX in women and girls was similar to that of men and boys.

Funding: Bio Products Laboratory

Objectives:

Contemporary real-world data on units dispensed and expenditures associated with use of standard half-life (SHL) and extended half-life (EHL) factor VIII replacement products in U.S. patients with hemophilia A are limited. This exploratory analysis of real-world administrative data was conducted to determine units dispensed and factor replacement product-related direct expenditures associated with currently marketed recombinant SHL and EHL FVIII products, and to examine inter-product switches.

Methods:

De-identified claims data from the commercially available Truven Health MarketScan® Research US claims database were used to identify direct expenditures and number of international units (IUs) dispensed for all patients with a diagnosis code of ICD-9 286.0/ICD-10 D66 who used SHL (SHL group) and/or EHL (EHL group) during the study period from Aug 1, 2014 to Jan 31, 2017. Data on switching from an SHL to an EHL factor VIII replacement product were captured in patients with continuous pharmacy enrollment for whom claims data were available for at least 1 calendar quarter and up to 1 year before and after the index date of a product switch. Descriptive statistics were used to analyze results.

Summary:

Cross-sectional analysis.
The SHL group comprised 415 patients, among whom six distinct SHL FVIII products had been dispensed, and the EHL group included 91 patients, among whom two EHL FVIII products had been dispensed. The age distribution of the two groups was similar (p =0.57), although the proportion of patients under 18 years of age was somewhat higher in the SHL group than in the EHL group (46.9% vs 36.2%). The median FVIII product dispensation per calendar quarter was 46,409 IU (IQR, 12,760-87,670 IU) (SHL) versus 67,375 IU (IQR, 50,524-98,264 IU) (EHL). Median expenditures per calendar quarter were substantially higher for EHL ($135,519; IQR, $100,320-186,557) than for SHL ($61,152; IQR, $18,593-115,845).

Switching analysis.
Of the patients in the EHL group, 29 had switched from one of three SHL FVIII products to one of two EHL FVIII products during the study period. The total median IU dispensation per calendar quarter increased following the switch from 58,598 IU (pre-switch, SHL) to 68,036 IU (post-switch, EHL; 16% increase), as did the factor-related expenditure ($76,553, SHL, versus $141,101, EHL; 84% increase).

Conclusion:

Real-world data derived from a large claims database, unadjusted for treatment regimen or hemophilia severity, reveal marked differences in metric units and expenditures among hemophilia A patients to whom SHL and/or EHL products were dispensed. Switching from an SHL to an EHL FVIII replacement product was associated with a substantial increase in units dispensed and factor expenditures. Further analyses, incorporating essential clinical characteristics, should be explored.

Objective:

People with hemophilia frequently experience joint bleeds, resulting in pain and functional impairment. The P-FiQ study formally evaluated patient-reported pain descriptions, responses to standardized patient-reported outcomes (PROs) related to pain, and pain management strategies.

Methods:

Participants completed a pain/hemophilia history and 5 PRO instruments. Pain was assessed via 3 PRO instruments: EQ-5D-5L, Brief Pain Inventory v2 Short Form (BPI), and Short Form-36 v2 (SF- 36v2), and these instruments were assessed for reliability, consistency, and correlation with factors including patient-reported characteristics.

Summary:

P-FiQ enrolled 381 adult males with mild-severe hemophilia and a history of pain and/or joint bleeding. Most (65%) self-reported having arthritis/bone/joint problems. Thirty-two percent of participants reported experiencing both acute and chronic pain, 35% chronic pain only, 20% acute pain only, and 15% no pain. Of those reporting acute pain, most described the sensation as “sharp” (77%) or “aching” (65%); for those reporting chronic pain, most described the pain as “aching” (80%) or “nagging” (50%). Ankles (37%) and knees (24%) were commonly reported as the most painful joints. Many participants with acute/chronic pain reported using acetaminophen (62%/55%) or nonsteroidal anti-inflammatory drugs (34%/49%) to treat their pain in the past 6 months. Some participants indicated having moderate/severe/extreme (28%/12%/2%) pain/discomfort “today” as measured by the EQ-5D-5L pain/discomfort domain. For BPI (scale 0-10, 10 is most severe pain), median pain severity scores were 6.0 for worst pain, 3.0 for average pain, 2.0 for current pain, and 1.0 for least pain. Median BPI pain interference scores indicated interference with general activity (3.0), mood (3.0), walking ability (3.0), normal work (3.0), and enjoyment of life (2.0). On SF-36, most participants (90%) reported experiencing bodily pain, and 75% indicated that pain interfered with normal work in the last 4 weeks. Assessments of pain on PROs were highly correlated with one another. The following formal PRO assessments were associated with self-reported pain: pain/discomfort domain of EQ-5D-5L, BPI worst pain, least pain, average pain, and current pain, and SF-36 bodily pain. Greater extent of lifetime routine infusions was also associated with EQ-5D-5L pain/discomfort and SF-36 bodily pain.

Conclusion:

Pain severity and interference in people with hemophilia were identified consistently across several PROs, and correlated with patient-reported pain. In the comprehensive care setting, greater use of formalized assessment tools over time would improve dialogue and pain assessment between healthcare professionals and patients, document and validate the presence and extent of pain, establish and monitor individual goals for pain management interventions, and encourage the exploration of various pain management strategies and the evaluation of their overall quality and effectiveness.

Dr. Tine Wyseure obtained her Master’s degree in Drug Discovery and Development, and earned her Ph.D. in Pharmaceutical Sciences at the University of Leuven, Belgium. Since 2015, she has been a research associate in the lab of Dr. Laurent Mosnier at The Scripps Research Institute in San Diego. Dr. Wyseure’s 2016 JGP research fellowship award project is focused on investigating the effects of impaired TAFI activation in hemophilia on the progression of hemophilic joint disease. The lack of active TAFI worsens joint bleeding and chronic inflammation and drives the striking development of fragile blood vessels in diseased joints. In search of the missing link, Dr. Wyseure has discovered a novel paradigm on how the formation of new blood vessels is controlled by TAFI and suggests that patients with hemophilia may lack this control switch, causing the formation of unstable and leaky blood vessels.

Objective:

The aim of this study was to determine if the young boys with hemophilia at our clinic have gross motor delays that may have been missed during the annual physical therapy evaluation. By identifying delays, our clinic can improve the standard of care and promote gross motor development in our patients to enhance their ability to be physically active and protect their joints and muscles from injury.

Method:

Over a one year period, boys with hemophilia A or B between the ages of 4 to 14 were tested by the physical therapist at our clinic using the Bruinink’s-Oseretsky Test of Motor Proficiency, Second Addition, BOT2. The BOT2 is a valid and reliable gross motor test for 4 to 21 year olds and is widely used to detect mild to moderate motor delays. The five gross motor subtests used in this study included upper extremity (UE) coordination, bilateral coordination, balance, strength, running speed and agility (run/agility). A total of 42 boys completed the study with scores distributed between three age groups: Group 1=4-7 year olds; Group 2=8- 11 year olds; and Group 3=12-14 year olds. Exclusion criteria included a bleed within the last week that was unresolved or other physical limitation preventing participation. All severities of hemophilia were included in the study, but were not separately analysed in the results.

Results:

Each age group mean scores for the subtests were within the normal mean range of 15±4 except for strength in Group 2. Group 1 had some participants score above average for four of the subtests, while Group 2 and 3 only scored above average on one subtest. Group 1 had 6-18% score below average on four of the subtests while Group 2 had 27-47% and Group 3 had 30-50% score below average on all 5 subtests. No adverse events or bleeds occurred during or as a result of the gross motor testing.

Conclusion:

At our Hemophilia Treatment Center, more than 50% of the boys tested had gross motor dels. The percentage of boys showing deficits increased and persisted after age 7. This reinforces the need to include some standardized gross motor testing during the annual physical therapy evaluation of our patients with hemophilia to identify boys with scores below average and make referrals at an early age to prevent persisting gross motor delays.