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.
Background:
Emicizumab was approved by the FDA in 2017 for routine prophylaxis in PwHA with inhibitors. HAVEN 1, a phase III study in adolescent and adult PwHA with inhibitors, demonstrated that emicizumab prophylaxis significantly reduced annualized treated bleed rate by 87% (P<0.001) vs no prophylaxis. In this retrospective, post-hoc analysis, we examined the use of BPAs to treat breakthrough bleeds before and after emicizumab initiation in HAVEN 1.
Methods:
HAVEN 1 patients were included from emicizumab-treated Arms A (previously treated with only episodic BPA) and C (previously treated with prophylactic BPA) and who had participated in the non-interventional study (NIS). In both studies, bleed and treatment data collection were comparable. In the study protocol, no guidance for the treatment of bleeds was provided; and hemostatic efficacy was not measured, thus optimal treatment of bleeds cannot be accurately assessed. Additionally, only data before October 7th, 2016 are included in this analysis to better represent treatment patterns before amended BPA guidance was provided. We describe the total number of patients and bleeds, number of infusions per bleed, and the cumulative dose/kg per bleed before and after emicizumab initiation.
Results:
This analysis (48 total patients) included 24 patients each from Arm A and Arm C who participated in the NIS prior to enrollment in the HAVEN 1 trial. On average, patients received numerically fewer activated prothrombin complex concentration (aPCC) infusions with lower cumulative doses while on emicizumab as compared to prior to emicizumab administration. In Arm A, 11 bleeds were treated with aPCC resulting in an average of 1.2 aPCC infusions/ bleed and an average cumulative aPCC dose/ bleed of 95.9 U/kg while on emicizumab as compared to 136 bleeds resulting in an average of 1.7 infusions/ bleed and cumulative dose 134 U/kg prior to emicizumab. Similar findings were seen in Arm C (bleeds, aPCC infusion/cumulative dose numbers: 14,2.3/166.6 U/kg on emicizumab compared to 205, 2.6/189 U/kg prior to emicizumab.) Fewer bleeds were treated with rFVIIa and no clear trend was seen regarding how rFVIIa was used to treat bleeds. In Arm A, 11 bleeds were treated with rFVIIa resulting in an average of 1.5 infusions/ bleed and cumulative dose 212.2 µg/kg on emicizumab, vs 97 bleeds, 1.4 infusions/ bleed and cumulative dose 181.6 µg/kg prior. In Arm C, 14 bleeds were treated with rFVIIa resulting in 4.4 infusions/ bleed and cumulative dose 555.6 µg/kg on emicizumab vs 58 bleeds, 8.6 infusions/ bleed and cumulative dose 1829 µg/kg prior.
Conclusions:
Treatment of bleeds with aPCC in HAVEN 1 resulted in numerically fewer infusions and lower cumulative doses of aPCC per bleed while on emicizumab when compared to bleeds treated prior to emicizumab initiation. Treatment of bleeds with rFVIIa showed no clear trend.
As a social worker at Gulf States Hemophilia & Thrombophilia Treatment Center, I have the privilege of serving patients across their lifespan. I would like to initiate grass roots education about hemophilia in Houston, Texas, by offering educational programming to specialized health care professionals who work directly with the aging population in nursing homes and assisted living communities. This would include executive directors and administrators of these facilities as well as direct clinical staff.
