The United States Supreme Court’s ruling to overturn Roe v. Wade has potential grave implications, impacting access to reproductive healthcare for women across the country. Similarly, women and ...adolescent girls with bleeding disorders need access to high-quality reproductive health care because there is a significant risk of bleeding complications in these patients. Treatment decisions need to be made by patients and treating physicians and not as a consequence of political ideology. Women including those with bleeding disorders should be given the autonomy to make their own reproductive health decisions.
Unresolved hemostasis issues in haemophilia Sidonio, Robert F.; Weisel, John W.; Stafford, Darrel
Haemophilia : the official journal of the World Federation of Hemophilia,
April 2024, Letnik:
30, Številka:
S3
Journal Article
Recenzirano
Despite rapid technological advancement in factor and nonfactor products in the prevention and treatment of bleeding in haemophilia patients, it is imperative that we acknowledge gaps in our ...understanding of how hemostasis is achieved. The authors will briefly review three unresolved issues in persons with haemophilia (PwH) focusing on the forgotten function that red blood cells play in hemostasis, the critical role of extravascular (outside circulation) FIX in hemostasis in the context of unmodified and extended half‐life FIX products and finally on the role that skeletal muscle myosin plays in prothrombinase assembly and subsequent thrombin generation that could mitigate breakthrough muscle hematomas.
Summary
Haemophilia A carriers have historically been thought to exhibit normal haemostasis. However, recent data demonstrates that, despite normal factor VIII (FVIII), haemophilia A carriers ...demonstrate an increased bleeding tendency. We tested the hypothesis that obligate haemophilia carriers exhibit an increase in clinically relevant bleeding. A cross‐sectional study was performed comparing haemophilia A carriers to normal women. Questionnaire assessment included a general bleeding questionnaire, condensed MCMDM‐1VWD bleeding assessment tool and Pictorial Bleeding Assessment Chart (PBAC). Laboratory assessment included complete blood count, prothrombin time, activated partial thromboplastin time, fibrinogen activity, FVIII activity (FVIII:C), von Willebrand factor antigen level, ristocetin cofactor, platelet function analyser‐100TM and ABO blood type. Forty‐four haemophilia A carriers and 43 controls were included. Demographic features were similar. Laboratory results demonstrated a statistically significant difference only in FVIII:C (82·5 vs. 134%, P < 0·001). Carriers reported a higher number of bleeding events, and both condensed MCMDM‐1 VWD bleeding scores (5 vs. 1, P < 0·001) and PBAC scores (423 vs. 182·5, P = 0·018) were significantly higher in carriers. Haemophilia A carriers exhibit increased bleeding symptoms when compared to normal women. Further studies are necessary to fully understand the bleeding phenotype in this population and optimize clinical management.
Gene therapy has the potential to overcome many of the limitations of prophylactic hemophilia therapies. Several clinical trials evaluate investigational adeno-associated virus (AAV)-mediated gene ...transfer approaches for the treatment of hemophilia A and B. The practical application of these approaches is nuanced by differences in AAV serotypes, transgene modifications, manufacturing, dosing, administration, and approach to follow-up. This guide explores mechanisms of AAV gene transfer, identification of appropriate candidates for clinical trial participation, anticipated trial events that follow infusion of an investigational gene therapy including outcomes to be monitored, and future considerations. Patient-accessible infographic summaries of these topics are included to serve as potential visual aids that healthcare providers may choose to utilize or adapt to guide informed consultation. The fundamentals of AAV-mediated, liver-directed gene transfer for hemophilia are reviewed, to facilitate discussion between healthcare providers, patients, and their families and advocates if considering a trial of investigational gene therapy.
Introduction
The formation of neutralizing antifactor VIII (fVIII) antibodies, called inhibitors, is the most common complication in modern haemophilia A care. Novel non‐factor replacement therapies, ...such as emicizumab, have sought to address the limitations of bypassing agents for bleeding management in patients with inhibitors. However, immune tolerance induction (ITI) remains the primary method for eradicating inhibitors and restoring the hemostatic response to fVIII.
Aim
The aim of this study was to review a case series of paediatric patients with haemophilia A and inhibitors who have received ITI for inhibitor eradication concomitantly with emicizumab prophylaxis for bleeding prevention.
Methods
Single institution retrospective chart review of paediatric patients with severe haemophilia A receiving ITI and emicizumab.
Results
Seven patients were included in this cohort. Six patients used three different recombinant fVIII products at 100 IU/kg three times per week, and one patient used a plasma‐derived fVIII product at an initial dose of 50 IU/kg three times per week. Three patients achieved a negative inhibitor titre <0.6 Chromogenic Bethesda Units per mL (CBU/mL), and two patients achieved a normal fVIII recovery ≥66%. There were nine bleeding events in four patients, but no thrombotic events. All patients remained on ITI and emicizumab.
Conclusion
Immune tolerance induction while on emicizumab prophylaxis is a feasible approach in paediatric haemophilia A patients with inhibitors. This is the first report of the concomitant use of ITI in patients receiving emicizumab prophylaxis described as the ‘Atlanta Protocol’.
Introduction
Women and girls affected by haemophilia, including haemophilia carriers (WGH) are at risk of bleeding symptoms that may go unrecognized, including heavy menstrual bleeding (HMB) and ...musculoskeletal bleeding. Terminology continues to evolve.
Aim
To describe the current recommendations for nomenclature surrounding WGH, and the current understanding of HMB, iron deficiency, and musculoskeletal complaints in these patients.
Methods
Literature was reviewed and summarized.
Results
With regards to nomenclature, women with factor levels less than 50% should be classified as having haemophilia, while carriers with normal levels should be characterized accordingly to symptomatology. HMB and resultant iron deficiency are common among WGH, have a multitude of downstream effects, and maybe overlooked due to stigma around menstruation. Musculoskeletal bleeding and resultant joint changes are increasingly recognized in this population but do not necessarily correlate with factor levels.
Conclusion
Although progress has been made in the care of WGH, much work remains to further improve their care.
Background
Sickle cell disease (SCD) is associated with hypercoagulability, but adults with SCD also have an increased incidence of bleeding including heavy menstrual bleeding (HMB). HMB is common ...among adolescent females, but the impact of HMB in pediatric SCD is unclear. The objectives of this study were to examine menstrual health status, knowledge, and quality of life (QOL).
Methods
We performed a single‐institutional multi‐clinic cross‐sectional study comprised of a five‐part survey in pediatric participants with SCD. The survey included the validated Menstrual Bleeding Questionnaire (MBQ) and Self‐administered Bleeding Assessment Tool (Self‐BAT).
Results
Forty‐eight participants with a median age of 16 years (range: 12–21 years) completed the study. The mean age at onset of menarche was 13 ± 1.3 years. On the MBQ, 29% reported heavy/very heavy menstrual flow, 61% reported moderate or severe dysmenorrhea, and 96% had menses lasting less than 1 week. The Self‐BAT revealed that 42% of participants reported a history of HMB. Participants with severe dysmenorrhea or HMB had higher MBQ scores, corresponding to worse QOL. Despite this, less than 20% of participants had attempted any hormonal therapy for menstrual regulation. The odds of hormonal therapy utilization were comparable among participants on hydroxyurea versus not on hydroxyurea (odds ratio 1.58, 95% confidence interval CI: 0.33–7.56).
Conclusions
The prevalence of HMB and dysmenorrhea is high among adolescents and young women with SCD. Strategies that incorporate menstrual health assessment into routine medical care in this population would help address this important area of pediatric health.
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