Specific guidance is lacking for delivery planning in terms of how high a factor level should be achieved for pregnant women with von Willebrand disease (VWD) who, by the third trimester, do not have von Willebrand factor (VWF) (or factor VIII) levels greater than 50-100%. Specifically, guidance is lacking on whether replacement therapy should target a VWF minimum level in the 100–150% range, i.e., a range closer to the 200–250% levels observed in normal pregnancy.
Objectives:
The primary objective is to document the rate of primary postpartum hemorrhage (PPH) and thereby the effectiveness of targeting minimum VWF levels of 100–150% for delivery. The secondary objective is to document further effectiveness outcomes and safety. Patient VWF levels will be maintained at 100-150% for the immediate 72-hour postpartum period, and thereafter maintained at 50-100% target VWF levels through days 5-7 postpartum after normal vaginal delivery or days 7–10 postpartum after caesarean section.
Methods:
This is a prospective, open-label, cohort study of the dosing of Wilate in pregnant patients with VWD to achieve minimum VWF levels of 100–150% for delivery. Outcome parameters will be assessed among patients termed non-correctors and correctors. Patients with a third trimester (gestational week 34–38) VWF level <100% will be enrolled in the non-corrector group. Patients with VWF levels ≥100% at gestational weeks 34–38 will be enrolled in the corrector group. Sample size is based on 65 pregnant VWD non-corrector patients and up to 30 corrector patients. Both correctors and non-correctors will be given tranexamic acid post-partum for 14 days.
Inclusion Criteria: includes VWD patients diagnosed prepartum as type 1 per NHLBI criterion of VWF level <30%, or type 2, or type 3. Exclusion Criteria includes age <18 years, presence of other concurrent disorder of hemostasis, platelet dysfunction, or collagen disorders; presence of liver disease or renal disease, clinical suspicion or diagnosis of preeclampsia or eclampsia, HELLP syndrome, TTP, DIC, or other acquired vasculopathy or coagulopathy, or inability to perform local laboratory monitoring. Primary outcome parameter will be the rate of primary PPH, defined as estimated blood loss ≥1000 mL, or severe PPH defined as estimated blood loss >2000 mL within 24 hours postpartum. Other outcomes are secondary PPH, laboratory measures, and safety. Screening will begin in Q3 2019 and end in Q2 2023, with recruitment ending 6 months before (i.e., Q4 2022).
Summary:
This planned study aims to determine in VWD if VWF levels postpartum should be attained at levels closer to levels achieved physiologically in a normal pregnancy.
Conclusions:
Results from this study will hopefully lead to reduction of the relatively high rate of PPH in VWD women with levels <50-100% in the third trimester.
The hemophilia and thrombosis centers in Tucson and Phoenix would like to join efforts to make a meaningful contribution to our understanding of the mental health profile of our pediatric population. This knowledge could contribute to a more tailored approach when designing clinics and programming, and, by identifying mental health issues, inform the development of targeted interventions. We hope to look at the prevalence of depression and anxiety in children with bleeding disorders including hemophilia, von Willebrand disease, and other congenital coagulopathies. We expect that the existence of a chronic health condition could affect a child's psychological development. We're also aware of the critical impact of family culture so our survey will include data on the mental health of the participants’ primary caretakers as well as other significant socioeconomic markers.
Dr. Satish Nandakumar is currently a postdoctoral fellow in the laboratory of Dr. Vijay Sankaran at the Boston Children's Hospital. Previously, he did his graduate work at the St. Jude's Children's Research Hospital in Memphis, Tennessee. In his JGP Fellowship project, Dr. Nandakumar aims to develop a novel gene therapy approach for hemophilia that involves activation of the endogenous factor VIII or IX genes within hematopoietic stem cells by taking advantage of the CRISPR/Cas9 gene activation system. This work has the potential to benefit patients with mild hemophilia mutations.
Helping teens with bleeding disorders prepare to manage their care as they transition to adulthood is a national priority for US Hemophilia Treatment Centers (HTC). The National HTC Patient Satisfaction Surveys (PSS) reveal high satisfaction with HTC teen transition services. Yet how satisfaction differs comparing HTCs that primarily care for children to HTCs that care for patients throughout the lifespan is unknown.
Objective:
To assess variation in patient satisfaction with US HTC teen transition services by HTC type.
Methods:
The US HTC Network conducted nationally uniform patient satisfaction surveys in 2015 and 2018 on care received, respectively, in 2014 and 2017. A Regional workgroup devised, piloted, and finalized an electronic, two-page survey for self-administration at clinic, or at home, in English or Spanish. Participation was voluntary. Respondents were anonymous but identified their HTC. Parents completed surveys for children under age 18. The PSS included two teen transition questions for respondents age 12-17 to complete. HTC type was categorized as ‘pediatric’ if >80% of responses were from patients/caregivers of individuals under age 18, and ‘adult’ if >80% were from patients over age 24. All other HTCs were categorized as ‘lifespan’. For both years, approximately 26% of HTCs were classified as pediatric, 52% as life-span, and 22% as adult.
Results:
Over 700 teens age 12-17 (or their parents/guardians) from an average of 130 HTCs (94.0%) from all US regions participated in 2015 and 2018. Approximately 96.5% of teens at pediatric HTCs (96.4% - 96.5%) and 96.2% at lifespan HTCs (95.9% - 96.5%) reported being ‘always’ or ‘usually’ (A/U) satisfied with HTC services overall. On average, 90.4% of teens at pediatric HTCs (90.1% - 90.7%) and 91.0% at lifespan HTCs (90.3%–91.6%) reported being A/U satisfied with how HTC clinic staff talked about how to care for the bleeding disorder as they became an adult. Similarly, 92.5% (92.0%– 92.9%) of teens at pediatric HTCs and 92.5% (92.3%-92.7%) reported being A/U satisfied with how the HTC clinic staff encouraged them to become more independent in managing their bleeding disorder.
Conclusions:
HTC patients age 12-17 years consistently report very high levels of satisfaction with HTC teen transition services, regardless if the HTC primarily cares for patients up to age 17, or throughout the life-span. This suggests teens receive support and tools to successfully transition to adult care across the US HTC Network. A national uniform HTC Patient Satisfaction Survey provides vital information, is feasible to conduct using a regional structure, and well received nationwide.
