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Background: Patient-reported outcomes measurement information system (PROMIS) measures can be used to measure patient-reported outcomes. PROMIS measures, including computer adaptive tests (CATs) and short forms, have demonstrated the ability to adequately assess outcomes in patients with hemophilia. It is, however, unclear if PROMIS measures are suitable for patients with von Willebrand disease (VWD), inherited platelet function disorders (IPFDs), and rare bleeding disorders (RBDs)., Objectives: To evaluate the feasibility, measurement properties, and relevance of PROMIS measures in adults with VWD, IPFDs, and RBDs., Methods: In this cross-sectional multicenter study, adults with VWD, IPFDs, and RBDs completed 9 PROMIS measures and the Short Form-36 version 2 (SF-36v2) electronically. Feasibility was determined by the number of completed items and floor/ceiling effects. Measurement properties included construct validity based on a multitrait-multimethod analysis and reliability using the reliability coefficient and greatest lower bound. Relevance was evaluated based on comparison with the Dutch general population., Results: In total, 111 patients (median age, 57 years [IQR, 44-67]; 60% VWD, 16% IPFD, 24% RBD) participated. Mean number of items answered varied from 5.3 to 8.7 (range, 4-12) per PROMIS CAT in patients with VWD. Construct validity was supported for all CATs and all instruments had a good reliability (≥0.70). The PROMIS measures had less ceiling effects than the SF-36v2., Conclusion: The PROMIS measures are a feasible, valid, and reliable alternative for the SF-36v2 in patients with primarily nonsevere forms of VWD. The relevance of the selected measures was limited. Additional research is necessary to evaluate the PROMIS measures in adults with IPFDs and RBDs., (© 2024 The Authors.)

Background: Although desmopressin (DDAVP) is an accessible and inexpensive hemostatic drug, its use in pregnancy is still debated due to safety uncertainties., Objectives: We aimed to review the safety and effectiveness of DDAVP in women with an inherited bleeding disorder during pregnancy and delivery., Methods: Databases were searched for articles up to July 25, 2022, reporting maternal and/or neonatal outcomes. PRISMA methodology for systematic reviews and meta-analyses was followed (PROSPERO CRD42022316490)., Results: Fifty-three studies were included, comprising 273 pregnancies. Regarding maternal outcomes, DDAVP was administered in 73 women during pregnancy and in 232 during delivery. Safety outcome was reported in 245 pregnancies, with severe adverse events reported in 2 (1%, hyponatremia with neurologic symptoms). Overall, DDAVP was used as monotherapy in 234 pregnancies, with effectiveness reported in 153 pregnancies (82% effective; 18% ineffective). Regarding neonatal outcomes, out of 60 pregnancies with reported neonatal outcomes after DDAVP use during pregnancy, 2 children (3%) had a severe adverse event (preterm delivery n = 1; fetal growth restriction n = 1). Of the 232 deliveries, 169 neonates were exposed to DDAVP during delivery, and in 114 neonates, safety outcome was reported. Two children (2%) experienced a moderate adverse event (low Apgar score n = 1; transient hyperbilirubinemia not associated with DDAVP n = 1)., Conclusion: DDAVP use during pregnancy and delivery seems safe for the mother, with special attention to the occurrence of hyponatremia and for the child, especially during delivery. However, due to poor study designs and limited documentation of outcomes, a well-designed prospective study is warranted., Competing Interests: Declaration of competing interests L.G.R.R. received a travel grant in 2019 as well as the Young Investigators Award in 2020, both from Sobi. F.W.G.L. has received unrestricted research grants from CSL Behring, Takeda, Sobi, and uniQure; is a consultant for CSL Behring, Takeda, Biomarin, and uniQure, of which the fees go to the University; and was a Data and Safety Monitoring Board (DSMB) Guidelines | National Institute of Dental and Craniofacial Research (nih.gov) member of a study sponsored by Roche. M.J.H.A.K. received funding for research outside this project from Sobi and speaker fees from Roche, Sobi, and BMS; all payments (funding and speakers fee) were made to the institute (Erasmus MC). M.H.C. has received investigator-initiated research and travel grants over the years from the Netherlands Organization for Scientific Research, the Netherlands Organization for Health Research and Development, the Dutch “Innovatiefonds Zorgverzekeraars,” Pfizer, Baxter/Baxalta/Shire, Bayer Schering Pharma, CSL Behring, Sobi, Novo Nordisk, Novartis, and Nordic Pharma, and has served as a steering board member for Roche and Bayer. All grants, awards, and fees go to the institution. The other authors declare no conflicts of interest relevant to the contents of this manuscript. This study was performed on behalf of the SYMPHONY consortium (NWA.1160.18.038.) which is funded by a grant from the Netherlands Organization for Scientific Research., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Individuals with von Willebrand disease (VWD) require desmopressin testing because of interindividual response differences. However, testing is burdensome, while not all patients may need extensive testing., Objectives: To provide von Willebrand factor (VWF) cutoffs that predict desmopressin nonresponse and thereby identify individuals who do not need extensive testing in a retrospective cohort. We validated these cutoffs in a prospective cohort., Patients and Methods: We included 376 patients (Type 1 VWD with VWF activity [VWF:Act] <0.30 IU/ml: n  = 112; with VWF:Act 0.30-0.50 IU/ml: n  = 206; Type 2 VWD: n  = 58; ages, 5-76 years) from January 2000 to July 2020. We collected VWF:Act and factor VIII activity (FVIII:C) at baseline and several time points after desmopressin (T1-T6). We defined response as VWF:Act and FVIII:C 0.50 IU/ml or greater at T1 and T4. We compared VWF:Act and FVIII:C distribution (historically lowest level, baseline, and T1) between responders and nonresponders and determined cutoffs discriminating between these groups. Results were validated in a group of 30 individuals., Results: All individuals with Type 1 VWD and Type 2 VWD, respectively, with baseline VWF:Act 0.34 IU/ml or greater or 0.28 IU/ml or greater were responders. In individuals with T1 VWF:Act ≥0.89 IU/ml (Type 1 VWD) or T1 VWF:Act 1.10 IU/ml or greater (Type 2 VWD), response remained at T4., Conclusion: Desmopressin testing is not needed when lowest historical VWF:Act is 0.30 IU/ml or greater. In patients with Type 1 VWD who require testing, measurements after T1 are often not needed. In patients with Type 2 VWD who require testing, we advise performing T1 and T4 measurements., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Aim: Currently, it is unknown which patient-reported outcomes are important for patients with autosomal inherited bleeding disorders. Therefore, the purpose of this study is to systematically review the available literature assessing patient-reported outcomes and their measurement methods in autosomal inherited bleeding disorders., Methods: The Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trails and Google Scholar databases were searched from inception until 14 August 2020. Studies on patient-reported outcomes in patients with von Willebrand disease, inherited platelet function disorders and coagulation factor deficiencies were included., Results: Twenty-one articles met the inclusion criteria. Three studies were assessed as having poor quality, and therefore a high risk of bias. Nineteen studies had fair quality rating. Different measurements methods were used, ranging from predefined to self-developed questionnaires. The majority of included studies focused on von Willebrand disease. Patients with von Willebrand disease reported lower health-related quality of life compared to the general population. Overall, this trend was especially visible in the following domains: vitality, physical and social functioning and pain. Women with inherited bleeding disorders scored lower on health-related quality of life compared to men, especially women with heavy menstrual bleeding. Patients with joint bleeds or heavy menstrual bleeding reported an increased level of pain., Conclusion: Patients with autosomal inherited bleeding disorders report lower health related quality of life, especially those with joint bleeds or heavy menstrual bleeding. Numerous measurement methods are used in patients with autosomal inherited bleeding disorders, highlighting the need for studies using established, standardized measurement methods., (© 2022 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Introduction: Von Willebrand disease (VWD) is a bleeding disorder, caused by a deficiency or defect of von Willebrand factor (VWF). In case of medical procedures or bleeding, patients are treated with desmopressin and/or VWF-containing concentrates to increase plasma VWF and factor VIII (FVIII). However, in many cases these factor levels are outside the targeted range. Therefore, population pharmacokinetic (PK) models have been developed, which aim to quantify and explain intraindividual and interindividual differences in treatment response. These models enable calculation of individual PK parameters by Bayesian analysis, based on an individual desmopressin test or PK profile with a VWF-containing concentrate. Subsequently, the dose necessary for an individual to achieve coagulation factor target levels can be calculated., Methods and Analysis: Primary aim of this study is to assess the predictive performance (the difference between predicted and measured von VWF activity and FVIII levels) of Bayesian forecasting using the developed population PK models in four different situations: (A) desmopressin testing (n≥30); (B) medical procedures (n=70; 30 receiving desmopressin, 30 receiving VWF-containing concentrate and 10 receiving a combination of both); (C) bleeding episodes (n=20; 10 receiving desmopressin and 10 receiving VWF-containing concentrate) and (D) prophylaxis with a VWF-containing concentrate (n=3 to 5). Individuals with all types of VWD and individuals with low VWF (VWF 0.30-0.60 IU/mL) will be included. Reliability and feasibility of PK-guided dosing will be tested by assessing predictive performance, treatment duration, haemostasis, patient satisfaction and physician satisfaction., Ethics and Dissemination: The OPTI-CLOT:to WiN study was approved by the medical ethics committee of the Erasmus MC, University Medical Centre Rotterdam, the Netherlands. Results of the study will be communicated through publication in international scientific journals and presentation at (inter)national conferences., Trial Registration Number: NL7212 (NTR7411); Pre-results, EudraCT 2018-001631-46., Competing Interests: Competing interests: JMH has received an award from CSL Behring outside the submitted work. CMZ had received research grants from Pfizer, Celgene, Daiichi-Sankyo and is a consultant for Incyte, Sanofi and Pfizer. FWGL has received unrestricted research grants from CSL Behring, Takeda and uniQure, and is consultant for Takeda, uniQure and Biomarin. He is DSMB member for a study sponsored by Roche. RAAM has received travel grants from Shire and Bayer. MHC has received grants from governmental research institutes such as NWO, ZonMW, Innovation fund, institutional grants and unrestricted investigator research grants/educational and travel funding from the following companies over the years: Pfizer, Baxter/Baxalta/Shire, Bayer Schering Pharma, CSL Behring, Sobi Biogen, Novo Nordisk, Novartis and Nordic Pharma, and has served as a member on steering boards of Roche, Bayer and Octapharma. The remaining authors declare no competing financial interests. All unrestricted research grants, awards, educational grants and consultancy fees of all authors were forwarded to the respective institutions., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A 47-years-old man presented with the complaint that he could not open his eyes in the morning. Facial myxedema caused by hypothyroidism was evident. Pictures taken after treatment for six months with levothyroxine showed complete recovery. Myxedema is caused by accumulation of glycosaminoglycans in the dermis.