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This article discusses the treatment and outcomes of patients with acquired hemophilia A (AHA) at a single center. The study found that the implementation of a treatment algorithm standardized care and improved outcomes for patients. The use of recombinant porcine factor VIII (rpFVIII) as the first-line hemostatic agent and rituximab as a treatment option increased. The study also found that outpatient treatment with hemostatic agents was feasible and allowed for reimbursement. The study acknowledges its limitations, including its small sample size and retrospective design. Overall, the findings suggest that the treatment algorithm improved the management of AHA patients at the center. [Extracted from the article]

Introduction: Von Willebrand disease (VWD) is the most common inherited bleeding disorder. The bleeding phenotype is variable, and some individuals have persistent symptoms post‐diagnosis. Aim: To characterize bleeding patterns in patients with VWD before and after diagnosis. Methods: De‐identified claims data for commercially insured patients in the IQVIA PharMetrics® Plus US database (Jan‐2006 to Jun‐2015) were extracted. Eligible patients had ≥2 claims for VWD (ICD‐9 code 286.4), and continuous health‐plan enrolment for ≥2 years before and after diagnosis. Bleeding event, treatment and treating‐physician type were analysed for 18 months before and 7‐24 months after diagnosis, according to pre‐diagnosis bleeding phenotype (claims from one vs multiple bleed sites) and post‐diagnosis bleeding status (resolved [no post‐diagnosis bleed claims] vs continued [≥1 claim]). Results: Data for 3756 eligible patients (72.6% female; 71.0% aged ≥18 years at diagnosis) were analysed. Overall, 642 (17.1%) and 805 (21.4%) patients had single‐ and multiple‐site bleed claims pre‐diagnosis, respectively, and 1263 (33.6%) patients (38.5% of women, 20.8% of men) continued to bleed post‐diagnosis. Multiple‐site bleeding was associated with pre‐diagnosis heavy menstrual bleeding (HMB), oral contraceptive (OC) use and nasal cauterization. Continued bleeding post‐diagnosis was associated with pre‐diagnosis gastrointestinal bleeding, HMB and epistaxis; pre‐diagnosis use of OCs, aminocaproic acid and nasal cauterization; and younger age at diagnosis. Few patients consulted a haematologist for bleed management. Conclusion: Many patients with VWD have persistent bleeding from multiple sites and continue to bleed post‐diagnosis. Our findings suggest a need to optimize management to reduce the symptomatic burden of VWD following diagnosis. [ABSTRACT FROM AUTHOR]

Background: Extended half‐life (EHL) factor VIII (FVIII) and IX (FIX) products are intended to decrease the burden of prophylaxis for patients with haemophilia A or B. Whether these newer concentrates have led to meaningful clinical practice change remains vague. Aim: To characterize the longitudinal use of standard (SHL) and EHL factor concentrates at haemophilia treatment centres (HTCs), using the ATHNdataset, a US database of 138 ATHN‐affiliated HTCs. Methods: Factor concentrate use among moderate and severe haemophilia A and B patients without inhibitors was analysed at three time points over 18 months. Results: Use of EHL concentrates rose from 10% of patients to 22% during this study. EHL FVIII prophylaxis is prescribed to the minority of patients, 28%; EHL FIX now predominates for prophylaxis, 52%. Rates of prescribed EHL products varied significantly by age group and HTC region. Median prescribed prophylaxis for SHL compared to EHL products was FVIII 6240 and 5200 and FIX 6968 and FIX 3900 IU/kg/y, respectively. On‐demand EHL use has grown but has minimal contribution to overall usage (2%). Conclusion: Haemophilia treatment centre region and patient age impact the rate of adoption of EHL products; however, EHL prescribing continues to rise nationally, particularly for EHL FIX. Careful attention to annual cost of prophylaxis is imperative as the decrease in median EHL prophylaxis consumption is not offset by the higher unit cost of these products. It is unclear how further growth in use of EHLs will be impacted by emerging non‐factor replacement and gene therapies. [ABSTRACT FROM AUTHOR]

Spontaneous bleeding and poor bleeding response with extended half-life factor IX products: A survey of select US haemophilia treatment centres Factor IX (FIX) has distinct pharmacokinetic properties compared to factor VIII (FVIII) including distribution to the extravascular space. This included 24 (34%) who received recombinant factor IX (FIX) albumin fusion protein (rFIX-FP) and 31 (44%) who received recombinant factor IX Fc fusion protein at some point. [Extracted from the article]

rFVIIIFc (Eloctate) is an extended-half-life recombinant factor VIII-Fc fusion protein that may promote factor VIII (FVIII) tolerance through Fc immunoregulatory properties. Yet, little is known regarding its immunogenicity in patients with hemophilia A (HA) or in HA with inhibitors (HA-I), including tolerized, immune tolerance induction (ITI)-refractory, or ITI-naïve. We reviewed medical records of 60 patients, including 2 previously-untreated patients (PUPs) and 58 previously-treated patients (PTPs), cared for between 01/01/06 and 06/01/17, on whom anti-FVIII antibody data were available before and after initiating rFVIIIFc. Continuous data were analyzed by student's t- test, and discrete data by chi square or Fisher's exact test. After initiating rFVIIIFc, one of two HA PUPs developed a low-responding (LR) inhibitor after 10 exposures, which resolved (anti-VIII<0.6 B.U.) within 8 additional exposures, while none of 41 HA PTPS developed an inhibitor. Among 19 HA-I PTPs with detectable inhibitors prior to rFVIIIFc, 5 developed an anamnestic response to rFVIIIFc, including 1 of 8 (12.5%) low-responding (LR), and 4 of 9 (44.9%) high-responding (HR), of whom 3 were ITI-naïve and 1 ITI-refractory. Inhibitors resolved in 4 HR within 2 months of continuing rFVIIIFc (median) but persisted in 1 LR at low titer. The remaining 11 HA-I PTPs, including 4 HR and seven LR, had no detectable inhibitor at the time of or after initiating rFVIIIFc. rFVIIIFc was immunogenic in HA PUPs and in HA-I PTPs persistently ITI-naïve or ITI-refractory, with inhibitor resolution in the majority. rFVIIIFc immunogenicity appears to be similar to other FVIII products. [ABSTRACT FROM AUTHOR]

Background Despite treatment, women with von Willebrand disease (VWD) have lower von Willebrand factor (VWF) levels and greater blood loss at delivery than controls. Current weight-based dosing does not account for the ~ 1.5-fold increase in blood volume in pregnancy. Methods To evaluate the feasibility of a trial to prevent postpartum hemorrhage (PPH), we reviewed pre-pregnancy and 8th month VWF levels in women with VWD with and without PPH following vaginal delivery, assessed VWF concentrate use at delivery by U.S. hemophilia treatment center physician survey, and reviewed thrombosis risk with VWF concentrate by literature review. We determined trial interest and acceptability by structured interviews of physicians and patients. Analysis was by Student's t -test for continuous data, and chi-square or Fisher's exact test for discrete data. Results PPH was associated with lower pre-pregnancy VWF:RCo, p < 0.005; higher pre-pregnancy, 8th and 9th-month weight, each p < 0.001; a family bleeding history, p = 0.036; and VWF concentrate treatment, p = 0.005. Surveyed physicians reported first-line therapy at delivery was VWF concentrate, at a mean dose 50 IU/kg. A trial of a 1.5-fold volume-based dose increase was acceptable to physicians and patients, if it is safe and if costs and visits are minimized. A literature review determined thrombosis risk with VWF concentrate is low, 0.4%. Conclusions This study suggests pre-pregnancy VWF:RCo may predict PPH, but 50–80 IU/kg VWF concentrate dosing may not prevent PPH. If pharmacokinetic modeling confirms volume-based dosing achieves VWF levels comparable to pregnant controls, it may be possible to determine if volume-modified VWF concentrate dosing will reduce PPH in VWD. [ABSTRACT FROM AUTHOR]

Background: Despite treatment, women with von Willebrand disease (VWD) have lower von Willebrand factor (VWF) levels and greater blood loss at delivery than controls. Current weight-based dosing does not account for the ~1.5-fold increase in blood volume in pregnancy., Methods: To evaluate the feasibility of a trial to prevent postpartum hemorrhage (PPH), we reviewed pre-pregnancy and 8th month VWF levels in women with VWD with and without PPH following vaginal delivery, assessed VWF concentrate use at delivery by U.S. hemophilia treatment center physician survey, and reviewed thrombosis risk with VWF concentrate by literature review. We determined trial interest and acceptability by structured interviews of physicians and patients. Analysis was by Student's t-test for continuous data, and chi-square or Fisher's exact test for discrete data., Results: PPH was associated with lower pre-pregnancy VWF:RCo, p<0.005; higher pre-pregnancy, 8th and 9th-month weight, each p<0.001; a family bleeding history, p=0.036; and VWF concentrate treatment, p=0.005. Surveyed physicians reported first-line therapy at delivery was VWF concentrate, at a mean dose 50IU/kg. A trial of a 1.5-fold volume-based dose increase was acceptable to physicians and patients, if it is safe and if costs and visits are minimized. A literature review determined thrombosis risk with VWF concentrate is low, 0.4%., Conclusions: This study suggests pre-pregnancy VWF:RCo may predict PPH, but 50-80IU/kg VWF concentrate dosing may not prevent PPH. If pharmacokinetic modeling confirms volume-based dosing achieves VWF levels comparable to pregnant controls, it may be possible to determine if volume-modified VWF concentrate dosing will reduce PPH in VWD., (Copyright © 2017 Elsevier Ltd. All rights reserved.)