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European Union funding: 821205, 821003, 820829. Wellcome Trust: 205212/Z/16/Z

INTRODUCTION In good risk patients (historic inhibitor peak

Background It is unclear whether asthma and its allergic phenotype are risk factors for hospitalization or severe disease from SARS‐CoV‐2. Methods All patients over 28 days old testing positive for SARS‐CoV‐2 between March 1 and September 30, 2020, were retrospectively identified and characterized through electronic analysis at Stanford. A sub‐cohort was followed prospectively to evaluate long‐term COVID‐19 symptoms. Results 168,190 patients underwent SARS‐CoV‐2 testing, and 6,976 (4.15%) tested positive. In a multivariate analysis, asthma was not an independent risk factor for hospitalization (OR 1.12 [95% CI 0.86, 1.45], p = .40). Among SARS‐CoV‐2‐positive asthmatics, allergic asthma lowered the risk of hospitalization and had a protective effect compared with non‐allergic asthma (OR 0.52 [0.28, 0.91], p = .026); there was no association between baseline medication use as characterized by GINA and hospitalization risk. Patients with severe COVID‐19 disease had lower eosinophil levels during hospitalization compared with patients with mild or asymptomatic disease, independent of asthma status (p = .0014). In a patient sub‐cohort followed longitudinally, asthmatics and non‐asthmatics had similar time to resolution of COVID‐19 symptoms, particularly lower respiratory symptoms. Conclusions Asthma is not a risk factor for more severe COVID‐19 disease. Allergic asthmatics were half as likely to be hospitalized with COVID‐19 compared with non‐allergic asthmatics. Lower levels of eosinophil counts (allergic biomarkers) were associated with a more severe COVID‐19 disease trajectory. Recovery was similar among asthmatics and non‐asthmatics with over 50% of patients reporting ongoing lower respiratory symptoms 3 months post‐infection., Asthma is not a risk factor for more severe COVID‐19 disease. Allergic asthmatics are half as likely to be hospitalized compared with non‐allergic asthmatics and lower levels of eosinophil counts (allergic biomarkers) are associated with a more severe COVID‐19 disease trajectory. Recovery is similar among asthmatics and non‐asthmatics.

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.

Background Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality and its incidence is increasing in many countries despite management guidelines. A national quality improvement programme called the Obstetric Bleeding Strategy for Wales (OBS Cymru) was introduced in all obstetric units in Wales. The aim was to reduce moderate PPH (1000 mL) progressing to massive PPH (> 2500 mL) and the need for red cell transfusion. Methods A PPH care bundle was introduced into all 12 obstetric units in Wales included all women giving birth in 2017 and 2018 (n = 61,094). The care bundle prompted: universal risk assessment, quantitative measurement of blood loss after all deliveries (as opposed to visual estimation), structured escalation to senior clinicians and point-of-care viscoelastometric-guided early fibrinogen replacement. Data were submitted by each obstetric unit to a national database. Outcome measures were incidence of massive PPH (> 2500 mL) and red cell transfusion. Analysis was performed using linear regression of the all Wales monthly data. Results Uptake of the intervention was good: quantitative blood loss measurement and risk assessment increased to 98.1 and 64.5% of all PPH > 1000 mL, whilst ROTEM use for PPH > 1500 mL increased to 68.2%. Massive PPH decreased by 1.10 (95% CI 0.28 to 1.92) per 1000 maternities per year (P = 0.011). Fewer women progressed from moderate to massive PPH in the last 6 months, 74/1490 (5.0%), than in the first 6 months, 97/1386 (7.0%), (P = 0.021). Units of red cells transfused decreased by 7.4 (95% CI 1.6 to 13.2) per 1000 maternities per year (P = 0.015). Red cells were transfused to 350/15204 (2.3%) and 268/15150 (1.8%) (P = 0.001) in the first and last 6 months, respectively. There was no increase in the number of women with lowest haemoglobin below 80 g/L during this time period. Infusions of fresh frozen plasma fell and there was no increase in the number of women with haemostatic impairment. Conclusions The OBS Cymru care bundle was feasible to implement and associated with progressive, clinically significant improvements in outcomes for PPH across Wales. It is applicable across obstetric units of widely varying size, complexity and staff mixes.

ObjectiveDoes TEN4 categorisation of bruises to the torso, ear or neck or any bruise in DesignProspective comparative longitudinal study.SettingCommunity.PatientsChildren InterventionsThe number and location of bruises compared for 2568 data collections from 328 children in the community, 1301 from 106 children with IBD and 342 abuse cases.Main outcome measuresLikelihood ratios (LRs) for the number of bruises within the TEN and non-TEN locations for pre-mobile and mobile children: abuse vs accidental injury, IBD vs accident, abuse vs IBD.ResultsAny bruise in a pre-mobile child was more likely to be from abuse/IBD than accident. The more bruises a pre-mobile child had, the higher the LR for abuse/IBD vs accident. A single bruise in a TEN location in mobile children was not supportive of abuse/IBD. For mobile children with more than one bruise, including at least one in TEN locations, the LR favouring abuse/IBD increased. Applying TEN4 to collections from abused and accidental group ConclusionsThese data support further child protection investigations of a positive TEN4 screen in any pre-mobile children with a bruise and in mobile children with more than one bruise. TEN4 did not discriminate between IBD and abuse, thus IBD needs to be excluded in these children. Estimated sensitivity and specificity of TEN4 was appreciably lower than previously reported.

As the Coronavirus disease 2019 (COVID-19) pandemic spread to the US, so too did descriptions of an associated coagulopathy and thrombotic complications. Hospitals created institutional protocols for inpatient management of COVID-19 coagulopathy and thrombosis in response to this developing data. We collected and analyzed protocols from 21 US academic medical centers developed between January and May 2020. We found greatest consensus on recommendations for heparin-based pharmacologic venous thromboembolism (VTE) prophylaxis in COVID-19 patients without contraindications. Protocols differed regarding incorporation of D-dimer tests, dosing of VTE prophylaxis, indications for post-discharge pharmacologic VTE prophylaxis, how to evaluate for VTE, and the use of empiric therapeutic anticoagulation. These findings support ongoing efforts to establish international, evidence-based guidelines., Highlights • COVID-19 protocols agreed on heparin-based venous thromboembolism prophylaxis. • Disagreement on thrombosis risk and diagnosis, D-dimer, empiric anticoagulation • Cumulative incidence of COVID-19 did not correlate with specific recommendations. • Framework for frontline providers and hospitals to evaluate practices and outcomes

Acquired hemophilia A (AHA), a rare bleeding disorder caused by neutralizing autoantibodies against coagulation factor VIII (FVIII), occurs in both men and women without a previous history of bleeding. Patients typically present with an isolated prolonged activated partial thromboplastin time due to FVIII deficiency. Neutralizing antibodies (inhibitors) are detected using the Nijmegen-modified Bethesda assay. Approximately 10% of patients do not present with bleeding and, therefore, a prolonged activated partial thromboplastin time should never be ignored prior to invasive procedures. Control of acute bleeding and prevention of injuries that may provoke bleeding are top priorities in patients with AHA. We recommend treatment with bypassing agents, including recombinant activated factor VII, activated prothrombin complex concentrate, or recombinant porcine FVIII in bleeding patients. Autoantibody eradication can be achieved with immunosuppressive therapy, including corticosteroids, cyclophosphamide and rituximab, or combinations thereof. The median time to remission is 5 weeks, with considerable interindividual variation. FVIII activity at presentation, inhibitor titer and autoantibody isotype are prognostic markers for remission and survival. Comparative clinical studies to support treatment recommendations for AHA do not exist; therefore, we provide practical consensus guidance based on recent registry findings and the authors’ clinical experience in treating patients with AHA.

Introduction SHP656 is the first factor VIII (FVIII) product developed using polysialylation (PSA) technology, in which full‐length recombinant (r) FVIII (anti‐haemophilic factor [recombinant]) is conjugated with a 20 kDa PSA polymer. Aim To compare the safety, immunogenicity and pharmacokinetics of SHP656 vs the parent rFVIII (octocog alfa) after single infusions of 25‐75 IU/kg in patients with severe haemophilia A (FVIII activity

Western honey bees (Apis mellifera), a cornerstone to crop pollination in the U.S., are faced with an onslaught of challenges from diseases caused by parasites, pathogens, and pests that affect this economically valuable pollinator. Natural products (NPs), produced by living organisms, including plants and microorganisms, can support health and combat disease in animals. NPs include both native extracts and individual compounds that can reduce disease impacts by supporting immunity or directly inhibiting pathogens, pests, and parasites. Herein, we describe the screening of NPs in laboratory cage studies for their effects on honey bee disease prevention and control. Depending on the expected activity of compounds, we measured varied responses, including viral levels, honey bee immune responses, and symbiotic bacteria loads. Of the NPs screened, several compounds demonstrated beneficial activities in honey bees by reducing levels of the critical honey bee virus deformed wing virus (DWV-A and-B), positively impacting the gut microbiome or stimulating honey bee immune responses. Investigations of the medicinal properties of NPs in honey bees will contribute to a better understanding of their potential to support honey bee immunity to fight off pests and pathogens and promote increased overall honey bee health. These investigations will also shed light on the ecological interactions between pollinators and specific floral food sources.

Background The hallmark of severe hemophilia (A or B) is recurrent bleeding into joints and soft tissues with progressive joint damage, despite on-demand treatment. Prophylaxis has long been used, but not universally adopted, because of medical, psychosocial, and cost controversies. Objectives To determine the effectiveness of clotting factor concentrate prophylaxis in managing previously-treated individuals with hemophilia A or B. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. In addition, we searched MEDLINE and Embase and online trial registries. Most recent search of Group's Coagulopathies Trials Register: 24 February 2021. Selection criteria Randomised controlled trials (RCTs) and quasi-RCTs evaluating people with hemophilia A or hemophilia B, who were previously treated with clotting factor concentrates to manage their hemophilia. Data collection and analysis Two authors independently reviewed trials for eligibility, assessed risk of bias and extracted data. The authors used the GRADE criteria to assess the certainty of the evidence. Main results Ten trials (including 608 participants) were eligible for inclusion. Eight of the trials (477 participants) had arms comparing two or more prophylactic regimens to one another and four of the trials (n = 258) compared prophylaxis to on-demand treatment (two trials had multiple arms and were included in both comparisons). Comparison of two or more prophylactic regimens For trials comparing one prophylaxis regimen to another, given the heterogeneity of the data, none of the data were pooled for this comparison. Considering the individual trials, three trials reported the primary outcome of joint bleeding, and none showed a dfference between dosing regimens (low-certainty evidence). For the secondary outcome of total bleeding events, prophylaxis with a twice-weekly regimen of FIX likely results in reduced total bleeds compared to a once-a-week regimen of the same dose, mean difference (MD) 11.2 (5.81 to 16.59) (one trial, 10 participants, low-certainty evidence). Transient low-titer anti-FVIII inhibitors were reported in one of the trials. Blood-transmitted infections were not identified. Other adverse events reported include hypersensitivity, oedema, and weight gain. These were, however, rare and unrelated to study drugs (very low-certainty evidence). Comparison of prophylactic and on-demand regimens Four of the trials (258 participants) had arms that compared prophylaxis to on-demand treatment. Prophylaxis may result in a large decrease in the number of joint bleeds compared to on-demand treatment, MD -30.34 (95% CI -46.95 to -13.73) (two trials, 164 participants, low-certainty evidence). One of these trials (84 participants) also reported the long-term effects of prophylaxis versus on-demand therapy showing improved joint function, quality of life, and pain; but no differences between groups in joint structure when assessed by magnetic resonance imaging (MRI). In one trial (84 participants) validated measures for joint health and pain assessment showed that prophylaxis likely improves joint health compared to an on-demand regimen with an estimated change difference of 0.94 points (95% CI 0.23 to 1.65) and improves total pain scores, MD -17.20 (95% CI -27.48 to -6.92 (moderate-certainty evidence). Two trials (131 participants) reported that prophylaxis likely results in a slight increase in adverse events, risk ratio 1.71 (1.24 to 2.37) (moderate-certainty evidence). No inhibitor development and blood-transmitted infections were identified. Overall, the certainty of the body of evidence was judged to be low because of different types of bias that could have altered the effect. AUTHORS' CONCLUSIONS: There is evidence from RCTs that prophylaxis, as compared to on-demand treatment, may reduce bleeding frequency in previously-treated people with hemophilia. Prophylaxis may also improve joint function, pain and quality of life, even though this does not translate into a detectable improvement of articular damage when assessed by MRI. When comparing two different prophylaxis regimens, no significant differences in terms of protection from bleeding were found. Dose optimization could, however, result in improved efficacy. Given the heterogeneity of the data, pooled estimates were not obtained for most comparisons. Well-designed RCTs and prospective observational controlled studies with standardised definitions and measurements are needed to establish the optimal and most cost-effective treatment regimens.

Background\udThe TEG 6s is an automated cartridge-based device with limited description of use in obstetric haemorrhage. The aim of this analysis was to describe the utility of TEG 6s in identifying abnormal laboratory results of coagulation and platelet count, and inform an interventional treatment algorithm for postpartum haemorrhage.\udMethods\udA prospective observational cohort study of 521 women with moderate to severe obstetric haemorrhage (>1000 mL blood loss), including 372 women with at least one TEG 6s test. A non-pregnant control group was used for reference. TEG 6s test parameters Citrated Functional Fibrinogen (CFF), Citrated Kaolin TEG (CK) and Citrated Rapid TEG (CRT) were compared with paired laboratory tests of fibrinogen, PT/aPTT and platelet count, obtained during haemorrhage.\udResults\udAmong 456 TEG 6s tests, 389 were matched with laboratory coagulation results. The receiver operator characteristic area-under-the-curve (95% CI) for CFF amplitude by 10 min to detect Clauss fibrinogen ≤2 g/L was 0.95 (0.91 to 0.99) (P

This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) was hosted virtually from Philadelphia July 17-21, 2021. The conference, now held annually, highlighted cutting-edge advances in basic, population and clinical sciences of relevance to the Society. Despite being held virtually, the 2021 congress was of the same scope and quality as an annual meeting held in person. An added feature of the program is that talks streamed at the designated times will then be available on-line for asynchronous viewing. The program included 77 State of the Art (SOA) talks, thematically grouped in 28 sessions, given by internationally recognized leaders in the field. The SOA speakers were invited to prepare brief illustrated reviews of their talks that were peer reviewed and are included in this article. The topics, across the main scientific themes of the congress, include Arterial Thromboembolism, Coagulation and Natural Anticoagulants, COVID-19 and Coagulation, Diagnostics and Omics, Fibrinogen, Fibrinolysis and Proteolysis, Hemophilia and Rare Bleeding Disorders, Hemostasis in Cancer, Inflammation and Immunity, Pediatrics, Platelet Disorders, von Willebrand Disease and Thrombotic Angiopathies, Platelets and Megakaryocytes, Vascular Biology, Venous Thromboembolism and Women's Health. These illustrated capsules highlight the major scientific advances with potential to impact clinical practice. Readers are invited to take advantage of the excellent educational resource provided by these illustrated capsules. They are also encouraged to use the image in social media to draw attention to the high quality and impact of the science presented at the congress. ispartof: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS vol:5 issue:5 ispartof: location:United States status: published

Rurioctocog alfa pegol prophylaxis targeting factor VIII (FVIII) troughs ≥1% has shown to be efficacious with an acceptable safety profile in people with hemophilia A (PwHA). The PROPEL trial compared safety and efficacy of 2 target FVIII troughs in PwHA aged 12 to 65 years, with severe disease, annualized bleeding rate ≥2, and previous FVIII treatment. PwHA were randomized to 12 months’ pharmacokinetic (PK)-guided rurioctocog alfa pegol prophylaxis targeting FVIII troughs of 1% to 3% (reference arm) or 8% to 12% (elevated arm); first 6 months was treatment-adjustment period. The primary endpoint was absence of bleeds during the second 6 months, analyzed using multiple imputations (full analysis set [FAS]). In the 1% to 3% and 8% to 12% arms, respectively, point estimates (95% confidence interval) of proportions of PwHA with zero total bleeds were 42% (29% to 55%) and 62% (49% to 75%) in FAS (N = 115; P = .055) and 40% (27% to 55%) and 67% (52% to 81%) in per-protocol analysis set (N = 95; P = .015). Dosing frequency and consumption varied in each arm. Adverse events (AEs) occurred in 70/115 (60.9%) PwHA; serious AEs in 7/115 (6%) PwHA, including 1 treatment-related in 8% to 12% arm (transient anti–FVIII inhibitor). There were no deaths, serious thrombotic events, or AE-related discontinuations. PK-guided prophylaxis was achievable and efficacious in both arms. No new safety signals were observed in the 8% to 12% arm. These results demonstrate elevated FVIII troughs can increase the proportion of PwHA with zero bleeds and emphasize the importance of personalized treatment. This trial was registered at www.clinicaltrials.gov as #NCT02585960.

Introduction\ud One of the most often stated tenets of haemophilia care is that prophylaxis converts a person from a severe to a moderate phenotype. In this review, we argue that this is not an accurate assumption and that people on prophylaxis predominantly have factor VIII/IX levels in the mild range.\ud \ud Moderate haemophilia and prophylaxis\ud People with moderate haemophilia, who are treating with on‐demand regimens, experience joint bleeds and often develop significant arthropathy. This is especially true for people with a baseline level of 1‒3 IU/dl, as first reported 55 years ago, and confirmed in more recent studies. Evidence is emerging suggesting that people with severe haemophilia who are using prophylaxis have better musculoskeletal outcomes than people with moderate haemophilia treated episodically.\ud \ud Trough levels\ud The debate around the optimum trough level whilst on prophylaxis is ongoing. It is not appropriate to extrapolate information about baseline levels to recommendations about target trough levels on prophylaxis because these are different situations. Studies are emerging that support higher target trough levels than previously used, but in spite of this, the aim of achieving zero bleeds remains elusive with both factor replacement and non‐replacement therapies.\ud \ud Conclusions\ud We recommend that people with moderate haemophilia, especially those with a baseline of 1–3 IU/dl, should be offered prophylaxis based on the same criteria as people with severe haemophilia. Trough levels should be maintained above 3 IU/dl or higher if a level of 3 IU/dl does not control breakthrough bleeding and prophylaxis should be tailored to the bleeding phenotype. This advice is in line with recently published guidelines from the World Federation of Haemophilia and the UK Haemophilia Centre Doctors’ Organisation.

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.

Background: Prolonged symptoms after SARS-CoV-2 infection are well-documented. However, which factors influence development of long-term symptoms, how symptoms vary across ethnic groups, and whether long-term symptoms correlate with serologic biomarkers remain elusive. Methods: Adult inpatient and outpatient SARS-CoV-2 RT-PCR positive patients were recruited at Stanford from March 2020 to February 2021. Study participants were seen for in-person visits at diagnosis and every 1-3 months for up to one year after diagnosis; they completed symptom surveys and underwent sampling procedures (blood draw and nasal swab) at each visit. Findings: Our cohort (n=617) ranged from asymptomatic to critical COVID-19 infections. 40% of participants reported at least one symptom associated with COVID-19 six months after diagnosis. Median time from diagnosis to first resolution of all symptoms was 44 days, median time from diagnosis to sustained symptom resolution with no recurring symptoms for one month or longer was 214 days. Serum anti-nucleocapsid IgG level in the first week of infection was predictive of time to symptom resolution. A prior diagnosis of lung disease was associated with longer time to symptom resolution. COVID-19 disease severity, ethnicity, sex, cytomegalovirus (CMV) seropositivity, and remdesivir use did not affect time to sustained symptom resolution. More than 90% of participants had SARS-CoV-2-specific antibody>1000 AU/mL nine months after diagnosis. Interpretation: Our findings showed that all disease severities had a similar risk of developing post-COVID-19 syndrome in an ethnically diverse population. Comorbid lung disease and lower levels of initial IgG response to SARS-CoV-2 nucleocapsid antigen were associated with longer symptom duration. Trial Registration: National clinical trial database NCT04664309. Funding: NIH CTSA grant, U54 NIH Grant, R21 NIEHS, Sean N Parker Center for Allergy and Asthma Research at Stanford University, the Sunshine Foundation, the Crown Foundation, and the Parker Foundation. Declaration of Interest: Dr. Boyd received support for the current manuscript from Meso Scale Discovery and NIH; 418 received consulting fees by Regeneron for expert testimony, has stocks or stock options in 419 AbCellera Biologics; Dr. Chinthrajah reports grants from NIAID, CoFAR, Aimmune, DBV 420 Technologies, Astellas, Regeneron, Stanford Maternal and Child Health Research Institute 421 (MCHRI), and FARE. She is an Advisory Board Member at Alladapt Therapeutics, Novartis, 422 Genentech, Sanofi, Allergenis, and Nutricia; Dr. Manisha Desai received support from Chan 423 Zuckerberg Foundation; Dr. Maecker received grants or contracts from NIH, Bill & Melinda 424 Gates Foundation, Ionis Corporation, Amgen Corporation; Consulting fees from Magarray Corp; 425 payment or honoraria from UCLA, UC Davis; leadership or fiduciary role at Cytek SAB; stocks 426 or stock options at BD Biosciences; Dr. Nadeau reports grants from National Institute of Allergy and Infectious Diseases (NIAID), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Environmental Health Sciences (NIEHS), and Food Allergy Research & Education (FARE); Director of World Allergy Organization (WAO) , Advisor at Cour Pharma, Consultant for Excellergy, Red tree ventures, and Phylaxis, Co-founder of Before Brands, Alladapt, Latitude, and IgGenix; and National Scientific Committee member at Immune Tolerance Network (ITN), and National Institutes of Health (NIH) clinical research centers, outside the submitted work; patents include, “Mixed allergen composition and methods for using the same”, “Granulocyte-based methods for detecting and monitoring immune system disorders”, “Methods and Assays for Detecting and Quantifying Pure Subpopulations of White Blood Cells in Immune System Disorders,” and “Methods of isolating allergen-specific antibodies from humans and uses thereof”; Dr. Benjamin Pinsky received grants or contracts for the present manuscript from MesoScale Diagnostics; Dr. Angele Rogers was a Clinical Trials Advisory Board Member for Merck; Dr. Sindher reports support for the present manuscript from the NIH, Regeneron, DBV Technologies, Aimmune, Novartis, CoFAR, FARE, participated on a DSMB for Astra Zeneca, DBV, and received payment or honorarium from FARE; Neera Ahuja, Maja Artandi, Linda Barman, Catherine Blish, Andra Blomkalns, William Collins, MacKenzie Cox, Linda Geng, Xiaolin Jia, Megan Mahoney, Monali Manohar, Ruth O’hara, Rajan Puri, Katharina Roltgen, Laura Vaughan, Samuel Yang, Shu Cao, Iris Chang, Hena Din, Evan Do, Andrea Fernandez, Alexandra Lee, Natasha Purington, Yael Rosenberg-Hasson, Theo Snow, Daniel Solis, Michelle Verghese, and Yingjie Weng have no conflict of interest. Ethical Approval: This study was reviewed and approved by the Stanford Administrative Panel on Human Subjects in Medical Research.

Numerous synthetic and naturally-occurring biomaterials have been developed to provide such architectures to support the proliferation of mammalian cells in vitro and in vivo. Our group, and others, have shown that scaffolds derived from plants can be utilized for tissue engineering applications in biomedicine and in the burgeoning cultured meat industry. Such scaffolds are ideally straightforward and inexpensive to prepare, allowing researchers to take advantage of their intrinsic 3D microarchitectures. These efforts inspired us to continue to pursue the development of novel and unconventional biomaterials that are easily produced and high performing in vitro. With this in mind, few plant-derived materials are more ubiquitous than bread. Having observed the porosity of the crumb (i.e. the internal bulk) we sought to investigate whether it might support the proliferation of mammalian cells in vitro. Here, we develop and validate a yeast-free “soda bread” that maintains its mechanical stability over several weeks in culture conditions. Importantly, we also demonstrate that control over the mechanical stability of the scaffold can also be achieved with both chemical and enzymatic means. The scaffolding is a heterogeneous and complex structure of isolated and interconnected pores which allow for the proliferation of multiple cell types. We demonstrate here that mouse fibroblasts, myoblasts and pre-osteoblasts are able to proliferate up to four weeks in culture. Immunohistochemistry demonstrates that the fibroblasts are able to deposit their own fibronectin extracellular matrix and that mouse myoblasts are able to differentiate and fuse into myotubes. Although the pre-osteoblasts proliferated over the course of four weeks their ability to differentiate was inconclusive. Metabolic analyses of proliferation, cytotoxicity and oxidative stress reveal that cells remain highly viable and functional on these novel bread scaffolds. While the results presented in this proof-of-concept study create many new questions and opportunities, the results open up novel possibilities in the development of edible scaffolds that may be utilized in future food applications. Bread derived scaffolds represent a surprising alternative to synthetic or animal-derived scaffolds for addressing a diverse variety of tissue engineering challenges in food science. Future studies will delve deeper into investigating these how possibilities might take advantage of the immense breadth of knowledge about bread making and examine their applicability in the development of lab grown foods and broader applications in cellular agriculture.

INTRODUCTION Point-of-care viscoelastic haemostatic assays such as rotational thromboelastometry (including ROTEM and TEG) have been used in the management of postpartum haemorrhage (PPH). This study compared results obtained from the automated ROTEM Sigma with laboratory tests of coagulation and platelet count during PPH. METHODS A prospective observational cohort study recruited women with PPH ≥1000 mL (or clinical concern of bleeding). The Fibtem A5, Extem CT and Pltem (Extem A5 - Fibtem A5) results were compared with laboratory tests of fibrinogen, prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet count. RESULTS 521 women were recruited, including 274/277 (98.9%) of women with PPH ≥1500 mL. Fibtem A5 results were matched with laboratory fibrinogen in 552/644 (85.7%) samples. The incidence of abnormal laboratory results was low: fibrinogen ≤2 g/L 23/464 (5.0%), PT or APTT >1.5 × midpoint of reference range 4/464 (0.9%), and platelet count

Background Visual estimation of blood loss following delivery often under-reports actual bleed volume. To improve accuracy, quantitative blood loss measurement was introduced for all births in the 12 hospitals providing maternity care in Wales. This intervention was incorporated into a quality improvement programme (Obstetric Bleeding Strategy for Wales, OBS Cymru). We report the incidence of postpartum haemorrhage in Wales over a 1-year period using quantitative measurement. Methods This prospective, consecutive cohort included all 31,341 women giving birth in Wales in 2017. Standardised training was cascaded to maternity staff in all 12 hospitals in Wales. The training comprised mock-scenarios, a video and team drills. Uptake of quantitative blood loss measurement was audited at each centre. Data on postpartum haemorrhage of > 1000 mL were collected and analysed according to mode of delivery. Data on blood loss for all maternities was from the NHS Wales Informatics Service. Results Biannual audit data demonstrated an increase in quantitative measurement from 52.1 to 87.8% (P 1000 mL, > 1500 mL and > 2000 mL was 8.6% (8.3 to 8.9), 3.3% (3.1 to 3.5) and 1.3% (1.2 to 1.4), respectively compared to 5%, 2% and 0.8% in the year before OBS Cymru. The incidence (95% CI) of bleeds of > 1000 mL was similar across the 12 hospitals despite widely varied size, staffing levels and case mix, median (25th to 75th centile) 8.6% (7.8–9.6). The incidence of PPH varied with mode of delivery and was mean (95% CI) 4.9% (4.6–5.2) for unassisted vaginal deliveries, 18.4 (17.1–19.8) for instrumental vaginal deliveries, 8.5 (7.7–9.4) for elective caesarean section and 19.8 (18.6–21.0) for non-elective caesarean sections. Conclusions Quantitative measurement of blood loss is feasible in all hospitals providing maternity care and is associated with detection of higher rates of postpartum haemorrhage. These results have implications for the definition of abnormal blood loss after childbirth and for management and research of postpartum haemorrhage.

Background Factor VIII (FVIII) trough levels > 1 IU/dL in patients with severe hemophilia A receiving regular prophylaxis may optimize bleed protection. Objectives In this post hoc analysis of patients receiving tertiary prophylaxis for approximately 1 year, the relationship between estimated FVIII levels and reported bleeds was investigated to predict the potential for zero bleeds. Methods Sixty-three patients (median [range] age, 28 [7–59] years) with severe hemophilia A (229 bleeds) were included. FVIII levels at time of each bleed were estimated from single-dose individual pharmacokinetics. The highest estimated FVIII level at which patients experienced a bleed was considered the “potentially effective trough level” for that bleed type. Kaplan–Meier estimates of proportions of patients with no bleeds above certain estimated FVIII levels were determined. Those not experiencing a bleed in the trial were assumed to have a bleed at 0 IU/dL (pragmatic approach) or at their median trough level (conservative approach). Results Kaplan–Meier estimates based on pragmatic approach predicted zero all bleeds, joint bleeds, and spontaneous joint bleeds in 1 year in 40, 43, and 63% of patients, respectively, when the potentially effective trough FVIII level was set at 1 IU/dL. Between 1 and 10 IU/dL, every 1 IU/dL rise in estimated FVIII level was associated with an additional 2% of patients having zero all bleeds. Conclusion This post hoc analysis confirms benefits with trough levels of approximately 1 to 3 IU/dL in most patients starting tertiary prophylaxis; prophylaxis with higher trough levels may help patients to achieve zero bleeds.

Background The currently published population pharmacokinetic (PK) models used for PK-guided dosing in hemophilia patients are based on clinical trial data and usually not externally validated in clinical practice. The aim of this study was to validate a published model for recombinant factor VIII-Fc fusion protein (rFVIII-Fc) concentrate and to develop an enriched model using independently collected clinical data if required. Methods Clinical data from hemophilia A patients treated with rFVIII-Fc concentrate (Elocta) participating in the United Kingdom Extended Half-Life Outcomes Registry were collected. The predictive performance of the published model was assessed using mean percentage error (bias) and mean absolute percentage error (inaccuracy). An extended population PK model was developed using nonlinear mixed-effects modeling (NONMEM). Results A total of 43 hemophilia A patients (FVIII ≤ 2 IU/dL), aged 5 to 70 years, were included. The prior model was able to predict the collected 244 rFVIII-Fc levels without significant bias (–1.0%, 95% CI: –9.4 to 7.3%) and with acceptable accuracy (12.9%). However, clearance and central distribution volume were under predicted in patients Conclusion We concluded that the existing rFVIII-Fc population PK model is valid for patients ≥ 12 years. However, it is not reliable in younger patients. Our alternative model, constructed from real world patient data including children, allows for better description of patients ≥5 years.

Introduction\ud \ud Factor VIII inhibitor development is currently the most serious complication of the treatment of haemophilia A. Differences in manufacturing and the molecular structure of brands of recombinant factor VIII have led to speculation that concentrates may differ in immunogenicity. This has led to a regulatory focus on the immunogenicity of factor VIII concentrates both before and after licensure.\ud \ud \ud Aim\ud \ud To investigate the immunogenicity of ReFacto AF post licensure in a real‐world setting in previously untreated patients (PUPs) treated exclusively with this product until at least 50 exposure days (EDs).\ud \ud \ud Methods\ud \ud The United Kingdom Haemophilia Centre Doctors’ Organisation (UKHCDO) National Haemophilia Database (NHD) identified a consecutive cohort of patients with severe haemophilia A (

Emicizumab is a bispecific antibody that activates FX to FXa in the absence of FVIII. It has been shown to reduce bleeding episodes in people with haemophilia A complicated by a FVIII inhibitor. Despite the protection against bleeds, some breakthrough bleeds are inevitable and these may require additional haemostatic treatment. Emicizumab has been associated with severe adverse events when co-administered with activated prothrombin complex concentrate. To minimize the risk of adverse events, the UK Haemophilia Centre Doctors' Organisation issues the following updated interim guidance to its Inhibitor Guidelines for managing patients receiving Emicizumab based on the limit published information available in February 2018.

A multicenter, retrospective, observational study of 4-factor prothrombin complex concentrate (PCC) and/or fresh frozen\ud plasma (FFP) use within routine clinical care unrelated to vitamin K antagonists was conducted. The PCC was administered\ud preprocedure for correction of coagulopathy (prophylactic cohort) and treatment of bleeding postsurgery (treatment cohort). Of\ud the 445 patients included, 40 were in the prophylactic cohort (PCC alone [n ¼ 16], PCC and FFP [n ¼ 5], FFP alone [n ¼ 19]) and\ud 405 were in the treatment cohort (PCC alone [n ¼ 228], PCC and FFP [n ¼ 123], FFP alone [n ¼ 54]). Cardiovascular surgery was\ud the most common setting. PCC doses ranged between 500 and 5000 IU. Effectiveness (assessed retrospectively) was reported as\ud effective in 93.0% in the PCC-only group (95% confidence interval, 89.1% to 95.9%), 78.9% (70.8% to 85.6%) with PCC and FFP,\ud and 86.3% (76.2% to 93.2%) with FFP alone. In the treatment cohort, international normalized ratio was significantly reduced in all\ud 3 groups. In patients who received PCC, the rate of thromboembolic events (1.9%) was below rates in the literature for similar\ud procedures. PCCs offer a potential alternative to FFP in the management of perioperative bleeding unrelated to oral anticoagulant\ud therapy.

Introduction\udBetween 2017 and 2018 a national quality improvement initiative was introduced incorporating point-of-care viscoelastic haemostatic assays (VHA) to guide blood product transfusion. Laboratory coagulation profiles, use and results of VHA, and administration of blood products were investigated.\udMethods\udA two-year prospective cohort study of maternal outcomes of women experiencing massive postpartum haemorrhage (PPH) >1000 mL in Wales. In this study, cases of massive PPH (≥2500 mL and/or ≥5 units red blood cell (RBC) transfusion) were identified.\udResults\udMassive PPH occurred in 349 of 60 914 maternities (rate 5.7 per 1000). There were no deaths from PPH. Intensive care unit admission and/or hysterectomy occurred in 34/311 (10.9%) and 16/347 (4.6%), respectively. The leading cause of massive PPH was genital tract trauma (107/349, 30.6%). Two hundred and seventy-nine (80.6%) required RBC transfusion and 79/345 (22.9%) received at least one blood coagulation product. Results of VHA were recorded in 245/349 (70.2%), with 44/98 (44.9%) women tested in the first six months vs 63/77 (81.8%) in the final six months. Hypofibrinogenaemia (Clauss fibrinogen 1.5×reference range in 10/293 (3.4%).\udConclusion\udIn Wales, the use of VHA in cases of massive PPH increased over time, enabling clinicians to adopt a targeted, patient-specific approach to blood product administration, with only 22.9% of women receiving blood coagulation products and 17.1% having a documented clotting abnormality.

Introduction Haemtrack is an electronic home treatment diary for patients with inherited bleeding disorders, introduced in 2008. It aimed to improve the timeliness and completeness of patient-reported treatment records, to facilitate analysis of treatment and outcome trends. The system is easy to use, responsive and accessible. Methods The software uses Microsoft technologies with a SQL Server database and an ASP.net website front-end, running on personal computers, android and I-phones. Haemtrack interfaces with the UK Haemophilia Centre Information System and the National Haemophilia Database (NHD). Data are validated locally by Haemophilia Centres and centrally by NHD. Data collected include as follows: treatment brand, dose and batch number, time/date of bleed onset and drug administration, reasons for treatment (prophylaxis, bleed, follow-up), bleed site, severity, pain-score and outcome. Results Haemtrack was used by 90% of haemophilia treatment centres (HTCs) in 2015, registering 2683 patients using home therapy of whom 1923 used Haemtrack, entering >17 000 treatments per month. This included 68% of all UK patients with severe haemophilia A. Reporting compliance varied and 55% of patients reported ≥75% of potential usage. Centres had a median 78% compliance overall. A strategy for progressively improving compliance is in place. Age distribution and treatment intensity were similar in Haemtrack users/non-users with severe haemophilia treated prophylactically. Conclusion The Haemtrack system is a valuable tool that may improve treatment compliance and optimize treatment regimen. Analysis of national treatment trends and large-scale longitudinal, within-patient analysis of changes in regimen and/or product will provide valuable insights that will guide future clinical practice.

The western honey bee remains the most important pollinator for agricultural crops. Disease and stressors threaten honey bee populations and productivity during winter- and summertime, creating costs for beekeepers and negative impacts on agriculture. To combat diseases and improve overall bee health, researchers are constantly developing honey bee medicines using the tools of microbiology, molecular biology and chemistry. Below, we present a manifesto alongside standardized protocols that outline the development and a systematic approach to test natural products as ‘bee medicines.’ These will be accomplished in both artificial rearing conditions and in colonies situated in the field. Output will be scored by gene expression data of host immunity, bee survivorship, reduction in pathogen titers, and more subjective merits of the compound in question. Natural products, some of which are already encountered by bees in the form of plant resins and nectar compounds, provide promising low-cost candidates for safe prophylaxis or treatment of bee diseases.

Aims The TEN4 rule (bruising to the Trunk, Ear, Neck or in a child Methods Between 2003–2012, bruising patterns on three groups of children ( Results There were 781 children (350 PA, 103 IBD, 328 controls). Bruising frequency at any location increased with increasing mobility, and both PA and IBD children had a greater frequency and greater number of bruises than controls. In pre-mobile children one or more bruise in any location had >5 times the likelihood of PA and >7 times of IBD than controls, the more bruises that a child had, the greater the likelihood of PA/IBD. Pre-mobile children who had a bruise in the TEN location were significantly more likely to have PA than have IBD. Once mobile children had more than one bruise including one in a TEN location the likelihood of PA/IBD was higher than controls (LR PA >2.5, IBD >3.3). In children with multiple bruises (>2), children with a ‘TEN’ bruise were twice as likely to be PA than IBD. Conclusions Application of the TEN4 rule is effective at indicating pre-mobile children and mobile children with multiple bruises that warrant further investigation. However, as it is poorer at discriminating between IBD and abuse cases, all those children who score positively must have a coagulation screen in addition to child abuse evaluation.

Introduction\ud \ud The THUNDER study provides an analysis of treatment patterns and outcomes in UK patients with severe or moderate haemophilia A (SHA/MHA) in 2015.\ud \ud \ud Methods\ud \ud Patients with SHA or MHA registered with the UK National Haemophilia Database (NHD) were segregated by severity, inhibitor status and age. Haemophilia joint health score (HJHS) was derived from NHD records and treatment regimen and annualized bleed/joint‐bleed rate (ABR/AJBR) from Haemtrack (HT) in HT‐compliant patients.\ud \ud \ud Results\ud \ud We report 1810 patients with SHA and 864 with MHA. Prophylaxis was used in 94.9% (n = 130/137) of HT‐compliant children

Enhanced half-life factor VIII and IX products are being introduced into routine clinical practice. Published data report on clinical trials and there are limited data available on how to use these products in routine clinical practice. Many patients, for example, those with a past history of an inhibitor, have been excluded from clinical trials and there are limited data published on children. This guidance document is a consensus statement from the UK Haemophilia Centres Doctors' Organisation and aims to give pragmatic advice on the use of these products in routine practice.

Introduction: We previously showed that pharmacokinetic-guided prophylaxis (PKP) allows the dosing interval to be extended while maintaining a specific trough level. However, the associations of peak factor VIII (FVIII) levels and area under the curve (AUC) with breakthrough bleeding have not been investigated. Aim: The aim of this study was to analyse data from the PKP arm to determine whether peak FVIII levels, AUC and time with FVIII levels in a haemostatically effective range are independent predictors of bleeding during prophylaxis. Methods: Post hoc analysis of the association of FVIII levels and AUC with annualized bleeding rate in 34 patients on PKP. Results: During 1 year of PKP, 131 bleeding episodes occurred in 24/34 patients. Average peak FVIII levels ranged from 24 to 168 IU dL−1, with higher values associated with a decreased risk for all bleeding (joint and non-joint; P 20 IU dL−1 was 22%; median AUC was 1363. Both values were significantly associated with a lower ABR when targeting a 1% trough at 72 h. Conclusion: When PKP was administered every third day, higher peak FVIII levels, higher AUC and more time spent per week with FVIII levels >20 IU dL−1 provided increased protection from joint and non-joint bleeding. These data highlight the potential impact of variability in individual pharmacokinetic and bleeding risk and support the need for high peak levels and AUC in some patients treated every third day. The findings do not necessarily apply to alternate-day or other prophylactic dosing regimens.

Objective: To ascertain the incidence of massive transfusion (MT) in obstetrics in the UK, and describe its management and clinical outcomes. Design: A population‐based cross‐sectional study conducted through the UK Obstetric Surveillance System (UKOSS). Settings: All UK hospitals with consultant‐led maternity units. Population: Any pregnant woman at ≥20 weeks of gestation receiving ≥8 units of red blood cells within 24 hours of giving birth, from July 2012 to June 2013. Methods: Prospective case identification through the monthly mailing of UKOSS. Results: We identified 181 women who had undergone MT, making the estimated incidence of MT associated with postpartum haemorrhage (PPH) 23 per 100 000 maternities (95% confidence interval 19–26) per year. The median estimated blood loss was 6 l (interquartile range 4.5–8.0 l). The majority of women presented outside working hours (63%), 40% had had previous caesarean sections and 3% had normal vaginal births without risk factors. The main cause for MT was uterine atony (40%) and the main mode of birth was caesarean section (69%). Of the 181 women, 15 received >20 units of red blood cells. In total, 45% of women underwent hysterectomy, and among all causes of PPH, placenta accreta had the highest hysterectomy rate. Two women died, 82% were admitted to intensive care/high‐dependency units, and 28% developed major morbidities. Conclusion: Massive transfusion due to PPH is associated with high rates of morbidity and hysterectomy. Clinical and research efforts should focus on approaches to recognise and optimise timely resuscitation and management of these severe cases. Tweetable abstract: Massive transfusion due to postpartum haemorrhage is associated with high rates of morbidity and hysterectomy.

BackgroundPostpartum haemorrhage (PPH) contributes to substantial maternal morbidity. Research into PPH has led to improvements in care which have been incorporated into the Obstetric Bleeding Strategy for Wales.InterventionA national quality improvement team supported local teams in implementing multiple interventions including risk assessment, objective measurement of blood loss, multiprofessional assessment (at the bedside at 1000 mL blood loss) and point-of-care (POC) testing of coagulation to guide blood product resuscitation during PPH. The project was rolled out to all 12 obstetric units in 2017. The interventions were reinforced by an All Wales Guideline, PPH proforma and standardised training. A national database, biannual audits, and patient and staff surveys reported process and outcome measures.ResultsProcess measures: during 2017, there was an increase in the percentage of maternities with documented risk assessment (0%–76%), objective measurement of blood loss (52%–88%) and POC testing for coagulation for PPH ≥1500 mL (38%–59%). Maternity staff survey indicated that 94% were aware of the project and 87% stated that it had changed their unit’s management of PPH. Interim outcome measures: the incidence (95% CI) of PPH ≥2500 mL per 1000 maternities in 2017 was 6.03 (5.23–6.95). The annual number of women receiving any red blood cell transfusion, level 3 intensive care admission and hysterectomy for PPH was 19.7 (18.2 to 21.3), 0.702 (0.464 to 1.06) and 0.255 (0.129 to 0.504) per 1000 maternities, respectively.ConclusionsA high level of project awareness across Welsh maternity units has been achieved. Measurement of blood loss was reported to be the most important early change in practice, while PPH documentation and POC testing continue to be embedded. Combining qualitative and quantitative measures to inform implementation has improved project delivery and allowed teams to adapt to local contexts.

INTRODUCTION: Standard treatment of congenital haemophilia A is based on replacement therapy with coagulation factor VIII (FVIII) products. A major complication of FVIII therapy is the occurrence of IgG alloantibodies (inhibitors) that neutralize FVIII activity.AIM: The aim of the analysis was estimating the risk of high-titre inhibitor associated with the second-generation full-length product compared to third-generation full-length product and other recombinant FVIII (rFVIII).METHODS: We conducted a combined analysis of individual patient data from three large studies in previously untreated patients (PUPs) with severe haemophilia A.RESULTS: A total of 1109 PUPs were treated from 1993 to 2013 including 787 PUPs treated from 2004 onwards (primary analysis cohort). A total of 322 patients (29.0%) developed an inhibitor, of which 192 (17.3%) a high-titre inhibitor. In the primary analysis set, 29.9% of patients developed an inhibitor and 17.2% a high-titre inhibitor. The combined analysis indicated a lower risk of high-titre inhibitor development for the third-generation rFVIII product compared to the second-generation rFVIII product (primary analysis: adjusted hazard ratio (HR) = 0.72, 95% CI: 0.49 to 1.06). Adjusted HR for all inhibitor development was significantly lower for the third-generation product compared to the second-generation product.CONCLUSION: The trend of an increased risk of inhibitor development in PUPs for one recombinant product illustrates that extrapolation from one recombinant factor VIII product to other products might not be justified. (Less)

Intracranial haemorrhage in children with inherited bleeding disorders is a potentially life‐threatening complication and presents a significant therapeutic challenge. \ud \ud \ud Aim\ud \ud To define the characteristics, management and outcomes of intracranial haemorrhage presenting in UK children ≤16 years of age with inherited bleeding disorders from 2003 to 2015. \ud \ud \ud Method\ud \ud Retrospective analysis of children treated at UK haemophilia centres.\ud \ud \ud Results\ud \ud Of 66 children presenting with Intracranial haemorrhage (ICH), 82% had haemophilia A or B, 3% VWD and 15% a rare IBD. The IBD was a severe phenotype in 91%. The rates of ICH were 6.4 and 4.2 per 1000 patient years for haemophilia A and B, respectively. Median age at presentation was 4 months (33% neonates; 91% children 2 years (67%) than in children 1 month to 2 years (18%; P = .027). Prior to ICH, only 4.5% of children were on prophylaxis. 6% of haemophiliacs had an inhibitor. The median duration of initial replacement therapy was 15 days. Mortality was 13.5%. Neurological sequelae occurred in 39% of survivors, being more common following intracerebral bleeding. In haemophilia survivors, 52% subsequently developed a FVIII inhibitor. \ud \ud \ud Conclusion\ud \ud Intracranial haemorrhage occurs most frequently in children with severe IBDs, during the first 2 years of life and in children not receiving prophylaxis. Intracranial haemorrhage often occurs without documented trauma.

Objectives\ud \ud In a separate document, we have provided specific guidance on performing individual pharmacokinetic (PK) studies using limited samples in persons with hemophilia with the goal to optimize prophylaxis with clotting factor concentrates. This paper, intended for clinicians, aims to describe how to interpret and apply PK properties obtained in persons with hemophilia. \ud \ud \ud Methods\ud \ud The members of the Working Party on population PK (PopPK) of the ISTH SSC Subcommittee on Factor VIII and IX and rare bleeding disorders, together with additional hemophilia and PK experts, completed a survey and ranking exercise whereby key areas of interest in the field were identified. The group had regular web conferences to refine the manuscript’s scope and structure, taking into account comments from the external feedback to the earlier document. \ud \ud \ud Results\ud \ud Many clinical decisions in hemophilia are based on some form of explicit or implicit PK assessment. Individual patient PK profiles can be analyzed through traditional or PopPK methods, with the latter providing the advantage of fewer samples needing to be collected on any prophylaxis regimen, and without the need the for a washout period. The most useful presentation of PK results for clinical decision making are a curve of the factor activity level over time, the time to achieve a certain activity level, or related parameters like half‐life or exposure (AUC). Software platforms have been developed to deliver this information to clinicians at the point of care. Key characteristics of studies measuring average PK parameters were reviewed, outlining what makes a credible head‐to‐head comparison among different concentrates. Large data collections of PK and treatment outcomes currently ongoing will advance care in the future. \ud \ud \ud Conclusions\ud \ud Traditionally used to compare different concentrates, PK can support tailoring of hemophilia treatment by individual profiling, which is greatly simplified by adopting a PopPK/Bayesian method and limited sampling protocol.