The Joint Outcome Study (JOS), a randomized controlled trial, demonstrated that children with severe hemophilia A (HA) initiating prophylactic factor VIII (FVIII) prior to age 2.5 years had reduced joint damage at age 6 years compared with those treated with episodic FVIII for bleeding. The Joint Outcome Continuation Study (JOS-C) evaluated early vs delayed prophylaxis effects on long-term joint health, following JOS participants to age 18 years in an observational, partially retrospective study. Index joint magnetic resonance imaging (MRI) scores of osteochondral (OC) damage (primary outcome), joint physical examination scores, and annualized rates of joint/other bleeding episodes (secondary outcomes) were collected. Thirty-seven of 65 JOS participants enrolled in JOS-C, including 15 randomized to prophylaxis at mean age 1.3 years (“early prophylaxis”); 18 initially randomized to episodic treatment, starting “delayed prophylaxis” at mean age 7.5 years; and 4 with high-titer inhibitors. At JOS-C exit, MRI OC damage was found in 77% of those on delayed and 35% of those on early prophylaxis for an odds ratio of OC damage, in the delayed vs early prophylaxis group, of 6.3 (95% confidence interval, 1.3, 29.9; P = .02). Annualized bleeding rates were higher with delayed prophylaxis (mean plus or minus standard deviation, 10.6 ± 6.6 vs 3.5 ± 2.1; P < .001), including when only comparing time periods on prophylaxis (6.2 ± 5.3 vs 3.3 ± 1.9; P < .05). In severe HA, early initiation of prophylaxis provided continued protection against joint damage throughout childhood compared with delayed initiation, but early prophylaxis was not sufficient to fully prevent damage. This trial was registered at www.clinicaltrials.gov as #NCT01000844.

Options for management of haemophilia are increasing rapidly with completely novel therapeutic approaches that cannot be compared using traditional factor assays. In addition, as prophylaxis regimens have improved, bleeding rates have decreased, and consequently, it is difficult to show an impact of novel therapies on rates of spontaneous bleeding. There is currently an urgent need for a panel of outcome measures to compare therapies that are dissimilar in many essential ways. Conventional objective outcome measures including joint physical examination and joint imaging continue to hold a central importance. Factor assays are essential for evaluation of products derived from native factor genes, but are not applicable to some extended half‐life factors or non‐factor bypassing agents. Global assays including thrombin generation and chromogenic assays of factor X activation are under investigation for their usefulness in haemophilia assessment. Bleeding rate is a conventional subjective patient‐reported outcome that, while decreasing in frequency, is indispensable as an outcome given that the primary manifestation of haemophilia is bleeding. Other patient‐reported outcomes such as pain intensity and interference, health‐related quality of life and activities and participation are increasingly important to distinguish superior outcomes in comparative trials. This review of outcome measures for haemophilia presents examples of existing outcome measures with an emphasis on their strengths and limitations.

Background Emicizumab, a bispecific antibody factor VIII mimetic, is approved for prophylaxis in hemophilia, and has different risks and side effects compared to factor VIII products. Objective To better understand the early impact of emicizumab on our patients at the University of Colorado Hemophilia and Thrombosis Center (UCHTC), we evaluated adverse reactions, factor prophylaxis overlap, and bleeding rates after starting emicizumab through a quality improvement project. Patients/Methods A retrospective chart review and structured phone interview were conducted from June to September 2019 for all patients who had started emicizumab at the UCHTC. Data about emicizumab dosing, reactions, bleeding events, and bleeding treatment were collected in 68 children and adults (aged 0.55‐79.8 years, on emicizumab a median 213 days; range, 51‐1229 days) with hemophilia A (35.3% with past or current inhibitor). Results Adverse reactions were primarily skin reactions, with no anaphylactic reactions or thrombosis. Bleeding events, defined as pain or swelling treated with factor or supportive measures, demonstrated wide variability, with 25 of 68 experiencing zero bleeds and 5 of 68 experiencing >8 bleeds per year. The most prevalent bleed type was traumatic musculoskeletal bleeding. Bleeding events occurred more often in the first 10 weeks after starting emicizumab, but no time period was without bleeding events. The majority of patients were prescribed every‐week or every‐2‐week dosing, but some had alternative dosing frequency. Conclusions Real‐world emicizumab use in our center was characterized by variations in prescribing practices and bleeding outcomes and lack of severe adverse reactions.

Objective: To evaluate the impact of early disseminated intravascular coagulation (DIC) on illness severity in children using a database of ED encounters for children with suspected sepsis, in view of similar associations in adults.Study design: Laboratory and clinical data were extracted from a registry of Emergency Department (ED) encounters of children with suspected sepsis between April 01, 2012 and June 26, 2017. International Society of Thrombosis and Hemostasis DIC scores were calculated from laboratory values obtained within 24 hours of ED admission. Univariate logistic regression, multivariable logistic regression, and Cox regression were used to assess the influence of DIC scores on vasopressor use (primary outcome), mortality, ventilator requirement, pediatric intensive care unit admission, and hospital duration (secondary outcomes). The optimal DIC score cutoff for outcome prediction was determined.Results: Of 1,653 eligible patients, 284 had DIC scores within 24 hours, including 92 who required vasopressors and 23 who died within one year. An initial DIC score≥3 was the most sensitive and specific DIC score for predicting adverse outcomes. Those with a DIC score ≥3 vs.