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Item does not contain fulltext BACKGROUND: Accurate measurements of coagulation factor activity form an essential part of hemophilia management and are performed by the one-stage or chromogenic assay. Current literature suggests that approximately one-third of persons with nonsevere hemophilia A exhibit assay discrepancy, albeit with a high variability between studies. Such data are scarce in nonsevere hemophilia B. OBJECTIVES: To investigate the extent of factor VIII/IX one-stage and chromogenic assay discrepancy in moderate and mild hemophilia A and B. METHODS: Persons with previously diagnosed nonsevere hemophilia A and B with a factor level of 2 to 35 IU/dL were included from the international DYNAMO cohort study. Central measurements of the factor VIII and IX activity levels were performed by the one-stage and chromogenic assay. Relative and absolute discrepancy definitions were used, with the International Society on Thrombosis and Haemostasis-Scientific and Standardization Committee proposed ratio of >2.0 or 10 IU/dL between the assay results. In addition, with more lenient definitions, over 90% of participants (n = 197) had no discrepant results. Only 1 out of 13 persons with a mutation previously associated with discrepancy had significant assay discrepancy. CONCLUSION: Little assay discrepancy was observed despite the presence of mutations previously associated with discrepancy, suggesting that the presence and magnitude of assay discrepancy are largely determined by laboratory variables. 01 april 2023

Introduction and Objectives: Inhibitor development in nonsevere haemophilia A patients (FVIII:C, 2-40 IU/dL) has a heterogeneous clinical phenotype, ranging from irrelevant transient inhibitors to high titre neutralizing antibodies with severe bleeding complications. Data on inhibitor presentation are scarce and selected, favouring those with severe complications. The aim of current study was to describe the presenting symptoms of inhibitors in a large unselected cohort of nonsevere haemophilia patients. Materials and Methods: Clinical data were collected of 107 inhibitor patients derived from a source population of 2,709 nonsevere haemophilia A patients that were treated between 1980 and 2011 in 34 European and Australian centers (the INSIGHT consortium). Patients were subdivided according to age and calendar period at time of inhibitor development (10-year groups), aiming to search for age-related trends and trends over time. Results: Age at inhibitor detection varied widely between 1 and 85 years with a median age of 38 years (IQR, 15-61). Most inhibitors developed in the period of 2000-2010 (n = 64, 60%). Inhibitors developed after a median of 28 exposure days (IQR, 14-66), which was comparable between all age groups. Fifty-seven patients (56%) had high titre inhibitors (>5 BU/mL). About half of the high titre inhibitors developed in patients older than 40 years (n = 30, 53%) and 60% after the year 2000 (n = 34). In 13 (12%) inhibitor patients the inhibitor was detected during routine laboratory screening and no clinical signs of the inhibitor were present. More than half of the patients (n = 61) had an increased bleeding tendency at presentation with inhibitor. In 80 patients (80%) endogenous FVIII:C was decreased to below 5 IU/dL (including 33/44 patients with low titer inhibitors), of whom FVIII:C fell below ≤ 0.01 IU/mL in 49 patients (46%). Conclusion: Half of the patients with nonsevere haemophilia A and inhibitors developed high titre inhibitors; these were more common in the last decennium. More than half of the patients presented with bleeding complications and 46% had changed to a severe phenotype. These results stress the importance of close follow-up after exposure to therapeutic factor VIII concentrates in nonsevere haemophilia A patients.

Introduction and Objectives: Non-severe hemophilia A (baseline FVIII:C, 2-40 IU/dL) is caused by a mutation in the F8 gene. There is limited knowledge on the factors determining the variation in baseline FVIII:C. The aim is to identify the determinants of baseline FVIII:C in non-severe hemophilia A patients. Materials and Methods: We analyzed clinical data for non-severe hemophilia A patients, treated between 1980-2013, in European Haemophilia Treatment Centers (HTCs) participating in the INSIGHT/RISE project. We performed analyses on mutations that were present in ≥10 patients. Age (at FVIII:C measurement), F8 gene mutation, VWF:Ag, VWF:Act and HTC were analyzed as potential determinants by multivariate regression analyses. Results: We identified nine missense mutations present in ≥10 patients in 321 individuals, median age 23 years (IQR 7-47). From these individuals we had data on 667 FVIII:C measurements in 5 HTCs. Median baseline FVIII:C, VWF:Ag and VWF: Act were 17 IU/dL (IQR 11-22), 98 IU/dL (IQR 78-128) and 91 IU/dL (70-115) respectively. Baseline FVIII:C, VWF:Ag and VWF:Act all increased with age, both in the total population and within the two largest mutation groups (Asn618Ser, 113 patients; Arg593Cys, 107 patients). VWF:Ag, age and F8 mutation were significant predictors of baseline FVIII:C (p

Introduction and Objectives: Large inter-individual variation in DDAVP response is observed in non-severe hemophilia A patients. Prediction of the response to DDAVP may support its optimal clinical use. The aim is to analyze the predictive value of known determinants of the DDAVP response. Materials and Methods: We included non-severe hemophilia A patients (FVIII:C, 2- 40 IU/dL) from 34 hemophilia treatment centres in Europe, Australia and North America that participate in the RISE project. Data on the following potential determinants were analyzed: age at DDAVP test, blood group, F8 gene mutation, baseline FVIII:C, body mass index (BMI), VWF:Ag and VWF:Act. Main outcome, the response 1 h after DDAVP administration, is classified as complete (CR; FVIII: C > 50 IU/dL) or not complete (FVIII:C ≤ 50 IU/dL). Data were first analyzed by binary logistic regression analysis. Next, the predictive value of the combined determinants for a CR was used to construct a receiver operator curve (ROC). The area under the ROC curve (AUC) reflects the predictive value of the combined determinants as it represents the proportion of patients with correctly predicted CRs. AUC >80% is considered good, 70-80% fair, and 60-70% poor. Results: We included 850 non-severe hemophilia A patients; median age at time of DDAVP administration was 20 years (IQR 8-40), median baseline FVIII:C, VWF:Ag and VWF:Act levels were 17 IU/dL (IQR 10-25), 95 IU/dL (IQR 72-118), and 86 IU/ dL (IQR 67-111), respectively. A CR was present in 64% of the patients. In the total population, the predictive value for CR was 74% (fair). F8 genotype was known in 508 patients (60%), displaying 136 different missense mutations. Most prevalent were Asn618Ser (n = 105, CR in 84%), Arg593Cys (n = 91, CR in 62%), and Arg2150His (n = 17, CR in 59%). The predictive value of the combined determinants for a CR in the Arg593Cys group was 76% (fair), but was poor in the Asn618Ser group and the Arg2150His group (AUC = 62%, and 67%, respectively). Conclusions: The predictive value of the known determinants of DDAVP response is fair in the complete study group. However, it varies among different mutation groups between fair and poor. This suggests yet unidentified determinants of the response to DDAVP.

Introduction and Objectives: Neutralizing antibodies (inhibitors) directed against the FVIII protein may increase the bleeding frequency and compromise the management of bleeding episodes in nonsevere haemophilia A patients. The median annual bleeding frequency in patients without inhibitors is described to be 0 (IQR 0-3) for mild haemophilia and 1 (IQR 0-13) for moderate haemophilia. The aim of this study was to evaluate the burden of bleeding and to describe the treatment strategies that are used for bleeding episodes in a large group of unselected inhibitor patients with nonsevere haemophilia A. Materials and Methods: We included all inhibitor patients from the INSIGHT study, an international multicentre cohort study including all 2709 nonsevere HA patients (FVIII:C 2-4 IU/dL) that received at least 1 exposure to FVIII concentrate between 1980-2011. Data of the 1st inhibitor period were analyzed. Results: We included 107 nonsevere HA inhibitor patients (median baseline FVIII:C 9 IU/dL (IQR 6-16); median age of 38 years (IQR 15-61)). A high titre inhibitor (> 5 BU/mL) was present in 57 (53%) patients. In 30 (28%) patients the FVIII:C level was decreased ≤1 IU/dL. Eighty-nine patients (83%) received treatment for bleeding episodes. Most patients had spontaneous bleeds (n = 49, 46%); a higher proportion of high titre patients had spontaneous bleeds compared to low titre patients (83% vs. 53%, relative risk (RR) 2.7, 95% confidence interval (CI) 1.3-5.8). The median number of bleeding episodes per inhibitor year was 2 (IQR 1-5); this did not differ between patients with FVIII:C ≤ 1 IU/dL and those with measurable FVIII levels (p = 0.5), patients with low titre and high titre inhibitors (p = 0.5) and patients receiving eradication treatment or not (p = 0.7). In order to treat bleedings, FVIII concentrate was used in 59 patients (55%), FVIII bypassing agents in 50 (47%) and desmopressin in 18 patients (17%). Desmopressin was used more often in patients with remaining circulating FVIII:C levels compared to patients with a FVIII:C ≤ 1 IU/dL and in patients without eradication treatment compared to patients with eradication treatment (25% vs. 3%; RR 7.4, CI 1.0-53.5 and 25% vs. 0%; RR 14.0, CI 0.9 - 224.6, respectively). Conclusion: Inhibitor development in nonsevere HA patients aggravates the burden of bleeding with the majority (83%) of the patients needing treatment for bleeding episodes, at a median of 2 bleeding episodes per year.

Background This study investigates the effect of using patient reported outcomes (PROs) about health-related quality of life (HRQOL) in clinical practice on the type and amount of psychosocial topics discussed during a paediatric oncology consultation. Procedure Children (N?=?193) with cancer participated in a sequential cohort intervention study, with a control (no PRO was used) and intervention group (a PRO was used). For each child three consecutive consultations with the paediatric oncologist were audio recorded in order to assess the discussed psychosocial topics. One third of the audio recordings were qualitatively analysed. Results The type of the discussed psychosocial topics in the control and intervention group did not differ from each other. However, the discussion of psychosocial topics increased in the intervention group compared to the control group. In both groups, topics within the social domain occurred most frequently and topics regarding the emotional domain had the lowest incidence. Conclusions PROs do not change the psychosocial content of communication. Paediatric oncologists already address psychosocial issues during the consultation, regardless of the use of a PRO. However, with a PRO available they address these issues more systematically and more often. Pediatr Blood Cancer 2012; 59: 161166. (C) 2012 Wiley Periodicals, Inc