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The assessment of health-related quality of life (HRQoL) as a patient-reported outcome provides information about the patients' general well-being as well as the effects of the disease and its treatment. This study aimed to investigate HRQoL using both generic and haemophilia-specific QoL instruments and to assess the clinical factors associated with HRQoL among haemophilia patients in Korea. In this cross-sectional, multicenter, observational study, moderate-to-severe haemophilia patients aged 8-64 years were recruited between November 2012 and September 2013. The EQ-5D Questionnaire, EQ Visual Analogue Scale, and Haemophilia-Specific QoL (Haemo-QoL) Questionnaire (Haemo-QoL for 8-16 years and Haemo-A-QoL for ≥17 years) were used to assess HRQoL. A total of 605 participants with a mean age of 29.32 ± 12.62 years were enrolled. The mean Haemo-QoL scores revealed significant differences by age group (children vs. adolescent vs. adult, 26.44 ± 11.3 vs. 28.88 ± 11.1 vs. 38.43 ± 17.7, respectively, p < 0.001). "Sports and leisure," "family planning," and "view" in adults and "perceived support," "friends," and "dealing" in children and adolescents were identified as the domains with the greatest HRQoL impairments. HRQoL was significantly impaired in patients with the following clinical factors: hepatitis, haemophilia-induced disability, bleeding experiences within the last 6 months, joint bleedings within the last 6 months, and haemophilic arthropathy. According to the multivariate regression analysis, HRQoL showed a negative association with the presence of haemophilia-induced disability (β = 0.222, p < 0.0001), bleeding experiences within the last 6 months (β = 0.098, p = 0.010), and haemophilic arthropathy (β = 0.212, p < 0.0001). HRQoL decreased in patients with older age and impaired clinical conditions among moderate-to-severe haemophilia patients in Korea. These study findings may provide significant insights into the adequate haemophilia management using patient-reported measurements., Competing Interests: We have the following interests: This research was sponsored by Pfizer Pharmaceuticals Korea Ltd. We declare that the authors have no other competing interests. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Background: von Willebrand disease (VWD), characterized by quantitative or qualitative defects of von Willebrand factor (VWF), is the most common inheritable bleeding disorder. Data regarding the genetic background of VWD in Korean patients is limited. To our knowledge, this is the first comprehensive molecular genetic investigation of Korean patients with VWD., Methods: Twenty-two unrelated patients with VWD were recruited from August 2014 to December 2017 (age range 28 months-64 years; male:female ratio 1.2:1). Fifteen patients had type 1, six had type 2, and one had type 3 VWD. Blood samples were collected for coagulation analyses and molecular genetic analyses from each patient. Direct sequencing of all exons, flanking intronic sequences, and the promoter of VWF was performed. In patients without sequence variants, multiplex ligation-dependent probe amplification (MLPA) was performed to detect dosage variants. We adapted the American College of Medical Genetics and Genomics guidelines for variant interpretation and considered variants of uncertain significance, likely pathogenic variants, and pathogenic variants as putative disease-causing variants., Results: VWF variants were identified in 15 patients (68%): 14 patients with a single heterozygous variant and one patient with two heterozygous variants. The variants consisted of 13 missense variants, one small insertion, and one splicing variant. Four variants were novel: p.S764Efs*16, p.C889R, p.C1130Y, and p.W2193C. MLPA analysis in seven patients without reportable variants revealed no dosage variants., Conclusions: This study revealed the spectrum of VWF variants, including novel ones, and limited diagnostic utility of MLPA analyses in Korean patients with VWD., Competing Interests: No potential conflicts of interest relevant to this article were reported., (© The Korean Society for Laboratory Medicine.)

Inhibitor development is the most serious complication in patients with hemophilia. We investigated association of HLA genotypes with inhibitor development in Korean patients with severe hemophilia A (HA). HLA genotyping was done in 100 patients with severe HA including 27 patients with inhibitors. The allele frequencies between inhibitor-positive and inhibitor-negative patients were compared. HLA class I alleles were not associated with the inhibitor status. In HLA class II, DRB1*15 [n = 100, odds ratio (OR) 0.217, P = 0.028] and DPB1*05:01 [OR 0.461, P = 0.026] were negatively associated with inhibitor development. In a subgroup of patients with intron 22 inversion, C*07:02 was positively associated with inhibitor development [n = 30, OR 5.500, P = 0.043]. In the subgroup of patients without intron 22 inversion, the negative association between DPB1*05:01 and inhibitor development was reinforced [n = 70, OR 0.327, P = 0.010], and positive association of DRB1*13:02 and DPB1*04:01 with inhibitor development was identified [OR 3.059, P = 0.037 for both]. Previously reported risk alleles were not consistently associated with inhibitor risk in our series. This study demonstrated the profile of HLA alleles associated with inhibitor risk in Korean patients with severe HA was different from that in patients of other ethnicities, which needs to be considered in risk assessment and management.

Background/aims: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia., Methods: Patients (n=30) were enrolled between September 2015 and April 2016. Twenty-six patients were genotype 1 (1b, n=21; 1a, n=5) and four patients were genotype 2a/2b. Among 21 patients with genotype 1b, Y93H resistance-associated variants (RAVs) were detected in three patients (14.3%). We evaluated sustained virologic response (SVRs) at 12 weeks, as well as relapse and safety., Results: Five patients with genotype 1a and three patients with genotype 1b (RAV positive) received ledipasvir/sofosbuvir for 12 weeks. SVR12 rate was 100% (8/8). Eleven patients with genotype 1b were treatment-naïve and received daclatasvir plus asunaprevir for 24 weeks. SVR12 rate was 91% (10/11). One patient experienced viral breakthrough without RAV at 12 weeks. Seven treatment-experienced patients with genotype 1b received daclatasvir plus asunaprevir for 24 weeks. SVR12 rate was 85.7% (6/7). One patient experienced viral breakthrough with RAV (L31M, Y93H) at 12 weeks. Four patients with genotype 2a/2b received sofosbuvir plus ribavirin for 12 weeks. SVR12 rate was 100% (4/4). No serious adverse event-related discontinuations were noted., Conclusions: New direct acting antiviral treatment achieved high SVRs rates at 12 weeks in CHC patients with hemophilia without serious adverse events.

Coagulation factor VII (FVII) deficiency is a rare hereditary coagulopathy caused by mutations in the F7 gene. The aims of this study were to characterize the molecular defect of F7 in Korean patients with FVII deficiency and to find genotype-phenotype correlations. Study individuals consisted of 14 unrelated Korean patients with FVII deficiency with residual FVII activities ranging from 1 to 34%. To identify causative mutations, we performed PCR amplification and direct sequencing of all exons and flanking sequences of F7 gene. In all 14 patients, one (N = 4) or two (N = 10) mutant alleles were identified. A total of 11 unique mutations were detected, of which four were novel (c.-1C>T, p.V54RfsX53, p.R59&#95;R60dupRR, and p.L314 V). Four recurrent mutations were observed in 86% of patients (12 of 14) (C389G, C115X, G343S, and c.572-1G>A) and accounted for 71% of all mutant alleles (17 of 24). The residual FVII activity was more than 5% in all six asymptomatic patients (21%, range 6-34%), whereas it was 5% or less in all eight symptomatic patients (2%, range 1-5%). In addition, the mean residual FVII activity in four patients with a single mutant allele was 23.6% (range 3-34%), which was significantly higher than that in 10 patients with two mutant alleles that was 4.6% (range 1-19%) (P = 0.023). In summary, the data from this study on the largest number of FVII deficiency in Korea showed recurrent mutations in this population and suggested genotype-phenotype correlations.