Trisomy X conferring moderate hemophilia A by extremely skewed X-chromosome inactivation.

Background: Hemophilia carriers occasionally present with bleeding tendency due to skewed inactivation of normal carrying X chromosome.

Key Clinical Question: Can extreme skewing of X-chromosome inactivation (XCI) with trisomy X cause low factor (F) VIII activity and bleeding in a hemophilia carrier?.

Clinical Approach: A young female with low FVIII activity (2 IU/dL), who presented with history of frequent bleeding and variant, NP_000123.

Comprehensive comparison of global coagulation assays to differentiate lupus anticoagulant from acquired hemophilia A in patients with prolonged APTT.

There is no established method for differentiating acquired hemophilia A (AHA) from lupus anticoagulant (LA) positivity because both present with prolonged activated partial thromboplastin time. We compared various parameters of rotational thromboelastometry (ROTEM), thrombin generation assay (TGA), and clot waveform analysis (CWA) in patients with AHA (n = 10) and LA (n = 44). Compared with AHA, possible (n = 12) and definite (n = 32) LA showed significantly shorter clotting time (CT) in NATEM mode of ROTEM (> 3600 vs.

In vitro validation of chromogenic substrate assay for evaluation of surrogate FVIII-activity of emicizumab.

[Introduction] Emicizumab, a bispecific antibody mimicking activated factor VIII (FVIII), is increasingly used in prophylaxis against bleeding in hemophilia A. Human factor-based chromogenic substrate assay (hCSA) shows concentration-dependency between emicizumab and reported FVIII activity. However, the assay measurement settings have not been optimized for emicizumab, and the reported FVIII activity cannot be directly referred as surrogate FVIII activity.

Prolonged α-thrombin-related activation and delayed active protein C-associated degradation confer mild phenotype in a patient with severe hemophilia A with F8 p.H118R.

In hemophilia A, bleeding mostly correlates with factor VIII activity (FVIII:C), although some patients show discrepancy in bleeding severity and FVIII:C. We report a novel procoagulant mechanism associated with F8 p.H118R (c.

[Examination of the effect of immunosuppressive therapy on acquired hemophilia A in elderly patients with bloodstream infections].

Aim: Acquired hemophilia A (AHA) is an acquired autoantibody (inhibitor) against blood coagulation factor VIII (FVIII) that significantly reduces FVIII activity and causes a bleeding tendency. Immune acquired coagulation factor deficiency. The peak age of onset is in the 70s.

Coagulation assay discrepancies in Japanese patients with non-severe hemophilia A.

Patients with non-severe hemophilia A often show discrepancies in factor VIII (FVIII) activity. However, information on variant-specific coagulation assay characteristics in Japanese patients is limited. Pathogenic variants were classified into three groups, thrombin-cleavage site (TC), A1-A2-A3 interface (IF), and non-discrepant, with reference to previous studies.

Spectrum of F8 Genotype and Genetic Impact on Inhibitor Development in Patients with Hemophilia A from Multicenter Cohort Studies (J-HIS) in Japan.

Some genetic and treatment-related factors are risk factors for inhibitor development in patients with hemophilia A (PwHA). However, the genotype distribution of the factor VIII gene () and genetic impact on inhibitor development in Japanese PwHA remain unknown. In 2007, the Japan Hemophilia Inhibitor Study 2 (J-HIS2) was organized to establish a nationwide registry system for hemophiliacs and to elucidate risk factors for inhibitor development, designed for prospective investigation following a retrospective study (J-HIS1) which had already finished.

Successful Management of Acquired Factor V Inhibitor by Monitoring Factor V Activity, Antigen, and Inhibitor Values during Immunosuppressive Therapy.

Acquired factor V inhibitor (AFVI) results from the formation of autoantibodies to coagulation factor V (FV), and the clinical phenotype can range from asymptomatic laboratory abnormalities to life-threatening bleeds. We describe a 74-year-old man who developed AFVI along with a massive subcutaneous hematoma. He was initially treated with prednisolone (PSL), but AFVI recurred when the dose was reduced after a short period.

Emicizumab-mediated haemostatic function in patients with haemophilia A is down-regulated by activated protein C through inactivation of activated factor V.

Activated protein C (APC) inactivates activated factor V (FVa) and moderates FVIIIa by restricting FV cofactor function. Emicizumab is a humanized anti-FIXa/FX bispecific monoclonal antibody that mimicks FVIIIa cofactor function. In recent clinical trials in haemophilia A patients, once-weekly subcutaneous administration of emicizumab was remarkably effective in preventing bleeding events, but the mechanisms controlling the regulation of emicizumab-mediated haemostasis remain to be explored.

Identification of deep intronic individual variants in patients with hemophilia A by next-generation sequencing of the whole factor VIII gene.

Background: No genetic defects are found in the coagulation factor VIII gene () of approximately 2% of patients with hemophilia A. Recently, genomic variants causative of hemophilia A that were located deep within introns have been reported.

Objectives: We aimed to establish a comprehensive method of analysis of using next-generation sequencing (NGS) and investigate the variants located deep within the introns of .

[Development of asymptomatic acquired factor V inhibitor after the administration of antibiotics].

Acquired factor V (FV) inhibitor is a rare coagulation disorder, the causes and clinical symptoms of which are known to vary widely. Acquired FV inhibitor mostly occurs with exposure to fibrin glues during surgical procedures. We experienced a case with asymptomatic acquired FV inhibitor caused by antibiotic therapy for aspiration pneumonia.

Factor X M402T: a homozygous missense mutation identified as the cause of cross-reacting material-reduced deficiency.

We investigated a mildly hemorrhagic patient with factor X (FX) deficiency to identify the nature of his defect by comprehensive analyses. A 42-year-old Japanese man was admitted to our hospital for uncontrolled gingival hemorrhage. His FX activity based on prothrombin time (PT) and activated partial thromboplastin time (aPTT) and FX antigen were <1, 6.

Novel FV mutation (W1920R, FVNara) associated with serious deep vein thrombosis and more potent APC resistance relative to FVLeiden.

Factor V (FV) appears to be pivotal in both procoagulant and anticoagulant mechanisms. A novel homozygote (FVNara), a novel mechanism of thrombosis associated with Trp1920→Arg (W1920R), was found in a Japanese boy and was associated with serious deep vein thrombosis despite a low level of plasma FV activity (10 IU/dL). Activated partial thromboplastin time-based clotting assays and thrombin generation assays showed that FVNara was resistant to activated protein C (APC).

Genotypic and phenotypic features of Japanese patients with mild to moderate hemophilia A.

Hemophilia A is the most common inherited bleeding disorder. To better understand the genotypic and phenotypic features of Japanese patients with mild to moderate hemophilia A, we studied 29 unrelated patients with more than 1 % FVIII activity (FVIII:C). Differences were observed in nine of 21 patients in measured FVIII:C levels between the one-stage clotting and chromogenic assays.

Identification and characterization of an adenine to guanine transition within intron 10 of the factor VIII gene as a causative mutation in a patient with mild haemophilia A.

Haemophilia A is caused by various genetic mutations in the factor VIII gene (F8). However, after conventional analysis, no candidate mutation could be identified in the F8 of about 2% of haemophilia A patients. The F8 of a patient with mild congenital haemophilia A, in whom no candidate mutation was found in the exons or their flanking regions, was analysed in detail to identify the patient's aetiological genetic abnormality.

Mutations to the probe of Cobas TaqMan HIV-1 ver. 1.0 assay causing undetectable viral load in a patient with acute HIV-1 infection.

We encountered a human immunodeficiency virus (HIV)-1 in which the viral load was undetectable with the Cobas TaqMan HIV-1 ver. 1.0 (CTM v.