Disease relevance of Hemophilia A

• Long-term evaluation of HIV antigen and antibodies to p24 and gp41 in patients with hemophilia. Potential clinical importance [1].
• We gave danazol (600 mg per day orally for 14 days), an attenuated androgen, to four adults with classic hemophilia and one adult with Christmas disease [2].
• Myocardial infarction in a patient with hemophilia treated with DDAVP [3].
• Coincident classic hemophilia and "idiopathic" thrombocytopenic purpura in patients under treatment with concentrates of antihemophilic factor (factor VIII) [4].
• Autoantibodies which interfere with the function of enzyme cascade systems have also been described in diseases such as acquired haemophilia (anti-factor VIII antibodies) and glomerulonephritis (C3 nephritic factor) [5].

Psychiatry related information on Hemophilia A

• It constitutes the best marker on the X chromosome and should be of great use for the genetic study of three important diseases: hemophilia A, mental retardation with a fragile X chromosome, and adrenoleukodystrophy [6].
• The adequacy of the evaluation was not related to race, intravenous drug abuse, homosexuality, hemophilia, the diagnosis of known AIDS, or being a public patient [7].
• We describe acute hepatic and renal toxicity of paracetamol in a 36-year-old patient with haemophilia B, chronic hepatitis C and chronic alcohol abuse [8].

High impact information on Hemophilia A

• Haemophilia A is a classic X-linked disease which affects 1 in 5-10,000 males in all populations and is caused by defects in coagulation factor VIII [9].
• Synergy between transcription factors DBP and C/EBP compensates for a haemophilia B Leyden factor IX mutation [10].
• Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia A. recombinant Factor VIII Study Group [11].
• Induction of immune tolerance in patients with hemophilia and antibodies to factor VIII by combined treatment with intravenous IgG, cyclophosphamide, and factor VIII [12].
• We examined the possibility that this problem might be alleviated by desmopressin acetate (DDAVP), which increases the plasma level of von Willebrand factor and improves hemostasis in mild hemophilia and other conditions associated with defective platelet function [13].

Chemical compound and disease context of Hemophilia A

• The structure explains, in part, mutations in the C2 region of factor VIII that lead to bleeding disorders in haemophilia A [14].
• Deficiencies in this plasma glycoprotein result in haemophilia B (or Christmas disease) and occur in about 1 in 30,000 males [15].
• Two mutations in this domain, Asp 47----Glu, and Asp 64----Asn, present in patients with haemophilia B, reduce calcium binding to the domain greater than 4-fold and greater than 1,000-fold, respectively [16].
• Twenty-three patients with severe hemophilia were given single or multiple doses of diphenhydramine hydrochloride, chlorpromazine hydrochloride, or guaifenesin to test their effects on hemostasis [17].
• Reactions of complete identity occurred between normal, a warfarin treated and a hemophilia B subject's plasmas [18].

Biological context of Hemophilia A

• A pre-trans-splicing molecule (PTM) corrected endogenous FVIII mRNA in F8 knockout mice with the hemophilia A phenotype, producing sufficient functional FVIII to correct the hemophilia A phenotype [19].
• The five hemophilia B dogs treated showed stable, vector dose-dependent partial correction of the whole blood clotting time and, at higher doses, of the activated partial thromboplastin time [20].
• Disruption of a C/EBP binding site in the factor IX promoter is associated with haemophilia B [21].
• Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC) [22].
• Using an mRNA-based method to examine haemophilia A mutations we provide an explanation for the puzzling report that half of the mutations causing severe disease are not detected by analysis of the putative promoter, exons, and most exon/intron boundaries of the factor VIII gene [23].

Anatomical context of Hemophilia A

• We have previously shown that a single portal vein infusion of a recombinant adeno-associated viral vector (rAAV) expressing canine Factor IX (F.IX) resulted in long-term expression of therapeutic levels of F.IX in dogs with severe hemophilia B [24].
• Asymptomatic hemophilia patients receiving Factor VIII concentrate were found to have normal natural killer (NK) cells and B cells, and an inverted T helper/suppressor ratio due to an increase in cells of T suppressor phenotype [25].
• In this study, we evaluated ex vivo retroviral gene transfer of a high-expression porcine fVIII transgene into bone marrow-derived stromal and hematopoietic stem/progenitor cells (MSCs and HSCs, respectively) and transplantation into genetically immunocompetent hemophilia A mice [26].
• We report that high doses of FVIII inhibit the restimulation of FVIII-specific memory B cells and their differentiation into antibody-secreting plasma cells in vitro and in vivo in a murine model of hemophilia A [27].
• We used a murine model of anti-factor VIII (FVIII) antibody responses in hemophilia A to study the requirements for the restimulation of FVIII-specific memory B cells and their differentiation into anti-FVIII antibody-producing cells [28].

Gene context of Hemophilia A

• Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study [29].
• This is the first report of a mutation altering FVIII binding to phospholipids and occurring in patients with hemophilia A [30].
• These results suggest that a clinical evaluation of the effects of rhIL-11-induced vWf/FVIII elevation in maintaining hemostasis in mild hemophilia A or von Willebrand disease would be worthwhile [31].
• Our data provide further evidence for the hypothesis that the rapid inactivation of TF/FVIIa by TFPI in combination with the absence of either FVIII or FIX causes the bleeding tendency of patients with hemophilia A or B [32].
• We have previously implicated the PAR domain D-site-binding protein (DBP) as well as an upstream element, site 5, as playing important roles in the phenotypic recovery of hemophilia B Leyden [33].

Analytical, diagnostic and therapeutic context of Hemophilia A

• Factor IX antigen by radioimmunoassay. Abnormal factor IX protein in patients on warfarin therapy and with hemophilia B [18].
• Prenatal diagnosis by linkage: hemophilia A and polymorphic glucose-6-phosphate deydrogenase [34].
• Thus, the use of engineered autologous BOECs, which here resulted in sustained and therapeutic levels of FVIII, may comprise an effective therapeutic strategy for use in gene therapy for hemophilia A [35].
• In a phase 1 dose escalation study, 13 subjects with hemophilia A received by peripheral intravenous infusion a retroviral vector carrying a B-domain-deleted human factor VIII (hFVIII) gene [36].
• Intravenous injection of an HC-Ad vector into a hemophilia A dog at a dose of 4.3 x 10(9) IU/kg led to transient therapeutic canine FVIII levels that partially corrected whole-blood clotting time [37].

References