Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684275 (haemophilia)
 10,958 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Factor VIII therapy has been reported to cause anaphylactic reactions in patients with hemophilia. Desensitization attempts have been complicated by severe allergic reactions that have prevented the achievement of protective factor VIII levels. We report successful administration of factor VIII by a graded dose desensitization protocol in a 36-year-old man with hemophilia A who had previously experienced anaphylactic reactions to factor VIII infusions. The reactions were manifested by urticaria, choking, and bronchospasm and were not prevented by pretreatment with antihistamines and corticosteroids. Intradermal skin test with factor VIII was positive. Serum levels of circulating immune complexes were slightly elevated. Persistently low serum C2 levels were consistent with genetic C2 deficiency. These findings suggest the possibility of Type I (IgE mediated) and Type III (immune complex) immunopathogenic mechanisms. Our experience suggests that administration of factor VIII by graded dose desensitization protocol may offer a practical therapeutic approach for management of hemorrhage in patients with classic hemophilia who are allergic to factor VIII.
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PMID:Desensitization to factor VIII in a patient with classic hemophilia and C2 deficiency. 310 96

Factor VIII deficient plasma was made from pooled, HIV antibody and hepatitis B antigen screened, normal human plasma by cryoprecipitation and immuno-depletion, using three different monoclonal antibodies bound to Sepharose columns, in series. These monoclonal antibodies are specific respectively for von Willebrand factor, factor VIII heavy chain and factor VIII light chain. The immunodepleted plasma contained less than 0.002 u/ml factor VIII coagulation activity (VIII:C) less than 0.0001 u/ml von Willebrand factor antigen and 1-2 g/l fibrinogen, while the levels of other clotting factors were unchanged. This immunodepleted plasma was compared with commercial factor VIII deficient plasma obtained from a severe haemophilia A patient as substrate in the one-stage factor VIII assay. Plasmas obtained from 20 normal subjects and 28 patients with von Willebrand's disease or haemophilia A were assayed for VIII:C using the two substrates. The results were very highly correlated (r = 0.96). The columns have high capacity and can be regenerated at least 10 times. Large-scale production of a substrate for factor VIII assays free of virus contamination is now feasible.
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PMID:Production of factor VIII deficient plasma by immunodepletion using three monoclonal antibodies. 311 89

Four patients with classical rheumatoid arthritis who developed acquired haemophilia are described. They developed a spontaneous bleeding diathesis and diagnosis was based on low or absent Factor VIII levels and the presence of a circulating anticoagulant directed against Factor VIII. The course is variable and cyclophosphamide together with control of the underlying rheumatoid arthritis are recommended as treatment.
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PMID:Acquired haemophilia and rheumatoid arthritis. 311 57

Studies of Factor VIII pharmacokinetics in haemophiliacs can be classified into 2 groups depending on whether single-dose or multiple-dose Factor VIII curves are used. This review analyses information published so far in both these areas, with particular emphasis on the choice of appropriate models for pharmacokinetic analysis. Single-dose studies of Factor VIII kinetics have previously used a wide variety of methods for pharmacokinetic analysis (empirical methods of Factor VIII level prediction, graphical techniques for semilog analysis, 1-compartment and 2-compartment models). However, Factor VIII poses unique problems to the pharmacokineticist because decay curves can be either monophasic (monoexponential) or biphasic (biexponential) for unknown reasons, and because Factor VIII concentrations are generally subject to significant assay error. Problems of compartmental analysis that occurred in previous studies are highlighted, and a model-independent non-compartmental approach for analysing Factor VIII curves is proposed. To date, fewer data have been published on multiple-dose kinetics of Factor VIII. From a clinical point of view, repeated-dose regimens are most commonly required in patients undergoing surgery and in patients with severe bleeding. A fairly well defined 'therapeutic window' of optimal Factor VIII plasma concentrations has been identified, particularly in surgical patients. This fact has spurred research aimed at applying to haemophilia patients the pharmacokinetic dosing methods commonly used for therapeutic monitoring of drugs (e.g. Bayesian method for dosage individualization). A few papers have already been published in this field, and this review summarises problems encountered by previous investigators, and evaluates comparatively the pharmacokinetic methods used.
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PMID:Clinical pharmacokinetics of factor VIII in patients with classic haemophilia. 312 1

Enzyme-linked immunosorbent assays (ELISA) for factor VIII antigen (VIII:Ag) and von Willebrand factor antigen (vWF:Ag) have been developed, each employing monoclonal antibodies. In the majority of severe haemophilic plasmas tested, VIII:Ag was undetectable by ELISA and also by immunoradiometric assay (IRMA) using haemophilic VIII:C antibodies. In haemophilic plasmas with mild/moderate deficiency of coagulant factor VIII (VIII:C), there was no significant difference between the two immunoassays although there was a general trend for ELISA VIII:Ag results to be higher. Assay of von Willebrand's disease (vWd) plasmas with the ELISA for vWF:Ag demonstrated reduced levels of this antigen in type I vWd, normal levels in type IIA, and a severe reduction of vWF:Ag in type III vWd. The discrimination of obligate carriers of haemophilia from normal was determined using ratios of factor VIII/vWF. Factor VIII antigen/von Willebrand factor antigen measured by IRMA and Laurell immunoelectrophoresis respectively, gave a superior discriminant to that of VIII:C/vWF:Ag (Laurell), but optimal discrimination was obtained with the combination of ELISAs for VIII:Ag and vWF:Ag.
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PMID:The combined use of monoclonal antibody-based enzyme-linked immunosorbent assays (ELISA) for factor VIII antigen (VIII:Ag) and von Willebrand factor antigen (vWF:Ag) for the detection of carriers of haemophilia A. 314 Nov 5

The pharmacokinetics of Factor VIII was evaluated by mathematical modeling in a large-scale study in 62 haemophilia-A subjects, in whom 137 plasma Factor VIII-time curves were measured during single dose (n = 87) and repeated-dose (n = 47) treatments for prophylaxis or minor bleeding episodes. The pharmacokinetic parameters [mean (SD)] estimated from single-dose curves were: clearance 3.85 ml.h-1.kg-1, volume of distribution 58.2 ml.kg-1, mean residence time 15.9 h. Parameters calculated from repeated-dose curves were: clearance 3.93 ml.h-1.kg-1, volume of distribution 61.8 ml.kg-1, and half-life 12.2 h. In patients with mild haemophilia, pharmaco-statistical analysis revealed that the endogenous synthesis of Factor VIII was constant and was not influenced by the administration of exogenous Factor VIII. The coefficient of variation for intra-individual variability of Factor VIII kinetics (estimated according to the Standard Two-Stage method) was 20.7% in single-dose curves and 23.2% in repeated-dose curves.
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PMID:Multi-variate analysis of factors governing the pharmacokinetics of exogenous factor VIII in haemophiliacs. 314 73

Two patients with hemophilia and spinal epidural hematoma, who were treated successfully with serial Factor VIII infusions, are reported. This form of conservative therapy may circumvent the need for decompressive laminectomy and its attendant complications in instances in which the neurologic deficit is mild or stable. Somatosensory evoked potential studies were useful in documenting spinal cord dysfunction in 1 of the 2 patients.
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PMID:Conservative management of spinal epidural hematoma in hemophilia. 314 80

By 1987, only 3 cases of acquired immunodeficiency syndrome (AIDS) had been reported in Hong Kong. All 3 involved males who had been infected through sexual contact with a European or North American. In 2 cases, the sexual contact was homosexual; the 3rd case involved a man who had frequent sexual contact in New York and Miami with female prostitutes. The Government of Hong Kong moved rapidly to establish an AIDS Expert Advisory Committee to carry out a public educational campaign and formulated clear guidelines for health workers. In recognition of the need for epidemiologic data, a seroprevalence program was initiated in 1985 to define risk groups and the prevalence of infection. During a 21-month surveillance period, 38,312 individuals were screened for antibodies to human immunodeficiency virus (HIV), 72 (0.2%) of whom were confirmed to be seropositive. Of the 61 individuals for whom a history was available, 12 (20%) were homosexual or bisexual men, 46 (75%) had a history of transfusions of blood or blood products (largely for hemophilia), and 3 reported sexual contact with female prostitutes outside of Hong Kong. Only 2 of the 72 positive tests involved women. None of the sera from the 1123 intravenous drug abusers and 1360 prostitutes screened contained antibodies to HIV. Consistent with a lack of documented local heterosexual spread of HIV infection is the absence of cases among infants and children. To reduce the risk of parenterally spread infection, universal blood donor unit screening for HIV antibody and the introduction of heat-treated Factor VIII have been implemented. In addition, an AIDS Education and Publicity Committee was established in 1986 to heighten public awareness of the risk factors involved in HIV infection.
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PMID:The many epidemiological faces of AIDS with special reference to Hong Kong and implications for prevention and control. 345 2

Single-dose kinetics of 4 Factor VIII concentrates (Kryobulin, Hemofil T, Koate, cryoprecipitate) were studied in 41 patients with haemophilia-A. Model-independent methods were adopted for calculating the kinetic parameters (area under the curve, clearance, area under the moment curve, mean residence time, volume of distribution at steady-state). No substantial difference was observed in the kinetic characteristics of the 4 Factor VIII concentrates. A considerable interindividual variability of the calculated kinetic parameters was demonstrated for all concentrates. Our findings support the need to individualize Factor VIII dosage.
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PMID:Kinetic evaluation of four Factor VIII concentrates by model-independent methods. 391 40

3 patients with haemophilia A and inhibitor against Factor VIII were developing progressive haemophiliac arthropathy due to the non-feasibility of prophylactic treatment. In order to suppress inhibitor formation, long-term treatment with high-dose Factor VIII (100 units per kg body weight twice daily) was initiated. Prothrombin complex concentrate was given only for bleeding episodes. Though all 3 patients were high responders, they presented different treatment courses. 2 became low responders after 4 and 11 months' treatment, respectively. 1 patient had no demonstrable inhibitor after start of treatment. In all 3 patients, prophylactic treatment was established, in 1 case still with increased doses compared to non-inhibitor patients. The high-dose Factor VIII treatment makes in possible to provide prophylactic treatment for the high-responder inhibitor patients. However, the extremely high costs represent a serious obstacle to this treatment.
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PMID:Long-term high dose factor VIII treatment of 3 haemophiliacs with factor VIII inhibitor. 392 44


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