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Query: UMLS:C0684275 (haemophilia)
 10,958 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors report a rare case of eosinophilic cystitis presenting with heavy haematuria which led to the discovery of attenuated haemophilia B. Bleeding and clotting times in this patient, with no past history of haemorrhage, were normal. Complete coagulation studies led to the diagnosis in the presence of poor plasma prothrombin consumption and a moderate deficit in clotting factor IX, defining haemophilia B. Despite two partial cystectomies for haemorrhagic lesions of the dome of the bladder (eosinophilic cystitis), carried out with transfusion cover and the administration of P.P.S.B., recurrence of haematuria made it necessary to "rest" the bladder by a cutaneous ureterostomy. Subsequently, the restoration of urinary continuity was possible by uretero-ileo-cystoplasty, without any haemorrhagic complications by virtue of the use of P.P.S.B. The value of the association of epsilon amino-caproic acid with P.P.S.B. is emphasised in the prevention of haemorrhagic complications during surgery in haemokphilia B patients. In attenuated forms of haemophilia B (factor IX level between 5 and 15%) haemorrhages may be only occasional and occur only late in life.
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PMID:[Heavy haematuria as the presentation of attenuated haemophilia B (author's transl)]. 740 Jun 17

In plasma samples of 11 fetuses of about 20 weeks of gestational age the following coagulation factors have been determined (mean values found are given in parentheses): fibrinogen (0.30 U/ml), prothrombin (+/-0.17 U/ml), factor V (0.28 U/ml), factor VII (0.21 U/ml), factor VIII coagulant activity (factor VIII:C) (0.12 U/ml), factor VIII-related antigen (factor VIIIR:Ag) (1.04 U/ml), coagulant factor VIII-related antigen (factor VII:CAg) (0.19 U/ml), factor IX coagulant activity (0.05 U/ml), factor IX antigen (less than or equal to 0.03 U/ml), factor X (0,19 U/ml) and antithrombin III (AT-III) (0.23 U/ml). Our data support the evidence that prenatal diagnosis of haemophilia A is at present possible; less optimism is warranted where haemophilia B is concerned. the number of samples is sufficient to establish normal values for the age group. Means of quality control of the sample-which is often difficult to obtain-are disscussed.
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PMID:Coagulation factors in the human fetus of about 20 weeks of gestational age. 742 42

There are rational, effective choices available for the treatment of common inherited bleeding disorders, according to assessment of safety, efficacy and cost. All currently available products for patients with haemophilia A (factor VIII deficiency) are comparable in terms of efficacy and viral safety. However, high purity products are recommended for those with coexisting human immunodeficiency virus (HIV) infection. Many patients with mild haemophilia A and most with von Willebrand's disease can be treated with desmopressin, which can be given as an intranasal spray in some countries. For the treatment of patients with factor XI deficiency, fresh frozen plasma remains the standard care, although solvent-detergent-treated fresh frozen plasma and factor XI concentrate are currently being investigated as alternatives. In the treatment of haemophilia B (factor IX deficiency), purified factor IX concentrates are particularly useful in clinical settings where large amounts of concentrate are to be used (e.g. surgical prophylaxis). Their usefulness in other contexts needs clarification. Treatment of inhibitors that may develop in response to administered coagulation factors is still limited to the use of prothrombin complex concentrates and porcine factor VIII. Active clinical trials are currently assessing the efficacy and safety of recombinant factor VIIa, Xa and tissue factor in this indication.
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PMID:Congenital bleeding disorders. Rational treatment options. 768 74

The results of bleedings treatment in 11 children with haemophilia A and factor VIII (f. VIII) inhibitor was presented. Concentrates of human and porcine f. VIII and activated prothrombin complex concentrate were used in the treatment. The method of treatment depended on the level of human and porcine f. VIII inhibitors. In patients with level of human f. VIII inhibitor lower than 10 jB/ml the concentrates of human f. VIII in doses 2-3 times higher than usually used in haemophiliacs without inhibitor were successful. When inhibitor level was higher than 10 jB/ml, but low cross-reactivity of porcine f. VIII was stated, concentrates of porcine f. VIII were used with good result. In children with high level of antibody against human and porcine f. VIII, the best results were achieved using activated prothrombin complex concentrates.
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PMID:[Outcome of hemorrhage treatment in children with hemophilia A related to factor VIII inhibitor]. 784 36

Acquired hemophilia is a very rare disease characterized by the presence of an autoantibody (mainly IgG) to factor VIII, with a clinical presentation resembling hemophilia A. It is associated with various autoimmune or dermatologic diseases, pregnancy, cancer, or drug ingestion, but in almost 50% of patients no underlying disorder is found. The treatment of acquired hemophilia is particularly complex because response to therapy is unpredictable. If an acute hemorrhage occurs despite preventive measures, two complementary strategies must be employed: stopping the bleeding and decreasing the factor VIII inhibitor with human or porcine factor VIII, DDAVP, prothrombin complex concentrates, intravenous immunoglobulin, immunosuppression, or by extracorporeal removal of the inhibitor. Autoantibody titer, previous response to a given treatment, and severity of clinical presentation must be taken into account when choosing between these different therapeutic options, which must often be associated.
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PMID:Acquired hemophilia. 789 16

A prospective cross-over study was carried out on 19 patients with haemophilia B. comparing the pharmacokinetics of a purified factor IX concentrate prepared by metal chelate affinity chromatography (9MC) with a conventional three-factor prothrombin complex concentrate (9A). The highly purified factor IX concentrate was shown to have a half-life comparable to the PCC; the in vivo recovery of the purified concentrate was significantly greater than that of the complex (P < 0.01). The 20% change in the value of the International Standard for Factor IX Concentrate, introduced in 1988, might have been expected to lower the recovery values. However, the in vivo recovery for both concentrates was somewhat higher than reported previously, particularly in the older literature. In nine patients, serial assays for fibrinopeptide A, prothrombin fragment F1+2 and thrombin-antithrombin complexes (TAT) were performed to assess the potential thrombogenicity of the two concentrates. Evidence was obtained that there was significantly less activation of coagulation following administration of purified factor IX (9MC), as compared to the activation that occurred after the PCC.
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PMID:A cross-over pharmacokinetic and thrombogenicity study of a prothrombin complex concentrate and a purified factor IX concentrate. 798 19

A subset of hemophilia B patients have a prolonged bovine-brain prothrombin time. These CRM+ patients are classified as having hemophilia Bm. The prolongation of the prothrombin time has been reported only with bovine brain (referred to as ox brain in some literature) as the source of thromboplastin; prothrombin times determined with thromboplastin from rabbit brain or human brain are not reported to be prolonged. Factor IX from a hemophilia Bm patient (factor IX Hilo) was isolated. The activity of factor IX Hilo was compared to that of normal factor IX in prothrombin time assays when the thromboplastin source was of bovine, rabbit, or human origin. Factor IX, either normal or Hilo, prolonged a prothrombin time regardless of the tissue factor source. However, unless thromboplastin was from a bovine source, this prolongation required high concentrations of factor IX. Further, factor IX normal was as effective as factor IX Hilo in prolonging the prothrombin time when rabbit or human thromboplastin was used. With bovine thromboplastin, factor IX Hilo was significantly better than factor IX normal at prolonging the prothrombin time. The amount of prolongation was dependent on the amount of factor IX Hilo added. In addition, the prolongation was dependent on the concentration of factor X present in the sample. The prothrombin time changed as much as 20 seconds when the factor X concentration was varied from 50% to 150% to normal (fixed concentration of factor IX Hilo). These results demonstrate the difficulty of classifying the severity of a hemophilia Bm patient based on the bovine brain prothrombin time unless both the factor IX and factor X concentrations are known.
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PMID:Comparison of the behavior of normal factor IX and the factor IX Bm variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources. 780 43

We have looked for evidence of coagulation activation in six subjects with haemophilia B by performing a single-blind active control cross-over study comparing a recently developed factor IX concentrate with a conventional prothrombin complex concentrate (PCC). Samples were obtained before infusion and at 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36 and 48 h for assay of factor IX, prothrombin time, fibrinopeptide A (FPA), prothrombin fragment F1 + 2, D-dimer, thrombin-antithrombin complexes (TAT) and antithrombin III (ATIII). Following administration of the PCC there was evidence of coagulation activation in five of the six recipients for up to 6 h after the infusion. The factor IX concentrate induced a moderate degree of coagulation activation in one subject. There was no significant difference between the two products in respect of either recovery or half-life. This study provides further evidence that the new high purity preparations of factor IX concentrates produce significantly less coagulation activation than currently available PCCs. It remains to be established whether this will result in a corresponding reduction in thromboembolic complications in clinical use.
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PMID:Reduced coagulation activation following infusion of a highly purified factor IX concentrate compared to a prothrombin complex concentrate. 839 31

Utilizing polymerase chain reaction and directly sequencing the amplified exon 6 of the factor IX gene derived from a mild hemophilia Bm patient, we have identified a T to C mutation at nucleotide 20,525. This point mutation predicted a Val182 to Ala substitution in the abnormal factor IX molecule, designated as factor IX Tokyo. The patient manifested a low factor IX activity and a moderately prolonged ox-brain prothrombin time but a normal factor IX antigen level in plasma. Immunopurified factor IX derived from the patient was found to have a normal molecular weight but a reduced specific activity (23% of normal). Limited proteolysis by activated factor XI or by a snake venom-derived factor X-activating enzyme was considerably delayed, indicating the presence of structural alteration(s) most probably at or near the second enzyme-cleavage site. Once activated, however, factor IXa Tokyo was able to activate factor X normally and was inactivated by antithrombin III also in a normal fashion. The structural model of factor IXa and a docking model of factor IX and activated factor VII (factor VIIa) suggested that the Val182 to Ala substitution would not affect the local conformation of the catalytic domain. This mutation would rather loosen the fitness of the molecule into the substrate-binding pocket of factor VIIa due to a shorter side chain of the Ala substitution at the P2' position of the second cleavage site.
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PMID:Molecular defect in factor IX Tokyo: substitution of valine-182 by alanine at position P2' in the second cleavage site by factor XIa resulting in impaired activation. 851 23

We report a successful treatment of extracorporeal shock wave lithotripsy (ESWL) on a renal stone in a patient with severe hemophilia B. The patient was 44 years old man who had suffered left flank colicky pain with gross hematuria. A radiographic study showed a left renal stone, 22 x 14 mm in size. Before treatment, the intravenous administration of 1,000 U of the missing factor IX was tried, which induced the recovery of the prothrombin and partial thromboplastin times to the normal levels. One thousand units of factor IX were infused 30 minute before ESWL and 2,363 shock waves (Dornier MPL-9000) were administered at 17 kV under intravenous anesthesia by pentazocine. After the treatment, ultrasound and CT did not detect any perirenal hematoma. Antihemophilic therapy was continued with 1,000 U of factor IX per 12 hours for 2 days, 1,000 U per 24 hours for the succeeding 8 days and 500 U per 24 hours for the last 7 days. Gross hematuria disappeared on the 3rd day. We could successfully treat a renal stone in a patient with hemophilia.
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PMID:[Extracorporeal shock wave lithotripsy in a patient with hemophilia B]. 851 46


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