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)

The present study compares two new factor VIII preparations currently used in the treatment of haemophilia. A Factor VIII was partially purified from plasma obtained from unpaid voluntary Belgian donors in the blood transfusion centers of Lille and Amsterdam and virus-inactivated by exposure to solvent-detergent (FVIII-SD) or by pasteurization (FVIII-P) respectively. The factor VIII content and the purity of both preparations were assessed in vitro, whereas in vivo we studied the recovery and the plasma half-life of both concentrates. The higher purity of FVIII-SD was confirmed. Factor VIII-P preparations contained more factor VIII than mentioned on the label. Both preparations gave good in vivo recoveries and half-lives. Patients who did not have antibodies to hepatitis B, hepatitis C or HIV at the initial screening, remained negative after six months treatment with the new concentrates. No patients developed neutralizing factor VIII antibodies. Furthermore patients appreciated the ease of administration of both preparations. In conclusion both FVIII concentrates are suited for the treatment of haemophilia A patients.
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PMID:In vitro and in vivo evaluation of two factor VIII concentrates virally inactivated by solvent-detergent or by pasteurization. 166 50

This study was aimed at assessing the reproducibility of Factor VIII assays between different laboratories using the same reagents. A total of 176 post-dose plasma samples were obtained from 8 Italian subjects with hemophilia-A treated with a single dose of Factor VIII concentrates. Three laboratories (in FRG, Italy, and Sweden) participated in the study. Frozen aliquots of each sample were dispatched to each of the laboratories, where the aliquots were assayed using the same one-stage, two-stage and chromogenic methods. The one-stage and the chromogenic methods were well reproducible between the three centers: pairwise correlation analyses yielded r-values ranging from 0.88 to 0.91 for the one-stage method and from 0.91 to 0.96 for the chromogenic method. The agreement between these two assays was less evident in samples with activity below 200 IU/L in which the one-stage gave, on average, higher Factor VIII concentrations than those provided by the chromogenic method. The two-stage method was not well reproducible, and the pairwise r-values ranged from 0.48 to 0.73. Our study emphasises the need to develop multi-center quality control programs to verify the reproducibility of Factor VIII assays.
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PMID:Reproducibility of one-stage, two-stage and chromogenic assays of factor VIII activity: a multi-center study. 190 48

Hemophiliacs often have mild anemia, and hemolysis has been suggested as the likely mechanism on the basis of the reduced serum haptoglobin values frequently observed in these patients. It has been suggested that hypohaptoglobinemia results from isohemagglutinins or other contaminating proteins in the infused factor concentrates. The advent and increased utilization of Factor VIII concentrates that are highly purified by use of monoclonal antibodies have provided the opportunity to study whether proteins other than Factor VIII contained in the concentrate induce hemolysis. Of 49 consecutively studied Factor VIII-deficient hemophiliacs, 19 (39%) had a reduced serum haptoglobin level (less than 27 mg/dl). In particular, 16 of 35 (46%) of patients receiving only monoclonally purified Factor VIII products (Monoclate or Hemofil-M) had a reduced serum haptoglobin value. Haptoglobin measurements were variable on repeat measurement in 8 patients. Haptoglobin levels did not correlate with type or severity of hemophilia, hemoglobin value, or alterations in liver function. Low serum haptoglobin values were also observed in children with leukemia, without apparent hemolysis, who had extensive cutaneous hemorrhage associated with thrombocytopenia. We propose that reduced serum haptoglobin values in hemophiliacs do not result from immune-mediated hemolysis due to contaminating proteins in the concentrate. Moreover, hypohaptoglobinemia may not be due to hemolysis at all but may instead result from dissolution of hematomas and other foci of internal hemorrhage.
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PMID:Reduced serum haptoglobin values in hemophiliacs receiving monoclonally purified factor VIII concentrates. 210 38

Desmopressin acetate (1-desamino-8-D-arginine vasopressin, DDAVP) has mostly been given by the parenteral route for the treatment of mild hemophilia A and von Willebrand's disease type I. In the present study the hemostatic effects of desmopressin acetate administered intranasally by spray in a dose of 300 micrograms and intravenously 0.3-0.4 micrograms/kg were assessed and compared in 8 patients with hemophilia A and 22 patients with von Willebrand's disease type I. A bioequivalent response to intravenous and intranasal desmopressin acetate was found in Factor VIII coagulant activity (VIII:C) in the hemophilia patients. In the von Willebrand patients, an equivalent shortening of the bleeding time was seen after the two modes of administration, even though intravenous injection gave a higher increase in plasma levels of VIII:C and vWF:Ag. In five patients with von Willebrand's disease the duration of the spray effect on VIII:C and vWF:Ag was followed for 24 h. After 12 h the mean level of VIII:C was 1.4, and of vWF:Ag 1.5, times the basal level. The findings suggest that the spray can be recommended for home or prophylactic treatment of patients with mild hemophilia A and von Willebrand's disease.
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PMID:Intranasal desmopressin (DDAVP) by spray in mild hemophilia A and von Willebrand's disease type I. 210 87

Six hemophilia patients previously seronegative for human immunodeficiency virus (HIV) seroconverted between September 1986 and September 1987. None had risk factors for HIV infection other than hemophilia. We compared the factor concentrates received by these patients with the concentrates received by 10 seronegative hemophilia patients. A statistically significant association was observed between seropositivity and the receipt of two lots of Factor VIII produced from the same plasma pool (odds ratio 77, p = 0.0014); five of the six case subjects but none of the control subjects had received concentrate from one of the two lots. Available evidence suggests that the sixth case subject had also received concentrate from an implicated lot. Symptoms including rash and fever were reported in five cases within 6 weeks after the implicated concentrate had been given. The implicated lots were produced from plasma from paid donors that had been screened and then heated at 60 degrees C for 30 hours in the lyophilized state. Subsequent to our investigation all concentrate produced by this process was removed from distribution.
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PMID:HIV transmission to patients with hemophilia by heat-treated, donor-screened factor concentrate. 211 26

Thirteen semiconstrained total knee arthroplasties (TKA) were performed in nine men with classic hemophilia. The average age at surgery was 38 years, the average Factor VIII administration during hospitalization was 84.222 units, and the average hospitalization time was 33 days. Four patients (44%) died during the observation period, three from acquired immunodeficiency syndrome (AIDS) contracted through contaminated Factor VIII plasma concentrates and one from sudden cardiac arrest. One of the patients who died from AIDS had a positive test for human immunodeficiency virus (HIV) at surgery. He died three months after the arthroplasty. The remaining two patients contracted AIDS one year and four years after the arthroplasty. All but one patient were followed for at least one year, with an average follow-up period of 43 months. Using The Hospital for Special Surgery Knee Rating Scale, the overall result was excellent in nine knees and good in three knees. All patients were completely relieved of pain. TKA in hemophiliacs is an effective treatment for otherwise intractable chronic knee pain due to severe joint degeneration. However, caution should be taken in HIV-positive patients owing to the challenge of the patient's immune system and the risk of transmitting the virus to the hospital staff.
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PMID:Total knee arthroplasty in classic hemophilia. 211 46

Factor VIII (FVIII) response to desmopressin (deamino-8-D-arginine vasopressin, abbreviated DDAVP) was studied in patients with mild Hemophilia A and von Willebrand Disease (vWD) who attend our Hemophilia Clinic. Thirty eight children and 9 adults had their F VIII components assayed 60 minutes after intravenous (IV) administration of DDAVP, 0.35 microgram/kg. Among 27 hemophiliacs, F VIII coagulant activity (F VIII: C) increased from a mean of 16.8 to 59.2 u/dL; with an average 3.2-fold increase. In 20 vWD patients, the mean F VIII:C and von Willebrand Factor increased from a mean of 50.1 to 136%; and from 22.6 to 75.6%; with an average 3.0 and 5.7-fold increase, respectively. The overall F VIII:C response was good or excellent in 81.5% of the hemophiliacs, and in 89.5% of the vWD patients tested. No significant side effects were observed. This study has demonstrated that IV DDAVP can cause an increase of F VIII:C and vWF to hemostatic levels, and thus it may be useful for the control of bleeding episodes in most of the patients tested in our clinic.
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PMID:Response of patients with hemophilia A and von Willebrand disease to desmopressin (DDAVP). 211 85

Acquired antibodies to factor VIII:C in nonhemophiliac patients are uncommon in adulthood and exceedingly rare in childhood. We report a girl, 9 years of age, with no personal or familial bleeding history who presented with hematuria and bruising 2 weeks after an upper respiratory infection. The activated partial thromboplastin time was 71.9 s (normal, 25-40 s) and did not correct by mixing 1:1 with normal plasma, suggesting the presence of an inhibitor. Factor VIII:C levels were detectable at 0.03 U/ml, but inhibition experiments demonstrated the presence of an inhibitor with an activity of 24 Bethesda U/ml. This inhibitor was localized to the immunoglobulin (IgG) fraction of the patient's plasma. Incubation of the patient's IgG with normal pooled plasma resulted in a 66% decrease in factor VIII:C activity. Unlike the antibodies found in most hemophilia patients, the autoantibody produced by this patient demonstrated type II kinetics and did not inhibit all factor VIII:C activity even at very high concentrations. In addition, the rate of factor VIII:C inactivation by this autoantibody was much slower than that seen with type I inhibitors. The treatment of the patient with prednisone, 2.5 mg/kg/day, resulted in the rapid disappearance of detectable inhibitor and a rise in factor VIII:C levels to 0.70 U/ml. Normal factor VIII:C levels persisted after the discontinuation of steroids. This case is most unusual in that it occurred in a child without any evidence of an underlying autoimmune disorder, and unlike classical hemophiliac factor VIII:C inhibitors, there was a rapid response to steroids.
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PMID:Steroid-responsive type II anti-factor VIII:C autoantibody in a nonhemophiliac child. 211 97

Factor VIII inhibitors are antibodies of the IgG class that neutralize the procoagulant activity of FVIII. They arise as alloantibodies in multitransfused haemophilia A patients and spontaneously in some individuals. Therapeutic strategy must be separated into two concepts: treatment of bleeding episodes and treatment of the inhibitor itself. Treatment of an haemorrhagic complication is dependent on the inhibitor titre and the status of the patient as a 'high' or 'low' responder. The choice has to be made between massive amounts of human FVIII concentrate, porcine FVIII and plasma preparations with 'bypassing' activity. Adjuvant therapy such as plasma exchange or extracorporeal passage of plasma over a Protein A sepharose column might be helpful. More recent products are still under evaluation such as FVIIa or recombinant tissue factor. Intravenous immunoglobulins have proven to be helpful mainly in patients with spontaneous inhibitors. Treatment of the inhibitor itself must be started as soon as possible. Several approaches are being used, immunosuppressive therapy or induction of immune tolerance using high intermediate or low doses of FVIII concentrate.
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PMID:Treatment of factor VIII inhibitors. 213 Sep 31

Desmopressin (1-deamino-8-D-arginine vasopressin, DDAVP) is a synthetic analogue of the antidiuretic hormone L-arginine vasopressin. Because it can raise circulating levels of Factor VIII and of von Willebrand's factor, DDAVP is used for nontransfusional treatment of mild and moderate hemophilia and von Willebrand's disease. DDAVP also shortens the prolonged skin bleeding time in patients with uremia, liver cirrhosis, and platelet dysfunctions and is given to prevent or stop excessive bleeding in such conditions. Finally, there is evidence that DDAVP can reduce blood loss and transfusion requirements during and after surgical operations in which blood losses are unusually large. Hence DDAVP is useful as a nontransfusional hemostatic agent in many of the bleeding disorders frequently encountered in clinical practice.
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PMID:Desmopressin: a nontransfusional hemostatic agent. 218 48


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