Detection of hemophilia A carriers by use of frozen plasma samples.

1978 ◽  
Vol 24 (9) ◽  
pp. 1628-1630 ◽  
Author(s):  
H C Yang ◽  
J Hardin ◽  
C Vaudreuil
Keyword(s):  
Regression Analysis ◽  
Factor Viii ◽  
Hemophilia A ◽  
Carrier State ◽  
Immunoradiometric Assay ◽  
Plasma Samples ◽  
Factor Viii Activity ◽  
Factor Viii Antigen ◽  
Normal Women ◽  
Frozen Plasma

Abstract The efficacy of using promptly frozen plasma samples in the diagnosis of the carrier state for hemophilia A was evaluated by simultaneous measurement of factor VIII acitivity and antigen in 20 normal women and 20 obligate carriers. Factor VIII antigen was measured by two methods, electroimmunoassay and immunoradiometric assay. When the factor VIII activity and antigen data were evaluated by regression analysis, 94% of the carriers were correctly identified at the 95% confidence level.

Partial Reconstitution of Factor VIII Activity from a Mild Crm+ Hemophilia A Patient by Replacement of the Defective A2 Domain

1998 ◽  
Vol 79 (05) ◽  
pp. 943-948 ◽  
Author(s):  
W. C. Pieneman ◽  
P. Fay ◽  
E. Briët ◽  
P. H. Reitsma ◽  
R. M. Bertina
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Wild Type ◽  
Coding Region ◽  
Factor Viii Activity ◽  
Factor Ixa ◽  
Factor Viiia ◽  
Factor Viii Antigen ◽  
A2 Domain ◽  
Reduced Activity

SummaryWe further characterised the abnormal factor VIII molecule (factor VIII Leiden) of a Crm+, mild hemophilia A patient with a factor VIII activity of 0.18 IU/ml and a factor VIII antigen of 0.95 IU/ml. Mutation analysis of the coding region, promoter and 3’ untranslated region of the factor VIII gene revealed the presence of a C to T substitution at codon 527. This nucleotide change predicts the replacement of an arginine to tryptophan in the A2 domain close to a suggested binding site for factor IXa. Since a previous study of this mutant factor VIII protein suggested that this protein had a reduced affinity for factor IXa, position 527 in the protein might be involved in the interaction with factor IXa.In this study we gathered evidence for our hypothesis that the Arg to Trp mutation at position 527 is the cause of the reduced activity of factor VIII Leiden. Replacement of the mutated A2 domain by wild type A2 domain partially corrected the defect.Factor VIII from normal and factor VIII Leiden plasma was concentrated by cryoprecipitation, activated with thrombin and incubated with excess wild type A2 domain. Competition with excess isolated human A2 domain resulted in a partial reconstitution of the factor VIIIa activity of thrombin treated factor VIII Leiden. This supports the hypothesis that the mutation in the A2 domain is the cause of the reduced factor VIII activity.

Factor VIII Ise (R2159C) in a Patient with Mild Hemophilia A, an Abnormal Factor VIII with Retention of Function but Modification of C2 Epitopes

1997 ◽  
Vol 77 (05) ◽  
pp. 0862-0867 ◽  
Author(s):  
Hiroshi Suzuki ◽  
Midori Shima ◽  
Morio Arai ◽  
Kazuhiko Kagawa ◽  
Katuyuki Fukutake ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Factor Viii ◽  
Missense Mutation ◽  
Hemophilia A ◽  
Sscp Analysis ◽  
C2 Domain ◽  
Factor Viii Activity ◽  
Normal Plasma ◽  
Factor Viii Antigen

SummaryWe found a patient with mild hemophilia A who had no detectable factor VIII antigen (FVIII:Ag), as shown by two-site ELISA using inhibitor alloantibodies (TK). We then analyzed A2, A2/B, and C2 antigen of the patient's DDAVP-induced FVIII using several anti-FVIII monoclonal antibodies. Factor VIII activity (FVIII : C) was increased from 12 to 42 Uldl by the administration of DDAVP. The DDAVPinduced increases in the A2 and A2/B antigens were 40 and 36 Uldl, respectively. However, the increase in the C2 antigen was only 7.5 Uldl. SSCP analysis and subsequent sequencing demonstrated an Arg to Cys transition at codon 2159. The anti-FVII1:C titer of monoclonal antibody, NMC-VIII15 which recognized the C2 domain, against normal plasma was 450 Bethesda Ulmg of IgG. However, the titer against DDAVP-treated patient's plasma was only 15 Bethesda Ulmg. We also tested DDAVP-induced increase in the FVIII : Ag in another mild hemophilia A patient with the same mutation at Arg2159. Increase in his C2 antigen levels was only 19% of those in the A2 and A2/B antigen. We designate this abnormal FVIII as FVIII Ise. Our results show that a missense mutation at Arg2159 to Cys modifies the antigenicity of the C2 domain.

Immunoreactive Factor VIII in Carriers of Hemophilia A+ and A-

1973 ◽  
Vol 29 (02) ◽  
pp. 240-246 ◽  
Author(s):  
K Lechner
Keyword(s):  
Biological Activity ◽  
Factor Viii ◽  
Hemophilia A ◽  
Neutralization Test ◽  
Carrier State ◽  
Factor Viii Activity ◽  
Neutralizing Capacity

SummaryFactor VIII activity and inhibitor-neutralizing capacity of plasmas of 30 probable or definite carriers of hemophilia A were compared. The inhibitor-neutralization test is less useful to recognize the carrier-state than the factor VIII assay. Plasmas of two carriers belonging to families (in which, in at least one member, the diagnosis of hemophilia A+ was established) had an inhibitor neutralizing capacity twice as high as expected from the biological activity, while 28 carriers from hemophilia A- families had an inhibitor neutralizing-capacity equivalent to their factor VIII activity.

scholarly journals Prenatal diagnosis of classic hemophilia (hemophilia A) by immunoradiometric assays

Blood ◽  
1985 ◽  
Vol 65 (6) ◽  
pp. 1312-1317 ◽  
Author(s):  
LW Hoyer ◽  
CA Carta ◽  
MS Golbus ◽  
JC Hobbins ◽  
MJ Mahoney
Keyword(s):  
Prenatal Diagnosis ◽  
Factor Viii ◽  
Hemophilia A ◽  
The United States ◽  
Carrier State ◽  
Immunoradiometric Assay ◽  
Fetal Plasma ◽  
Laboratory Error ◽  
Normal Males ◽  
Hemophilia Carriers

Abstract During the period from 1978 to 1983, 92 pregnancies have been evaluated by fetoscopy for the prenatal diagnosis of hemophilia A. Satisfactory fetal plasma samples were obtained in 80 instances and the diagnosis-- or exclusion--of hemophilia was made by immunoradiometric assay of the factor VIII coagulant protein (VIII:CAg). The accuracy of the diagnosis established by fetoscopy has been verified after delivery or termination, and there have been no misdiagnoses resulting from laboratory error. Additional evidence for the accuracy of the analysis was the observation that the frequency of hemophilia in pregnancies of obligate carriers of the hemophilia gene, and of women whose plasma assays were indicative of the carrier state, was 29 of 59 fetuses at risk. In one case of cross-reacting material-positive hemophilia, samples obtained at fetoscopy and from the newborn infant had normal VIII:CAg levels but the infant had decreased factor VIII procoagulant activity. There were five fetal deaths resulting from fetoscopy in 55 pregnancies not intentionally terminated. Although only a small percentage of pregnant hemophilia carriers in the United States have elected to undergo fetoscopy for prenatal diagnosis, this procedure has allowed a number of pregnancies to go to term with delivery of normal males in families that were not willing to accept the risk of a hemophilic child. In eight instances, fetoscopic evaluation was sought for two successive pregnancies.

scholarly journals Detection of Hemophilia a Carriers by Repeated Factor VIII Activity/Antigen Determinations

1977 ◽  
Author(s):  
U. Seligsohn ◽  
A. Zivelin ◽  
H. Peretz ◽  
M. Modan
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Bayes Theorem ◽  
Plasma Samples ◽  
Factor Viii Activity ◽  
Relative Odds ◽  
Specificity And Sensitivity ◽  
Fviii Activity ◽  
Fresh Plasma ◽  
The Mean

Detection of hemophilia A carriers (C), using factor VIII (fVIII) activity (Ac) and antigenicity (Ag) measurements, has been hampered by an overlap of results obtained in normal females (NF) and obligatory carriers (OC). In an attempt to improve the specificity and sensitivity of C detection, 29 OC and 33 NF were examined 3 times. FVIII Ac and fVIII Ag were determined in fresh plasma samples, employing a one stage method and the Laurell technic with rabbit anti fVIII antiserum, respectively. Using the mean of the 3 pairs of measurements, a discriminant function, based on Bayes’ theorem, was obtained for calculating the probability that a woman is a C. Three ranges of measurements were defined: Definite C, possible C and definite NF. The results were as follows:If only the first pair of measurements was used, the results were much less satisfactory:Thus, for each suspected C, the relative odds of being a C can be assigned by using this function, but the results should be based on the mean of 3 measurements.

Leukemia and Hemophilia

PEDIATRICS ◽  
1986 ◽  
Vol 78 (3) ◽  
pp. 544-544
Author(s):  
SINASI OZSOYLU
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Fresh Frozen Plasma ◽  
Fresh Frozen ◽  
Viii And Ix ◽  
Immune Changes ◽  
Frozen Plasma

To the Editor.— I enjoyed reading the paper by Aronis et al,1 and would like to bring to your attention that we have also recently observed leukemia in two patients with hemophilia A and B, 10 and 1½ years of age, respectively.2 Because commercial factor VIII and IX were not used and only blood, fresh frozen plasma, and plasma were given on a few occasions, it was less likely that AIDS-like immune changes were responsible for the leukemia in our patients.

Use of Plasma Segments for Estimating Factor VIII Activity in Pools of Fresh Frozen Plasma

Vox Sanguinis ◽  
1987 ◽  
Vol 52 (3) ◽  
pp. 254-256
Author(s):  
F.A. Ofosu ◽  
L.M. Smith ◽  
M.A. Blajchman ◽  
J. (b) Campbell ◽  
C. De Vries ◽  
...  
Keyword(s):  
Factor Viii ◽  
Fresh Frozen Plasma ◽  
Factor Viii Activity ◽  
Fresh Frozen ◽  
Frozen Plasma

scholarly journals Postpartum Acquired Hemophilia: A Rare Cause of Postpartum Hemorrhage

2013 ◽  
Vol 2013 ◽  
pp. 1-2 ◽  
Author(s):  
Srikanth Seethala ◽  
Sumit Gaur ◽  
Elizabeth Enderton ◽  
Javier Corral
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Factor Vii ◽  
Normal Vaginal Delivery ◽  
Factor Viii Inhibitor ◽  
Activity Levels ◽  
Factor Viii Activity ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Viii Inhibitor

A 36-year-old female started having postpartum vaginal bleeding after normal vaginal delivery. She underwent hysterectomy for persistent bleeding and was referred to our institution. An elevation of PTT and normal PT made us suspect postpartum acquired hemophilia (PAH), and it was confirmed by low factor VIII activity levels and an elevated factor VIII inhibitor. Hemostasis was achieved with recombinant factor VII concentrates and desmopressin, and factor eradication was achieved with cytoxan, methylprednisolone, and plasmapheresis.

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