Collaborative Study on Assays of Activated FIX (FIXa) On Behalf of the Factor VIII and Factor IX Subcommittee of the ISTH

1996 ◽  
Vol 76 (06) ◽  
pp. 1114-1117 ◽  
Author(s):  
Elaine Gray ◽  
Dawn Walker ◽  
Alan Heath ◽  
Trevor W Barrowcliffe
Keyword(s):  
Collaborative Study ◽  
Factor Ix ◽  
Test Material ◽  
Local Method ◽  
Degradation Study ◽  
Accelerated Degradation ◽  
Local Standard ◽  
Coefficients Of Variation ◽  
Reference Preparation

SummaryA collaborative study has been organised by NIBSC to examine the performance of FIXa assays between laboratories, and to investigate the need for a standard. Ampoules of 3 materials, one monocomponent concentrate (coded C) and 2 different preparations of purified human FIXa (one proposed reference preparation, coded A and a test material coded B), have been assayed in 11 laboratories for FIXa using either the NIBSC method or a local method, with local standards (if available, coded D) to determine their potencies. The data showed high between assay variability; with the exception of one laboratory, most of the between assay variation expressed as %geometric coefficients of variation (gcv) were over 15%The interlaboratory gcv when preparation B was assayed against the local standard was over 1700%, suggesting that most of the local standards are poorly calibrated. The %gcv was improved to 80% when reference A was used as the standard. These data clearly show that an international reference standard for FIXa would help to standardise FIXa preparations and would also improve in house assays for FIXa. However, an accelerated degradation study has shown that reference A is not suitable as a long term standard and another material with suitable stabilisers has to be established as an international standard for FIXa.

The Stability of the WHO Reference Thromboplastin NIBS & C 67/40

1979 ◽  
Vol 42 (04) ◽  
pp. 1135-1140 ◽  
Author(s):  
G I C Ingram
Keyword(s):  
Human Brain ◽  
Collaborative Study ◽  
Calibration Constant ◽  
Long Term Stability ◽  
Freeze Dried ◽  
Show Evidence ◽  
Human Material ◽  
Reference Preparation ◽  
The Stability

SummaryThe International Reference Preparation of human brain thromboplastin coded 67/40 has been thought to show evidence of instability. The evidence is discussed and is not thought to be strong; but it is suggested that it would be wise to replace 67/40 with a new preparation of human brain, both for this reason and because 67/40 is in a form (like Thrombotest) in which few workers seem to use human brain. A �plain� preparation would be more appropriate; and a freeze-dried sample of BCT is recommended as the successor preparation. The opportunity should be taken also to replace the corresponding ox and rabbit preparations. In the collaborative study which would be required it would then be desirable to test in parallel the three old and the three new preparations. The relative sensitivities of the old preparations could be compared with those found in earlier studies to obtain further evidence on the stability of 67/40; if stability were confirmed, the new preparations should be calibrated against it, but if not, the new human material should receive a calibration constant of 1.0 and the new ox and rabbit materials calibrated against that.The types of evidence available for monitoring the long-term stability of a thromboplastin are discussed.

THE FIRST INTERNATIONAL STANDARD FOR HUMAN URINARY FSH AND FOR HUMAN URINARY LH (ICSH), FOR BIOASSAY

1976 ◽  
Vol 83 (4) ◽  
pp. 700-710 ◽  
Author(s):  
P. L. Storring ◽  
H. Dixon ◽  
D. R. Bangham
Keyword(s):  
Elevated Temperatures ◽  
Collaborative Study ◽  
Storage Conditions ◽  
Working Standard ◽  
International Standard ◽  
Accelerated Degradation ◽  
Reference Preparation ◽  
Degradation Studies ◽  
The Stability ◽  
Working Standards

ABSTRACT This paper describes the preparation and nature of the First International Standard for Human Urinary Follicle Stimulating Hormone and for Human Urinary Luteinizing Hormone, for Bioassay, and of two batches of working standard which were prepared from the same material. A collaborative study of these materials was carried out by six laboratories in six different countries. The FSH and LH activities of the Standard were assayed in terms of those of the Second International Reference Preparation of Human Menopausal Gonadotrophins, Urinary, for Bioassay, which it replaces. The results from 20 valid FSH assays and 30 valid LH assays (using four different methods) obtained in this way gave a weighted combined potency estimate for FSH of 53.7 IU, with 95 fiducial limits of 47.2–61.1 IU, and for LH of 46.2 IU, with 95% fiducial limits of 43.3–49.3 IU. Accelerated degradation studies of the Standard stored at elevated temperatures suggested that the stability of both FSH and LH activities under normal storage conditions would be satisfactory. The FSH and LH activities of the two batches of working standard (WS-A and WS-B) were compared with those of the Standard and were not found to differ significantly, except for the LH activity of WS-B which appeared to be slightly higher than that of the Standard. Accelerated degradation studies did not show any significant differences in stability between the Standard and batches of working standards. On the basis of these results the Standard has been established by WHO and allocated a potency for FSH of 54 IU per ampoule and for LH 46 IU per ampoule. The International Units for FSH, Human Urinary, for Bioassay and for LH (ICSH), Human Urinary, for Bioassay are thus defined as the activities contained in 0.11388 mg and 0.13369 mg of the International Standard, respectively.

INTERNATIONAL COLLABORATIVE STUDY OF N.I.B.S.C. RESEARCH STANDARD FOR HUMAN PARATHYROID HORMONE FOR IMMUNOASSAY

1980 ◽  
Vol 86 (2) ◽  
pp. 291-304 ◽  
Author(s):  
JOAN M. ZANELLI ◽  
ROSE E. GAINES DAS
Keyword(s):  
Parathyroid Hormone ◽  
Biological Activities ◽  
Collaborative Study ◽  
Human Parathyroid Hormone ◽  
In Vitro Bioassay ◽  
Accelerated Degradation ◽  
Reference Preparation ◽  
Working Standards ◽  
International Collaborative Study

The use of a Research Standard for human parathyroid hormone (PTH) in a collaborative study by 17 laboratories in ten countries is described. Results of this study showed that the Research Standard was not distinguishable by immunoreactive criteria from the other preparations and laboratory working standards of human PTH included in the study. It was, however, shown to be distinguishable from the International Reference Preparation for Parathyroid Hormone, Bovine, for Immunoassay by immunoreactive criteria and by heterogeneity of estimates in terms of bovine PTH. The Research Standard had appropriate biological activities in three different in-vitro bioassay systems and appeared to be stable under conditions of accelerated degradation. This material in ampoules coded 75/549 is now available internationally as N.I.B.S.C. Research Standard for human PTH for immunoassay.

Standardization of Factor VIII – III. Establishment of a Stable Reference Plasma for Factor VIII-Related Activities

1983 ◽  
Vol 50 (03) ◽  
pp. 690-696 ◽  
Author(s):  
T W Barrowcliffe ◽  
M S Tydeman ◽  
T B L Kirkwood ◽  
D P Thomas
Keyword(s):  
Factor Viii ◽  
Collaborative Study ◽  
Expert Committee ◽  
Normal Plasma ◽  
Freeze Dried ◽  
Biological Standardization ◽  
Reference Preparation ◽  
The One ◽  
Good Agreement

SummaryAn international collaborative study has been carried out to establish a reference plasma for Factor VIII-related activities. The freeze-dried reference plasma, coded 80/511, was assayed against fresh normal plasma, local standards and another freeze- dried plasma. There was good agreement between laboratories for the comparison of the two freeze-dried plasmas, but wide variation in the comparison of plasma 80/511 with fresh normal plasma and local standards, indicating the differences in Factor VIII content of local pooled plasmas. There were no significant differences between the one-stage and two-stage assays of VIII :C, or between electroimmunoassay (EIA) and immuno- radiometric (IRMA) assays of VIII R:Ag. However, in VIII R: RCoF (ristocetin co-factor) assays, the aggregometry methods gave lower values than the macroscopic and counting methods for the comparison of freeze-dried against fresh normal plasmas. From the combined results of assays against each laboratory’s fresh normal plasma, potencies were assigned to plasma 80/511.Results from accelerated degradation studies indicated that losses of each VIII-related activity in plasma 80/511, when stored at -20° C, should be less than 0.01% per year, indicating its suitability to serve as a long-term reference preparation. Plasma 80/511 has been established by the WHO Expert Committee on Biological Standardization as the 1st International Reference Preparation for Factor VIII-Related Activities in Plasma.

Multi-Center Calibration of the Third BCR Reference Material for Thromboplastin, Rabbit, Plain, Coded CRM 149S

1995 ◽  
Vol 74 (06) ◽  
pp. 1465-1467 ◽  
Author(s):  
A M H P van den Besselaar
Keyword(s):  
Reference Material ◽  
Collaborative Study ◽  
Sensitivity Index ◽  
Term Stability ◽  
Long Term Stability ◽  
Reference Preparation ◽  
The Mean ◽  
The Relationship ◽  
International Sensitivity Index

SummaryIn a collaborative study by eleven laboratories performed within the framework of the European Community Bureau of Reference (BCR), a third reference material for thromboplastin, rabbit, plain, has been calibrated against RBT/90, the current WHO international reference preparation for thromboplastin, rabbit, plain. This third reference material (coded CRM 149S) has a mean International Sensitivity Index (ISI)of 1.257 with a standard error of the mean of 0.013.The previous BCR reference material for thromboplastin, rabbit, plain (coded CRM 149R) and the reference material for thromboplastin, bovine, combined (coded OBT/79) were also included in the trial for assessment of the long-term stability of the ISI values. The relationship between ISI values determined in the present study was nearly identical to that of the historical values. These results offer reassurance with regard to the long-term stability of these reference materials.

A Collaborative Study to Establish the Second International Standard for Streptokinase

1990 ◽  
Vol 64 (02) ◽  
pp. 267-269 ◽  
Author(s):  
A B Heath ◽  
P J Gaffney
Keyword(s):  
High Purity ◽  
Collaborative Study ◽  
World Health Organisation ◽  
World Health ◽  
Clot Lysis ◽  
Current Standard ◽  
International Standard ◽  
Accelerated Degradation ◽  
The World ◽  
International Collaborative Study

SummaryAn International Standard for Streptokinase - Streptodomase (62/7) has been used to calibrate high purity clinical batches of SK since 1965. An international collaborative study, involving six laboratories, was undertaken to replace this standard with a high purity standard for SK. Two candidate preparations (88/826 and 88/824) were compared by a clot lysis assay with the current standard (62/7). Potencies of 671 i.u. and 461 i.u. were established for preparations A (88/826) and B (88/824), respectively.Either preparation appeared suitable to serve as a standard for SK. However, each ampoule of preparation A (88/826) contains a more appropriate amount of SK activity for potency testing, and is therefore preferred. Accelerated degradation tests indicate that preparation A (88/826) is very stable.The high purity streptokinase preparation, coded 88/826, has been established by the World Health Organisation as the 2nd International Standard for Streptokinase, with an assigned potency of 700 i.u. per ampoule.

scholarly journals Gene Therapy in Hemophilia: Recent Advances

2021 ◽  
Vol 22 (14) ◽  
pp. 7647
Author(s):  
E. Carlos Rodríguez-Merchán ◽  
Juan Andres De Pablo-Moreno ◽  
Antonio Liras
Keyword(s):  
Gene Therapy ◽  
Adverse Events ◽  
Factor Viii ◽  
Coagulation Factor ◽  
Cost Savings ◽  
Factor Ix ◽  
Clotting Factors ◽  
Advanced Therapies ◽  
Potential Benefits

Hemophilia is a monogenic mutational disease affecting coagulation factor VIII or factor IX genes. The palliative treatment of choice is based on the use of safe and effective recombinant clotting factors. Advanced therapies will be curative, ensuring stable and durable concentrations of the defective circulating factor. Results have so far been encouraging in terms of levels and times of expression using mainly adeno-associated vectors. However, these therapies are associated with immunogenicity and hepatotoxicity. Optimizing the vector serotypes and the transgene (variants) will boost clotting efficacy, thus increasing the viability of these protocols. It is essential that both physicians and patients be informed about the potential benefits and risks of the new therapies, and a register of gene therapy patients be kept with information of the efficacy and long-term adverse events associated with the treatments administered. In the context of hemophilia, gene therapy may result in (particularly indirect) cost savings and in a more equitable allocation of treatments. In the case of hemophilia A, further research is needed into how to effectively package the large factor VIII gene into the vector; and in the case of hemophilia B, the priority should be to optimize both the vector serotype, reducing its immunogenicity and hepatotoxicity, and the transgene, boosting its clotting efficacy so as to minimize the amount of vector administered and decrease the incidence of adverse events without compromising the efficacy of the protein expressed.

LRF and TRF test during long-term danazol treatment: increase of the LH and FSH responses but decrease of the prolactin and TSH responses

1983 ◽  
Vol 104 (1) ◽  
pp. 1-5 ◽  
Author(s):  
J. Leppäluoto ◽  
L. Rönnberg ◽  
P. Ylöstalo
Keyword(s):  
Clinical Symptoms ◽  
Follicular Phase ◽  
Blood Samples ◽  
Hormone Levels ◽  
Coefficients Of Variation ◽  
The Mean ◽  
Thyroid Hormone Levels ◽  
Low Serum

Abstract. Seven patients suffering from severe endometriosis were treated with danazol 200 mg × 3 daily for 6 months. Clinical symptoms were alleviated and menses disappeared in response to the treatment. After cessation of the treatment the menstrual bleedings returned in 1–3 months. Blood samples for determination of gonadotrophins, prolactin (Prl), oestradiol (E2), progesterone, thyroid hormones and thyrotrophin in radioimmunoassays were taken and a combined TRF and LRF test carried out in the follicular phase before treatment, at the 6th month of treatment and after reappearance of the first menses. There were no statistically significant changes in the basal levels of serum FSH, LH or TSH during the danazol treatment. Neither was there any change in episodic secretions of FSH, LH or Prl, as determined by the mean coefficients of variation of the hormone levels in seven consecutive samples taken at 20 min intervals. On the other hand, serum E2, Prl and thyroid hormone levels were significantly decreased in the 6th month of treatment. In the TRF-LRF test the responses of serum FSH and LH were significantly higher and those of serum Prl and TSH significantly lower during danazol treatment than before. Prl responses remained lowered after the treatment. It appears that low serum oestrogen levels, induced by the danazol treatment, sensitize the pituitary gonadotrophs to exogenous LRF, but make the sensitivity of thyrotrophs and lactotrophs lower to exogenous TRF. These results thus indicate that danazol does not make the pituitary gonadotrophs insensitive to LRF, but danazol may rather inhibit the secretion of hypothalamic LRF.

scholarly journals Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 439-445 ◽  
Author(s):  
Hulya Ozsahin ◽  
Marina Cavazzana-Calvo ◽  
Luigi D. Notarangelo ◽  
Ansgar Schulz ◽  
Adrian J. Thrasher ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Collaborative Study ◽  
Hematopoietic Stem ◽  
Long Term Outcome ◽  
Wiskott Aldrich Syndrome

Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency with microthrombocytopenia, eczema, recurrent infections, autoimmune disorders, and malignancies that are life-threatening in the majority of patients. In this long-term, retrospective, multicenter study, we analyzed events that occurred in 96 WAS patients who received transplants between 1979 and 2001 who survived at least 2 years following hematopoietic stem-cell transplantation (HSCT). Events included chronic graft-versus-host disease (cGVHD), autoimmunity, infections, and sequelae of before or after HSCT complications. Three patients (3%) died 2.1 to 21 years following HSCT. Overall 7-year event-free survival rate was 75%. It was lower in recipients of mismatched related donors, also in relation with an older age at HSCT and disease severity. The most striking finding was the observation of cGVHD-independent autoimmunity in 20% of patients strongly associated with a mixed/split chimerism status (P < .001), suggesting that residual-host lymphocytes can mediate autoimmune disease despite the coexistence of donor lymphocytes. Infectious complications (6%) related to splenectomy were also significant and may warrant a more restrictive approach to performing splenectomy in WAS patients. Overall, this study provides the basis for a prospective, standardized, and more in-depth detailed analysis of chimerism and events in long-term follow-up of WAS patients who receive transplants to design better-adapted therapeutic strategies.

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