A Rebuttal: Issues with the Assay of Factor VIII Activity in Plasma and Factor VIII Concentrates

2001 ◽  
Vol 86 (10) ◽  
pp. 1132-1133 ◽  
Author(s):  
Steffen Rosén
Keyword(s):  
Factor Viii ◽  
Factor Viii Activity ◽  
Factor Viii Concentrates

scholarly journals Further Experience on the Effect of High Pre-Donation Factor VIII Levels in Blood Donors on the Factor VIII Content of Small-Pool Fractions

1977 ◽  
Author(s):  
H. Beeser ◽  
H. Eqli
Keyword(s):  
Factor Viii ◽  
High Plasma ◽  
Activity Levels ◽  
Factor Viii Activity ◽  
Factor Viii Level ◽  
Plasma Factor ◽  
Viii Level ◽  
Factor Viii Concentrates ◽  
Small Pool ◽  
Concentrate Preparation

Because of the well known wide normal range of the factor VIII activity between 60 to 170% I man, selecting of donors with high activity levels would be of advantaae for the preparation of factor VIII concentrates. This is especially true for preparing small-pool fractions, as for technical reasons the final product cannot be controlled for its factor VIII content. In preliminary investigations, we reported on elsewhere, high factor VIII activity in donors estimated before a donation had been rarely reproducible before a second donation after 8-12 weeks. So as a preliminary result of finding a donor’s factor VIII level varying from donation to donation selecting of plasmas with high factor VIII content for concentrate preparation could only be establishedby re-estimating the activity before each donation. Proceeding in this way would be much too troublesome. To get more reliable information whether a healthy subject’s high factor VIII plasma level is distinctly varying or rather constant we assayed the plasma of 200 donors with factor VIII activity > 120% two times more before donation. The results confirmed our preliminary findings, especially the fact that a high plasma factor VIII activity in experienced donors was rarely reproducible when re-estimated before a second and third donation. As a consequence selecting of donors with high factor VIII procoaqulant activity for preparing small-pool factor VIII concentrates is impracticable.

An Improved Method of Making Factor VIII Concentrates

1979 ◽  
Author(s):  
G. Rock ◽  
D.S. Palmer ◽  
E.S. Tackaberry ◽  
M. Wickerhauser
Keyword(s):  
Factor Viii ◽  
Present Method ◽  
Batch Preparation ◽  
Improved Method ◽  
Factor Viii Activity ◽  
Peg 4000 ◽  
Plasma Factor ◽  
Factor Viii Concentrates ◽  
The Cost ◽  
Plasma Activity

The yields from batch preparation of Factor VIII concentrates can be substantially improved by collecting the blood into heparin rather than into CPD as anticoagulant. The resultant cryoprecipitate contains 78 ± 9% of the original plasma activity if 20 mls of supernatant per litre of starting plasma are left with the cryoprecipitate to maintain heparin levels. This cryoprecipitate was further purified by solubilization at 37°C for 5 minutes using 40 cc of saline per litre of starting plasma. This preparation was adjusted to pH 6.3 and 4.5% PEG 4000. Then, after removal of the precipitate by centrifugaron, the 4.5% PEG supernatant is adjusted to pH 6.0 and 11% PEG. The 11% PEG precipitate obtained after centrifugation is resolubilized in 1/100th the original plasma volume with buffer (0.1 M glycine, 20 mM citrate, 0.15 H saline) containing 1 unit of heparin per ml. Experiments using plasma pools containing 1-15 donor units gave yields ranging from 390-490 plasma Factor VIII equivalents per litre of the starting plasma. The final product retains an average of 90% of the initial Factor VIII activity after 24 hours at 22°C. It is believed that the present method could substantially reduce the cost of producing Factor VIII concentrates.

Pharmacokinetics of two pasteurized Factor VIII concentrates by different and multicenter assays of Factor VIII activity

1992 ◽  
Vol 65 (6) ◽  
pp. 699-708 ◽  
Author(s):  
A. Messori ◽  
M. Morfini ◽  
M. Blomback ◽  
S. Cinotti ◽  
G. Longo ◽  
...  
Keyword(s):  
Factor Viii ◽  
Factor Viii Activity ◽  
Factor Viii Concentrates

Brief Report: Factor VIII (AHF) Concentration in pH 6.5 Citrate-Plasma

Blood ◽  
1966 ◽  
Vol 28 (3) ◽  
pp. 479-482 ◽  
Author(s):  
FRANCIS S. MORRISON
Keyword(s):  
Factor Viii ◽  
Assay System ◽  
Platelet Concentrates ◽  
Factor Viii Activity ◽  
Factor Viii Concentrates ◽  
System Factor ◽  
Citrate Plasma

Abstract A by-product of the preparation of platelet concentrates, by recently proposed methods, is fresh citrate-plasma at pH 6.5. Because this plasma might be a useful source of Factor VIII, the activity was investigated. Compared to unaltered citrate-plasma, the activity was found to be 54 per cent. However, after incubation with washed fresh erythrocytes the "acidified" plasma had the same Factor VIII activity as the control. This suggests that, after infusion, pH 6.5 plasma is probably as effective a source of Factor VIII as ordinary ACD-plasma. This conclusion was supported by observations on Factor VIII concentrates prepared by cryoprecipitation. In such preparations additional ACD and pH are eliminated as factors in the assay system. Factor VIII concentration in the precipitates prepared from acidified plasma was found to be as high as in precipitates prepared from untreated plasma.

scholarly journals Use of prothrombin complex concentrates in the treatment of a hemophilic patient with an inhibitor of factor VIII

Blood ◽  
1976 ◽  
Vol 47 (6) ◽  
pp. 983-989
Author(s):  
T Sonoda ◽  
A Solomon ◽  
S Krauss ◽  
P Cruz ◽  
FS Jones ◽  
...  
Keyword(s):  
Factor Viii ◽  
Therapeutic Benefit ◽  
Factor Viii Activity ◽  
High Concentration ◽  
Prothrombin Complex Concentrates ◽  
Hemophilic Patient ◽  
Life Threatening ◽  
Factor Viii Concentrates ◽  
Activated Prothrombin Complex Concentrates ◽  
And Control

The course and treatment of a life-threatening hemorrhagic episode in a patient with hemophilia A whose plasma contained a high concentration of an inhibitor of factor VIII activity is presented. The inhibitor of factor VIII was localized to the most anodal fractions of immunoglobulin G on electrophoresis, and was thus presumed to be an antibody directed against factor VIII. No therapeutic benefit occurred with infusions of massive amounts of fresh blood and factor VIII concentrates, or with a brief course of immunosuppressive therapy. Administration of standard and activated prothrombin complex concentrates resulted in reduction of the partial thromboplastin time to almost normal values and control of hemorrhage. Eight months later, another hemorrhagic episode occurred. Although a higher titer of inhibitor of factor VIII activity was still present in the patient's plasma, a beneficial therapeutic response was again achieved with standard prothrombin complex infusions.

scholarly journals Use of prothrombin complex concentrates in the treatment of a hemophilic patient with an inhibitor of factor VIII

Blood ◽  
1976 ◽  
Vol 47 (6) ◽  
pp. 983-989 ◽  
Author(s):  
T Sonoda ◽  
A Solomon ◽  
S Krauss ◽  
P Cruz ◽  
FS Jones ◽  
...  
Keyword(s):  
Factor Viii ◽  
Therapeutic Benefit ◽  
Factor Viii Activity ◽  
High Concentration ◽  
Prothrombin Complex Concentrates ◽  
Hemophilic Patient ◽  
Life Threatening ◽  
Factor Viii Concentrates ◽  
Activated Prothrombin Complex Concentrates ◽  
And Control

Abstract The course and treatment of a life-threatening hemorrhagic episode in a patient with hemophilia A whose plasma contained a high concentration of an inhibitor of factor VIII activity is presented. The inhibitor of factor VIII was localized to the most anodal fractions of immunoglobulin G on electrophoresis, and was thus presumed to be an antibody directed against factor VIII. No therapeutic benefit occurred with infusions of massive amounts of fresh blood and factor VIII concentrates, or with a brief course of immunosuppressive therapy. Administration of standard and activated prothrombin complex concentrates resulted in reduction of the partial thromboplastin time to almost normal values and control of hemorrhage. Eight months later, another hemorrhagic episode occurred. Although a higher titer of inhibitor of factor VIII activity was still present in the patient's plasma, a beneficial therapeutic response was again achieved with standard prothrombin complex infusions.

Measurement of factor VIII activity of B-domain deleted recombinant factor VIII

2001 ◽  
Vol 38 (2, Suppl 4) ◽  
pp. 13-23 ◽  
Author(s):  
M. Mikaelsson ◽  
U. Oswaldsson ◽  
M. A. Jankowski
Keyword(s):  
Factor Viii ◽  
Recombinant Factor Viii ◽  
Factor Viii Activity

Automation of Two-Stage Factor VIII Assay

1978 ◽  
Vol 39 (02) ◽  
pp. 455-465 ◽  
Author(s):  
Yvonne Stirling ◽  
D J Howarth ◽  
Marguerite Vickers ◽  
W R S North ◽  
T W Meade
Keyword(s):  
Factor Viii ◽  
Optical Density ◽  
Electric Circuit ◽  
Clotting Time ◽  
Two Stage ◽  
Laboratory Error ◽  
Premature Closure ◽  
Factor Viii Concentrates ◽  
Experimental Findings ◽  
Automated Methods

SummaryTwo automated methods for two-stage factor VIII assays have been compared with one another, and evaluated in practice. The Depex method records the clotting time when an electric circuit is completed by the formation of a fibrin thread across a hook-type electrode; the Electra method is based on an optical density technique of clot detection. The two methods gave comparable results for measured levels of factor VIII when haemophilic or “normal” plasmas were assayed. Results from the two methods in practice also suggest that both are valid at low and “normal” factor VIII levels. The Electra method is also probably suitable for assays of concentrates; however, the Depex method appears to give falsely high values in these circumstances, and experimental findings suggest that the reason may be that increased viscosity due to the high fibrinogen levels in factor VIII concentrates causes premature closure of the circuit between the two ends of the Depex electrode. The main advantage of the Depex method is that, provided 3 or 4 machines are available, a given number of assays can be completed more quickly than on Electra. The main advantages of Electra are that it is probably subject to less laboratory error than Depex, and that it is suitable for assaying concentrates as well as haemophilic and “normal” plasmas.

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