In vitro and in vivo Evaluation of a Factor VIII Concentrate Heat-Treated to Inactivate HTLV-III/LAV Viruses

Vox Sanguinis ◽  
1987 ◽  
Vol 52 (4) ◽  
pp. 265-271
Author(s):  
Claudine Mazurier ◽  
Christophe de Romeuf ◽  
Armelle Parquet-Gernez ◽  
Sylvie Jorieux ◽  
Maurice Goudemand
Vox Sanguinis ◽  
1987 ◽  
Vol 52 (4) ◽  
pp. 265-271 ◽  
Author(s):  
Claudine Mazurier ◽  
Christophe Romeuf ◽  
Armelle Parquet-Gernez ◽  
Sylvie Jorieux ◽  
Maurice Goudemand

1991 ◽  
Vol 46 (5) ◽  
pp. 298-304 ◽  
Author(s):  
K. Peerlinck ◽  
J. Amout ◽  
M. Tamise ◽  
A. Vanherle ◽  
P. Fondu ◽  
...  

2013 ◽  
Vol 109 (01) ◽  
pp. 53-60 ◽  
Author(s):  
Mia Golder ◽  
Jeffrey Mewburn ◽  
David Lillicrap

SummaryFactor VIII (FVIII), a procoagulant cofactor, plays a crucial role in the intrinsic coagulation cascade. A causal association between elevated FVIII levels and venous thrombosis incidence has been established; no such association has been confirmed with arterial thrombosis. The independent role of elevated FVIII levels in arteriolar thrombosis was evaluated in a mouse model to determine the thrombogenic potential of elevated levels of FVIII. The in vitro thrombogenic effect of elevated FVIII levels was examined using thrombin-antithrombin (TAT) complex generation and thromboelastography (TEG) assays. The thrombogenic potential of acute and extended elevation of circulating FVIII levels was assessed using ferric chloride induced injury of the cremaster arterioles. The rate of TAT complex formation, and the final concentration of TAT complexes, significantly increased as FVIII levels were elevated from 100% to 400% FVIII activity. TEG analysis of fibrin and clot formation showed that as FVIII levels were elevated, the time to initial fibrin formation decreased and the rate of fibrin formation increased. The acute elevation of circulating FVIII to 400% FVIII activity resulted in significantly decreased times to vessel occlusion. Prolonged elevation of FVIII activity did not significantly affect time to vessel occlusion. In conclusion, acute elevations in FVIII levels result in a nonlinear thrombogenic effect, with non-significant increases in thrombogenic risk within the physiological range (FVIII levels up to 200%). Prolonged elevation of plasma FVIII did not further increase the thrombogenic potential of elevated FVIII levels.


1987 ◽  
Author(s):  
E Berntorp ◽  
S Lethagen ◽  
I M Nilsson

As all commercial factor VIII concentrates in current use have been subjected to some form of virus-inactivation, we wanted to compare their in vitro biochemical characteristics. Of the 10 concentrates studied, inactivation takes the form of dry heat treatment, varying from 60°C for 30 h to 72°C for 68 h, in six products (Octonativ, KabiVitrum; Hemofil T, Hyland; Factorate HP, Armour - heated two different ways; Monoclate, Armour; Nordiocto, Nordisk Gentofte). In the 4 remaining concentrates, inactivation is either by steam treatment (Kryobulin Tim 3, Immuno), heating at 60°C for 20 h as dry material slammed in heptane (Profilate, Alpha), wet-heating at 60°C for 10 h (Hemate, Behring), or by the New York Blood Center (solvent/detergent) method (OCTA-V. I., Octopharm). The variables studied were VIII:C by one-stage and chromogenic assay, and VI11 :Ag, vW:Ag, by electroimmunoassay, immunoradiometric assay (IRMA), crossed immunoelectrophoresis and SDS agarose gel electrophoresis followed by staining with radioactive antibody and fibrinogen. VIII :C activity values ranged from 20-53 IU/ml in all products but Monoclate (94 IU/ml). All products gave higher values of VIII:Ag than of VI11 :C, indicating partial inactivation of VIII :C during preparation; the ratios ranged from 1.2 to 1.3 for Kryobulin, Nordiocto, OCTA-V. I., and Hemofil T, and from 2 to 4 for the other products, being highest in Profilate and Monoclate. Specific activity was higher in Monoclate, Nordiocto, Hemate, OCTA-V. I. and Factorate HP (16.0, 7.4, 7.1, 4.8 and 3.3 IU/ml protein, respectively) than in the other products (1.3-2.3 IU/mg). All concentrates contained vW:Ag, and non-parallel dose-response curves indicated abnormality in the vWF molecule in all cases; and thus multimeric sizing failed to demonstrate the largest multimers of the vWF in any product. We conclude that although virus-inactivated F VIII concentrates are general ly comparable with regard to VIII :C content, they vary considerably in the degree of VIII :C inactivation during preparation, and in specific activity. No concentrate tested here contained native vWF. In vivo studies have shown VIII :C recovery and half-life to be comparable in heat-treated and non-heat-treated concentrates.


Planta Medica ◽  
2010 ◽  
Vol 76 (12) ◽  
Author(s):  
J Bauer ◽  
F Dehm ◽  
A Koeberle ◽  
F Pollastro ◽  
G Appendino ◽  
...  

1969 ◽  
Vol 22 (03) ◽  
pp. 577-583 ◽  
Author(s):  
M.M.P Paulssen ◽  
A.C.M.G.B Wouterlood ◽  
H.L.M.A Scheffers

SummaryFactor VIII can be isolated from plasma proteins, including fibrinogen by chromatography on agarose. The best results were obtained with Sepharose 6B. Large scale preparation is also possible when cryoprecipitate is separated by chromatography. In most fractions containing factor VIII a turbidity is observed which may be due to the presence of chylomicrons.The purified factor VIII was active in vivo as well as in vitro.


1981 ◽  
Vol 45 (03) ◽  
pp. 285-289 ◽  
Author(s):  
J P Allain ◽  
A Gaillandre ◽  
D Frommel

SummaryFactor VIII complex and its interaction with antibodies to factor VIII have been studied in 17 non-haemophilic patients with factor VIII inhibitor. Low VIII:C and high VIIIR.Ag levels were found in all patients. VIII:WF levels were 50% of those of VTIIRrAg, possibly related to an increase of poorly aggregated and electrophoretically fast moving VIIIR:Ag oligomers.Antibody function has been characterized by kinetics of VIII :C inactivation, saturability by normal plasma and the slope of the affinity curve. Two major patterns were observed:1) Antibodies from 6 patients behaved similarly to those from haemophiliacs by showing second order inhibition kinetics, easy saturability and steep affinity slope (> 1).2) Antibodies from other patients, usually with lower titres, inactivated VIII :C according to complex order kinetics, were not saturable, and had a less steep affinity slope (< 0.7). In native plasma, or after mixing with factor VIII concentrate, antibodies of the second group did not form immune complexes with the whole factor VIII molecular complex. However, dissociation procedures did release some antibodies from apparently low molecular weight complexes formed in vivo or in vitro. For appropriate management of non-haemophilic patients with factor VIII inhibitor, it is important to determine the functional properties of their antibodies to factor VIII.


1995 ◽  
Vol 74 (03) ◽  
pp. 868-873 ◽  
Author(s):  
Silvana Arrighi ◽  
Roberta Rossi ◽  
Maria Giuseppina Borri ◽  
Vladimir Lesnikov ◽  
Marina Lesnikov ◽  
...  

SummaryTo improve the safety of plasma derived factor VIII (FVIII) concentrate, we introduced a final super heat treatment (100° C for 30 min) as additional virus inactivation step applied to a lyophilized, highly purified FVIII concentrate (100 IU/mg of proteins) already virus inactivated using the solvent/detergent (SID) method during the manufacturing process.The efficiency of the super heat treatment was demonstrated in inactivating two non-lipid enveloped viruses (Hepatitis A virus and Poliovirus 1). The loss of FVIII procoagulant activity during the super heat treatment was of about 15%, estimated both by clotting and chromogenic assays. No substantial changes were observed in physical, biochemical and immunological characteristics of the heat treated FVIII concentrate in comparison with those of the FVIII before heat treatment.


1974 ◽  
Vol 31 (03) ◽  
pp. 420-428 ◽  
Author(s):  
M Fainaru ◽  
S Eisenberg ◽  
N Manny ◽  
C Hershko

SummaryThe natural course of defibrination syndrome caused by Echis colorata venom (ECV) in five patients is reported. All patients developed afibrinogenemia within six hours after the bite. Concomitantly a depression in factor V was recorded. Factor VIII and thrombocyte count in blood were normal in most patients. In the light of the known effects of ECV on blood coagulation in vivo and in vitro it is concluded that the afibrinogenemia is due to intravascular clotting.Four patients had transient renal damage, manifested by oliguria, azotemia, albuminuria and cylindruria, ascribed to microthrombi in the renal glomeruli.After the bite, the natural course was benign, no major bleeding was observed, and all signs of coagulopathy reverted to normal within 7 days. Therefore we recommend no specific treatment for this condition. In the case of heavily bleeding patients, administration of antiserum against ECV and/or heparin should be considered.


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