<i>In Vitro</i> Spontaneous Thrombin Generation in Human Factor‐IX Concentrates

Sas, G.; Owens, Rosemary; Smith, J. K.; Middleton, S.; Cash, J. D.

doi:10.1111/j.1365-2141.1975.tb00828.x

Cited by 46 publications

(16 citation statements)

References 13 publications

(1 reference statement)

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“…The TFT was determined as in Sas et al [18]. 0.2 ml of undiluted concentrate was added to 0.2 ml of 1% fibrinogen (CRTS, Lille) in 0.15 M NaCl and incubated in plastic tubes at 37 or 20°C.…”

Section: Activated Factor Assaysmentioning

confidence: 99%

Large-Scale Production and Properties of a Solvent-Detergent-Treated Factor IX Concentrate from Human Plasma

Michalski¹,

Bal²,

Burnouf³

et al. 1988

Vox Sanguinis

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A human solvent-detergent (SD)-treated factor IX concentrate has been produced from cryoprecipitatepoor plasma using DEAE-Sepharose CL-6B and heparin-Sepharose CL-6B chromatography. The DEAE eluate was incubated with an SD mixture [0.3% tri(n-butyl) phosphate-1% Tween 80, 6-h at 24°C] which was found to inactivate, in less than 1 h, more than 3.8 log(10) of vesicular stomatitis virus and more than 4.8 log(10) of Sindbis virus; the SD was removed by a subsequent heparin adsorption step. The specific activity of the concentrate was 10.9 ± 1.3 IU factor IX: c/mg protein (n= 15). The factor IX coagulant to antigen ratio was 0.7 ± 0.1. The concentrate was essentially free of factors II, VII and X, and protein C. The usual major contaminants of prothrombin complex concentrate (PCC) were absent: the concentrate contained about 94% alpha-1 proteins, and only 4 major proteins were resolved by SDS-PAGE (respective apparent molecular weight: 130, 86, 76 and 69 kilodaltons), and by crossed immunoelectrophoresis against an anti-PCC serum. The nonactivated partial thromboplastin time was equivalent to that of PCC; the product was devoid of factor IXa, of other activated procoagulant factors and of coagulant-active phospholipids (removed with SD in the heparin breakthrough fraction). Animal studies using the Wessler test and acute-toxicity test in rabbits revealed no adverse side effects. SD treatment could thus be used to inactivate viruses in factor IX concentrate and improve the safety of replacement therapy in hemophilia B.

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Section: Activated Factor Assaysmentioning

confidence: 99%

Large-Scale Production and Properties of a Solvent-Detergent-Treated Factor IX Concentrate from Human Plasma

Michalski¹,

Bal²,

Burnouf³

et al. 1988

Vox Sanguinis

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“…Several tests were developed and implemented to screen products for thrombogenic materials. These included: the thrombin time, using fibrinogen or plasma as a substrate; the non-activated partial thromboplastin time (NAPIT) [25], the thrombin generation test [26] or the factor Xa generation test. These were used either singly or in combination [27].…”

Section: Detection Of Thrombogenicity In Factor IX Complex Con Centratesmentioning

confidence: 99%

Coagulation factor IX concentrate: historical perspective

Ménaché

1995

Haemophilia

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Several historical findings have led to the development of a plasma-derived virus inactivated concentrate largely composed of factor IX with only traces of the other vitamin K dependent clotting factors and used exclusively for treating factor IX deficient patients (haemophilia B). The observations that have led to the identification of haemophilia B as a different entity from haemophilia A will be reviewed first. The development of a plasma-derived product for replacement therapy in haemophilia B patients, the specific complications associated with its use, and the approaches taken to try to understand and prevent these complications, will be considered next. The development of techniques that allowed the separation of factor IX from the other vitamin K dependent clotting factors will be reviewed, as will the characteristics of Coagulation Factor IX apart from the other vitamin K dependent clotting factors. The characteristics of Coagulation Factor IX for therapeutic use and the results obtained using animal models will also be analysed. The advances that have resulted in the decreased risk of virus transmission due to more detailed screening of blood donors and submitting the concentrate to a virus inactivation treatment will not be considered here.

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“…We measured thrombin generation after recalcification (TGt5") ac cording to Sas et al [33] as modified by Cash et al [24], Human fibri nogen was purchased from Haemochrom. The NAPTT was assayed according to Kingdon et al [9], Platelet-poor plasma was from Immu no and phospholipid from Boehringer.…”

Section: In Vitro Characterization Of the Pcc B2 And Cmentioning

confidence: 99%

Factor VII and Activated- Factor-VII Content of Prothrombin Complex Concentrates

Hellstern¹,

Beeck²,

Fellhauer³

et al. 1997

Vox Sanguinis

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Background and objectives: The aim of this study was to determine the potencies of factor VII (FVII) and of activated FVII (FVIIa) in prothrombin complex concentrates (PCC). Materials and methods: We examined 56 lots of PCC from 5 manufacturers. Three brands were licensed preparations, and 1 product scries had been involved in thromboembolic complications. FVII and FVIIa were measured using a two-stage amidolytic assay and a specific clotting assay, respectively. We also quantified FVII clotting activity by a one-stage assay reflecting a mixture of FVII zymogen and FVIIa. Results: All PCC contained substantial amounts of FVII, and FVIIa could be detected in all lots. There were marked differences between manufacturers and some significant variabilities between batches. The two lots involved in thromboembolic events contained considerably more FVIIa than the PCC still licensed. The lowest FVIIa potencies were observed in an experimental product series, indicating that PCC can be produced without activation of FVII during the manufacturing process. Conclusion: FVIIa is present in all PCC containing FVII. High FVIIa potencies may contribute to the thrombogenic potential of these preparations, and determination of FVIIa potencies should be included in the in vitro characterization of PCC.

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In Vitro Spontaneous Thrombin Generation in Human Factor‐IX Concentrates

Cited by 46 publications

References 13 publications

Large-Scale Production and Properties of a Solvent-Detergent-Treated Factor IX Concentrate from Human Plasma

Large-Scale Production and Properties of a Solvent-Detergent-Treated Factor IX Concentrate from Human Plasma

Coagulation factor IX concentrate: historical perspective

Factor VII and Activated- Factor-VII Content of Prothrombin Complex Concentrates

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