In Vitro Thrombogenicity Tests of Factor IX Concentrates

Prowse, Christopher V.; Chirnside, Ann; Elton, R. A.

doi:10.1055/s-0038-1657035

Cited by 11 publications

(3 citation statements)

References 10 publications

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“…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]. The NAPTT is currently the test of choice used by most manufacturers.…”

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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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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“…It has been proposed that contributions to thrombogenic activity may be made by overload of factors II and X (11), by thrombin, VIla, Xa and IXa (12) and by coagulant-active phospholipids (13). While in vitro assays have been developed to exclude potentially thrombogenic concentrates (14,15), tests in animal models suggest that such assays are not completely predictive of in vivo thrombogenic activities (16,17).…”

Section: Introductionmentioning

confidence: 99%

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

et al. 1991

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SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

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“…However, the relevance of this model in man is uncertain as it measures an immediate thrombotic effect whereas the dog experiments and clinical experience indicate that there may be a considerable delay between concentrate infusion and the appearance of symptoms. Furthermore, while there is clear evidence that the NAPTT and TGt 50 in vitro tests measure different activities (13,14,15) it is not apparent which of these tests is a better indicator of the thrombogenic effects of concentrates, although preliminary evidence would suggest the TGt 50 assay is more relevant (11).…”

Section: Introductionmentioning

confidence: 99%

A Comparison of the in Vitro and in Vivo Thrombogenic Activity of Factor IX Concentrates Using Stasis (Wessler) and Non-Stasis Rabbit Models

Prowse

Williams

1980

Thromb Haemost

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SummaryThe thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vitro tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo.These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.

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In Vitro Thrombogenicity Tests of Factor IX Concentrates

Cited by 11 publications

References 10 publications

Coagulation factor IX concentrate: historical perspective

Coagulation factor IX concentrate: historical perspective

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

A Comparison of the in Vitro and in Vivo Thrombogenic Activity of Factor IX Concentrates Using Stasis (Wessler) and Non-Stasis Rabbit Models

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