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Thromb Haemost 1993; 70(05): 768-773
DOI: 10.1055/s-0038-1649667
Clinical Studies
Schattauer GmbH Stuttgart

Biochemical and In Vivo Properties of High Purity Factor IX Concentrates

Erik Berntorp
1   Department for Coagulation Disorders, University of Lund, Malmö, Sweden
,
Sven Björkman
2   Hospital Pharmacy, Malmö General Hospital, Malmö, Sweden
,
Maj Carlsson
2   Hospital Pharmacy, Malmö General Hospital, Malmö, Sweden
,
Stefan Lethagen
1   Department for Coagulation Disorders, University of Lund, Malmö, Sweden
,
Inga Marie Nilsson
1   Department for Coagulation Disorders, University of Lund, Malmö, Sweden
› Author Affiliations
Further Information

Publication History

Received 06 April 1993

Accepted after revision 04 June 1993

Publication Date:
05 July 2018 (online)

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Summary

The purified factor IX concentrates Nanotiv (Kabi Pharmacia), Immunine (Immuno), Factor IX VHP (Bio-transfusion), Alphanine (Alpha) and Mononine (Armour) have been studied in vitro and compared with the prothrombin complex concentrates (PCCs) Preconativ (Kabi Pharmacia) and Prothromplex TIM4 (Immuno). The measured values for factor IX coagulant activity (IX: C) were in good agreement with the manufacturer’s label values. In contrast to the PCCs, most of the purified concentrates were virtually devoid of other vitamin K-dependent coagulation factors, the inhibitors protein C and S as well as fibrinogen, fibronectin and immunoglobulins. Indicators of thrombin generation, namely prothrombin fragments 1 and 2 (F 1 + 2) and thrombin-antithrombin complex (TAT), were present in varying amounts in all preparations. The specific activity in the purified concentrates exceeded that in the PCCs by a factor of 50-100. Some differences in purity were found between the purified concentrates.

In vivo, Nanotiv was compared with Preconativ and Immunine with Prothromplex TIM4 in crossover studies in patients with severe hemophilia B, and Mononine was tested in a single drug study. Most of the preparations yielded postinfusion increases in TAT, but not in FI + 2. Pharmacokinetic variables were analyzed with non-linear curve-fitting combined with model-independent methods. In retrospective comparisons, there were no apparent differences between Nanotiv, Preconativ and Mononine, whereas in vivo recovery seemed lower and the apparent clearance higher for Immunine and Prothromplex. Purified factor IX concentrates were successfully used as cover for surgery or in immune tolerance induction.

 

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