The coagulant-active phospholipid content is a major determinant of in vivo thrombogenicity of prothrombin complex (Factor IX) concentrates in rabbits

Giles, AR; Nesheim, ME; Hoogendoorn, H; Tracy, PB; Mann, KG

doi:10.1182/blood.v59.2.401.bloodjournal592401

Cited by 4 publications

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“…The potential causes of thrombogenic complications after PCC administration remain a subject for debate. Early studies in animal models implicated activated factor IX or the presence of procoagulant phospholipids as potential thrombogenic determinants in PCCs [ 26 , 27 ]. A reduction in thromboembolic complications among haemophilia B patients was observed when highly-purified factor IX began to replace PCCs.…”

Section: Pccs and Thrombotic Risk: Pathogenesismentioning

confidence: 99%

Clinical review: Prothrombin complex concentrates - evaluation of safety and thrombogenicity

et al. 2011

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Prothrombin complex concentrates (PCCs) are used mainly for emergency reversal of vitamin K antagonist therapy. Historically, the major drawback with PCCs has been the risk of thrombotic complications. The aims of the present review are to examine thrombotic complications reported with PCCs, and to compare the safety of PCCs with human fresh frozen plasma. The risk of thrombotic complications may be increased by underlying disease, high or frequent PCC dosing, and poorly balanced PCC constituents. The causes of PCC thrombogenicity remain uncertain but accumulating evidence indicates the importance of factor II (prothrombin). With the inclusion of coagulation inhibitors and other manufacturing improvements, today's PCCs may be considered safer than earlier products. PCCs may be considered preferable to fresh frozen plasma for emergency anticoagulant reversal, and this is reflected in the latest British and American guidelines. Care should be taken to avoid excessive substitution with prothrombin, however, and accurate monitoring of patients' coagulation status may allow thrombotic risk to be reduced. The risk of a thrombotic complication due to treatment with PCCs should be weighed against the need for rapid and effective correction of coagulopathy.

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Section: Pccs and Thrombotic Risk: Pathogenesismentioning

confidence: 99%

Clinical review: Prothrombin complex concentrates - evaluation of safety and thrombogenicity

et al. 2011

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“…The thrombotic complications that have occurred in patients treated with PCCs are thought to be related to the presence of both activated and unactivated vitamin K dependent coagulation proteins and phos pholipid contaminants in these preparations (5)(6)(7). Complications re lated to the use of PCCs have motivated the development of high purity factor IX concentrates for the treatment of patients with hemophilia B.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Characterization of High Purity Factor IX Concentrates for the Treatment of Hemophilia B

1995

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SummaryThis study employed sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis and immunoblotting to assess the purity of seven high purity factor IX concentrates: Aimafix (Aima), AlphaNine-SD (Alpha Therapeutic), Factor IX VHP (Biotransfusion), Immunine (Immuno), Mononine (Armour Pharmaceutical), Nanotiv (Kabi Pharmacia), and 9MC (Blood Products Laboratory). The mean specific activity of these products ranged from 68 U factor IX/mg (Aimafix) to 246 U factor IX/mg (Mononine). SDS-PAGE analysis showed that the highest purity product, Mononine, had a single contaminating band under non-reducing conditions. Two additional bands were detected when this product was analyzed under reducing conditions. All other products had multiple contaminating bands that were more apparent under reducing than non-reducing conditions. The immunoblot for factor IX showed a dominant factor IX band for all products. In addition, visible light chain of factor IX was detected for AlphaNine-SD, Factor IX VHP, Immunine, Mononine, Nanotiv, and 9MC, suggesting that the factor IX in these products had undergone partial activation to factor IXa. Another contaminating band was visible at 49,500 for all of the products except 9MC. In addition to this band, high molecular weight contaminants were apparent for some products, most notably AlphaNine-SD. The identity of these bands is unknown. Immunoblotting failed to demonstrate factor VII as a contaminant of any of the high purity products, although factor Vila could be detected in some lots of Immunine, Nanotiv, and 9MC by a clot-based assay. Factor X contaminated Aimafix, AlphaNine-SD, Factor IX VHP, Immunine, Nanotiv, and 9MC, but activation products of factor X were not detected. Prothrombin contaminated all of the products except Mononine. Activation products of prothrombin were identified for three of four lots of Immunine and for one lot of Factor IX VHP. These results thus demonstrate that high purity factor IX concentrates differ substantially in the degree to which they are contaminated by potentially thrombogenic materials.

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Response: Mechanism of Action of High-Dose Factor VIIa

Mann

Butenas

2003

ATVB

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The coagulant-active phospholipid content is a major determinant of in vivo thrombogenicity of prothrombin complex (Factor IX) concentrates in rabbits

Cited by 4 publications

References 0 publications

Clinical review: Prothrombin complex concentrates - evaluation of safety and thrombogenicity

Clinical review: Prothrombin complex concentrates - evaluation of safety and thrombogenicity

In Vitro Characterization of High Purity Factor IX Concentrates for the Treatment of Hemophilia B

Response: Mechanism of Action of High-Dose Factor VIIa

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