A cross‐over pharmacokinetic and thrombogenicity study of a prothrombin complex concentrate and a purified factor IX concentrate

Thomas, D.; Hampton, K. K.; Dasani, H.; Lee, C. A.; Giangrande, Paul; Harman, Ciara; Lee, M. L.; Preston, F. E.

doi:10.1111/j.1365-2141.1994.tb06738.x

Cited by 27 publications

(23 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consumption coagulopathy and fibrinolysis may be present to different extents and do not necessarily parallel hypercoagulopathy. These findings are consistent with the results of previous work comparing the thrombogenicity of PCCs with highly purified factor IX concentrates in hemophilia B patients [15,17,18]. In our patients, a short peak of elevated markers indicating activation of the coagulation system leading to thrombin formation was observed, but neither prolonged consumption of thrombin nor a parallel increase in fibrinolytic activity could be found.…”

Section: Discussionsupporting

confidence: 93%

Influence of prothrombin complex concentrates on plasma coagulation in critically ill patients

Staudinger¹,

Frass²,

Rintelen³

et al. 1999

Intensive Care Med

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 93%

Influence of prothrombin complex concentrates on plasma coagulation in critically ill patients

Staudinger¹,

Frass²,

Rintelen³

et al. 1999

Intensive Care Med

View full text Add to dashboard Cite

show abstract

“…The in vivo models, in contrast with in vitro assays, clearly differentiate the thrombogenic potential of PCCs from the nonthrombogenic character of HP-FIX concentrates. Thus far, ongo ing clinical studies, using surrogate markers of potential thrombogenicity, also indicate that the HP-FIX products may be less thrombogenic [22][23][24][25]. However, only a con tinued lack of clinical thrombogenicity associated with these products will confirm this hypothesis.…”

Section: Validity Of In Vivo Modelsmentioning

confidence: 58%

In vivo Models of Thrombogenic Potential: Usefulness and Limitations

et al. 1995

View full text Add to dashboard Cite

The thrombogenicity of prothrombin complex concentrates (PCCs) has been known as a risk factor since their first clinical use about 30 years ago. The development of in vivo models to define the thrombogenic components in PCCs was instrumental in providing a logical basis for selecting in vitro assays to screen for the distribution of such components during the manufacture of PCCs, and to minimize their appearance in the final product. Even so, these thrombogenic components are not completely removed, as shown in our canine nonstasis model of thrombogenicity: PCCs were still found to elicit a thrombogenic response, shown by increased fibrinopeptide A, fibrin(ogen) degradation products, activated partial thromboplastin time, and decreased fibrinogen and platelet counts when clinically relevant doses were used. The new generation of high-purity factor IX (HP-FIX) concentrates differs from PCCs because these products contain only negligible amounts of clotting factors other than factor IX, lower amounts of activated clotting factors, and, in products we have assayed, no coagulant-active phospholipids. When we infused a number of HP-FIX products in the canine nonstasis model, no thrombogenic response was observed at doses considerably greater than PCC doses that did elicit a response. Likewise, HP-FIX products were much less thrombogenic than PCCs when tested in small-animal stasis and nonstasis thrombogenicity models. Small-animal models are also useful for evaluating the role of factor IXa as a potential thrombogenic contaminant of concentrates and ensuring minimal amounts in the final product. The limitations associated with extrapolating in vivo model data will be shown to be minimal if ongoing clinical studies continue to demonstrate the low thrombogenic potential of HP-FIX concentrates in humans.

show abstract

“…Several studies by Mannucci et al [35,36], Tho mas et al [37], and others showed that highly purified products tested in a few patients caused no postinfusion activation of the coagulation cascade, as indicated by sen sitive markers such as prothrombin fragment] +2, fibrinopeptide A (FPA), factor X activation peptide, fibrin monomers, or D dimers. These markers increased signifi cantly after infusion with crude PCCs [38].…”

Section: Evidence Of Reduced Risk With High-purity Productsmentioning

confidence: 99%

The Need for Highly Purified Products to Treat Hemophilia B

Scharrer¹

1995

Acta Haematol

View full text Add to dashboard Cite

Thromboembolic complications of prothrombin complex concentrate (PCC) therapy were first reported by Kasper in 1973 [N Engl J Med 1973;289:160]. The following contaminants were discussed as possible contributors to the thrombogenicity risk: the presence of other zymogens in PCCs, the presence of activated factor IX or activated factor X, or the presence of phospholipids from platelets resulting from insufficient centrifugation of the donor plasma. Activated factor IX is now accepted as a major causative factor. After numerous additional reports of thromboembolic complications in patients treated with PCCs, the International Society on Thrombosis and Haemostasis (ISTH) Scientific and Standardization Committee (SSC) Thrombogenicity Registry was established in 1988. Lusher collected 72 cases worldwide for the SSC/ ISTH in 1988 and 1989. Thromboembolic complications and myocardial infarctions, however, continue to be serious problems associated with PCC therapy – even in the 1990s – underscoring the urgent need for high-purity factor IX products. Results from several studies by Mannucci, Bauer, and other authors demonstrated that patients treated with high-purity products developed no activation of prothrombin or thrombin, as indicated by appearance of thrombogenicity markers such as fibrinopeptide A and the amino-terminal fragments of prothrombin (F₁₊₂). Other authors demonstrated that in patients at high risk for thrombotic complications, particularly those with liver disease, or postsurgery, or in those requiring repeated treatments, high-purity concentrates appear to be safe, regarding both thrombosis and risk of virus transmission.

show abstract

A cross‐over pharmacokinetic and thrombogenicity study of a prothrombin complex concentrate and a purified factor IX concentrate

Cited by 27 publications

References 27 publications

Influence of prothrombin complex concentrates on plasma coagulation in critically ill patients

Influence of prothrombin complex concentrates on plasma coagulation in critically ill patients

In vivo Models of Thrombogenic Potential: Usefulness and Limitations

The Need for Highly Purified Products to Treat Hemophilia B

Contact Info

Product

Resources

About