The effect of homo- and heterologous thromboplastins on plasmas of man, seven mammalian and two avian species: A comparative study

Kaše, F

doi:10.1016/0300-9629(78)90278-5

Cited by 10 publications

(8 citation statements)

References 10 publications

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“…The interaction between tissue factor and factor VIIa is species specific [1,2]. Human factor VII has been shown to have reduced activity when it is exposed to porcine thromboplastin.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2005

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Preclinical studies in animals and ex vivo human blood have provided a solid rationale for conducting prospective randomized trials in trauma patients. Small animal models have been utilized to study the efficacy of recombinant activated factor VII (rFVIIa; NovoSeven®) in treating thrombocytopenic rabbits and for the reversal of anticoagulation. Safety models in the rabbit also exist to test for systemic activation of clotting and pathologic thrombosis. Animal models simulating traumatic injuries in humans have primarily been performed in pigs because of species similarities in terms of coagulation characteristics and the larger internal organs. The pig studies, utilizing human rFVIIa, have shown increased strength of clot formation, decreased bleeding, and improved survival. However, these findings are not uniform and are dependant on the model chosen. All of the animal models described have provided good safety data and suggest that the use of rFVIIa is not associated with systemic activation of coagulation or microthrombosis of end organs.

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“…The interaction between tissue factor and factor VIIa is species specific [1,2]. Human factor VII has been shown to have reduced activity when it is exposed to porcine thromboplastin.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2005

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“…In studieswith swine,however,species-specificity must be considered. Bothrabbit and humanthromboplastins induce coagulation more efficiently in humanplasma thaninporcine plasma.Additionally, porcine thromboplastin inducesc oagulation more efficiently in porcine plasma thaninhuman plasma (11,12). WhenrFVIIa is administered to swine,amixtureof native porcine FVIIa and human rFVIIae xists; both of these must reactwith pig tissue factor in vivo.Incontrast, both FVIIa's must interact with rabbit tissue factor in astandard PT in vitro .It is therefore conceivablethat adose of rFVIIathat is not active in the pig in vivo could yield a"false positive" in vitro when using astandard PT withrabbit-derivedreagents.…”

Section: Resultsmentioning

confidence: 99%

“…Theothermechanism of action requires binding of rFVIIa to exposed tissue factor on an appropriate surface followedb y enzymatic activation of factor X (10). The tissue factor-FVIIa interaction is species-specific (11,12). Forexample, human factor VII (FVII) appears to have reduced activity when exposed to porcine thromboplastin (11,12).…”

Section: Introductionmentioning

confidence: 99%

“…The tissue factor-FVIIa interaction is species-specific (11,12). Forexample, human factor VII (FVII) appears to have reduced activity when exposed to porcine thromboplastin (11,12). Furthermore,standard in vitro coagulation tests commonlyu se as at issue factor source rabbit brain thromboplastin, whichreactsdifferently withhuman versus pig plasma (11).When rabbit-derived reagentsa re used to assaypig blood that contains human rFVIIa, yetathirdspecies is introducedinto the assaysystem.…”

Section: Introductionmentioning

confidence: 99%

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Effects of increasing doses of activated recombinant factor VII on haemostatic parameters in swine

Ryan¹,

Delgado²,

Martínez³

et al. 2005

Thromb Haemost

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This study examined dose-response relationships between activated recombinant factor VII (rFVIIa) and (1) in vivo haemostasis and (2) in vitro measures of coagulation and platelet function. Anesthetized swine were used. Ear bleeding time (BT) was measured and blood was sampled following increasing doses of rFVIIa (0, 90, 180, 360 and 720 microg/kg; n=6) or saline (n=6). BT was not altered by rFVIIa. Prothrombin time (PT) using standard or pig-specific methods was decreased by rFVIIa. Activated clotting time (ACT) was decreased by rFVIIa. Thromboelastography using collagen (COLL) or pig thromboplastin (p-ThP) as agonist demonstrated shorter reaction times, shortened time to reach maximum velocity of clot formation, and increased alpha-angle in the presence of rFVIIa. rFVIIa dosing increased maximum velocity of clot formation when p-ThP was used to initiate the reaction but not when COLL was used. rFVIIa at the highest concentration increased maximum amplitude when COLL was used to initiate the reaction. Platelet aggregation was not altered by rFVIIa. Following completion of the dose escalation phase, a severe liver injury was produced. rFVIIa altered neither blood loss nor survival time following injury but improved mean arterial pressure. A small increase in systemic thrombin-antithrombin III complex occurred after administration of rFVIIa at doses of 180 microg/kg and above. However, there was no histological evidence of intravascular coagulation after rFVIIa administration. In summary, rFVIIa activity was detectable in vitro but did not change haemostasis in normal swine.

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“…Mechanical principles to determine plasma coagulation are divided into two categories: (1) monitoring turbidity of plasma during plasma coagulation [e.g., ACL series, Beckman, Lexington, MA (currently, the same apparatus is obtained from Instrumentation Laboratory, Lexington, MA); CA series, Sysmex, Kobe, Japan], and (2) monitoring plasma viscosity during coagulation (e.g., STA series, Roche Diagnostica Stago, Asnleres, France; KC series, Amelung, Lehbrinksweg, Germany). It is known that PT varies depending on the PT reagents employed (Kase, 1978). Therefore, it is necessary to establish a reference range in each laboratory, and under each experimental condition.…”

Section: Prothrombin Timementioning

confidence: 99%

Blood Coagulation Tests in Toxicological Studies-Review of Methods and Their Significance for Drug Safety Assessment-

Kurata

Horii²

2004

J. Toxicol. Sci.

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In general toxicological studies, prothrombin time and activated partial thromboplastin time are routinely measured to assess blood coagulation. Special (problem-driven) tests for blood coagulation are of significance to detect abnormalities and investigate the mechanism of toxicity in detail. In this review, we compiled widely scattered information on blood coagulation testing from different fields in the biological area, and reviewed the methods available and their significance in toxicological studies. The relevant literature cited here reports large species differences in platelet aggregation, coagulation factors or fibrinolysis, and technical limitations. However, the following tests are basically applicable to laboratory animals; (1) assays for individual coagulation factors and protein induced by vitamin K absence or antagonists (PIVKA) to investigate coagulation factor abnormalities; (2) platelet aggregation-, platelet adhesion-, platelet release-tests and von Willebrand factor assay to screen and/or investigate platelet dysfunction; (3) fibrin/fibrinogen degradation products (FDP), D-dimer and thromboelastogram to detect fibrinolitic abnormalities, and assays for plasminogen, plasmin and their activator/inhibitor to investigate fibrinolysis in detail; and (4) bleeding-time to grossly evaluate blood coagulation capability in vivo. An appropriate battery of these tests provides significant information for risk assessment of drugs.

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The effect of homo- and heterologous thromboplastins on plasmas of man, seven mammalian and two avian species: A comparative study

Cited by 10 publications

References 10 publications

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Effects of increasing doses of activated recombinant factor VII on haemostatic parameters in swine

Blood Coagulation Tests in Toxicological Studies-Review of Methods and Their Significance for Drug Safety Assessment-

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