Vampire Bat Salivary Plasminogen Activator Evokes Minimal Bleeding Relative to Tissue-Type Plasminogen Activator as Assessed by a Rabbit Cuticle Bleeding Time Model

Michael J Mellott; Denise R Ramjit; Inez I Stabilito; Timothy R Hare; Edith T Senderak; Joseph J Lynch Jr; Stephen J Gardell

doi:10.1055/s-0038-1653800

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1995; 73(03): 478-483
DOI: 10.1055/s-0038-1653800

Original Articles

Fibrinolysis

Schattauer GmbH Stuttgart

Vampire Bat Salivary Plasminogen Activator Evokes Minimal Bleeding Relative to Tissue-Type Plasminogen Activator as Assessed by a Rabbit Cuticle Bleeding Time Model

Michael J Mellott

¹The Department of Pharmacology, West Point, PA, USA

,

Denise R Ramjit

¹The Department of Pharmacology, West Point, PA, USA

,

Inez I Stabilito

¹The Department of Pharmacology, West Point, PA, USA

,

Timothy R Hare

²The Department of Biological Chemistry, Merck Research Laboratories, West Point, PA, USA

,

Edith T Senderak

³The Department of Biometrics Research, Merck Research Laboratories, West Point, PA, USA

,

Joseph J Lynch Jr

¹The Department of Pharmacology, West Point, PA, USA

,

Stephen J Gardell

²The Department of Biological Chemistry, Merck Research Laboratories, West Point, PA, USA

› Institutsangaben

Abstract

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Summary

Cuticle bleeding time (CBT) measurements in anesthetized rabbits were performed to assess the potential bleeding risks which may accompany the administration of tissue-type plasminogen activator (tPA) or vampire bat salivary plasminogen activator (BatPA). The dose of BatPA or tPA used in this study, 42 nmol/kg, was previously shown to be efficacious using a rabbit femoral artery thrombosis model (Gardell et al, Circulation 84:244, 1991). CBT was determined by severing the apex of the nail cuticle and monitoring the time to cessation of blood flow. CBT was minimally elevated (1.6-fold, p<NS) following bolus intravenous administration of BatPA; in contrast, bolus intravenous administration of tPA dramatically elevated CBT (6.2-fold, p<0.05). Rabbits treated with tPA, but not BatPA, displayed profound activation of systemic plasminogen and consequent degradation of Factor VIII and fibrinogen. Elevations in CBT after the administration of tPA were reversed by the replenishment of plasma Factor VIII activity to 40% of control, but were unaffected by complete replenishment of plasma fibrinogen. The results of this study suggest that the administration of BatPA, at a dose that promotes thrombolysis, may evoke a minimal bleeding risk, relative to an equi-efficacious dose of tPA. In addition, the tPA-provoked proteolytic consumption of Factor VIII may be a key contributor to the heightened bleeding risk.

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Referenzen

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