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

1995 ◽  
Vol 73 (03) ◽  
pp. 478-483 ◽  
Author(s):  
Michael J Mellott ◽  
Denise R Ramjit ◽  
Inez I Stabilito ◽  
Timothy R Hare ◽  
Edith T Senderak ◽  
...  
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Intravenous Administration ◽  
Bleeding Time ◽  
Bleeding Risk ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Plasma Factor ◽  
Vampire Bat

SummaryCuticle 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.

scholarly journals A comparative study of amyloid-beta (1-42) as a cofactor for plasminogen activation by vampire bat plasminogen activator and recombinant human tissue-type plasminogen activator

2004 ◽  
Vol 92 (09) ◽  
pp. 559-567 ◽  
Author(s):  
Wolf-Dieter Schleuning ◽  
Egbert Kruithof
Keyword(s):  
Plasminogen Activator ◽  
Amyloid Beta ◽  
Human Tissue ◽  
Tissue Type ◽  
Plasminogen Activation ◽  
Chromogenic Substrate ◽  
Stringent Requirement ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Vampire Bat

SummaryThe activity of both human tissue-type plasminogen activator (t-PA) and the PA from the saliva of the vampire bat, Desmodus rotundus, (DSPA) is critically dependent on the presence of a cofactor. The most efficient cofactor for both PAs is fibrin, but fibrinogen and amyloid beta peptides also have cofactor activities for human t-PA. Compared to t-PA, DSPA has a more stringent requirement for fibrin as a cofactor. The present study was undertaken to compare cofactor activities of amyloid beta 1-42 (Aβ1-42) for plasminogen activation by DSPA-α1 or by t-PA. The two PAs were incubated with different concentrations of glu-plasminogen, a chromogenic substrate for plasmin and 100 µg mL-1 of Aβ1-42, fibrinogen or fibrin as cofactor. Using the kinetic parameters directly determined from the chromogenic substrate conversion curves, we derived the relative efficacies of DSPA or t-PA in the presence of cofactor at the physiological plasminogen concentration of 2 µM. In the presence of fibrin, the activity of DSPA was comparable to that of t-PA and 23,270-fold higher than its activity without cofactor, whereas fibrin induced only a 248-fold increase in t-PA activity. The activity of DSPA with Aβ1-42 or fibrinogen as cofactor was 485-fold lower than its activity in the presence of fibrin, while for t-PA this difference was only 26-fold. The much lower activity of DSPA as compared to t-PA with Aβ1-42 or fibrinogen might lead to fewer side effects when used for the thrombolytic therapy of stroke.

Limiting Systemic Plasminogenolysis Reduces the Bleeding Potential for Tissue-type Plasminogen Activators but not for Streptokinase

1996 ◽  
Vol 75 (06) ◽  
pp. 915-920 ◽  
Author(s):  
G Roger Thomas ◽  
Harold Thibodeaux ◽  
Carol J Errett ◽  
Julie M Badillio ◽  
Daisy T Wu ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Clinical Experience ◽  
Bleeding Time ◽  
Plasminogen Activators ◽  
Embolic Stroke ◽  
Tissue Type ◽  
Stroke Model ◽  
Tissue Type Plasminogen Activator ◽  
Cerebral Bleeding ◽  
Type Plasminogen Activator

SummaryClinical experience suggests that thrombolytic-induced bleeding is associated with systemic activation of the thrombolytic system. Using fibrin specific variants of tissue-type plasminogen activator (t-PA) and making use of the apparent fibrin specificity of streptokinase (SK) in the rabbit we tested the hypothesis that minimizing systemic plasmin production and fibrinogenolysis will decrease hemorrhages in models of peripheral bleeding and embolic stroke. t-PA consumed 51% of the available fibrinogen; caused cerebral bleeds and increased peripheral bleeding time. Fibrin-specific variants of t-PA depleted less than 20% of the fibrinogen and did not cause peripheral or cerebral bleeding. However, an equipotent dose of SK converted only 12% of the available fibrinogen but increased bleeding time and caused hemorrhagic conversion in 75% of embolic stroke model animals treated. The data suggest that bleeding associated with tissue-type plasminogen activators is linked to systemic plasmin generation and subsequent fibrinogenolysis. This hypothesis does not explain the mechanism(s) of SK-in-duced bleeding.

scholarly journals Vampire Bat Salivary Plasminogen Activator (Desmoteplase) Inhibits Tissue-Type Plasminogen Activator-Induced Potentiation of Excitotoxic Injury

Stroke ◽  
2005 ◽  
Vol 36 (6) ◽  
pp. 1241-1246 ◽  
Author(s):  
Courtney Reddrop ◽  
Randal X. Moldrich ◽  
Philip M. Beart ◽  
Mark Farso ◽  
Gabriel T. Liberatore ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Excitotoxic Injury ◽  
Type Plasminogen Activator ◽  
Vampire Bat

Haemostatic responses and vasopressin release during colonoscopy in man

1991 ◽  
Vol 81 (2) ◽  
pp. 257-260 ◽  
Author(s):  
K. K. Hampton ◽  
P. J. Grant ◽  
J. Primrose ◽  
H. G. Dean ◽  
J. A. Davies ◽  
...  
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Plasma Concentrations ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Plasminogen Activator Activity ◽  
Plasma Vasopressin ◽  
Type Plasminogen Activator ◽  
Coagulant Activity ◽  
Von Willebrand

1. During major abdominal surgery there are increases in Factor VIII and plasminogen activator activity, associated with elevated plasma concentrations of vasopressin, of a magnitude shown to affect haemostasis. 2. To investigate the mechanisms involved in the haemostatic response to surgery, 12 patients undergoing fibre-optic colonoscopy were studied, of which six had a complete and six had an incomplete examination. 3. Venous blood samples were taken before, during and after the procedure for assay of plasma vasopressin, adrenaline and noradrenaline concentrations, Factor VIII coagulant activity, von Willebrand factor antigen level, euglobulin clot lysis time, tissue-type plasminogen activator activity and tissue-type plasminogen activator inhibition. 4. In the six patients who underwent a complete procedure the median plasma vasopressin concentration rose from 0.6 pg/ml to 153 pg/ml during colonoscopy. Factor VIII coagulant activity rose from 0.9 to 2.4 i.u./ml and von Willebrand factor antigen level rose from 139 to 224%. Plasminogen activator activity increased from 20 to 144 units and tissue-type plasminogen activator activity rose from 107 to 1338 m-i.u./ml, whereas tissue-type plasminogen activator inhibition fell from 4.8 to 1.0 i.u./ml. 5. In the six patients in whom a limited procedure was performed, there were no changes in haemostatic function or in plasma vasopressin concentration. Plasma concentrations of adrenaline and noradrenaline did not change in either group. 6. The results indicate that vasopressin regulates the intrinsic coagulation pathway and fibrinolytic system in the absence of adrenaline release.

Sign in / Sign up

Export Citation Format

Share Document