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.

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.

Pharmacokinetics and Effects on Fibrinolytic and Coagulation Parameters of Two Doses of Recombinant Tissue-Type Plasminogen Activator in Healthy Volunteers

1986 ◽  
Vol 56 (01) ◽  
pp. 001-005 ◽  
Author(s):  
M Verstraete ◽  
C A P F Su ◽  
P Tanswell ◽  
W Feuerer ◽  
D Collen
Keyword(s):  
Healthy Volunteers ◽  
Plasminogen Activator ◽  
Degradation Products ◽  
Plasma Concentrations ◽  
State Level ◽  
Compartment Model ◽  
Tissue Type ◽  
Maximum Plasma ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

SummaryPharmacokinetics and pharmacological effects of two intravenous doses of recombinant tissue-type plasminogen activator (rt-PA) (40 and 60 mg over 90 min) were determined in healthy volunteers. Mean maximum plasma concentrations were 1080 and 1560 ng/ml respectively. The steady state level during subsequent maintenance infusion of 30 mg over 6 h was 250 ng/ml. The pharmacokinetics of rt-PA showed a bi-exponential disappearance from plasma consistent with a 2-compartment model of t½α = 5.7 min, a t½β = 1.3 h and a total clearance of 380 ml/min.Mean fibrinogen levels at the end of the infusions of 40 mg or 60 mg rt-PA over 90 min, measured in thawed plasma samples collected on citrate/aprotinin, decreased to 74% and 57% of the preinfusion values respectively. Plasminogen fell to 55% and 48%, and α2-antiplasmin to 28% and 18% of initial values. No further decrease of these parameters was observed during the infusion of 30 mg rt-PA over 6 h. Only 2% of the preinfusion fibrinogen levels could be recovered as fibrinogen-fibrin degradation products. This moderate extent of systemic fibrinogenolysis is much less than that reported for therapeutic i.v. infusions of streptokinase.

Increased tissue-type plasminogen activator activity in orthotopic but not heterotopic liver transplantation: The role of the anhepatic period

Hepatology ◽  
1992 ◽  
Vol 16 (2) ◽  
pp. 404-408 ◽  
Author(s):  
C. Minke Bakker ◽  
Herold J. Metselaar ◽  
Theo N. Groenland ◽  
Maria J. Gomes ◽  
Eduard A. R. Knot ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Plasminogen Activator Activity ◽  
Type Plasminogen Activator ◽  
Anhepatic Period

The Simultaneous Acute Release of Tissue-Type Plasminogen Activator and von Willebrand Factor in the Perfused Rat Hindleg Region

1990 ◽  
Vol 63 (03) ◽  
pp. 454-458 ◽  
Author(s):  
N Tranquille ◽  
J J Emeis
Keyword(s):  
Plasminogen Activator ◽  
Von Willebrand Factor ◽  
Time Course ◽  
Platelet Activating Factor ◽  
Calcium Ionophore ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryIn perfused rat hindlegs, platelet-activating factor and bradyki-nin induced the acute release of both tissue-type plasminogen activator (t-PA) and von Willebrand Factor (vWF). The time course of release was similar for both proteins, and the amounts of t-PA and vWF released under various conditions were closely correlated. Release of both t-PA and vWF required extracellular calcium, and could be induced by the calcium ionophore A-23187. Protein synthesis was not required for release to occur.Phorbol myristate acetate also induced release of t-PA and vWF, though with a different time course; DDAVP was inactive.The results suggest that the release of t-PA, and that of vWF, are closely linked at the cellular level.

The Role of Cyclic Nucleotides in the Release of Tissue-Type Plasminogen Activator and von Willebrand Factor

1993 ◽  
Vol 69 (03) ◽  
pp. 259-261 ◽  
Author(s):  
N Tranquille ◽  
J J Emeis
Keyword(s):  
Plasminogen Activator ◽  
Von Willebrand Factor ◽  
Cyclic Nucleotides ◽  
Atrial Natriuretic Factor ◽  
Platelet Activating Factor ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe modulation of the induced acute release of tissue-type plasminogen activator (t-PA) and of von Willebrand factor (vWF) by compounds affecting cyclic nucleotide levels was studied, using an isolated rat hindleg perfusion system. Platelet-activating factor (PAF; 5 nM) or bradykinin (0.8 (μM) were used to induce release of t-PA and vWF.The guanylate cyclase activators sodium nitroprusside and atrial natriuretic factor reduced the induced release of t-PA and vWF. Release was not affected by inhibiting nitric oxide production with NG-nitro-L-arginine. The effects of nitroprusside and atrial natriuretic factor could not be reproduced by infusion of 8-bromo-cGMP.The adenylate cyclase activator forskolin had no effect on bradykinin-induced release of t-PA and vWF, reduced PAF-induced t-PA release, but potentiated PAF-induced vWF release. These modulatory effects were only partially mimicked by infusion of 8-bromo-cAMP.None of the compounds tested was able to induce the release of t-PA or of vWF in the absence of stimulation by bradykinin or platelet-activating factor. Cyclic nucleotides can thus modulate, but not induce, the acute release of t-PA and vWF from perfused rat hindlegs.

Stanozolol-Induced Changes in Fibrinolysis and Coagulation in Healthy Adults

1984 ◽  
Vol 51 (02) ◽  
pp. 157-164 ◽  
Author(s):  
C Kluft ◽  
F E Preston ◽  
R G Malia ◽  
R M Bertina ◽  
G Wijngaards ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Protein C ◽  
Plasma Lipids ◽  
Therapeutic Potential ◽  
Healthy Adults ◽  
Tissue Type ◽  
Coagulation System ◽  
Tissue Type Plasminogen Activator ◽  
Plasminogen Activator Activity ◽  
Type Plasminogen Activator

SummaryThe effects of orally-administered stanozolol, 5 mg b. d. on fibrinolysis, coagulation and on various haematological and biochemical parameters have been studied in 16 healthy adults, 8 males and 8 females. Statistically significant enhancement of extrinsic (tissue-type) plasminogen activator activity was detected in all subjects studied. This was associated with significant increases in plasma plasminogen and a concomitant reduction in histidine-rich glycoprotein. There were no changes in plasma urokinase activity. Changes in the coagulation system included significant reduction in plasma fibrinogen and elevation of protein C and anti thrombin III. Changes in plasma lipids included significant reduction of HDL cholesterol associated with an increase in LDL triglycerides. No change occurred in total cholesterol. There were no major differences between the sexes, nor were there serious side effects.The effects of stanozolol on extrinsic (tissue-type) plasminogen activator activity, “free” plasminogen, protein C and antithrombin III, argue strongly in favour of its therapeutic potential.

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