Bleeding time prolongation with streptokinase and its reduction with 1-desamino- 8-D-arginine vasopressin

Michael T. Johnstone, Thomas Andrews, J. Anthony Ware, M. Audrey Rudd, Dorinda George, Mark Weinstein, Joseph Loscalzo

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The mechanism by which treatment with thrombolytic agents causes bleeding is not known. Recently, frequency of bleeding events has been shown to correlate with bleeding time, particularly in individuals treated with aspirin. We examined the effects of streptokinase (20,000-60,000 IU/kg) on bleeding time in 40 rabbits pretreated with aspirin, a model for fibrinolytic therapy. We then tested the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) (0.3 μg/kg), an agent known to reduce bleeding time in a variety of bleeding disorders, in 20 rabbits and compared the results with those of a control group of rabbits receiving normal saline placebo. Aspirin increased the bleeding time from a baseline mean±SEM value of 119±15 to 191±34 seconds in the control group and from 114±6 to 188±18 seconds in the experimental group. The addition of streptokinase increased the bleeding time to 592±119 seconds in the control group and 810±114 seconds in the experimental group (p=NS). Subsequent infusion of DDAVP decreased the bleeding time in the experimental group to 302±29 seconds (p<0.01 versus streptokinase) compared with 57±79 seconds (p=NS versus streptokinase) in the control animals given saline placebo. In a subset of rabbits receiving aspirin and streptokinase (40,000-60,000 IU/kg), samples were obtained for platelet aggregation (n=16), von Willebrand factor antigen concentration (n=17), and von Willebrand factor multimer distribution (n=14). Maximal rates of ADP-induced platelet aggregation were not affected by DDAVP infusion, nor was the plasma concentration of von Willebrand factor antigen, quantified by an immunoradiometric assay, significantly affected by DDAVP infusion. Furthermore, the von Willebrand factor multimer ratio decreased with DDAVP administration. These findings indicate that aspirin and streptokinase combined result in a marked increase in bleeding time that can be reduced by DDAVP. This effect of DDAVP is not accompanied by an increase in platelet aggregation response, plasma von Willebrand factor antigen concentration, or von Willebrand factor multimer ratio.

Original languageEnglish (US)
Pages (from-to)2142-2151
Number of pages10
JournalCirculation
Volume82
Issue number6
StatePublished - 1990

Fingerprint

Deamino Arginine Vasopressin
Bleeding Time
Streptokinase
von Willebrand Factor
Aspirin
Platelet Aggregation
Rabbits
Hemorrhage
Control Groups
Placebos
Immunoradiometric Assay
Fibrinolytic Agents
Thrombolytic Therapy
Adenosine Diphosphate

Keywords

  • Platelet function
  • Thrombolysis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Johnstone, M. T., Andrews, T., Ware, J. A., Audrey Rudd, M., George, D., Weinstein, M., & Loscalzo, J. (1990). Bleeding time prolongation with streptokinase and its reduction with 1-desamino- 8-D-arginine vasopressin. Circulation, 82(6), 2142-2151.

Bleeding time prolongation with streptokinase and its reduction with 1-desamino- 8-D-arginine vasopressin. / Johnstone, Michael T.; Andrews, Thomas; Ware, J. Anthony; Audrey Rudd, M.; George, Dorinda; Weinstein, Mark; Loscalzo, Joseph.

In: Circulation, Vol. 82, No. 6, 1990, p. 2142-2151.

Research output: Contribution to journalArticle

Johnstone, MT, Andrews, T, Ware, JA, Audrey Rudd, M, George, D, Weinstein, M & Loscalzo, J 1990, 'Bleeding time prolongation with streptokinase and its reduction with 1-desamino- 8-D-arginine vasopressin', Circulation, vol. 82, no. 6, pp. 2142-2151.
Johnstone MT, Andrews T, Ware JA, Audrey Rudd M, George D, Weinstein M et al. Bleeding time prolongation with streptokinase and its reduction with 1-desamino- 8-D-arginine vasopressin. Circulation. 1990;82(6):2142-2151.
Johnstone, Michael T. ; Andrews, Thomas ; Ware, J. Anthony ; Audrey Rudd, M. ; George, Dorinda ; Weinstein, Mark ; Loscalzo, Joseph. / Bleeding time prolongation with streptokinase and its reduction with 1-desamino- 8-D-arginine vasopressin. In: Circulation. 1990 ; Vol. 82, No. 6. pp. 2142-2151.
@article{c683d1bc7d264a79bcefce777bc8089a,
title = "Bleeding time prolongation with streptokinase and its reduction with 1-desamino- 8-D-arginine vasopressin",
abstract = "The mechanism by which treatment with thrombolytic agents causes bleeding is not known. Recently, frequency of bleeding events has been shown to correlate with bleeding time, particularly in individuals treated with aspirin. We examined the effects of streptokinase (20,000-60,000 IU/kg) on bleeding time in 40 rabbits pretreated with aspirin, a model for fibrinolytic therapy. We then tested the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) (0.3 μg/kg), an agent known to reduce bleeding time in a variety of bleeding disorders, in 20 rabbits and compared the results with those of a control group of rabbits receiving normal saline placebo. Aspirin increased the bleeding time from a baseline mean±SEM value of 119±15 to 191±34 seconds in the control group and from 114±6 to 188±18 seconds in the experimental group. The addition of streptokinase increased the bleeding time to 592±119 seconds in the control group and 810±114 seconds in the experimental group (p=NS). Subsequent infusion of DDAVP decreased the bleeding time in the experimental group to 302±29 seconds (p<0.01 versus streptokinase) compared with 57±79 seconds (p=NS versus streptokinase) in the control animals given saline placebo. In a subset of rabbits receiving aspirin and streptokinase (40,000-60,000 IU/kg), samples were obtained for platelet aggregation (n=16), von Willebrand factor antigen concentration (n=17), and von Willebrand factor multimer distribution (n=14). Maximal rates of ADP-induced platelet aggregation were not affected by DDAVP infusion, nor was the plasma concentration of von Willebrand factor antigen, quantified by an immunoradiometric assay, significantly affected by DDAVP infusion. Furthermore, the von Willebrand factor multimer ratio decreased with DDAVP administration. These findings indicate that aspirin and streptokinase combined result in a marked increase in bleeding time that can be reduced by DDAVP. This effect of DDAVP is not accompanied by an increase in platelet aggregation response, plasma von Willebrand factor antigen concentration, or von Willebrand factor multimer ratio.",
keywords = "Platelet function, Thrombolysis",
author = "Johnstone, {Michael T.} and Thomas Andrews and Ware, {J. Anthony} and {Audrey Rudd}, M. and Dorinda George and Mark Weinstein and Joseph Loscalzo",
year = "1990",
language = "English (US)",
volume = "82",
pages = "2142--2151",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Bleeding time prolongation with streptokinase and its reduction with 1-desamino- 8-D-arginine vasopressin

AU - Johnstone, Michael T.

AU - Andrews, Thomas

AU - Ware, J. Anthony

AU - Audrey Rudd, M.

AU - George, Dorinda

AU - Weinstein, Mark

AU - Loscalzo, Joseph

PY - 1990

Y1 - 1990

N2 - The mechanism by which treatment with thrombolytic agents causes bleeding is not known. Recently, frequency of bleeding events has been shown to correlate with bleeding time, particularly in individuals treated with aspirin. We examined the effects of streptokinase (20,000-60,000 IU/kg) on bleeding time in 40 rabbits pretreated with aspirin, a model for fibrinolytic therapy. We then tested the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) (0.3 μg/kg), an agent known to reduce bleeding time in a variety of bleeding disorders, in 20 rabbits and compared the results with those of a control group of rabbits receiving normal saline placebo. Aspirin increased the bleeding time from a baseline mean±SEM value of 119±15 to 191±34 seconds in the control group and from 114±6 to 188±18 seconds in the experimental group. The addition of streptokinase increased the bleeding time to 592±119 seconds in the control group and 810±114 seconds in the experimental group (p=NS). Subsequent infusion of DDAVP decreased the bleeding time in the experimental group to 302±29 seconds (p<0.01 versus streptokinase) compared with 57±79 seconds (p=NS versus streptokinase) in the control animals given saline placebo. In a subset of rabbits receiving aspirin and streptokinase (40,000-60,000 IU/kg), samples were obtained for platelet aggregation (n=16), von Willebrand factor antigen concentration (n=17), and von Willebrand factor multimer distribution (n=14). Maximal rates of ADP-induced platelet aggregation were not affected by DDAVP infusion, nor was the plasma concentration of von Willebrand factor antigen, quantified by an immunoradiometric assay, significantly affected by DDAVP infusion. Furthermore, the von Willebrand factor multimer ratio decreased with DDAVP administration. These findings indicate that aspirin and streptokinase combined result in a marked increase in bleeding time that can be reduced by DDAVP. This effect of DDAVP is not accompanied by an increase in platelet aggregation response, plasma von Willebrand factor antigen concentration, or von Willebrand factor multimer ratio.

AB - The mechanism by which treatment with thrombolytic agents causes bleeding is not known. Recently, frequency of bleeding events has been shown to correlate with bleeding time, particularly in individuals treated with aspirin. We examined the effects of streptokinase (20,000-60,000 IU/kg) on bleeding time in 40 rabbits pretreated with aspirin, a model for fibrinolytic therapy. We then tested the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) (0.3 μg/kg), an agent known to reduce bleeding time in a variety of bleeding disorders, in 20 rabbits and compared the results with those of a control group of rabbits receiving normal saline placebo. Aspirin increased the bleeding time from a baseline mean±SEM value of 119±15 to 191±34 seconds in the control group and from 114±6 to 188±18 seconds in the experimental group. The addition of streptokinase increased the bleeding time to 592±119 seconds in the control group and 810±114 seconds in the experimental group (p=NS). Subsequent infusion of DDAVP decreased the bleeding time in the experimental group to 302±29 seconds (p<0.01 versus streptokinase) compared with 57±79 seconds (p=NS versus streptokinase) in the control animals given saline placebo. In a subset of rabbits receiving aspirin and streptokinase (40,000-60,000 IU/kg), samples were obtained for platelet aggregation (n=16), von Willebrand factor antigen concentration (n=17), and von Willebrand factor multimer distribution (n=14). Maximal rates of ADP-induced platelet aggregation were not affected by DDAVP infusion, nor was the plasma concentration of von Willebrand factor antigen, quantified by an immunoradiometric assay, significantly affected by DDAVP infusion. Furthermore, the von Willebrand factor multimer ratio decreased with DDAVP administration. These findings indicate that aspirin and streptokinase combined result in a marked increase in bleeding time that can be reduced by DDAVP. This effect of DDAVP is not accompanied by an increase in platelet aggregation response, plasma von Willebrand factor antigen concentration, or von Willebrand factor multimer ratio.

KW - Platelet function

KW - Thrombolysis

UR - http://www.scopus.com/inward/record.url?scp=0025689897&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025689897&partnerID=8YFLogxK

M3 - Article

VL - 82

SP - 2142

EP - 2151

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 6

ER -