Abstract |
Intracerebral hemorrhage (ICH) is the most serious side effect of antithrombotic agents, especially in cases of cerebrovascular disease. In the present study, we compared the exacerbation of ICH and prolongation of bleeding time (BT) in guinea pigs with recombinant tissue plasminogen activator (rt-PA), heparin, aspirin, and FK419, a novel nonpeptide platelet glycoprotein ( GP) IIb/IIIa receptor antagonist. ICH was induced by injection of bacterial collagenase into the caudate nucleus; BT was measured with a Simplate R device. Neither heparin nor aspirin prolonged BT. In contrast, rt-PA at the highest dose used in the study did prolong BT, and FK419 caused a dose-dependent prolongation of BT. Moreover, rt-PA and heparin increased the degree of ICH in a dose-dependent manner, leading to death in more than half of the animals treated with higher doses of these drugs. These findings show that the prohemorrhagic mechanisms underlying the prolongation of BT differ from those in collagenase-induced ICH, and that the risk of an agent with antithrombotic effects potentiating hemorrhage in the collagenase-induced model of ICH more closely parallels that in stroke patients than does the effect of the agent on BT. The findings also suggest that antiplatelet agents, including FK419, may be safer than thrombolytic or anticoagulant agents for use in patients at risk for ICH, such as those with stroke or cerebral aneurysm.
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Authors | Kayoko Mihara, Toshiaki Aoki, Akira Moriguchi, Masashi Maeda, Yasuhisa Furuichi, Nobuya Matsuoka, Seitaro Mutoh |
Journal | Journal of neurotrauma
(J Neurotrauma)
Vol. 22
Issue 11
Pg. 1362-73
(Nov 2005)
ISSN: 0897-7151 [Print] United States |
PMID | 16305324
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- ((S)-2-acetylamino-3-((R)-(1-(3-(piperidin-4-yl)propionyl)piperidin-3-ylcarbonyl))amino) propionic acid trihydrate
- Fibrinolytic Agents
- Piperidines
- Platelet Glycoprotein GPIIb-IIIa Complex
- Propionates
- Recombinant Proteins
- Heparin
- Tissue Plasminogen Activator
- Collagenases
- Aspirin
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Topics |
- Animals
- Aspirin
(pharmacology)
- Bleeding Time
- Collagenases
(pharmacology)
- Dose-Response Relationship, Drug
- Fibrinolytic Agents
(pharmacology)
- Guinea Pigs
- Heparin
(pharmacology)
- Intracranial Hemorrhages
(chemically induced, mortality)
- Male
- Piperidines
(pharmacology)
- Platelet Aggregation
(drug effects)
- Platelet Glycoprotein GPIIb-IIIa Complex
(antagonists & inhibitors)
- Propionates
(pharmacology)
- Recombinant Proteins
(pharmacology)
- Tissue Plasminogen Activator
(pharmacology)
- Whole Blood Coagulation Time
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