ヘパリンは,エンドトキシン誘発の凝固活性化を阻害する.
T Pernerstorfer1, U Hollenstein, J Hansen
1Department of Clinical Pharmacology-The Adhesion Research Group Elaborating Therapeutics (TARGET), University of Tromsø, Norway. thomas.pernerstorfer@univie.ac.at
Circulation
|December 22, 1999
まとめ
未分化ヘパリン (UFH) と低分子量ヘパリン (LMWH) は,ヒト内毒症モデルにおいて,リポポリサッカリド (LPS) によって誘発された凝固活性化を効果的に減少させた. 両方の抗凝固剤は,トロンビン生成と上流/下流の凝固因子活性化を阻害しました.
科学分野:
- 凝固科学とは,凝固の科学である.
- 薬理学 薬理学とは
- セプシスの研究
背景:
- リポポリサッカリド (LPS) は,組織因子 (TF) /因子VIIa経路経由でセプシス誘発の分散型血管内凝固 (DIC) を引き起こす.
- LPS誘発の凝固における抗凝固剤の臨床的使用は,まだ十分に調査されていない.
- この研究では,LPS誘発の凝固に対するUFHとLMWHの影響を調査しています.
研究 の 目的:
- 断片化されていないヘパリン (UFH) と低分子量ヘパリン (LMWH) の効果をプラセボと比較するために.
- 実験的なLPS誘発凝固モデルで抗凝固効力を評価する.
- トロンビン生成の抑制と凝固因子の活性化を評価する.
主な方法:
- 30人の健康な男性ボランティアのランダム化,ダブルブラインド,プラセボ対照試験.
- LPS (2ng/kg IV) の投与に続いて,UFH,LMWH,またはプラセボを注入する.
- プロトロンビン断片F(1+2),血栓前駆体タンパク質 (TpP),TF陽性モノサイト,活性化因子VII,およびTF経路阻害剤レベルの測定.
主要な成果:
- プラセボ群はF(1+2) とTTPの有意な増加を示し,TF陽性単細胞は倍増した.
- UFHとLMWHは,F1+2とTPPのレベルを大幅に低下させた.
- 両ヘパリンは,単細胞のTF発現を低下させ,TF経路阻害剤を増加させ,因子VIIaレベルを低下させた.
結論:
- UFHとLMWHは,初期の実験LPS誘発凝固において抗凝固作用を示す.
- トロンビン生成の成功抑制が観察されました.
- ヘパリンは,血栓の上流と下流の凝固因子の鈍い活性化を引き起こします.
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