Inhibition of clot-bound α2-antiplasmin enhances in vivo thrombolysis

Guy L. Reed, Gary R. Matsueda, Edgar Haber

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Recent experiments in vitro have shown that inhibition of human α2-antiplasmin by a monoclonal antibody (MAb RWR) markedly enhances clot lysis by plasminogen activators. To extend these studies in vivo, we tested whether inhibition of clot or fibrin-bound α2-antiplasmin by MAb RWR could enhance the lysis of a human clot by tissue-type plasminogen activator (t-PA) in a rabbit jugular vein thrombosis model. Compared with a saline placebo or a control antibody, MAb RWR significantly increased thrombolysis by endogenous plasminogen activator in rabbits to which no t-PA was administered (p<0.05). In rabbits that received t-PA, the combination of MAb RWR and t-PA caused significantly greater thrombolysis than equivalent doses of t-PA alone (p<0.05). However, compared with equipotent doses of t-PA alone, the combination of MAb RWR and t-PA did not increase the nonspecific consumption of fibrinogen. These experiments suggest that the combination of an α2-antiplasmin inhibitor and a plasmin-ogen activator could be a more potent thrombolytic strategy.

Original languageEnglish (US)
Pages (from-to)164-168
Number of pages5
JournalCirculation
Volume82
Issue number1
DOIs
StatePublished - 1990
Externally publishedYes

Keywords

  • Antiplasmin
  • Fibrinolysis
  • Monoclonal antibodies
  • Plasminogen activator

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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