Tissue factor pathway inhibitor: an update of potential implications in the treatment of cardiovascular disorders.
Review published in Expert opinion on investigational drugs (2001)
Abstract
Tissue factor (TF) plays a crucial role in the pathogenesis of thrombotic, vascular and inflammatory disorders. Thus, the inhibition of this membrane protein provides a unique therapeutic approach for prophylaxis and/or treatment of various diseases. Tissue factor pathway inhibitor (TFPI), the only endogenous inhibitor of the TF/Factor VIIa (FVIIa) complex, has recently been characterised biochemically and pharmacologically. Studies in patients demonstrated that both TF and TFPI may be indicators for the course and the outcome of cardiovascular and other diseases. Based on experimental and clinical data, TFPI might become an important drug for several clinical indications. TFPI is expected to inhibit the development of post-injury intimal hyperplasia and thrombotic occlusion in atherosclerotic vessels as well as to be effective in acute coronary syndromes, such as unstable angina and myocardial infarction. Of special interest is the inhibition of TF-mediated processes in sepsis and disseminated intravascular coagulation (DIC), which are associated with the activation of various inflammatory pathways as well as of the coagulation system. A Phase II trial of the efficacy of TFPI in patients with severe sepsis showed a mortality reduction in TFPI- compared to placebo-treated patients and an improvement of organ dysfunctions. TFPI can be administered exogenously in high doses to suppress TF-mediated effects, alternatively high amounts of TFPI can be released from intravascular stores by other drugs, such as heparin and low molecular weight heparins (LMWH). Using this method high concentrations of the inhibitor are provided at sites of tissue damage and ongoing thrombosis. At present, clinical studies with TFPI are rather limited so that the clinical potential of the drug cannot be assessed properly. However, TFPI and its variants are expected to undergo further development and to find indications in various clinical states.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Резюме
Tissue factor (TF) plays a crucial role in the pathogenesis of thrombotic, vascular and inflammatory disorders. Thus, the inhibition of this membrane protein provides a unique therapeutic approach for prophylaxis and/or treatment of various diseases.
Почему это важно для гирудотерапии
This review discusses the biochemical and pharmacological characterization of tissue factor pathway inhibitor (TFPI) and its potential therapeutic implications for cardiovascular disorders. It highlights a Phase II trial in which TFPI showed a reduction in mortality and an improvement in organ dysfunction for patients with severe sepsis compared to placebo, and notes that heparin and low molecular weight heparins can release endogenous TFPI from intravascular stores. While TFPI represents an important avenue for anticoagulant and anti-inflammatory drug development, this article holds no direct relevance for the American Society of Hirudotherapy. The abstract explores an endogenous human protein and exogenous drug administration without making any reference to leeches, hirudotherapy, or the leech secretome.
Цитирование
Tissue factor pathway inhibitor: an update of potential implications in the treatment of cardiovascular disorders.
Kaiser et al. · Expert opinion on investigational drugs, 2001
Связанный клинический контекст
Узнайте, как это исследование связано с клинической практикой
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