Invited commentary

Abstract

In this translational study, Dr Dansdill and the group from Loyola show that the synthetic organic compound vepoloxamer (P-188) can potentiate the effects of heparin and tissue plasminogen activator in a rat model. This is a triblock, organic, synthetic, and amphipathic molecule that improves the rheology of blood. It has been studied in the sickle cell population with no reports of bleeding complications. To date, the use of anticoagulants to prevent thromboembolism and recurrent thrombosis in the arterial and venous circulation has been plagued by a very real and problematic attendant risk of bleeding. Whereas the advent of the direct oral anticoagulants has provided a breakthrough in convenience for the patient, the true “Holy Grail” of anticoagulant therapy is to establish a way to prevent pathologic thrombosis with minimal or no bleeding risk. Major bleeding rates for low-molecular-weight heparin approximate 2%, and even for the direct oral anticoagulants, major and clinically nonmajor bleeding may be as high as 8% to 10%.1Crowther M.A. Warkentin T.E. Bleeding risk and the management of bleeding complications in patients undergoing anticoagulant therapy: focus on new anticoagulant agents.Blood. 2008; 111: 4871-4879Crossref PubMed Scopus (225) Google Scholar, 2Yeh C.H. Gross P.L. Weitz J.I. Evolving use of new oral anticoagulants for treatment of venous thromboembolism.Blood. 2014; 124: 1020-1028Crossref PubMed Scopus (101) Google Scholar As such, this work represents a priority issue in anticoagulation pharmacology. If vepoloxamer allows a lower dose of heparin to be used and potentiation of tissue plasminogen activator, then the use of such a compound could have significant clinical impact and benefit. Importantly, this medication has been shown to be safe in phase I and II trials (albeit for different indications) and thus represents a tangible and realistic translation of bench research. Although this work is interesting and potentially important, areas that need to be clarified include the dose of heparin that was used and how it relates to clinical dosage (the amount of heparin in the current study seems to be low compared with what is clinically used in patients although previously used in other rat studies) and the establishment of parameters by which to monitor the effect of the drug with standard tests. Nonetheless, the data are provocative and the concept an important one. We should all applaud the efforts to look at improving the safety of patients by decreasing dosages of anticoagulants and fibrinolytic agents while maintaining therapeutic efficacy. The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. Synthetic, organic compound vepoloxamer (P-188) potentiates tissue plasminogen activatorJournal of Vascular SurgeryVol. 67Issue 1PreviewPoloxamer-188 is a synthetic, organic compound that acts by binding hydrophobic pockets on damaged lipid bilayers in the circulation. P-188 reduces blood viscosity and confers anti-inflammatory and cytoprotective effects. Vepoloxamer (Mast Therapeutics, San Diego, Calif) is a purified version of this compound that has limited side effects. The aim of this study was to investigate drug interactions between vepoloxamer and heparin and tissue plasminogen activator (tPA). Full-Text PDF Open Archive