bivalirudin and Hemolysis

The use of extracorporeal membrane oxygenation (ECMO) support for cardiac and respiratory failure has increased in recent years. Improvements in ECMO oxygenator and pump technologies have aided this increase in utilization. Additionally, reports of successful outcomes in supporting patients with respiratory failure during the 2009 H1N1 pandemic and reports of ECMO during cardiopulmonary resuscitation have led to increased uptake of ECMO. Patients requiring ECMO are a heterogenous group of critically ill patients with cardiac and respiratory failure. Bleeding and thrombotic complications remain a leading cause of morbidity and mortality in patients on ECMO. In this review, we describe the mechanisms and management of hemostatic, thrombotic and hemolytic complications during ECMO support.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Cardiac Output, Low; Cardiac Tamponade; Extracorporeal Membrane Oxygenation; Hemolysis; Hemorheology; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Respiratory Insufficiency; Thrombosis; von Willebrand Diseases

Thermosensitive injectable hydrogels have been used for the delivery of pharmacological and cellular therapies in a variety of soft tissue applications. A promising class of synthetic, injectable hydrogels based upon oligo(ethylene glycol) methacrylate (OEGMA) monomers has been previously reported, but these polymers lack reactive groups for covalent attachment of therapeutic molecules. In this work, thermosensitive, amine-reactive and amine-functionalized polymers were developed by incorporation of methacrylic acid N-hydroxysuccinimide ester or 2-aminoethyl methacrylate into OEGMA-based polymers. A model therapeutic peptide, bivalirudin, was conjugated to the amine-reactive hydrogel to investigate effects on the polymer thermosensitivity and gelation properties. The ability to tune the thermosensitivity of the polymer in order to compensate for peptide hydrophilicity and maintain gelation capability below physiological temperature was demonstrated. Cell encapsulation studies using an H9 T-cell line (CD4+) were conducted to evaluate feasibility of the hydrogel as a carrier for cellular therapies. Although this class of polymers is generally considered to be non-toxic, it was found that concentrations required for gelation were incompatible with cell survival. Investigation into the cause of cytotoxicity revealed that a hydrolysis byproduct, diethylene glycol monomethyl ether, is likely a contributing factor. While modifications to structure or composition will be required to enable viable cell encapsulation, the functionalized injectable hydrogel has the potential for controlled delivery of a wide range of drugs.

Topics: Amines; Animals; Anticoagulants; Cell Line; Cell Survival; Cell- and Tissue-Based Therapy; Copper; Drug Carriers; Drug Compounding; Drug Delivery Systems; Hemolysis; Hirudins; Hot Temperature; Humans; Hydrogels; In Vitro Techniques; Methacrylates; Mice; NIH 3T3 Cells; Peptide Fragments; Polyethylene Glycols; Polymethacrylic Acids; Recombinant Proteins