IMPROVED HEMOSTATICS FOR TRAUMATIC HYPHEMA

BLEEDING INTO THE ANTERIOR OR VITREAL CHAMBERS OF THE EYE MAY RESULT FROM BLUNT TRAUMA OR AS A COMPLICATION OF VITRECTOMY. TRAUMATIC HYPHEMA IS HEMORRHAGE INTO THE ANTERIOR CHAMBER OFTEN RESULTING FROM BLUNT TRAUMA. HYPHEMAS MAY LEAD TO CORNEAL BLOOD STAINING, SECONDARY GLAUCOMA, CHRONIC OPEN ANGLE GLAUCOMA, OR CENTRAL RETINAL ARTERY OCCLUSION. THE HEMOSTATIC INHIBITOR OF PLASMINOGEN ACTIVATION EPSILON-AMINOCAPROIC ACID (EACA) AT DOSES UP TO 30 G/DAY HAS BEEN DEMONSTRATED TO BE EFFECTIVE IN CLINICAL MANAGEMENT OF TRAUMATIC HYPHERMA. THE SIDE FFECTS AND HIGH COST OF SUCH LARGE DOSES OF THE DRUG HAVE LIMITED ITS USE AS A GENERAL PROPHYLAXIS AGAINST SECONDARY HEMORRHAGE IN CASES OF BLUNT TRAUMA TO THE EYE AND IN VITRECTOMY. THIS PROJECT WILL INVOLVE THE DESIGN AND SYNTHESIS OF ANALOGS OF EACA AND RELATED HEMOSTATICS, AND IS EXPECTED TO PRODUCE INHIBITORS WHICH WILL BIND ORDERS OF MAGNITUDE MORE TIGHTLY TO PLASMINOGEN. SUCH DRUGS WOULD ALLOW THE USE OF MUCH LOWER DOSES LEADING TO REDUCED COST OF TREATMENT AND FEWER SIDE EFFECTS.