Accession Number : ADA185895

Title :   Development of Novel, Reversible, Non-Toxic Anticoagulants for Greatly Extended Platelet Storage.

Descriptive Note : Annual rept. 7 Apr 86-6 Apr 87,

Corporate Author : EAST CAROLINA UNIV SCHOOL OF MEDICINE GREENVILLE NC

Personal Author(s) : Miller, David T ; Bode, Arthur P

PDF Url : ADA185895

Report Date : 19 Jun 1987

Pagination or Media Count : 9

Abstract : The first phase of the development of a new anticoagulant formulation for extended storage of platelets is largely complete. Compounds which inhibit plasma proteases or platelet activation were screened for irreversible effects on platelets in short-term storage studies. Several combinations of reversible compounds were used as new anticoagulant formulations in long terms storage studies which showed remarkable improvements in platelets viability by in vitro markers for up to 15 days at room temperature. The best results were obtained with the combined strategy of: elevation of cyclic AMP (PGE-1 plus theophylline) inhibition of plasmin and contact activation (aprotinin), and inhibition of thrombin (hirudin or thromstop). Platelets stored with these inhibitors showed signs of a lowered metabolic load and therefore could be contained in bags with a reduced surface-to-volume ratio. Further studies will be undertaken to finalize the formulation and bag geometry before proceeding to toxicity and efficacy studies in animal models. Keywords: Human blood donors; Anticoagulant; Platelets concentrates; Protease inhibitors; Platelet activation inhibitors; plasmin; thrombin.

Descriptors :   *ANTICOAGULANTS, *BLOOD PLATELETS, *SHELF LIFE, *BLOOD STORAGE, ACTIVATION, ADENOSINE PHOSPHATES, ANIMALS, BAGS, BLOOD, BLOOD DONORS, CYCLIC COMPOUNDS, ELEVATION, FORMULATIONS, HUMANS, IN VITRO ANALYSIS, INHIBITION, INHIBITORS, IRREVERSIBLE PROCESSES, MARKERS, METABOLISM, MODELS, PEPTIDE HYDROLASES, PLASMIN, SHORT RANGE(TIME), THROMBIN, TOXICITY, VIABILITY

Subject Categories : Medical Facilities, Equipment and Supplies
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE