Preservation of in vitro function of platelets stored in the presence of inhibitors of platelet activation and a specific inhibitor of thrombin.
We prepared platelet concentrates (PCs) in an experimental anticoagulant consisting of citrate-phosphate-dextrose-adenine formula 1 (CPDA-1) containing inhibitors of platelet activation (prostaglandin E1 and theophylline) and a specific thrombin inhibitor (hirudin or D-phenylalanyl-L-prolyl-L-arginine-chloromethyl ketone-2HCl). Over a 15-day storage period, these PCs showed by in vitro markers (pH, lactic dehydrogenase, PO2, PCO2, glucose consumption, morphology, and hypotonic shock recovery) greatly improved function and integrity relative to PCs in CPDA-1 only. At day 10 of storage, the experimental PCs had higher pH (P = 0.02), better morphology scores (P less than 0.001), more rapid recovery from hypotonic shock (P = 0.03), and higher PCO2 levels (P less than 0.001) than controls in CPDA-1 only. Additional storage time increased these differences to a significance level of p less than 0.01 in all tests. The experimental anticoagulant was less effective when hirudin was absent. Plasma pH was well maintained, and less glucose was consumed in the experimental anticoagulant without the aid of an increase of buffering capacity or gas transport. These findings indicate that thrombin and platelet activation play a major role in the development of the platelet storage lesion.
Bode
A P
AP
Department of Pathology, North Carolina Memorial Hospital Blood Bank, Chapel Hill.
Miller
D T
DT
D000225:Adenine / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology*; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000032:analysis; D001792:Blood Platelets / Q000032:analysis / Q000166:cytology / Q000502:physiology*; D001793:Blood Preservation / Q000379:methods*; D002951:Citrates / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007038:Hypotonic Solutions / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D010710:Phosphates / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D001786:Blood Glucose; C034876:CPDA solutions; D002951:Citrates; D007038:Hypotonic Solutions; D010710:Phosphates; D010975:Platelet Aggregation Inhibitors; D007770:L-Lactate Dehydrogenase; D013917:Thrombin; D005947:Glucose; D000225:Adenine