Effects of alcohol withdrawal on responses of platelets from alcoholics--a study using platelet-rich plasma from blood anticoagulated with D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketone (FPRCH2Cl).
Platelet responses stimulated by a range of concentrations of ADP or collagen were studied in platelet-rich plasma (PRP) from alcoholics 24-36 h and 6 days after cessation of drinking, and in PRP from age- and sex-matched controls. The studies were done using plasma from blood anticoagulated with the specific thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketone (FPRCH2Cl, PPACK); the use of this compound permits the study of platelet responses in plasma at physiological concentrations of ionized calcium. Responses of platelets to ADP (primary aggregation) and collagen (aggregation, secretion of [14C]serotonin from prelabelled platelets, and thromboxane formation) were lower in alcoholics 24-36 h after withdrawal of alcohol compared with controls. This inhibition of platelet function was not due to the presence of alcohol in the blood of the alcoholics. Aggregation in response to ADP did not change during the withdrawal period studied, while collagen-induced aggregation and secretion increased significantly and collagen-induced thromboxane formation tended to increase towards control values. The reduced platelet responses observed in alcoholics and the different rates of "recovery" of different pathways of aggregation towards control values must be due to alterations either in the platelets themselves and/or in the plasma brought about by the chronic presence of ethanol, and its withdrawal.
Rand
M L
ML
Department of Biochemistry, University of Toronto, Ontario, Canada.
Neiman
J
J
Jakowec
D M
DM
Packham
M A
MA
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000097:blood*; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000925:Anticoagulants / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010949:Plasma; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count / Q000187:drug effects; D010979:Platelet Function Tests; D013375:Substance Withdrawal Syndrome / Q000097:blood*
D000590:Amino Acid Chloromethyl Ketones; D000925:Anticoagulants; D003094:Collagen; C040308:phenylalanyl-prolyl-arginine-chloromethyl ketone