Thromb Haemost 1990; 63(02): 178-182
DOI: 10.1055/s-0038-1645191
Original Article
Schattauer GmbH Stuttgart

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 (FPRCH2CI)

Margaret L Rand
The Department of Biochemistry, University of Toronto, and the Neurology Program, Addiction Research Foundation, Toronto, Ontario, Canada
,
Jack Neiman
The Department of Biochemistry, University of Toronto, and the Neurology Program, Addiction Research Foundation, Toronto, Ontario, Canada
,
Donna M Jakowec
The Department of Biochemistry, University of Toronto, and the Neurology Program, Addiction Research Foundation, Toronto, Ontario, Canada
,
Marian A Packham
The Department of Biochemistry, University of Toronto, and the Neurology Program, Addiction Research Foundation, Toronto, Ontario, Canada
› Author Affiliations
Further Information

Publication History

Received 07 August 1989

Accepted after revision 06 December 1989

Publication Date:
02 July 2018 (online)

Summary

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-pheny1a1any1-T,-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.

 
  • References

  • 1 Hutton RA, Fink R, Wilson DT, Marjot DH. Platelet hyperaggrega-bility during alcohol withdrawal. Clin Lab Haematol 1981; 3: 223-229
  • 2 Fink R, Hutton RA. Changes in the blood platelets of alcoholics during alcohol withdrawal. J Clin Pathol 1983; 36: 337-340
  • 3 Desai K, Owen JS, Wilson DT, Hutton RA. Platelet aggregation and plasma lipoproteins in alcoholics during alcohol withdrawal. Thromb Haemostas 1986; 55: 173-177
  • 4 Haut MJ, Cowan DH. The effect of ethanol on hemostatic properties of human blood platelets. Am J Med 1974; 56: 22-33
  • 5 Mikhailidis DP, Jenkins WJ, Barradas MA, Jeremy JY, Dandona P. Platelet function defects in chronic alcoholism. Br Med J 1986; 293: 715-718
  • 6 Hillbom M, Neiman J. Platelet thromboxane formation capacity after ethanol withdrawal in chronic alcoholics. Haemostasis 1988; 18: 170-178
  • 7 Hillbom M, Muuronen A, Löwbeer C, Änggård E, Beving H, Kangasaho M. Platelet thromboxane formation and bleeding time is influenced by ethanol withdrawal but not by cigarette smoking. Thromb Haemostas 1985; 53: 419-422
  • 8 Mustard JF, Perry DW, Kinlough-Rathbone RL, Packham MA. Factors responsible for ADP-induced release reaction of human platelets. Am J Physiol 1975; 228: 1757-1765
  • 9 Packham MA, Kinlough-Rathbone RL, Mustard JF. Thromboxane A2 causes feedback amplification involving extensive thromboxane A2 formation upon close contact of human platelets in media with a low concentration of ionized calcium. Blood 1987; 70: 647-651
  • 10 Packham MA, Bryant NL, Guccione MA, Kinlough-Rathbone RL, Mustard JF. Effect of the concentration of Ca2+ in the suspending medium on the responses of human and rabbit platelets to aggregating agents. Thromb Haemostas 1989; 62: 968-976
  • 11 Zucker MB, Peterson J. Inhibition of adenosine diphosphate-induced secondary aggregation and other platelet functions by acetylsalicylic acid ingestion. Proc Soc Exp Biol Med 1968; 127: 547-551
  • 12 Massini P, Lüscher EF. The induction of the release reaction in human blood platelets by close cell contact. Thromb Diath Haemorrh 1971; 25: 13-20
  • 13 Detwiler TC, Huang EM. Interactions of platelet activating pathways: Interrelationships of aggregation and secretion. In: Platelet Responses and Metabolism Holmsen H. (ed) CRC Press; Boca Raton, FL: 1986. pp 235-249
  • 14 Kettner C, Shaw E. D-Phe-Pro-ArgCH2Cl-A selective affinity label for thrombin. Thromb Res 1979; 14: 969-973
  • 15 Neiman J, Rand ML, Jakowec DM, Packham MA. Platelet responses to platelet-activating factor are inhibited in alcoholics undergoing alcohol withdrawal. Thromb Res 1989; 56: 399-405
  • 16 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Third Edition-Revised American Psychiatric Association; Washington: 1987
  • 17 Sellers EM, Naranjo CA, Harrison M, Devenyi P, Sykora K. Diazepam loading: Simplified treatment of alcohol withdrawal. Clin Pharmacol Ther 1983; 34: 822-826
  • 18 Kornecki E, Lenox RH, Hardwick DH, Ehrlich YH. A role for platelet activating factor in neuronal function: Specific inhibition of platelet activation by triazolobenzodiazepines and interactions of PAF with cultured neural cells. In: New Horizons in Platelet Activating Factor Research Winslow CM, Lee ML. (eds) John Wiley; Chichester: 1987. pp 285-292
  • 19 Cazenave JP, Packham MA, Mustard JF. Adherence of platelets to a collagen-coated surface: Development of a quantitative method. J Lab Clin Med 1973; 82: 978-990
  • 20 Lalau Keraly C, Kinlough-Rathbonc RL, Packham MA, Suzuki II, Mustard JF. Conditions affecting the response of human platelets to epinephrine. Thromb Hnemostns 1988; 60: 209-216
  • 21 Ethanol BonnichsenR. Determination with alcohol dehydrogenase and DPN. In: Methods of Enzymatic Analysis Bergmeyer HU. (ed) Academic Press; New York: 1965. pp 285-287
  • 22 Rand ML, Gross VL, Jakowec DM, rackliain MA, Mustaid JF. In vitro effects of ethanol on rabbit platelet aggregation, secretion of granule contents, and cyclic AMP levels in the presence of prostacyclin. Thromb Haemostas 1989; 61: 254-258
  • 23 Herrmann RG, Lacefield WB, Crowe VG. Effect of ionic calcium and magnesium on human platelet aggregation. Proc Soc Exp Biol Med 1970; 135: 100-103
  • 24 Lages B, Weiss HJ. Dependence of human platelet functional responses on divalent cations: Aggregation and secretion in heparin-and hirudin-anticoagulated platelet-rich plasma and the effects of chelating agents. Thromb Haemostas 1981; 45: 173-179
  • 25 Davis JW, Phillips PE. The effect of ethanol on human platelet aggregation in vitro. Atherosclerosis 1970; 11: 473-477
  • 26 McGregor L, Rcnaud S. Inhibitory effect of alcuhul uii platelet functions of rats fed saturated fats. Thromb Res 1981; 22: 221-225
  • 27 Fenn CG, Littleton JM. Inhibition of platelet aggregation by ethanol in vitro shows specificity for aggregating agent used and is influenced by platelet lipid composition. Thromb Haemostas 1982; 48: 49-53
  • 28 Rand ML, Packham MA, Kinlough-Rathbone RL, Mustard JF. Effects of ethanol on pathways of platelet aggregation in vitro. Thromb Haemostas 1988; 59: 383-387
  • 29 Rand ML, Groves HM, Kinlough-Rathbone RL, Packham MA, Mustard JF. Effects of ethanol on rabbit platelet responses to collagen in vitro and ex vivo and on platelet adhesion to de endothelialized aortae in vivo. Thromb Res 1988; 48: 379-388
  • 30 Hoek JB, Taraschi TF. Cellular adaptation to ethanol. TIBS 1988; 13: 269-274
  • 31 Neiman J, Curstedt T, Cronholm T. Composition of platelet phos-phatidylinositol and phosphatidylcholine after ethanol withdrawal. Thromb Res 1987; 46: 295-301
  • 32 Alling C, Jönsson G, Gustavsson L, Jensen L, Simonsson P. Anionic glycerophospholipids in platelets from alcoholics. Drug Alcohol Depend 1986; 16: 309-320
  • 33 Hornstra G. Relationship between dietary fat type, platelet fatty acid composition and eicosanoid formation by activated platelets. In: Dietary Fats, Prostanoids and Arterial Thrombosis Martinus Nijhoff Publishers; The Hague: 1982. pp 138-166
  • 34 Avogaro P, Cazzolato G, Belussi F, Bittoli Bon G. Altered apoprotein composition of HDL2 and HDL3 in chronic alcoholics. Artery 1982; 10: 317-328
  • 35 Ekman R, Fex G, Johansson BG, Nilsson-Ehle P, Wadstein J. Changes in plasma high density lipoproteins and lipolytic enzymes after long-term, heavy ethanol consumption. Scand J Clin Lab Invest 1981; 41: 709-715
  • 36 Taskinen MR, Välimäki M, Nikkilä EA, Kuusi T, Ehnholm C, Ylikahri R. High density lipoprotein subfractions and posllieparin plasma lipases in alcoholic men before and after ethanol withdrawal. Metabolism 1982; 31: 1168-1173
  • 37 Desai K, Hnttnn RA, Bruckdorfer KR, Owen JS. Aggregation of isolated platelets is inhibited by the plasma high-density lipoprotein sub-class, IIDLx. Biuuheni Sue Turns 1986; 14: 723-724
  • 38 Cowan DH. Effect of alcoholism on hemostasis. Semin Hematol 1980; 17: 137-147
  • 39 Neiman J. Effects of ethanol on platelet thromboxane formation after ethanol withdrawal in chronic alcoholics: An in vitro study. Res Exp Med 1988; 188: 175-181
  • 40 Levine RF, Spivak JL, Meagher RC, Sieber F. Effect of ethanol on thrombopoeisis. Br J Haematol 1986; 62: 345-354
  • 41 Hillbom ME. What supports the role of alcohol as a risk factor for stroke. Acta Med Scand 1987; Suppl (Suppl. 717) 93-106
  • 42 Donahue RP, Abbott RD, Reed DM, Yano K. Alcohol and hemorrhagic stroke. The Honolulu Heart Program. JAMA 1986; 255: 2311-2314
  • 43 Tanaka H, Ueda Y, Hayashi M, Date C, Baba T, Yamashita H, Shoji H, Tanaka Y, Owada K, Detels R. Risk factors for cerebral hemorrhage and cerebral infarction in a Japanese rural community. Stroke 1982; 13: 62-73
  • 44 Hillbom M, Kaste M. Does alcohol intoxication precipitate aneurysmal subarachnoid hemorrhage?. J Neurol Neurosurg Psychiatry 1981; 44: 523-526
  • 45 Neiman J. Association of transient ischaemic attack in alcohol withdrawal with changes in haemostasis. Br J Addiction 1988; 83: 1457-1459