This paper reviews studies which have investigated the effect of anaesthetic agents on platelet function The results of these studies suggest that halothane is the only agent in current use which inhibits platelet function in concentrations used clinically. Nitrous oxide appears to cause only a modest inhibition, while enflurane and isoflurane appear to have minimal or negligible effects. There is no current evidence that intravenous induction agents opiates, or muscle relaxants affect platelet function. Reports indicate that local anaesthetic agents inhibit platelet aggregation, but only at concentrations far greater than peak plasma concentrations found during clinical use. Epidural anaesthesia may be associated with a reduction in platelet aggregation through a mechanism unrelated to direct local anaesthetic inhibition. The clinical significance of the effect of halothane on platelet function is not known. However, it is possible that halothane may affect bleeding or thrombotic complications in a similar manner to other ‘anti-platelet’ drugs.
GeorgeJ.N., ShattilS.J.The clinical importance of acquired abnormalities of platelet function. N Engl J Med1991; 324: 27–39.
9.
BuchananG.R., MartinV., LevineP.H., ScoonK., HandinR.I.The effects of anti-platelet drugs on bleeding time and platelet aggregation in normal human subjects. Am J Clin Pathol1977; 68: 355–359.
10.
PackhamM.A.Platelet function inhibitors. Thromb Haemost1983; 50: 610–619.
CronbergS., WallmarkE., SoderbergI.Effect on platelet aggregation or oral administration of 10 non-steroidal analgesics to humans. Scand J Haematol1984; 33: 155–159.
13.
DaleJ., LandmarkK.H., MyhreE.The effects of nifedipine, a calcium antagonist, on platelet function. Am Heart J1983; 105: 103–105.
14.
LehmannH.D.Experimental studies on the antiaggregatory effect of calcium antagonists. Eur Heart J1984; 5: 456–463.
15.
HsuC.Y., KnappD.R., HalushkaP.V.The effects of alpha adrenergic agents on human platelet aggregation. J Pharmacol Exp Ther1979; 208: 366–370.
16.
CampbellW.B., CallahanK.S., JohnsonA.R., GrahamR.M.Anti-platelet activity of beta-adrenergic antagonists: Inhibition of thromboxane synthesis and platelet aggregation in patients receiving long-term propranolol treatment. Lancet1981; ii: 1382–1384.
17.
LichtenthalP.R., RossiE.C., LouisG.Dose-related prolongation of bleeding time by intravenous nitroglycerin. Anesth Analg1985; 64: 30–33.
18.
MehtaJ., MehtaP.Platelet function studies in heart disease. VI. Enhanced platelet aggregate formation activity in congestive heart failure: Inhibition by sodium nitroprusside. Circulation1979; 60: 497–503.
19.
HinesR., BarashP.G.Infusion of sodium nitroprusside induces platelet dysfunction in vitro. Anesthesiology1989; 70: 611–615.
20.
RapaportS.I.Pre-operative hemostatic evaluation: Which tests, if any?Blood1983; 61: 229–231.
21.
HandinR.Bleeding and thrombosis. In WilsonJ.D., BraunwaldE., IsselbacherK.J., PetersdorfR.G., MartinJ.B., FauciA.S., RootRK (eds). Harrison's Principles of Internal Medicine. 12th Ed. McGraw-Hill, New York1991; 344–353.
22.
YardumianD.A., MackieI.J., MachinS.J.Laboratory investigation of platelet function: A review of methodology. J Clin Pathol1986; 39: 701–712.
23.
LindS.E.Prolonged bleeding time. Am J Med1984; 77: 305–313.
24.
MielkeC.H.Aspirin prolongation of the template bleeding time: Influence of venostasis and direction of incision. Blood1982; 60: 1139–1142.
25.
MielkeC.H., KaneshiroM.M., MaherI.A., WeinerJ.M., RapaportS.I.The standardized normal Ivy bleeding time and its prolongation by aspirin. Blood1969; 34: 204–215.
26.
ZahaviJ., KakkarW.B-thromboglobulin — a specific marker of in-vivo platelet release reaction. Thromb Haemost1980; 44: 23–29.
27.
ButlerM.J.Thromboelastography during and after elective abdominal surgery. Thromb Haemost1978; 39: 488–495.
28.
SaleemA., BlifeldC., SalehS.A., YawnD.H., MaceML, SchwartzM., CrawfordE.S.Viscoelastic measurement of clot formation: A new test of platelet function. Ann Clin Lab Sci1983; 13: 115–124.
29.
TumanK.J., SpiessB.D., McCarthyR.J., IvankovichA.D.Comparison of viscoelastic measures of coagulation after cardiopulmonary bypass. Anesth Analg1989; 69: 69–75.
30.
KangY.G., MartinD.J., MarquezJ.Intraoperative changes in blood coagulation and thromboelastographic monitoring in liver transplantation. Anesth Analg1985; 64: 888–896.
31.
UedaI.The effects of volatile general anesthetics on adenosine diphosphate-induced platelet aggregation. Anesthesiology1971; 34: 405–408.
32.
BjorakerD.G.Failure of clinical concentrations of halothane to block adenosine diphosphate-induced platelet aggregation in vitro. Br J Anaesth1979; 51: 187–191.
33.
Dalsgaard-NielsenJ., GormsenJ.Effects of halothane on platelet function. Thromb Haemost1980; 44: 143–145.
34.
WalterF., VulliemozY., VeroskyM., TrinerL.Effects of halothane on the cyclic 3’, 5'-adenosine monophosphate enzyme system in human platelets. Anesth Analg1980; 59: 856–861.
35.
CambriaR.P., MegermanJ., L'ItalienG., WarnockD., StraussH.W., AbbottW.M.The effect of halothane anesthesia on platelet aggregation in vivo: Decreased deposition on polytetrafluorethylene arterial grafts in dogs. Surgery1983; 93: 752–757.
36.
FaussB.G., MeadowsJ.C., BruniC.Y., QureshiG.D.The in vitro and in vivo effects of isoflurane and nitrous oxide on platelet aggregation. Anesth Analg1986; 65: 1170–1174.
37.
BerthaB.G., FoltsJ.D., NugentM., RusyB.F.Halothane, but not isoflurane or enflurane, protects against spontaneous and epinephrine-exacerbated acute thrombus formation in stenosed dog coronary arteries. Anesthesiology1989; 71: 96–102.
38.
FoltsJ.D., GallagherK., RoweG.G.Blood flow reductions in stenosed canine coronary arteries: Vasospasm or platelet aggregation?Circulation1982; 65: 248–255.
39.
O'BrienJ.R., EtheringtonM., JamiesonS.Refractory state of platelet aggregation with major operations. Lancet1971; ii: 741–743.
40.
KokoresJ.A., EconomopoulosTC, AlexopoulosC., PyrovolakisJ., PapayannisA.G.Platelet function tests during major operation for gastro-intestinal carcinoma. Br J Surg1977; 64: 147–149.
41.
LichtenfeldK.M., SchifferC.A., HelrichM.Platelet aggregation during and after general anesthesia and surgery. Anesth Analg1979; 58: 293–296.
42.
GottaA.W., GouldP., SullivanC.A., GoldinerP.L.The effect of enflurane and fentanyl anaesthesia on human platelet aggregation in vivo. Canad Anaesth Soc J1980; 27: 319–322.
43.
Dalsgaard-NielsenJ., RisboA., SimmelkjaerP., GormsenJ.Impaired platelet aggregation and increased bleeding time during general anaesthesia with halothane. Br J Anaesth1981; 53: 1039–1041.
44.
FymanP.N., TrinerL., SchranzH.Effect of volatile anaesthetics and nitrous oxide-fentanyl anaesthesia on bleeding time. Br J Anaesth1984; 56: 1197–1200.
45.
SweeneyD., WilliamsV.The effect of halothane general anaesthesia on platelet function. Anaesth Intens Care1987; 15: 278–281.
46.
RosenD., RosenK., CovelerL., RamsbacherL., SaleemA.A comparison of anesthetic induced platelet dysfunction between fluothane, ethrane and isoflurane. Anesth Analg1988; 67: S188 (abstract).
GlenJ.B., HunterS.C., BlackburnT.P., WoodP.Interaction studies and other investigations of the pharmacology of propofol (‘Diprivan’). Postgrad Med J1985; 61(Suppl 3): 7–14.
49.
OlesenA.S., JorgensenK.A.Effect of etomidate and metronidazole on platelet aggregation. Br J Anaesth1988; 61: 514–515.
50.
MoncadaS., BuntingS., MullaneK., ThorogodP., VaneJ.R., NeedlemanP.Imidazole: A selective inhibitor of thromboxane synthetase. Prostaglandins1977; 13: 611–618.
51.
NaeshO., FriisJ.T., HindbergI., WintherK.Platelet function in surgical stress. Thromb Haemost1985; 54: 849–852.
52.
MayneA., JouckenK., CollardE., RandourP.Intravenous infusion of propofol for induction and maintenance of anaesthesia during endoscopic carbon dioxide laser ENT procedures with high frequency jet ventilation. Anaesthesia1988; 43: 97–100.
53.
O'BrienJ.R.Platelet aggregation (part I). Some effects of the adenosine phosphates, thrombin, and cocaine upon platelet adhesiveness. J Clin Pathol1962; 15: 446–456.
54.
FeinsteinM.B., FiekersJ., FraserC.An analysis of the mechanism of local anesthetic inhibition of platelet aggregation and secretion. J Pharmacol Exp Ther1976; 197: 215–228.
55.
CazenaveJ-P, BenvenisteJ., MustardJ.F.Aggregation of rabbit platelets by platelet-activating factor is independent of the release reaction and the arachidonate pathway and inhibited by membrane-active drugs. Lab Invest1979; 41: 275–285.
56.
LuostarinenV., EversH., LyytikainenM-T, ScheinenA., WahlenA.Antithrombotic effects of lidocaine and related compounds on laser-induced microvascular injury. Acta Anaesth Scand1981; 25: 9–11.
57.
BorgT., ModigJ.Potential anti-thrombotic effects of local anaesthetics due to their inhibition of platelet aggregation. Acta Anaesth Scand1985; 29: 739–742.
58.
ScottD.B., JebsonP.J.R., BraidD.P., OrtengrenB., FrischP.Factors affecting plasma levels of lignocaine and prilocaine. Br J Anaesth1972; 44: 1040–1049.
59.
MooreD.C., MatherL.E., BridenbaughP.O., BridenbaughL.D., BalfourR.I., LysonsD.F., HortonW.G.Arterial and venous plasma levels of bupivacaine following epidural and intercostal nerve blocks. Anesthesiology1976; 45: 39–45.
60.
TuckerG.T., MatherL.E.Properties, absorption and disposition of local anesthetics. In CousinsM.J., BridenbaughPO (eds). Neural blockade in clinical anesthesia and the management of pain. 2nd Ed. J. B. Lippincott, Philadelphia1988; 47–110.
61.
OdoomJ.A., SturkA., DokterP.W.C., BovillJ.G., ten CateJ.W., OostingJ.The effects of bupivacaine and pipecoloxylidide on platelet function in vitro. Acta Anaesth Scand1989; 33: 385–388.
62.
GrantG.J., RamanathanS., PatelN., TurndorfH.The effects of local anaesthetics on maternal and neonatal platelet function. Acta Anaesth Scand1989; 33: 409–412.
63.
HennyC.P., OdoomJ.A., ten CateH., ten CateJ.W., OosterhoffR.J.F., DabhoiwalaN.F., SihI.L.Effects of extradural bupivacaine on the haemostatic system. Br J Anaesth1986; 58: 301–305.
64.
OdoomJ.A., DokterP.W.C., SturkA., ten CateJ.W., SihI.L., BovillJ.G.The influence of epidural analgesia on platelet function and correlation with plasma bupivacaine concentrations. Eur J Anaesthesiol1988; 5: 305–312.
65.
NielsenT.H., NielsenH.K., HustedS.E., HansenS.L., OlsenK.H., FjeldborgN.Stress response and platelet function in minor surgery during epidural bupivacaine and general anaesthesia: Effect of epidural morphine addition. Eur J Anaesthesiol1989; 6: 409–417.
66.
MustardJ.F., MurphyE.A., RowsellH.C., DownieH.G.Factors influencing thrombus formation in vivo. Am J Med1962; 33: 621–647.
67.
CarrollG., O'RourkeM., FeneleyM.Preventative strategies in management of acute myocardial infarction. Aust NZ J Med1990; 20: 615–619.
68.
ModigJ., HjelmstedtA., SahlstedtB., MaripuuE.Comparative influences of epidural and general anaesthesia on deep venous thrombosis and pulmonary embolism after total hip replacement. Acta Chir Scand1981; 147: 125–130.
69.
ThorburnJ., LoudenJ.R., VallanceR.Spinal and general anaesthesia in total hip replacement: Frequency of deep venous thrombosis. Br J Anaesth1980; 52: 1117–1121.
70.
ModigJ., BorgT., KarlstromG., MaripuuE., SahlstedtB.Thromboembolism after total hip replacement: Role of epidural and general anaesthesia. Anesth Analg1983; 62: 174–180.
71.
JorgensenL.N., RasmussenL.S., NielsenP.T., LeffersA., Albrecht-besteE.Anti-thrombotic efficacy of continuous extradural analgesia after knee replacement. Br J Anaesth1991; 66: 8–12.
72.
DavisF.M., McDermottE., HicktonC.Influence of spinal and general anaesthesia on haemostasis during total hip arthroplasty. Br J Anaesth1987; 59: 561–571.
73.
ModigJ., MalmbergP., KarlstromG.Effect of epidural versus general anaesthesia on calf blood flow. Acta Anaesth Scand1980; 24: 305–309.
74.
BredbackaS., BlombackM., HagnevikK., IrestedtL., RaabeN.Per- and postoperative changes in coagulation and fibrinolytic variables during abdominal hysterectomy under epidural or general anaesthesia. Acta Anaesth Scand1986; 30: 204–210.
75.
CookeE.D., LloydM.J., BowcockS.A., PilcherM.F.Intravenous lignocaine in prevention of deep venous thrombosis after elective hip surgery. Lancet1977; ii: 797–799.
76.
TorosianM., MichelsonE.L., MorganrothJ., MacVaughH.Aspirin and coumarin related bleeding after coronary-artery bypass graft surgery. Ann Intern Med1978; 89: 325–328.
77.
MichelsonE.L., MorganrothJ., TorosianM., MacVaughH.Relation of pre-operative use of aspirin to increased mediastinal blood loss after coronary artery bypass graft surgery. J Thorac Cardiovasc Surg1978; 76: 694–697.
78.
RubinR.N.Aspirin and postsurgery bleedingAnn Intern Med1978; 89: 1006.
79.
HarrisW.H., SalzmanE.W., AthanasoulisC.A., WalthamA.C., De SanctisR.W.Aspirin prophylaxis of venous thromboembolism after total hip replacement. N Engl J Med1977; 297: 1246–1249.
