Acetylsalicylic acid--induced hemolysis and its mechanism.

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1、AcetylsalicylicAcid-InducedHemolysisandItsMechanismN.T.SHAHmIandD.W.WESTRINGFromtheDepartmentsofPediatricsandMedicine,UniversityofWisconsin,SchoolofMedicine,Madison,Wisconsin53706ABSTRACTAcetylsalicylicacid(ASA)isknowntoareclassifiedasmildhemolyticagentseven

2、inhighcauseseverehemolyticanemiainsomeglucose-6-phos-dosage(1).However,severeredcelldestructionfol-phate-dehydrogenase-deficient(G-6-PD-deficient)indi-lowingASAingestionhasbeenreportedonseveralviduals.Tostudyitsmechanism,erythrocytesfromanoccasions,mostlyinC

3、aucasians(1-4).InthemajorityASA-sensitivepatientweretransfusedintoanormalofthepatients(2-4)theseverehemolyticprocesshadoc-compatiblerecipient.Theadministrationof2,5-dihy-curredaftertheingestionofsmalltherapeuticdosesnotdroxybenzoic(gentisic)acid,aknownASAmet

4、aboliteexceeding2g/day.SinceinallinstancesASAhadwithredoxproperties,totherecipientresultedinabeengiventoalleviatefever,infectionratherthanASAmarkeddecreaseinthesurvivalofthepatient'serythro-itselfhadbeenincriminatedasthecauseoftheseveritycytes.Similarstudies

5、withredcellsfromindividualsofthehemolyticprocess(1).Recently,however,itwaswithA-andMediterraneanvariantsofG-6-PDre-demonstratedthatthesurvivaloftheredcellsfromavealednoalterationintheerythrocytes'survival.Fur-G-6-PD-deficientpatientmarkedlydecreasedinatherst

6、udiesdisclosedthatbothsalicylateandgentisatehealthycompatiblerecipientwhenthelatterwasgivenacompetitivelyinhibitedtheG-6-PDfromtheASA-dailydoseof1.8gofASA(4).ThisgreatindividualsensitivepatientresultinginamarkedchangeinthevariationintheseverityofASA-inducedh

7、emolysisandKmforNADP.ThesedrugsalsoinhibitedtheA-anditsmechanismremainsunexplained.Thepresentin-MediterraneanvariantsofG-6-PD.Themagnitudeofvestigationwasundertakeninanattempttoelucidateinhibition,however,wascomparativelysmallandnotthemechanismofASA-inducedh

8、emolysisinG-6-PD-differentfromthatobservedwithanormalenzyme.deficientindividualsandtoascertainthereasonsforTheabovestudiessuggestedthatenzymeinhibitiontheindividualvariationsinthedegreeofhemolys