內(nèi)科學(xué) ITP特發(fā)性血小板減少性紫癜

特發(fā)性血小板減少性紫癜

（idiopathicthrombocytopenicpurpura,ITP）

1IntroductionPathophysiologyManifestationDiagnosisTreatmentPrognosisContent2

1.Frequency（peryear）

50-100/millioninadults50/millioninchildren

Newrefractorycases:10/million

ITP?.Introduction3

2.Mortality/MorbidityThemortalityfromhemorrhage:

1%inchildren

5%inadults

InpatientswithseverePlt↓,5-yearmortality

frombleeding＞

60yrs:47.8%

＜

40yrs:2.2%

Spontaneousremission:＞

80%inchildren

uncommoninadults?.Introduction43.Sex:InchronicITP(adults),females＞72%

InacuteITP(children),males:52%females:48%4.Age:Adults:peakage20-50years.

Children:peakage2-4years,40%ofpatients＜10yearsold.ITP/Introduction5

Threeimportantelements:Antigen:Pltmembraneglycoproteins(GP):GPⅠb,Ⅱb,Ⅰa,Ⅱa,ⅢaAntibodyPltdestructioncausedbymacrophagesITPⅡ.Pathophysiology6AgFC-ROrgansproducingAb:SpleenBonemarrow(BM)Otherlymphatictissue

WherearePltsdestructed?SpleenLiverBM7

1.Bleeding◆Purpura◆Menorrhagia◆Epistaxis◆Gingivalbleeding◆GIbleeding◆Hematuria◆Retinalhemorrhages◆Intracranialhemorrhage2.Nonpalpablespleen:97%inadults

88%inchildrenSpontaneousbleedingwhenPlt＜

20x109/LITP/manifestationⅢ.Manifestation8>30%asymptomaticHeterogeneouspresentation9

血小板計(jì)數(shù)：①急性型多＜20×109/L

慢性型30～80×109/L②血小板形態(tài)：平均體積偏大，易見大型血小板③出血時(shí)間延長，血塊收縮不良；④血小板功能一般正常。InvestigationofLab10骨髓像：①急性型：巨核細(xì)胞數(shù)量輕度增加或正常慢性型：巨核細(xì)胞顯著增加②巨核細(xì)胞發(fā)育成熟障礙，急性型表現(xiàn)為

幼稚型巨核細(xì)胞增加；慢性型顆粒型巨核細(xì)胞顯著增加③產(chǎn)板型的巨核細(xì)胞顯著減少（<30%）④紅系及粒、單核系正常。11PAIg及PAC3：﹥80%的患者PAIg及PAC3+主要為IgG,亦可為IgM,偶然有兩種以上的抗體同時(shí)出現(xiàn)。其它：

90%以上患者血小板生存時(shí)間明顯縮短；可有程度不等的正常紅細(xì)胞或小細(xì)胞低色素貧血，少數(shù)可發(fā)現(xiàn)溶血證據(jù)（Evans綜合征）。12

1.Plt↓withorwithoutbleeding2.Noormildsplenomegaly3.Megakaryocytes↑ornormal4.NootherdiseasescausingPlt↓5.Goodresponsetosteroid6.Goodresponsetosplenectomy

ITP/diagnosisⅣ.Diagnosis13

BMmegakaryocytenumber,relationbetweenthenumberandprednisonresponse(70cases)

megakaryocytecases(%)prednisonresponseincreased38(54.3)betternormal24(34.3)decreased8(11.4)ITP/diagnosis14

AcuteITPChronicITPAge2－6ys20－24yssexNodifferenceMorecommoninfemale，ratioofman/woman:1：3ExcitingcauseHistoryofinfectionbefore1-3weeksNoobviouslyonsetSuddenly,chilly,feverslowingbleedingSeverity,mucousmembraneandinternalorgansbleedingPetechiae,menorrhagiaplatelet<20×109/L30－80×109/LmegalokaryocyteIncreaseornormal,ratioofinfantile↑,noplateletformationObviously↑,granularpattern↑，plateletformation↓thrombopoiesis1－6

hours1－3daysCourseofdisease2－6weeks，>80%spontaneousremissionRecurrentattacks,nospontaneousremissionDifferentialdiagnosisofacuteandchronicITP15

OtherProblemstobeConsidered:

OtherhematologicaldisordersAutoimmuneInfection(AIDS,ect.)Liverdisease,MalignancyDrug-inducedimmunePlt↓(alcohol,heparin,quinidine,sulfonamides)Pregnancy-associatedPlt↓TTP,DIC,TransfusionPseudo-Plt↓(PltclumpinginEDTA)ITP/diagnosis16皮膚粘膜出血實(shí)驗(yàn)室檢查1.血小板計(jì)數(shù)減少2.脾臟正?；蛏源?.骨髓巨核細(xì)胞增多或正常，成熟障礙4.有以下其中一項(xiàng)的:1)潑尼松治療有效；2)切脾治療有效；3)PAIgG增多；4)PAC3增多；5)血小板壽命縮短排除繼發(fā)性ITPSLE抗磷脂綜合征確診詢問病史查體1出血癥狀2疫苗接種情況3近期藥物應(yīng)用史4HIV感染的高危因素5家族史17Saftyvalueofplateletnumber

dentalcheck：≥10×109/Ltoothextractionorfilling：≥30×109/Lminorsurgery：≥50×109/Lmajoroperation：≥80×109/Lspontaneousdelivery：≥50×109/Lcaesareansection

：≥80×109/L18

BasicregimenEfficacyTimeofPlt↑Glucocorticoids80%2-5dSplenectomy80%1-2dIVIg2-3dⅤ.Treatment19

Guidelinesforspecialtherapy

ChildrenAdultsNotPlt>30x109/L:Plt>50x109/LtreatmentasymptomaticorPlt30-50x109/L:

onlyminorpurpura

onlyminorpurpura

TreatmentPlt<30x109/LPlt<50x109/Lwithsignificantmucousbleeding

Plt<10-20x109/LPlt<20-30x109/L

withminorpurpurawithriskfactorsforbleeding

RiskfactorsforbleedingHypertension,PepticulcerVigorouslifestyleITP/treatment20PrimaryITPinadults:therapySymptomaticBleedingPLT<20–30x109/LVariablesAge/sexOccupation/activitiesComorbidities/treatmentsPregnancyOtherGoalsPreventionofbleedingCureWhen?Whichpatients?Whichtherapy?

211.Glucocorticoids(thefirstoption)

◆Dose:1-2mg/kg/dQdorBidorallyisbetterthanQodResponseafterdays2-5Obviousefficacyonday5-14◆Pregnancy:Usuallysafebutbenefitsmustoutweightherisks

ITP/treatment22◆

Withdrawofsteroids：

when⑴Plttonormallevel⑵over3weeks⑶cannottolerancetosteroids

dosedropping:5mg/week◆Maintenance:5-10mg/dayfor6-12monthsITP/treatment232.Splenectomy

Indication:＞6monthscourseatleastdependentornotsensitivetosteroidsobvioussideeffects

ofsteroidsContraindication:＜6monthspregnancycannotreceivesurgicaltherapy

children:why?TherateofnaturalremissionandinfectiousrateafteroperationinchildrenishigherthaninadultEmergentsplenectomy:thepatientswithlife-threateningbleedingandmedicaltherapyfailsITP/treatment24

EfficacyofsteroidsandsplenectomyResponsiverateshortperiodlong-termSteroids80%10-15%Splenectomy80%45-60%Aftersplenectomy:Pltincreasewithin24-48hrs,mayreachto1000x109/Lwithin10daysUseanti-PltdurgsifPlt＞800x109/LITP/treatment253.Intravenousimmuneglobulin(IVIg)

●Indication:Severe,life-threateningbleeding,ChildrenwithPlt<20x109/Lwithpurpura●Dose:Adult0.4g/kgfor4-5dChildren1g/kgonce●Contraindications:HypersensitivityIgAdeficiency●Pregnancy:Safetyhasnotbeenestablished●Precautions:CheckserumIgAbeforeIVIgITP/treatment26●

Sideeffects:

ThromboemboliceventsUrticaria,pruritusPetechiae(2-30dpostinfusion)Asepticmeningitis(10%)Renaltubularnecrosisinelderlypatientsandpatientswithdiabetes6-foldincreaseinESRfor2-3wkHyponatremiaITP/treatment274.Plttransfusion◆Onlyforseverehemorrhage◆Dosage6-8Uor1U/10kg1Ucanincreasecount:5x109/Lfor70kgadult20x109/Lfor18kgchildITP/treatmentPltsurvivalisincreasedifthepltistransfusedimmediatelyafterIVIginfusion28

5.Othertherapies

CTXRituximabDanazolVincaalkaloidsDapsoneAccessorysplenectomyIFNalfaSplenicradiation6-MP

CasesaretoosmalltoshowasignificantreductioninbleedingormortalityrateITP/treatment29

6.TreatmentofpregnancywithITPInearly:don’tneedspecialtherapy:Plt＞50x109/Landnobleeding

pregnan