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HEMATOLOGY

SICKLECELLANEMIA: PatientswithsicklecellanemiacanundergoosteonecrosisofmajorbonesduetoRBC sickling,microinfarctions,andbonehyperplasia.Them.csitesarethehumeraland femoralheads. TxisPainmanagementandlimitationofweightbearing,andifthesefail,dosurgery(joint reconstruction). Inanypatientwithsicklecellanemiaandacutepain,theinitialmanagementis adequatehydrationandsupplementaloxygen,whilesearchingfor/treatingany precipitatingfactorsthatcausedthecrisis.Ifptshaveanacutevasoocclusivecrisis(ie stroke,priapism,intractablepain),doexchangetransfusion. Inpriapism,firstapplyacoldcompress,andpharmacologictx.Ifitdoesnotresolve,thendo exchangetransfusion(espifitresultedfromvasoocclusivecrisisinapatientwithsicklecell anemia).Ifstillnotresolve,thendosurgicalintervention. Hyposthenuriaisanimpairmentinapersonskidneytoconcentrateurine.Itisfoundinpeople withsicklecelldiseaseandtrait.ThisisthoughttoresultfromRBCsicklinginthevasarectaeof theinnermedulla,whichimpairscountercurrentexchangeandfreewaterabsorption. Patientswithsicklecellanemiabecomefunctionallyhyposplenicatanearlyageduetosplenic autoinfarction,Twicedailyadministrationofprophylacticpenicillinshouldbegiventochildren untiltheyreach5yearsofageandalsovaccinationswiththeconjugateds.pneumoniae vaccination. Inpatientswithsicklecellanemia,youhaveahemolyticanemia.Thebonemarrow compensatesbyincreasingRBCproduction.Butpatientsmayalsodevelopaplasticcrisis,which canbecausedbymanyconditions,includingfolicaciddeficiency.Thiscanleadtofailureofthe bonemarrowtocompensatefortheincreaseddestructionofRBC.Thussupplementationof folicacidisrecommendedinallpatients. Strokesinchildrenareuncommon,andmostchildhoodstrokesarecausedbysicklecell anemia. Hereditaryspherocytosis anautonomicdominantdisorderofspectrin,theproteinthatprovidesscaffoldingfor RBC.TheRBCisnotdeformableandgetstrappedinthefenestrationsofthespleens redpulp. Classicfindingsareapositivefamilyhistory,splenomegaly,andspherocytosiswith increasedreticulocytesonperipheralbloodsmear Chronichemolysiscancausejaundiceandpigmented(calciumbilirubinate)gallstones. Ptscanhaveacutecholecystitisduetopigmentedgallstones.Thetxisfolate supplementationandsplenectomy. Aspleenpalpated2cmbelowtheleftcostalmarginisSPLENOMEGALY.

VitaminB12deficiency mayoccurduetolowdietaryintakeofthisvitamin,thepresenceofantibodiesagainst intrinsicfactor(perniciousanemia),ormalaabsorption. Theschillingtesthelpsdifferentiatebetweenthesecauses. ThepatientisfirstgivenadoseofradiolabeledoralvitaminB12andanIMinjectionof unlabeledvitaminB12. TheurinaryexcretionofradioactiveB12isthenmeasured. NormalurinaryexcretionofradiolabeledvitaminB12suggestsnormalabsorptionand B12deficiencyinthissettingismostlikelyduetopoorintakeofvitaminB12inthediet. Todifferentiatebetweenperniciousanemiaandmalabsorption,thenextdoseofradio labeledB12isgivenwithintrinsicfactor. Normalexcretionaftertheadditionofintrinsicfactorisdiagnosticofperniciousanemia. LowexcretionofB12afteradministrationofintrinsicfactorrulesoutperniciousanemia andsuggestsamalabsorptionsyndromesuchaspancreaticinsufficiency,bacterial overgrowth,orshortgutsyndrome. VitaminB12deficiencyiscommonafteratotalorpartialgastrectomy. OthercommoncausesofB12deficiencyareperniciousanemia,gastritis,elderlyage, intestinaldisorderspreventingabsorption. B12isarequiredcofactorforthedemethylationofmethyltetrahydrofolatetoTHF.THF isusedasacofactorintheformationofpurinemoleculesforDNAsynthesis.Thus,B12 deficiencyinterferswithDNAsynthesis. *MegaloblasticanemiaandbasophilicstipplingareseeninvitaminB12andfolicacid deficiency.Bothfolateandcobalaminareinvolvedintheconversionofhomocysteine tomethionine.Thus,deficiencyineitherwillresultinelevatedhomocysteinelevels. Folateandcobalamindeficienciescanbedistinguishedbymeasuringmethylmalonic

Inhereditaryspherocytosis,ptsusuallypresentwithanemia,spherocytosis, splenomegaly,andanincreasederythrocyteosmoticfragilitytest.Itisusuallyfirst suspectedintheneonatalperiodbecauseofhyperbilirubinemiaalthoughthismaybe mildandmaygounrecognizeduntiladulthood.Byadultlifemanyofthesepatients developcholelithiasisandpresentwithcholecystitis.Chroniclegulcersmay complicatethisdisease.Thesepatientsareoftencomplicatedbyepisodesofaplastic crisisinwhicherythropoietinissuppressedandthehemolyticprocesscontinues.These episodesarelifethreateningandusuallybecauseofparvovirus.Severeanemiamay alsooccurwhentheintakeoffolicacidistoolow,soallptsshouldbeprescribedfolic acidsupplementation. Autoimmunehemolyticdiseaseandhereditaryspherocytosisarebothextravascular hemolyticanemias.Theformerisacquiredandthelatterhasanautonomicdominant transmission.Thusanegativefamilyhistoryandpositivecoombstestaresuggestiveof autoimmunehemolyticdisease,whereasapositivefamilyhistoryandanegative coombs(direct)testismorsuggestiveofhereditaryspherocytosis.Theperipheralblood smearinBOTHmayshowspherocytesbutinhereditaryspherocytosisyoumayseeloss ofcentralpallor.Alsoinboththeosmoticfragilitytestispositive!!! *LossofconcavityoftheRBCisseenindiseaseslikehereditaryspherocytosis.

acidconcentrations.Cobalamin,unlikefolicacid,isalsoinvolvedintheconversionof methylmalonlyCoAtosuccinylCoA.Thuscobalamindeficiencywillyieldincreased concentrationsofmethylmalonicacid,whereastheywillremainnormalinfolicacid. ThinkofvitaminB12deficiencywhenyouhaveamacrocyticanemia,glossitis,and neurologicalchangesthatincludeperipheralneuropathy.Perniciousanemiaisan autoimmunedisorderwherethebodymakesantiintrinsicfactoranbitodies,andisthe leadingcauseofb12deficiency. First,antiintrinsicfactorantibodiesdecreasetheamountoffunctionalintrinsicfactor availabletofacilitateB12absorption.Second,ptsdevelopachronicatrophicgastritis duetodecreasednumberofparietalcells.Thisatrophicgastritisincreasestheriskof intestinaltypegastriccancerandgastriccarcinoidtumors. Theseptsneedtobemonitoredforthedevelopmentofgastriccancer(periodicstool testingforthepresenceofblood). Them.ccausesofvitaminB12deficiencyincludeastrictvegetariandiet(after3or4 years)andperniciousanemia.

HUSandTTPcomeunderaspectrumofdiseases.Ifthepatienthasmoreneurologicsymptoms andlessofrenalfailure,itisconsideredTTP,andviceversa.Bothconditionsareveryserious andrequireemergentplasmapheresis. TTPpresentswiththefollowingpentad: 1.Severethrombocytopenia. 2.Microangiopathichemolyticanemia(RBCfragments) 3.Fluctuatingneurologicalsigns. 4.Renalfailure. 5.Fever. HUSistypicallyadiseaseofyoungchildren,andusuallyprecededbyanacutediarrhealillness duetopathogensE.coliserotype0157:H7.GIbleedingisacommonsymptom.Physicalexam frequentlyrevealspurpuraandHTN.Thehallmarkismicroangiopathichemolyticanemia.Pts alsoundergoacuterenalfailure,fever,oliguria/anuria,andthrombocytopenia.Theperipheral smearshowsschistocytesandgiantplatelets.Intravascularhemolyticresultsinelevatedlevels ofLDHandindirectbilirubinandanincreasedreticullocytecount.Theurinecontains hemoglobin,hemosiderin,albumin,RBCs,andWBCsandcasts. Patientswhohaverenalfailure,bleedduetoDYSFUNCTIONALplatelets TTPHUS: HIVincreasestheriskforTTP. Thesepatientscanalsohaverenalfailure(HIVcausesfocalsegmental glomerulosclerosis;HCVcausesmembranoproliferativeglomerulonephritis). IfthepatienthasahistoryofHCV,theycanhavesignsofliverdisease. AcluetothedxofTTPHUSisreticulocytosis. Aperipheralsmearwith>1%schistocyteswouldbevirtuallydiagnosticof microangiopathichemolyticanemia,acomponentofTTPHUS.Butthisalsooccursin DICandmalignanthypertension.

CoagulationtestswouldhelptoruleoutDIC.DICptsbleedandhaveabnormal coagulationstudies,whileTTPHUSpatientsdonotbleeddespitetheirlowplatelet count. ConsidermalignantHTNifthereisahistoryofHTNandevidenceofHTNsiveretinopathy onfundoscopicexam.

PatientswithperniciousanemiahaveachlorhydriaandELEVATEDLDH,MCH Unexplainedhemolyticanemiaandthrombocytopeniainapatientwithrenalfailureand neurologicsymptomsshouldraisestrongsuspicionsforTTP. IdiopathicTTPisthoughttobeduetoadeficiencyoforautoantibodyagainstaspecificvon Willebrandfactorcleavingprotease(ADAMTS13).Thiscausestheaccumulationoflargevon Willebrandfactormultimersandplateletaggregation.Itisfatalifnottreatedpromptly. *Plasmapheresis(plasmaexchange)isthetxofchoiceandshouldbestartedassoonas possible.Itremovestheoffendingautoantibodiesandrepletesthedeficientenzyme. PlatelettransfusioniscontraindicatedinptswithTTPasitcanworsentherenalfailure andneurologicsymptomsduetocontinuedconsumptionofplateletsbymicrothrombi. Recovery(usuallydefinedasnormalizationofplateletcountandLDHlevels)arehighif therapyisgivenpromptly. Renalfnimpairment(creatinineincrease)andperipheralbloodsmearschistocytesmay persistforseveralweeksfollowingclinicalrecovery Heparininducedthrombocytopenia: Mechanism: Heparininducedreleaseofplateletfactor4fromplateletgranulesspurstheformation ofimmunogenicheparinPF4complexes. IgGantibodiesdirectedagainstheparinPF4complexescauseplateletactivationby attachingtotheFcreceptorsonplatelets,endothelialcellactivation,andabnormal generationofintravascularthrombinwithouttheusualstimulusofsubendothelial collagenexposure. Thereiscomplementmediateddestructionofplatelets itismorecommonwithunfractionatedheparinderivedfrombovinelungthanporcine intestine.HITismuchmorecommonwiththeuseofunfractionated(highmolecular) heparincomparedtolowmolecularweightheparin. Paradoxicalthrombosis(whiteclotsyndrome)occursratherthanbleeding. Tx: Discontinueheparin.Resolutionofthrombocytopeniaoccurswithin45daysof discontinuationofheparin. Givedirectthrombininhibitorslikeargatrobanandlepirudin. MostrecommendationssaytouseenoxaparinandotherLMWHsinplaceof unfractionatedheparin.However,enoxaparindoesNOTprolongthePTT.Todecreasethe risk,useLMWheparinandcoadministrationoforalanticoagulants. Thrombocytopeniaisawellrecognizedseriouscomplicationofheparintherapy.There are2typesofHIT:

Lupusanticoagulant: Inpatientswithlupusandthromboembolicdisease,thelupusanticogulantor antiphospholipidantibodysyndromemustbesuspected. ThelupusanticoagulantisanIgMorIgGimmunoglobulinthatprolongsthePTTby bindingphospholipidsusedintheassay.ThusitisonlyalabartifactanddoesNOT promotebleeding.Infactitisnotananticoagulantatallandisassociatedwithin increasedriskofthrombosisandspontaneousabortion. ThePTTwillnotcorrectifmixedina1:1dilutionwithnormalplasma. TheRussellvipervenomtestisdesignedtotestforthelupusanticoagulantandwillbe prolongedinthedisease. ThePTwillbenormalorslightlyprolonged VonWillebrandsfactor,bleedingtime,andplateletcountwillbenormal. Ddimerwillbenormalorhigh.Ddimeristypicallyelevatedinthepresenceofblood clots. Antiphospholipidantibodysyndromeischaracterizedbyrecurrentarterialorvenous thrombosisorrecurrentfetallossesinthepresenceofantiphospholipidantibodies. Thereare3typesofantiphospholipidantibbodies. Thefirsttypeisresponsibleforfalsepositivesyphilisserology. Thesecondtypeislupusanticoagulant,anditfalselyelevatestheAPTTlevel.

HITIhasanonimmunemechanismandispossiblyduetothedirecteffectofheparinon plateletactivation.Itoccurswithinthefirst2daysofheparintherapy. HITIIisanautoimmunedisordercharacterizedbytheformationofantibodiesagainst theheparinplateletfactor4complex.HITIIusuallyoccurswithin4to10daysof heparintreatment. Thefirststepisimmediatecessationofallexposuretoheparin,includinglowmolecular weightheparin. G6PDisanxlinkedcondition.Thereisnochronichemolyticanemia,andepisodesof hemolyticoccurONLYduetooxidativestressforminfectionordrugs.Theperipheral bloodsmearisnormal.PlateletandWBCcountsarenormal.G6PDlevelsarenormal betweenhemolyticepisodes. HemoglobinprecipitationisseeninG6PDdeficiency.Inthisdisease,hemoglobin becomesoxidizedandformsinsolubleprecipitantcalledHeinzbodies.Theyappearin RBCafterstainingwithadyesuchascrystalviolet. NitrofurantoincanprecipitateG6PD. PNHVs.G6PD:InG6PDyouhaveSUDDENonsetofhemolysis SuspectG6PDdeficiencyinapatientwhodevelopsacutehemolytic(ielowhemoglobin, increasedindirectbilirubin,increasedLDH,decreasedhaptoglobin)afteringesting primaquineorsulfadrugs(bactrim).Itisanxlinkeddisorderandthem.cenzymatic disorderofRBCinhumans.Itism.cseeninblacks,Asians,andpeoplefrom Mediterraneanorigin.Interestingly,G6PDlevelsareoftenNORMALduringthe hemolyticepisode.Theperipheralbloodsmearrevealsbitecells. VariantsofG6PDareG6PDA(moderateenzymedeficiency)andG6PDMediterranean (severeenzymedeficiency)

SLE:itisachronicautoimmunedisorder.blackwomen.itismorecommoninwomenof childbearingage. Hematologicabnormalitiesoccurduetoformationofantibodiesagainstbloodcellsand representaformoftypeIIhypersensitivityreaction. AnemiainSLEisautoimmunehemolyticanddevelopsduetoformationofwarmIgG antibodiestoRBCs.Itischaracterizedbyspherocytosis,apositivedirectCoombstest, andextravascularhemolysis. ThepathogenesisofSLEassociatedthrombocytopeniaisidenticaltothatofITP; antibodiesagainstplateletsareformedcausingdestructionofplatelets. NeutropeniaduetoantibodymediateddestructionofWBCsalsooccurs,butthisisless common. PtswithSLEexhibitalackoforreducedsuppressorTcellfnandhyperproductionof helperTcells. Inaddition,concurrentBcellhyperactivityleadstoincreasedserumantibodiesandIgG autoantibodiesproduction,laterformingthecirculatingimmunecomplexes,whichare thehallmarksofthedisease. TRANSFUSIONPROBLEMS: Febriletransfusionreaction:characterizedbyfeverandchillsthatusuallyrespondto NSAIDS.Unlikemoreseriousreactions(iehemolyticreactionorbacterialcontamination ofthetransfusedblood),nohomodynamicabnormalitiesandrenaldysfunctioinare usuallypresent.Thefebrilereactionisbelievedtobecausedbyantibodiesinthe patientsplasmareactingwiththedonorsleukocytes.Thus,leukocytedepletion techniquescanreducethechancesoffebriletransfusionreaction.Theseincludecell washing,useoffrozendeglycerolizedredcells,leukocytedepletionRBCfilters,etc.The coombstestisnegative(directantglobulintest). Acutehemolytictransfusion:alsopresentsinasimilarway(feverandchillsarethem.c complaints).Theclassictriadoffever,backpain,andred/pinkurineisrarelyseen.So, thishastoberuledoutbystoppingthetransfusionandobtainingasampleforadirect coombstestandforplasmafreehemoglobin.Urinanalysiswillalsoshowthe presenceofhemoglobin. Patientswhohavereceivedtheequivalentofmorethanonebloodvolumeofblood transfusionsorPRBCover24hoursmaydevelopelevatedplasmalevelsofcitrate(a substanceaddedtostoredblood).Itchelatescalciumandmagnesiumandmayreduce theirplasmalevels,causingparesthesias.

Thethirdtypeisanticardiolipinantibody. Womenwithfetallossesduetoantiphospholipidantibodysyndromearethusmanaged duringpregnancywithheparinandaspirin.Warfarinisnotusedduetoits teratogenicity.AcutethrombosisistreatedwithheparinandfactorantiXaactivityis measured,sinceAPTTisnotreliableinsuchcases

Charcotarthritis,alsoknownascharcotsjoint,orNeuropathicosteoarthropathy,isjoint destructionresultingfromdeteriorationofproprioception,painsensation,andtemperature sensation.Itcanbeseenindiabeticneuropathy,syringomyelia,spinalcordinjury,vitaminB12 deficiency,tabesdorsalis,orperipheralnervedisease. Anabolicsteroidshavemanysideefx:suppressendogenoustesticularfunction(resultingin reducedfertility),gynecomastia(testosteroneconvertedtoestrogen),erythrocytes,cardiac disease,dyslipidemia(loweredHDLandelevatedLDL),prematureepiphsealfusion(growth stunt),psychologicaldisturbances,hepatotoxicity,increasedcoagulation. Postsplenectomycancausesepsis.Normallybloodborneantigensenterthespleenviathe splenicarteryandarephagocytesbydendriticcellsinthewhitepulp.Thesedendriticcellsthen presentantigensinassocationwithMHCIItoThcells,activatingthem.ActivatedThcellsthen migratetothemarginalzoneofthespleenwheretheycomeintocontactwithBcellsin primaryfollicles.Bcellactivationcausessecondaryfolliclesandplasmacellrichgerminal centerstoform.Antibodiesproducedbygerminalcenterplasmacellsenterthesystemic circulation,bindtheirspecificantigen,andfacilitatephagocytesofpathogenicorganismsby opsonization.Asplenicpatientsarelesslikelytomountthissortofantigenspecificantibody responseandarethereforeathighriskofoverwhelminginfectionbyencapsulatedorganisms likestrep.Pneumoniae,n.meningitides,andH.influenza. IntracellularkillingisdefectiveinpatientswithCGD,whichisadefectinNADPH oxidase. Chemotaxisisimpairedinpatientswithleukocyteadhesiondefect,anautonomic recessivedefectinintegrinbeta2. MicrocycticanemiashaveadecreasedMCVandMCH. Ontheotherhand,megaloblasticanemiashaveanelevatedMCVandelevatedMCH, andnormalMCHC. SideroblasticanemiaischaracterizedbyincreasedserumironlevelsandverylowTIBC. AnemiaofchronicdiseaseischaracterizedbyadecreasedTIBC *TeardropRBCsareseeninalldiseasesthatinfiltratethebonemarrowandcause myelofibrosis. *Basophilicstipplingcanalsobeseenindimorphicanemias. Paroxysmalnocturnalhemoglobinuria(PNH)isanacquireddisorderofhematopoieticcells. SucroselysistestandHamacidhemolytictestwereusedinthepastasscreeningand confirmatorytests,respectively.

Dilutionalpancytopenia:canoccurafteramassivepackedRBCtransfusionormassive infusionsofcrystalloidsolutionsduetoincreasedplasmavolumeoutofproportionto thenumberofbloodcells

However,currentlyflowcytometryhasreplacedbecauseitissimpleandhashigh sensitivityandspecificity.TheexpressionoftheGPIanchoredproteinsCD55andCD59 canbeanalyzedusingmonoclonalantibodiesandflowcytometry. ThusPNHshouldbeconsideredinthefollowingsituations: 1.Pancytopeniaaccompaniedbyhemolyticanemia(increasedreticulocytecountandLDHand lowhaptoglobinlevels) 2.Recurrentthrombosisatunusualsites,ie.PortalveinthrombosisorBuddChiarisyndrome. Anemiaofchronicdisease:usuallyitisnormocyticbutcanbemicrocytic. ThecauseofACDisthoughttoinvolveirontrappingwithinmacrophagesthatleadstoreduced serumironconcentrationsandpoorironavailabilityforhemoglobinsynthesis.Arelative decreaseinerythropoietinproductionandpoormarrowresponsetoerythropoietinmayalso playarole.ACDiscommonlyassociatedwithchronicinflammatorydisease. Treatingtheunderlyingcausewilloftenimprovetheanemia. Ie.Ifapatienthasrheumatoidarthritis,firstlineagentsincludemethotrexate, hydroxychloroquine,andTNFinhibitors(infliximab,etanercept). splenectomycantreat: Hereditaryspherocytosis, Idiopathicthrombocytopeniapurpura chronicidiopathicmyelofibrosiswithrefractoryanemia. ITP anautoimmunedisordercharacterizedbyisolatedthrombocytopenia.Coagulation studiesarenormal. Thebonemarrowexammaybenormaloritmayrevealanincreasednumberof megakaryocytes. Itisadxofexclusionyouhavetodofurtherevaluationoverwhetheritisprimary (hematologicdisease)orsecondary(i.e.duetoSLEorinfectiousagentssuchasCMV, toxoplasma,hepatitis,HIV)autoimmunedestructionofplatelets. Inordertoruleoutaprimaryhematologicaldisorder,bonemarrowexamis performedinsomecases(notrequiredinallcases) Howelljollybodiesare nuclearremnantswithinRBCthataretypicallyremovedbythespleen.Theyareevident onperipheralbloodsmearassingle,round,blueinclusionsonWrightstain. Theirpresenceusuallyindicatesphysicalabsenceofthespleenorfunctional hyposplenismduetosplenicautoinfarction,infiltrativedisordersofthespleenorsplenic congestion. Ineffectivehematopoiesisreferstobloodcellbreakdowninbonemarrowbeforereleaseinto circulation;thalassemiaandmyelodysplasticsyndromesareexamples.

Hypersplenism:resultsinabnormalpoolinginbloodcellsinthespleenwithsubsequent destructionofthesecells.Ptshavepancytopeniaandsplenomegaly.Thismayoccurin cirrhosis,malaria,sicklecelldisease,etc. Fanconisanemia Anautonomicrecessivedisordermarkedby: progressivebonemarrowfailure, areasofskinhypopigmentation, congenitalabnormalities(microcephaly,abnormalthumbsandhypogonadism), apredispositiontocancer. ThegenesinvolvedareseeninDNArepair. Thedefinitivetxforaplasticanemiaishematopoieticstemcelltransplantation. Benzeneisachemicalknowntocauseaplasticanemia. Thymictumorsareknowntocausepureredcellaplasia.(parvo,diamondblackfansyndrome) Patientswhohaveobstructivesleepapneahavetransientobstructionoftheupperairwaydue topharyngealcollapseduringsleep.Theseptstendtobeoverweightorobeseandhave excessivedaytimesleepiness,snoring,morningheadaches,impotence,andarterialHTN.The transientobstructiveepisodescauseshorttermhypoxemia,whichisasignalforincreased erythropoietinproduction,resultinginpolycythemia. FoodsrichinvitaminK(darkgreenvegetablesspinach,kale,mustardgreens,swisschard) willdecreasetheefficacyofwarfarin,whereasotherfood/supplementswillincreaseits activity(vitaminE,garlic,ginkgobiloba,ginseng,st.johnswort,alcohol,antibiotics). COpoisoning:Patientswhoworkaroundautomobilesorenclosedspaceswithvehiclesare exposedtoCOfromautomobileexhaust.ThiscancauseCOpoisoning,causingheadaches, chestpain,nausea,dizziness,andpolycythemia!!!.CObindstohemoglobinmorethanO2 does,thusdecreasingthebloodsoxygencarryingcapacity.Tocompensatefordecreased oxygendelivery,thebodyincreasesRBCproduction. AVshuntingcancausepolycythemiathroughmanyways.Forexample,alefttoright intracranialshuntcanincreasepulmonarybloodflow,resultinginpulmonaryHTN,which, whensevereenough,causessecondarypolycythemia.Additionally,arighttoleftintracranial shuntingcancausechronichypoxemia,towhichthebodycauseserythropoietinproduction. Monoismostlikelytoinvolvetheposteriorcervicallymphnodes,andcausesfever,pharyngitis, andbilaterallymphadenopathy. Bacterialinfectionscausefluctuantlymphadenopathy,andthesearepainful,NOTpainless lymphnodes. Glanzmannsthrombastheniais

Bernardsouliersyndrome:ableedingdisorderwhereyouhavethrombocytopenia,giant platelets,andableedingtendencythatisgreaterthanexpectedbleedingforthedegreeof thrombocytopenia.PlateletsfromthesepatientsdoNOTaggregateinthepresenceofnormal vWFandristocetinbecauseofthedecreaseorabnormalityintheGPIb.Giantplatelets. Chediakhigashisyndromeisastoragegranulocyteabnormalityresultingin hepatosplenomegaly,lymphadenopathy,anemia,thrombocytopenia,roentgenologicalchanges ofbones,lungs,andheart,skinandpsychomotorabnormalitiesandsusceptibilitytoinfection, usuallyresultingindeathinchildhood. Senilepurpuraisanecchymosedlesionthatoccursinareassusceptibletotraumainthe elderly.M.cisthedorsumofthehandsandforearms.Itoccursduetoperivascularconnective tissueatrophy.Thelesionsdeveloprapidlyandresolveoverseveraldays,leavingabrownish discolorationfromhemosiderindeposition. AlphamethyldopaandpenicillincancauseautoimmunehemolyticviaIgGautoantibodythat removetheRBCviathespleen. Sideroblasticanemia(2steps?) Resultsfromdefectivehemesynthesis,mostcommonlyduetopyridoxinedependant impairmentintheearlystepsofprotoporphyrinsynthesis. Isoniazidisawellknownpyridoxineantagonist.Acquiredsideroblasticanemia frequentlymanifestsasmicrocyctichypochromicanemiasimulatingirondeficiency anemia. Usually2groupsofRBCcanbedemonstratedonmicroscopyhypochromicandnorm chromic(dimorphicRBCpopulation). Ironstudiestypicallyrevealincreasedserumironconcentration,increasedtotaliron bindingcapacity,whichhelpstodifferentiatesideroblasticanemiafromirondeficiency anemia. IfapatienthasnormallabsbuttheRBC,ESR,Hb,Hctandreticulocytecountareabnormal,then thinkofpureredcellaplasia.Whenthisdisorderisassociatedwithtumor,itismostoftena thymustumor. RememberthatCMLandleukemiareactionareindistinguishableonaperipheralbloodfilm. Thesuddenelevationinthetotalleukocytecountandmarkedincreaseofgranulocyte precursors(leftshift)suggestaseriousinfectionwithorwithoutanunderlyingleukemiastate. TheLAPtestplaysasignificantroleindistinguishingthese2conditions.InCMLitisusually

autonomicrecessivethatresultsindeficientglycoproteinsIIbIIIacomplexsofibrinogen willnotcrossconnect. Plateletcountsmaybenormalontheperipheralbloodsmear,andtheyremainisolated anddonotexhibitclumpingthatisnormallyseen.Thusbleedingtimeismarkedly increasedandclotretractionisdecreased.

decreased(butitmaybeincreasedinthepresenceofsubsequentsecondaryinfection).Thus, fortheparenthesisreason,thepresenceofthePhiladelphiachromosomeshouldbe determinedinsuspiciouscasessinceitismorediagnosticforCML. ThebodygetsvitaminKfrom2sources:exogenousfromthefood,whichisabsorbedinthe smallintestine,andendogenousfromthebacterialproductionofvitaminKintheintestine.A patientwhoispostopandNPOandusingbroadspectrumantibioticsisatriskforvitaminK deficiencybecausebothsourcesarecompromised(inadequatedietaryintake,andantibiotics) a30daystoreofvitaminKisstoredinanormalliver;however,anacutelysickpersoncan becomedeficientin710days. ClinicallyyouseeaprolongedPTfollowedbyaprolongedPTT.ButthePT>>PTT.Potential vitaminKrapidlyrestoresthestoresin810hours.FPPisindicatedforthemanagementofan acutehemorrhage. SimilarpresentationofvitaminKdeficiencyisseeninanewbornwhohadnotreceived prophylacticvitaminK(homeborn)forthepreventionofhemorrhagicdiseaseofthenewborn. Polycythemiaveraisdistinguishedfromtheotherkindofmyeloproliferativediseasebythe increaseinRBCmassandtotalbloodvolume.Atypicalpatientisanoldplethoricmalewho maycomplainofpruritusafterbathing.hyperviscositycausesheadache,dizziness,and paresthesias. Boththrombosisandbleedingcanoccurduetoelevatedplateletcountandimpaired plateletfn. HTNfrequentlyoccursasaresultofexpandedbloodvolume.Ptsalsohave granulocytesandthrombocytosisonperipheralbloodsmearandsplenomegaly. Bonemarrowisvirtuallyalwayshypercellular. ThereisanelevatedLAPscore,normaloxygensaturation,andlowerythropoietin level. WhereassecondarypolycythemiaisusuallyonlycharacterizedbyelevationofRBCmass (therestofthecelllinesareusuallynormal). PolycythemiaveraPatientsalsohaveanincreasedchanceofgoutyarthritis(dueto increasedcellturnover),pepticulceration(histaminereleasefrombasophils). Onexam,theptsisplethoric,theyhavesplenomegaly,erythrocyteindicesmaybe normal,thebonemarrowisvirtuallyalwayshypercellular. ThetxisphlebotomytokeeptheHCT<45%.. YouneedaccurateassessmentoftheplasmavolumeandRBCmassfordiagnosis. Myelodysplasticsyndromesareclonalstemcelldisorders,whichmayprogresstoacute leukemias.Thesearecharacterizedbypancytopenia. Intheelderly,irondeficiencyisthem.ccauseofanemia;itismostlikelysecondarytoa nutritionaldeficiency.Otherverycommoncausesofirondeficiencyanemiainelderlyischronic bloodloss

Rememberthatanemiaofchronicdiseaseisseeninpatientswithchronicillnesses.Thisis usuallyseenwithinfectious,inflammatory,orneoplasticdiseases.Havinginflammatoryjoint disease,NOTdegenerativejointdisease,causesACD. Thalassemia:foralphaorbetaminor:thetreatmentofchoiceisreassuranceandfollowup monitoring. Incontrastpatientswiththalassemiamajorareseverelysymptomaticandtransfusion dependent. Deferoxamineisusedtotreatironoverloadinpatientswithtransfusiondependent hemoglobinopathies(iebetathalassemiamajor). HeparinactivatesantithrombinIII,whichinturninactivatesthrombin,factor9a,andfactor 10a. Aspirinisanantplateletagentthatinhibitscox1,therebyinhibitingthromboxaneA2synthesis. ClopidogrelisanantplateletthatblocksplateletesurfaceADPreceptors,thuspreventing plateletactivation. AutoimmunehemolyticanemiaisaconditionwhenantiRBCIgGcoverthecellmembranesof erythrocytesandcausetheirremovalfromthecirculationinthespleensreticuloendothelial cell.Inthesettingofamalignantlymphoproliferativedisorder,thisisoftenawarm autoimmunehemolyticanemia.Thecoombstestwillbepositive.Theinitialtxisprednisone. Ifitwontwork,dosplenectomy. Bonemarrowstainforironisthemostdefinitewaytodiagnoseirondeficiencyanemia. Alowserumironconc.Isnonspecificbecauseitislowinirondeficiencybutalsoinptswith ACD.TheTIBCisusuallyelevatedinirondeficiencyanemia,butmanyirondeficiencyptshavea normalTIBC.Alowerserumferritinlevelalmostalwaysreflectsirondeficiencyanemia,butit canbenormalorevenelevatedinptswithirondeficiencyanemiaasanacutephasereactant. Alcoholabuseisthem.ccauseofnutritionalfolatedeficiencyintheUSleadingto megaloblasticanemia.Itimpairsitsenterohepaticcycleandinhibitsabsorption. Alcoholcanalsocauseirondeficiencyfromchronicbloodloss(microcrystalanemia),ACD (normocyticormicrocrystal),thrombocytopenia,andmacrocytosis(mayappearevenbefore thedevelopmentofanemia). Inapatientwhohasacquiredthrombocytopenia,lookatthewholescenario. Itwouldnotbemarrowaplasiabecausethatwouldcausepancytopenia. Ifthereweremalignantinfiltrationofthebonemarrow,thenyouwouldalsohave pancytopeniaandextramedullaryhematopoiesiswithintheliverandspleenleadingto hepatosplenomegaly. Ifyouhadsplenicsequestrationofplatelts,thenyouwouldhavesplenomegaly(ie portalhypertension).Inadditionthiswouldnotcauseabnormalbleedingandthe plateletcountusuallyremainsabove30,000/uL.

CryoprecipitateisrequiredforcoagulationfactordeficienciessuchasfactorVIIIdeficiency. InapatientwhohaselevatedPT/INRlevelsthefirststepistogiveempiricadministrationof vitaminK.ifthepatientisbleedingactivelyorneedsimmediatesurgeryoraninvasive procedure,thengiveFFP.

Inessentialthrombocytopeniayouseeincreasedmarrowcellularitywith megakaryocytichyperplasia. Inaplasticanemiayouseeahypoplasticfatfilledmarrowwithnoabnormalcells. Inmyelofibroticdisordersyouseehypocellularandfibroticbonemarrow.

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