Normocytic Normochromic Normocytic Normochromic Anaemia Anaemia –– Case StudyCase Study

Adelien van SchalkwykAdelien van SchalkwykMed Lab SouthMed Lab South

June 2009June 2009

Doctorsfindings

PatientSymptoms

Chemistry

Haematology

DIAGNOSIS

Profile of PatientProfile of Patient

MaleMale57 years old57 years oldMalaiseMalaiseFrom rural communityFrom rural community

Hematology ResultsHematology ResultsMarch 2005March 2005

Hb 122 g/lHb 122 g/lPCV 0.36PCV 0.36MCV 83 flMCV 83 flMCH 28 pgMCH 28 pgNo further No further investigations investigations

Chemistry ResultsChemistry ResultsJune 2006June 2006

TP 91 g/lTP 91 g/lAlb 41 g/lAlb 41 g/lGlob 50 g/lGlob 50 g/lNo further No further investigationsinvestigations

Normocytic Normochromic Normocytic Normochromic AnaemiaAnaemia

MCV 80 MCV 80 –– 95 fl95 flMCH > 29 pgMCH > 29 pgHaemolytic anaemiaHaemolytic anaemiaAnaemia of chronic diseaseAnaemia of chronic diseaseAfter acute blood lossAfter acute blood lossRenal diseaseRenal diseaseMixed deficienciesMixed deficienciesBM failure e.g. postBM failure e.g. post--chemotherapy, infiltration chemotherapy, infiltration by carcinoma/myelomaby carcinoma/myeloma

Laboratory Work Up Laboratory Work Up --Normocytic Normochromic Normocytic Normochromic

AnaemiaAnaemiaFBCFBCReticsReticsTotal Iron, TIBC, TransferrinTotal Iron, TIBC, TransferrinFerritinFerritin? sTfR? sTfR

Chemistry ResultsChemistry ResultsMay 2009May 2009

TP 109 g/lTP 109 g/lAlb 38 g/lAlb 38 g/lGlob 71 g/lGlob 71 g/lIgG 6.0 g/lIgG 6.0 g/lIgA 46.0 g/lIgA 46.0 g/lIgM 0.5 g/lIgM 0.5 g/lLaboratory added Laboratory added SPESPE

Serum Protein ElectrophoresisSerum Protein Electrophoresis

AlphaAlpha--11--globulin decreasedglobulin decreasedHeavy monoclonal peak adjacent to Heavy monoclonal peak adjacent to betabeta--globulinsglobulinsImmunoparesisImmunoparesisImmunofixation revealed an IgA Immunofixation revealed an IgA kappa paraproteinkappa paraprotein

ImmunofixationImmunofixation

Other Protein StudiesOther Protein Studies

Urinary Protein 0.12 g/lUrinary Protein 0.12 g/lAlbumin was the predominant protein Albumin was the predominant protein presentpresentBence Jones Protein : A light band of Bence Jones Protein : A light band of intact monoclonal immunoglobulin with intact monoclonal immunoglobulin with attached kappa light chains was detected. attached kappa light chains was detected. No free monoclonal light chain (BJP) was No free monoclonal light chain (BJP) was detecteddetected

Clinical Symptoms Clinical Symptoms --MyelomaMyeloma

Anaemia i.e. lethargy, weakness, pallorAnaemia i.e. lethargy, weakness, pallorBone PainBone PainPathologic fractures & bone lesionsPathologic fractures & bone lesionsSpinal cord compressionSpinal cord compressionHypercalcemia & Renal failureHypercalcemia & Renal failureInfection due to neutropeniaInfection due to neutropeniaBleeding tendency i.e. platelet functionBleeding tendency i.e. platelet functionHyperviscosityHyperviscosityNeurological symptomsNeurological symptoms

Workup for MyelomaWorkup for Myeloma

FBC i.e. Hb, Platelets, WBCFBC i.e. Hb, Platelets, WBCTotal Protein, Albumin, Creatinine, Total Protein, Albumin, Creatinine, CalciumCalciumSPE, Immunofixation SPE, Immunofixation Urine for BJP Urine for BJP ImmunoglobulinsImmunoglobulinsBetaBeta--22--MicroglobulinMicroglobulinCRP vs ESRCRP vs ESR? Serum Viscosity? Serum Viscosity

Other TestsOther Tests

Bone Marrow Aspirate & BiopsyBone Marrow Aspirate & BiopsyXX--ray i.e. skull, long bones, spineray i.e. skull, long bones, spineMRI scanMRI scanSpecialist Tests:Specialist Tests:Cytogenic studies i.e. deletion of Cytogenic studies i.e. deletion of 17p13 on p53 tumor suppressor gene17p13 on p53 tumor suppressor geneChromosome 1 abnormalitiesChromosome 1 abnormalitiesCC--Myc defectsMyc defects

Bone Marrow ResultsBone Marrow Results

NormalNormal

Early Iron Early Iron DeficiencyDeficiencyAnaemia of Chronic Anaemia of Chronic DiseaseDiseaseRenal FailureRenal FailureLiver FailureLiver Failure

AbnormalAbnormal

InfiltrationInfiltrationLeukaemiaLeukaemiaMyelomaMyelomaMetastasesMetastases

Bone Marrow AspirateBone Marrow AspirateCellularity: IncreasedCellularity: IncreasedErythropoiesis: Reduced. NormoblasticErythropoiesis: Reduced. NormoblasticGranulopoiesis: Reduced. Normal morphology & Granulopoiesis: Reduced. Normal morphology & differentiationdifferentiationMegakaryocytes: Reduced numbers. Normal Megakaryocytes: Reduced numbers. Normal morphologymorphologyLymphocytes: NormalLymphocytes: NormalPlasma Cells: Comprise 75% of the cell total Plasma Cells: Comprise 75% of the cell total and include many large and atypical cellsand include many large and atypical cellsIron: Reduced iron stores and erythroblast Iron: Reduced iron stores and erythroblast siderotic granulationsiderotic granulationMyeloidMyeloid--Erythroid Ratio : 3:1Erythroid Ratio : 3:1Comment: Multiple MyelomaComment: Multiple Myeloma

Multiple MyelomaMultiple Myeloma

Proliferation of malignant plasma cellsProliferation of malignant plasma cellsProminent monoclonal protein (paraprotein), Prominent monoclonal protein (paraprotein), unless light chain myelomaunless light chain myelomaNo cure exists No cure exists

Causes of MyelomaCauses of MyelomaGeneticGeneticEnvironmental or occupational i.e. agriculture, Environmental or occupational i.e. agriculture, food, petrochemical industries, exposure to hair food, petrochemical industries, exposure to hair dyesdyesRadiation i.e. Hiroshima victims, Nuclear Plant Radiation i.e. Hiroshima victims, Nuclear Plant employeesemployeesMGUS can develop into MM within 2MGUS can develop into MM within 2--19 y19 yMedian survival with chemotherapy is 3Median survival with chemotherapy is 3--4 years 4 years with a 20% 5 year survivalwith a 20% 5 year survival

Plasma CellsPlasma Cells

Medical CareMedical Care

RadiationRadiationChemotherapy i.e. Vincristine, Adriamycin, Chemotherapy i.e. Vincristine, Adriamycin, Dexamethasone (VAD), Melphalan & PrednisoneDexamethasone (VAD), Melphalan & PrednisoneBiphosphonatesBiphosphonatesInterferonsInterferonsAntibioticsAntibioticsImmunosuppressant agentsImmunosuppressant agentsColonyColony--stimulating factors i.e. Epoetin Alfastimulating factors i.e. Epoetin AlfaTransplantation Transplantation

Other FactorsOther Factors

Patient visited 4Patient visited 4--5 different Doctors i.e. no 5 different Doctors i.e. no follow up regarding essential anemiafollow up regarding essential anemiaNo clinical details to guide laboratory No clinical details to guide laboratory Laboratory results reported without Laboratory results reported without interpretative commentinterpretative commentIn retrospect diagnosis could have been In retrospect diagnosis could have been established in 2005established in 2005Treatment could have started earlier, but ? Real Treatment could have started earlier, but ? Real outcome differenceoutcome difference

Laboratory PuzzleLaboratory Puzzle

ResultResult

SummarySummary

Patient history / symptomsPatient history / symptomsTransfer of patient files i.e. DoctorsTransfer of patient files i.e. DoctorsCommunication e.g. Haematology & Communication e.g. Haematology & ChemistryChemistryAll the pieces of PUZZLE should fit to All the pieces of PUZZLE should fit to reach DIAGNOSISreach DIAGNOSISPatient diagnosed too late Patient diagnosed too late

AcknowledgementsAcknowledgements

Essential Haematology Essential Haematology –– Hoffbrand, Pettit, Hoffbrand, Pettit, MossMossInterpretation of Diagnostic Tests Interpretation of Diagnostic Tests ––WallachWallachMultiple Myeloma Multiple Myeloma -- Grethlein, ThomasGrethlein, ThomasHaematovision 4 MediaHaematovision 4 MediaMedLab SouthMedLab South

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