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Hematology

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  • Sickle Lung may Resemble Infiltrate
  • Females Variable Population Secondary X Chromosome Activation
    Fe(III) does not carry Oxygen
  • Females Variable Population Secondary X Chromosome Activation
    Fe(III) does not carry Oxygen
  • Heinz Bodies used for Screening.
    False Negatives in Acute Phase
  • Transcript

    • 1. 11 Anemia OverviewAnemia Overview Anu Thummala, M.D.Anu Thummala, M.D. Hematology/Oncology and InternalHematology/Oncology and Internal MedicineMedicine Comprehensive Cancer Centers ofComprehensive Cancer Centers of NevadaNevada
    • 2. 22 AnemiaAnemia Three main mechanisms:Three main mechanisms: 1.1. DECREASED PRODUCTION OF RBCDECREASED PRODUCTION OF RBC (HYPOPROLIFERATION)(HYPOPROLIFERATION) 2. INCREASED DESTRUCTION OF RBC2. INCREASED DESTRUCTION OF RBC (HEMOLYSIS)(HEMOLYSIS) 3. ACUTE BLOOD LOSS3. ACUTE BLOOD LOSS
    • 3. 33 The most important first step in the diagnosis of Anemias…….
    • 4. 44 The Peripheral SmearThe Peripheral Smear RBC FragmentsRBC Fragments (Schistocytes)(Schistocytes) Microangiopathic HemolyticMicroangiopathic Hemolytic Anemia, Valve Hemolysis, BurnsAnemia, Valve Hemolysis, Burns SpherocytesSpherocytes AIHA, Hereditary SpherocytosisAIHA, Hereditary Spherocytosis Target cellsTarget cells Alcoholics, HemoglobinopathiesAlcoholics, Hemoglobinopathies SideroblastsSideroblasts Myelodysplasia, AlcoholicsMyelodysplasia, Alcoholics Teardrop cellsTeardrop cells Myelofibrosis/MyeloidMyelofibrosis/Myeloid metaplasia, Thalassemiametaplasia, Thalassemia Burr cellsBurr cells UremiaUremia Howell JollyHowell Jolly bodiesbodies Splenectomy, FunctionalSplenectomy, Functional aspleniaasplenia HypersegmentedHypersegmented PMNPMN Megaloblastic AnemiaMegaloblastic Anemia
    • 5. 55 ??  Young women withYoung women with surgery as child andsurgery as child and was told that shewas told that she could be at risk forcould be at risk for developing infections.developing infections.  CBC normalCBC normal
    • 6. 66 ??  74 male presents with74 male presents with neuropathy, loss ofneuropathy, loss of balance, WBC 1.9,balance, WBC 1.9, HGB 7, PLT 120,000HGB 7, PLT 120,000
    • 7. 77 ??  A 20 YO womanA 20 YO woman presents withpresents with increasing weaknessincreasing weakness over six weeks,feverover six weeks,fever and Hb = 5.9 g/dl.,and Hb = 5.9 g/dl., white cells 18.0white cells 18.0 x10ˆ9/l., platelets 35x10ˆ9/l., platelets 35 x10ˆ9/l.x10ˆ9/l.
    • 8. 88 ??  Young man withYoung man with recent travel presentsrecent travel presents with fever of unknownwith fever of unknown origin. WBC 18K,origin. WBC 18K, HGB 8 g, PLTHGB 8 g, PLT 461,000461,000
    • 9. 99 ??  Elderly gentlemanElderly gentleman presents with fatigue,presents with fatigue, pallor and SOB. WBCpallor and SOB. WBC 3K, HGB 6g, PLT3K, HGB 6g, PLT 566,000566,000
    • 10. 1010 ??  70 YO male admitted70 YO male admitted to ICU with severeto ICU with severe pancytopenia,pancytopenia, bleeding,bleeding, hypotensive. Patienthypotensive. Patient is intubatedis intubated  PT 15, PTT 40, PLTPT 15, PTT 40, PLT 36,000, WBC 2.2,36,000, WBC 2.2, HGB 8 g.HGB 8 g.
    • 11. 1111 ??  46 YO presents with46 YO presents with history of alcoholhistory of alcohol abuse, hypotension.abuse, hypotension.  WBC 3.2, HGB 10g,WBC 3.2, HGB 10g, PLT 72,000PLT 72,000  T. Bili 2.0, creatinineT. Bili 2.0, creatinine 4, BUN 684, BUN 68
    • 12. 1212
    • 13. 1313
    • 14. 1414 AnemiaAnemia MicrocyticMicrocytic MCV <80MCV <80 NormocyticNormocytic MCV 80-100MCV 80-100 MacrocyticMacrocytic MCV >100MCV >100 Iron DeficiencyIron Deficiency ACDACD B12 DeficiencyB12 Deficiency ACDACD Renal FailureRenal Failure Folate DeficiencyFolate Deficiency ThalassemiasThalassemias MDSMDS AlcoholAlcohol SideroblasticSideroblastic AnemiaAnemia Aplastic AnemiaAplastic Anemia HypothyroidismHypothyroidism Lead PoisoningLead Poisoning Hemolytic AnemiaHemolytic Anemia Liver diseaseLiver disease Mixed Micro andMixed Micro and Macrocytic AnemiaMacrocytic Anemia MDSMDS
    • 15. 1515 Case 1Case 1  51 YO female presents with fatigue,51 YO female presents with fatigue, occasional tingling of her hand and feet.occasional tingling of her hand and feet. She reports decrease in concentration andShe reports decrease in concentration and memorymemory  PSHx: cholecystectomy, gastric bypassPSHx: cholecystectomy, gastric bypass  Social Hx: negative for drug, tobacco andSocial Hx: negative for drug, tobacco and alcoholalcohol
    • 16. 1616 Case 1Case 1  LABS:LABS: WBC 1.7WBC 1.7 HGB 8.9 G/DLHGB 8.9 G/DL PLATELETS 109,000PLATELETS 109,000 MCV 109MCV 109 SEGS 52%SEGS 52% LYMPHS 40%LYMPHS 40% MONO 5%MONO 5% EOS 2%EOS 2% METAMYELOCYTES 1%METAMYELOCYTES 1%
    • 17. 1717 Case 1Case 1  Additional tests……Additional tests……
    • 18. 1818 SMEARSMEAR
    • 19. 1919 Macrocytic AnemiaMacrocytic Anemia  Abnormal maturation of nucleus in RBCAbnormal maturation of nucleus in RBC precursorsprecursors  CAUSES:CAUSES: - Alcoholism- Alcoholism – Pernicious Anemia (Vit B12 deficiency)Pernicious Anemia (Vit B12 deficiency) – Folic Acid deficiencyFolic Acid deficiency  Tropical SprueTropical Sprue  Scandinavia - Fish tapewormScandinavia - Fish tapeworm
    • 20. 2020 Macrocytic AnemiaMacrocytic Anemia MegaloblasticMegaloblastic Vitamin B12 (Cobalamin) DeficiencyVitamin B12 (Cobalamin) Deficiency Folate DeficiencyFolate Deficiency MDSMDS Chemotherapy (Methotrexate,Chemotherapy (Methotrexate, Hydroxyurea, AzathioprineHydroxyurea, Azathioprine SPURIOUSSPURIOUS Alcohol, Hypothyroidism, MM, LiverAlcohol, Hypothyroidism, MM, Liver disease, MDS, Aplastic Anemiadisease, MDS, Aplastic Anemia
    • 21. 2121 MEGALOBLASTIC DISEASEMEGALOBLASTIC DISEASE  Diagnosis: MCV> 100Diagnosis: MCV> 100  Macrocytosis may be blunted in presence ofMacrocytosis may be blunted in presence of Fe deficiency or thalasemiaFe deficiency or thalasemia  Low Reticulocyte countLow Reticulocyte count  Neutropenia and ThrombocytopeniaNeutropenia and Thrombocytopenia  WBC :Hypersegmentation. Almost alwaysWBC :Hypersegmentation. Almost always pathognomonicpathognomonic
    • 22. 2323 FOLIC ACIDFOLIC ACID  FOLIC ACID (pteroylmonoglutamic acid)FOLIC ACID (pteroylmonoglutamic acid) – Natural Source : fruits / vegetablesNatural Source : fruits / vegetables – May be destroyed by cookingMay be destroyed by cooking – Minimum daily requirement 50 micrograms/dayMinimum daily requirement 50 micrograms/day – Deficiency can develop within monthsDeficiency can develop within months – FDA ordered Folic acid supplementationFDA ordered Folic acid supplementation (January, 1998) to all enriched grains(January, 1998) to all enriched grains
    • 23. 2424
    • 24. 2525 FOLATE DEFICIENCYFOLATE DEFICIENCY  Inadequate IntakeInadequate Intake  Malabsortion due to Sprue,Malabsortion due to Sprue, Celiac diseaseCeliac disease
    • 25. 2626 FOLATE DEFICIENCYFOLATE DEFICIENCY Increased DemandIncreased Demand – Cells with high rate of turnoverCells with high rate of turnover – Chronic hemolytic anemiasChronic hemolytic anemias  PregnancyPregnancy – Deficiency in first few weeks - - > neural tubeDeficiency in first few weeks - - > neural tube defects in fetusdefects in fetus  MalignancyMalignancy  Chronic Exfoliative Skin DisordersChronic Exfoliative Skin Disorders  Hemodialysis ptsHemodialysis pts
    • 26. 2727 FOLATE DEFICIENCYFOLATE DEFICIENCY MedicationsMedications – 6 thioguanine, azathiprine, 6 mercaptopurine6 thioguanine, azathiprine, 6 mercaptopurine – 5 FU, cytosine, arabinoside5 FU, cytosine, arabinoside  Hydroxyurea, procarbazine, AZTHydroxyurea, procarbazine, AZT – Folate Antagonists - Methotrexate, pentamidine,Folate Antagonists - Methotrexate, pentamidine, trimethoprim, triamterene, pyrimethamine, Dilantintrimethoprim, triamterene, pyrimethamine, Dilantin
    • 27. 2828 COBALAMIN (VIT B12)COBALAMIN (VIT B12)  Cobalt cannot be synthesized - required in diet !Cobalt cannot be synthesized - required in diet !  ONLY SOURCE : Animal products (meat andONLY SOURCE : Animal products (meat and dairy)dairy)  Minimum daily requirement: 2.5 micrograms/dayMinimum daily requirement: 2.5 micrograms/day
    • 28. 2929
    • 29. 3030 COBALAMIN DEFICIENCYCOBALAMIN DEFICIENCY  Inadequate intake “vegetarian”Inadequate intake “vegetarian”  MalabsorptionMalabsorption – Defective Release of Cobalamin from FoodDefective Release of Cobalamin from Food – Inadequate Production of Intrinsic FactorInadequate Production of Intrinsic Factor
    • 30. 3131 COBALAMIN DEFICIENCYCOBALAMIN DEFICIENCY – Disorders of the terminal ileumDisorders of the terminal ileum  Tropical and Non Tropical SprueTropical and Non Tropical Sprue  Regional Enteritis, Crohn’s DiseaseRegional Enteritis, Crohn’s Disease  Intestinal ResectionIntestinal Resection – Competition for cobalaminCompetition for cobalamin  Fish Tapeworm (Scandinavian countries)Fish Tapeworm (Scandinavian countries)  Bacteria (“blind loop syndrome)Bacteria (“blind loop syndrome) – DrugsDrugs  p-aminosalicylic acid, colchicine, neomycinp-aminosalicylic acid, colchicine, neomycin
    • 31. 3232 COBALAMIN DEFICIENCYCOBALAMIN DEFICIENCY  BloodBlood – Macrocytic AnemiaMacrocytic Anemia – Pancytopenia, elevated LDH/ Indirect BilirubinPancytopenia, elevated LDH/ Indirect Bilirubin – Clin Sx: weakness, dizziness, vertigo, tinnitus, angina,Clin Sx: weakness, dizziness, vertigo, tinnitus, angina, palpitations and CHFpalpitations and CHF – Physical Exam: pale, icteric, rapid pulse, enlargedPhysical Exam: pale, icteric, rapid pulse, enlarged heart, systolic flow murmurheart, systolic flow murmur  GIGI – Based on rapidly proliferating GI epitheliumBased on rapidly proliferating GI epithelium  SORE TONGUESORE TONGUE  ANOREXIA / WEIGHT LOSSANOREXIA / WEIGHT LOSS  DIARRHEADIARRHEA
    • 32. 3333 COBALAMIN DEFICIENCYCOBALAMIN DEFICIENCY  NEURO (may be permanent)NEURO (may be permanent) – Demyelination -> axonal degeneration -> neuronalDemyelination -> axonal degeneration -> neuronal deathdeath – Peripheral nerves, spinal cord (posterior and lateralPeripheral nerves, spinal cord (posterior and lateral columns) , cerebrumcolumns) , cerebrum – SX: EARLY: Numbness and parethesias in extremitiesSX: EARLY: Numbness and parethesias in extremities  LATER: weakness, ataxia, sphincter disturbances,LATER: weakness, ataxia, sphincter disturbances,  Decreased vibratory sensationDecreased vibratory sensation  mild irritability --> dementia or psychosismild irritability --> dementia or psychosis  NEURO SX MAY BE PRESENT IN A PATIENTNEURO SX MAY BE PRESENT IN A PATIENT WHO IS NOT ANEMICWHO IS NOT ANEMIC
    • 33. 3434 COBALAMIN DEFICIENCYCOBALAMIN DEFICIENCY PERNICIOUS ANEMIAPERNICIOUS ANEMIA Autoimmune destruction or gastric mucosal atrophyAutoimmune destruction or gastric mucosal atrophy Etio: Lack of Intrinsic Factor (IF) secreted by parietal cellsEtio: Lack of Intrinsic Factor (IF) secreted by parietal cells EPIDEMIOLGYEPIDEMIOLGY  Males = females, often age >60Males = females, often age >60  See in pts from Northern Europe or AfricanSee in pts from Northern Europe or African AmericansAmericans OTHER DISEASE ASSOCIATIONSOTHER DISEASE ASSOCIATIONS Graves DiseaseGraves Disease MyxedemaMyxedema ThyroiditisThyroiditis VitiligoVitiligo Hypoparathyroidism AgammaglobulinemiaHypoparathyroidism Agammaglobulinemia Adrenocortical InsufficiencyAdrenocortical Insufficiency
    • 34. 3535 PERNICIOUS ANEMIAPERNICIOUS ANEMIA  ABNORMAL LABSABNORMAL LABS  Anti parietal cell antibody (anti Na,K ATPase (90%)Anti parietal cell antibody (anti Na,K ATPase (90%)  Anti IF antibody (60%)Anti IF antibody (60%) – RX; Glucocorticoids may reverse diseaseRX; Glucocorticoids may reverse disease – H Pylori does NOT cause parietal cell destructionH Pylori does NOT cause parietal cell destruction  ANATOMYANATOMY :: Gastric atrophy --> antrum is sparedGastric atrophy --> antrum is spared  TxTx: All reversible except neurological changes: All reversible except neurological changes  Complications :Complications : Gastric polyps 2x incidence ofGastric polyps 2x incidence of cancercancer
    • 35. 3636 Schilling TestSchilling Test (Cobalamin Deficiency verification)(Cobalamin Deficiency verification)  STAGE 1STAGE 1  STAGE 2STAGE 2 – Give Radioactive Cobalamin bound to IF by mouthGive Radioactive Cobalamin bound to IF by mouth – IM injection of nonradioactive B12IM injection of nonradioactive B12 – Measure 24 hour urineMeasure 24 hour urine – Will still be diminished ifWill still be diminished if  Bacterial Overgrowth Syndrome, Blind Loop,Bacterial Overgrowth Syndrome, Blind Loop, Pancreatic insufficiency, Celiac SpruePancreatic insufficiency, Celiac Sprue
    • 36. 3737
    • 37. 3838 FOLATE v COBALAMINFOLATE v COBALAMIN DEFICIENCY STATESDEFICIENCY STATES SerumSerum LevelsLevels FOLATEFOLATE DEFICIENCYDEFICIENCY COBALAMINCOBALAMIN DEFICIENCYDEFICIENCY HomocysteineHomocysteine HIGHHIGH HIGHHIGH MethylmalonicMethylmalonic AcidAcid NORMALNORMAL HIGHHIGH
    • 38. 3939 TREATMENTTREATMENT COBALAMIN DEFICIENCYCOBALAMIN DEFICIENCY IM Cbl: 1000 µg (1 mg) every day x week,IM Cbl: 1000 µg (1 mg) every day x week, followed by 1 mg every week x four weeks.followed by 1 mg every week x four weeks. If the underlying disorder persists (PA) 1 mgIf the underlying disorder persists (PA) 1 mg every month for lifeevery month for life Oral: 1000 to 2000 mcg/day.Oral: 1000 to 2000 mcg/day. May not be effective for PA (malabsorption)May not be effective for PA (malabsorption) Do not use timed release preparationsDo not use timed release preparations Transfusion- watch for CHFTransfusion- watch for CHF
    • 39. 4040 COBALAMIN DEFICIENCYCOBALAMIN DEFICIENCY Laboratory responseLaboratory response + Anemia--- reticulocytosis in 3-4 days+ Severe+ Anemia--- reticulocytosis in 3-4 days+ Severe Anemia--- serum iron and LDH levels fallAnemia--- serum iron and LDH levels fall HypokalemiaHypokalemia Hypersegmented neutrophils disappear at 10 to 14Hypersegmented neutrophils disappear at 10 to 14 days.days. Neurologic abnormalities often improve but may notNeurologic abnormalities often improve but may not reverse fullyreverse fully
    • 40. 4141 TREATMENTTREATMENT Folate DeficiencyFolate Deficiency – Exclude Cobalamin deficiency !!Exclude Cobalamin deficiency !! – A dose of 1 mg/day is usually sufficient,A dose of 1 mg/day is usually sufficient, even if malabsorption is present.even if malabsorption is present. – Neuro symptoms may be exacerbated withNeuro symptoms may be exacerbated with therapytherapy
    • 41. 4242 Case 2Case 2  70 YO male presents with fatigue, weight70 YO male presents with fatigue, weight loss, palpitationsloss, palpitations  Unremarkable PMHx, PSHxUnremarkable PMHx, PSHx  WBC 1.9, HGB 8, PLT 79,000, MCV 100,WBC 1.9, HGB 8, PLT 79,000, MCV 100, ANC 1.0ANC 1.0  Normal B12/folate and iron levelsNormal B12/folate and iron levels
    • 42. 4343 Case 2Case 2  What is the next diagnostic test…..What is the next diagnostic test…..
    • 43. 4444 Case 2Case 2  SmearSmear  Bone Marrow BiopsyBone Marrow Biopsy  Ultrasound to evaluate Liver and SpleenUltrasound to evaluate Liver and Spleen  Hepatitis / Viral panelHepatitis / Viral panel
    • 44. 4545 Case 2Case 2
    • 45. 4646 Case 2Case 2 LineageLineage BloodBlood MarrowMarrow ErythroidErythroid Oval macrocytesOval macrocytes Abnormal nuclearAbnormal nuclear shape and chromatinshape and chromatin patternpattern Basophilic stipplingBasophilic stippling Ring sideroblastsRing sideroblasts MyeloidMyeloid HypogranularHypogranular neutrophilsneutrophils Hypolobated formsHypolobated forms MegakaryocyticMegakaryocytic AgranularAgranular megakaryocytesmegakaryocytes MicromegakaryocyteMicromegakaryocyte sMononuclearsMononuclear megakaryocytesMegmegakaryocytesMeg akaryocytes withakaryocytes with seperated nucleiseperated nuclei
    • 46. 4747 MyelodysplasiaMyelodysplasia  Clonal stem cell disorder resulting inClonal stem cell disorder resulting in multilineage dysplasiamultilineage dysplasia  Can transform to acute leukemiaCan transform to acute leukemia  Under diagnosed disorderUnder diagnosed disorder  Can be secondary to therapyCan be secondary to therapy  Multiple bone marrow biopsies requiredMultiple bone marrow biopsies required  Cytogenetic abnormalitiesCytogenetic abnormalities
    • 47. 4848 MyelodysplasiaMyelodysplasia  WHO system includesWHO system includes ::  Refractory anemia (RA)Refractory anemia (RA)  Refractory anemia with ringed sideroblastsRefractory anemia with ringed sideroblasts (RARS)(RARS)  Refractory cytopenia with multilineageRefractory cytopenia with multilineage dysplasia (RCMD)dysplasia (RCMD)  Refractory cytopenia with multilineageRefractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS)dysplasia and ringed sideroblasts (RCMD-RS)  Refractory anemia with excess blasts I and IIRefractory anemia with excess blasts I and II  5q- syndrome5q- syndrome  Myelodysplasia unclassifiable (seen in thoseMyelodysplasia unclassifiable (seen in those cases of megakaryocyte dysplasia with fibrosiscases of megakaryocyte dysplasia with fibrosis and othersand others
    • 48. 4949 IPSS SCOREIPSS SCORE  Unfavorable cytogeneticsUnfavorable cytogenetics 11  Age > 60 yearsAge > 60 years 22  Hgb <10 (g dl-1)Hgb <10 (g dl-1) 11  Plt <50Plt <50 22  Plt >50 -250Plt >50 -250 11  1BM blasts >4%1BM blasts >4% 11  diploid and 5q only were favorable cytogenetic,diploid and 5q only were favorable cytogenetic, all others were considered as unfavorableall others were considered as unfavorable cytogenetics.cytogenetics.
    • 49. 5050 MyelodysplasiaMyelodysplasia  IPSS ScoreIPSS Score  Low risk0Low risk0  Intermediate risk 1 0.5 – 1Intermediate risk 1 0.5 – 1  Intermediate risk 2 1.5 – 2Intermediate risk 2 1.5 – 2  High risk  >2.5High risk  >2.5
    • 50. 5151 MyelodysplasiaMyelodysplasia  Low Risk MDSLow Risk MDS --Neutropenia or thrombocytopeniaNeutropenia or thrombocytopenia -symptomatic anemia is usually the initial problem-symptomatic anemia is usually the initial problem - Erythropoietin: highest response rate seen in patients with- Erythropoietin: highest response rate seen in patients with lower endogenous erythropoietin levels (< 500 IU) and lowerlower endogenous erythropoietin levels (< 500 IU) and lower transfusion requirements.transfusion requirements. -low-dose granulocyte colony-stimulating factor (G-CSF)-low-dose granulocyte colony-stimulating factor (G-CSF) -Erythropoietin resistance-Erythropoietin resistance -Red blood cell transfusions-Red blood cell transfusions
    • 51. 5252 Erythropoietic Growth FactorsErythropoietic Growth Factors  Caution in patients with uncontrolledCaution in patients with uncontrolled hypertensionhypertension  Risk of thrombosisRisk of thrombosis  Lack of responseLack of response  Survival benefit in patients withSurvival benefit in patients with malignancymalignancy
    • 52. 5353 MyelodysplasiaMyelodysplasia  High Risk MDSHigh Risk MDS -Refractory anemia/ thrmbocytopenia and-Refractory anemia/ thrmbocytopenia and neutropenianeutropenia -Higher Blast percentage but less than-Higher Blast percentage but less than 20%20% -Multiple Karyotypic abnormalities-Multiple Karyotypic abnormalities
    • 53. 5454 MyelodysplasiaMyelodysplasia  High Risk MDSHigh Risk MDS - Supportive Care- Supportive Care -Bone Marrow Transplant-Bone Marrow Transplant -Hypomethylating Agents-Hypomethylating Agents --5 Azacitadine--5 Azacitadine --Decitabine--Decitabine
    • 54. 5555 Case 3Case 3  47 YO African American Female presents47 YO African American Female presents with fatigue, heavy menstrual bleeding,with fatigue, heavy menstrual bleeding, body aches.body aches.  FHx: anemia of unknown etiologyFHx: anemia of unknown etiology  Social Hx, PMHx is unremarkableSocial Hx, PMHx is unremarkable  WBC 5K, HGB 9.8 g, PLT 166,000, MCVWBC 5K, HGB 9.8 g, PLT 166,000, MCV 5656  How do you approach this case?How do you approach this case?
    • 55. 5656 Case 3Case 3  Serum Ferritin 15Serum Ferritin 15  Iron saturation 9%Iron saturation 9%  TIBC 470TIBC 470  B12 and folate are normalB12 and folate are normal  Retic 2.6%Retic 2.6%  Bone marrow biopsyBone marrow biopsy
    • 56. 5757 Iron DeficiencyAnemiaIron DeficiencyAnemia
    • 57. 5858 Iron Deficiency AnemiaIron Deficiency Anemia EtiologyEtiology 1.1. Dietary deficiencyDietary deficiency 2.2. Malabsorption (Subtotal gastrectomy,Malabsorption (Subtotal gastrectomy, celiac sprue)celiac sprue) 3.3. Bleeding (Gastrointestinal,Bleeding (Gastrointestinal, Genitourinary, Hemoptysis, Epistaxis,Genitourinary, Hemoptysis, Epistaxis, Pregnancy)Pregnancy) 4.4. Intravascular hemolysis (PNH, Trauma,Intravascular hemolysis (PNH, Trauma, Hemosiderinuria)Hemosiderinuria) 5.5. Chronic renal failureChronic renal failure
    • 58. 5959 Iron DeficiencyAnemiaIron DeficiencyAnemia Poor correlation between hemoglobin level andPoor correlation between hemoglobin level and symptomssymptoms Symptoms may include:Symptoms may include: Pica - geophagia, pagophagia, amylophagiaPica - geophagia, pagophagia, amylophagia PallorPallor Smooth tongueSmooth tongue StomatitisStomatitis CheilosisCheilosis Koilonychia (spoon nails)Koilonychia (spoon nails) ParesthesiasParesthesias SplenomegalySplenomegaly
    • 59. 6060 Iron DeficiencyAnemiaIron DeficiencyAnemia LABORATORYLABORATORY Low iron, high TIBC, low ferritin, high serumLow iron, high TIBC, low ferritin, high serum transferrin receptortransferrin receptor Absent marrow ironAbsent marrow iron ThrombocytosisThrombocytosis TREATMENTTREATMENT 1. Oral1. Oral 2. Parenteral:2. Parenteral: Iron dextran < 70% utilizedIron dextran < 70% utilized Need Test doseNeed Test dose Total dose (mg) = deficit in Hb (gm/100ml) x weightTotal dose (mg) = deficit in Hb (gm/100ml) x weight (lb) +(lb) + 1000mg1000mg Watch for anaphylaxisWatch for anaphylaxis 3. Treat underlying3. Treat underlying
    • 60. 6161 Case 3Case 3  Patient was treated with oral iron for 3Patient was treated with oral iron for 3 months and follow-up labs showedmonths and follow-up labs showed – WBC 5.2, HGB 11, MCV 60, PLT 222,000WBC 5.2, HGB 11, MCV 60, PLT 222,000 – What is your next stepWhat is your next step
    • 61. 6262 Case 3Case 3  Patient was treated with oral iron for 3Patient was treated with oral iron for 3 months and follow-up labs showedmonths and follow-up labs showed – WBC 5.2, HGB 11, MCV 60, PLT 222,000WBC 5.2, HGB 11, MCV 60, PLT 222,000 – Ferritin 50, TIBC 300, Saturation 15%Ferritin 50, TIBC 300, Saturation 15% – What is the next step…….What is the next step…….
    • 62. 6363 Target cells: Seen in ETOH, Liver Disease, Hemoglobinopathies
    • 63. 6464
    • 64. 6565 THALASSEMIATHALASSEMIA A Defect in Hemoglobin SynthesisA Defect in Hemoglobin Synthesis Definition – defect in Hemoglobin subunitDefinition – defect in Hemoglobin subunit synthesis (2synthesis (2αα and 2and 2ββ)) Inadequate hemoglobin accumulationInadequate hemoglobin accumulation  Hypochromia/microcytosis and a host ofHypochromia/microcytosis and a host of clinical manifestations.clinical manifestations. Severe anemia will present in childhoodSevere anemia will present in childhood Three main variants: African, Asian,Three main variants: African, Asian, MediterraneanMediterranean
    • 65. 6666 THALASSEMIATHALASSEMIA TYPETYPE αα (alpha)(alpha) TYPES:TYPES: α−α−Thalassemia – alpha globin unit synthesisThalassemia – alpha globin unit synthesis decreased or absentdecreased or absent ββ subunits will pptsubunits will ppt Four subtypesFour subtypes Hydrops fetalis (4 loci)Hydrops fetalis (4 loci) Hemoglobin H (3 loci)Hemoglobin H (3 loci) α−α−Thalassemia Minor (2 loci) mild anemia,Thalassemia Minor (2 loci) mild anemia, microcytosismicrocytosis α−α−Thalassemia Minima (1 loci) no significantThalassemia Minima (1 loci) no significant anemiaanemia
    • 66. 6767 ThalassemiaThalassemia AlphaAlpha ThalassemiaThalassemia BetaBeta ThalassemiaThalassemia MCVMCV 74+/- 474+/- 4 63 +/- 463 +/- 4 HGB A2HGB A2 2.2 +/- 0.62.2 +/- 0.6 3.3+/- 0.23.3+/- 0.2 MCHMCH 24 +/-224 +/-2 27 +/- 227 +/- 2
    • 67. 6868 THALASSEMIATHALASSEMIA A Defect in Hemoglobin SynthesisA Defect in Hemoglobin Synthesis β−β−Thalassemia - beta globin unit synthesis decreasedThalassemia - beta globin unit synthesis decreased or absent,or absent, αα subunits will pptsubunits will ppt Beta – two Loci/ one GeneBeta – two Loci/ one Gene Major – Homozygous – Severe Anemia,Major – Homozygous – Severe Anemia, Jaundice, Hepatosplenomegaly, Fe OverloadJaundice, Hepatosplenomegaly, Fe Overload (High Ferritin), CHF(High Ferritin), CHF Onset: first year of life, transfusion dependent)Onset: first year of life, transfusion dependent) Minor – Heterozygous – Hypochromic, OftenMinor – Heterozygous – Hypochromic, Often MildMild Microcytic Anemia;Microcytic Anemia; ↓↓HgB A,HgB A, ↑↑HgB F,HgB F, ↑↑HgB AHgB A22
    • 68. 6969 THALASSEMIATHALASSEMIA A Defect in Hemoglobin SynthesisA Defect in Hemoglobin Synthesis Beta Major: These pts will be symptomatic only after 4 –Beta Major: These pts will be symptomatic only after 4 – 6 months because in Fetal Hb (6 months because in Fetal Hb (αα22 δδ22), the), the δδ subunit is notsubunit is not replaced with thereplaced with the ββ subunit until after birthsubunit until after birth
    • 69. 7070 THALASSEMIATHALASSEMIA Clinical ManifestationsClinical Manifestations  Skeletal-Skeletal- – Osteoporosis –Osteoporosis – vertebral compression Fxvertebral compression Fx (next slide)(next slide) – SkullSkull has a “hot cross bun” configurationhas a “hot cross bun” configuration – PneumatizationPneumatization of the sinuses is delayed (nextof the sinuses is delayed (next slide)slide)  Distortion of the maxillary bones, as well asDistortion of the maxillary bones, as well as poor development of the sinus cavitiespoor development of the sinus cavities  Hand: Metacarpals. Metatarsals, phalangeHand: Metacarpals. Metatarsals, phalange make it look rectangular and convex shaped.make it look rectangular and convex shaped.
    • 70. 7171 THALASSEMIATHALASSEMIA A Defect in Hemoglobin SynthesisA Defect in Hemoglobin Synthesis
    • 71. 7272
    • 72. 7373 THALASSEMIATHALASSEMIA CHF/ CARDIOMEGALYCHF/ CARDIOMEGALY Chest radiograph typical of severe β-Chest radiograph typical of severe β- thalassemia. widening of the rib ends andthalassemia. widening of the rib ends and cardiac dilation.cardiac dilation.
    • 73. 7474 THALASSEMIATHALASSEMIA Clinical ManifestationsClinical Manifestations  Shortened RBC survivalShortened RBC survival  DECREASED MCVDECREASED MCV  Iron- normal !!Iron- normal !!  Heart –Heart – CardiomegalyCardiomegaly  Growth + DevelopmentGrowth + Development – is retarded – both– is retarded – both skeletal and dental ages.skeletal and dental ages.  Secondary Iron OverloadSecondary Iron Overload
    • 74. 7575 THALASSEMIA –THALASSEMIA – Clinical ManifestationsClinical Manifestations  LiverLiver – Hepatomegaly due to extramedullary– Hepatomegaly due to extramedullary hematopoiesis.hematopoiesis. Later in disease hepatomegaly is associatedLater in disease hepatomegaly is associated with cirrhosis.with cirrhosis. Iron deposited in Kupffer cellsIron deposited in Kupffer cells  may look likemay look like idiopathic hemochromatosis.idiopathic hemochromatosis.  Viral Hepatitis may augment liver damage.Viral Hepatitis may augment liver damage.
    • 75. 7676 THALASSEMIATHALASSEMIA TherapyTherapy Trait –Trait – None indicatedNone indicated SplenectomySplenectomy –– ChelationChelation:Deferoxamine / Fe Chelation:Deferoxamine / Fe Chelation (Keep Iron Saturation <50%)(Keep Iron Saturation <50%) Iron SupplementationIron Supplementation ContraindicatedContraindicated
    • 76. 7777 THALASSEMIATHALASSEMIA TherapyTherapy  Genetic CounselingGenetic Counseling recommended.recommended.  Autosomal RecessiveAutosomal Recessive pattern of inheritancepattern of inheritance
    • 77. 7878 Hemolytic AnemiaHemolytic Anemia HemoglobinopathiesHemoglobinopathies  Sickle Cell Disease (HgB SS)Sickle Cell Disease (HgB SS) – 1 in 400 American Blacks1 in 400 American Blacks – Valine for Glutamate at position #6 inValine for Glutamate at position #6 in ββ ChainChain – Gelation of HgBGelation of HgB →→ DeoxygenationDeoxygenation →→ SickledSickled IrreversiblyIrreversibly – Electrophoresis Required for DifferentiationElectrophoresis Required for Differentiation – Trait- often no clinical symptomsTrait- often no clinical symptoms
    • 78. 7979
    • 79. 8080 What is Sickle cell diseaseWhat is Sickle cell disease  An inherited disease of red bloodAn inherited disease of red blood cellscells  Abnormal hemoglobin.Abnormal hemoglobin.  Sickle-shaped red cells interruptSickle-shaped red cells interrupt blood flow by blocking small bloodblood flow by blocking small blood vesselsvessels  Tissue damage due to lack of bloodTissue damage due to lack of blood flow and severe pain due to tissueflow and severe pain due to tissue hypoxiahypoxia
    • 80. 8181 Hemolytic AnemiaHemolytic Anemia Sickle Cell DiseaseSickle Cell Disease – MicroinfarctionMicroinfarction  Pulmonary (Acute Chest), Avascular Necrosis,Pulmonary (Acute Chest), Avascular Necrosis, CVA, CHF, RF, Skin ulcerationsCVA, CHF, RF, Skin ulcerations – PainPain  Joint, Musculoskeletal, AbdominalJoint, Musculoskeletal, Abdominal – AsplenismAsplenism – Sepsis, Recurrent InfectionSepsis, Recurrent Infection – Fetal loss, high Maternal MorbidityFetal loss, high Maternal Morbidity – Aplasic Crisis - Infection, Folate DeficiencyAplasic Crisis - Infection, Folate Deficiency – Sequestration Crisis -Sequestration Crisis - ↓↓↓↓ HgB,HgB, ↑↑Retics.,Retics., HepatosplenomegalyHepatosplenomegaly
    • 81. 8282 Hemolytic AnemiaHemolytic Anemia Sickle Cell Disease - TREATMENTSickle Cell Disease - TREATMENT  TreatmentTreatment  PAIN CRISISPAIN CRISIS – Supportive, Conservative & ExpectantSupportive, Conservative & Expectant – Treat Infections Early; Pneumococcal VaccineTreat Infections Early; Pneumococcal Vaccine – Folate Supplementation DailyFolate Supplementation Daily – Opiod Analgesics PRN; DependenceOpiod Analgesics PRN; Dependence Common in advanced StagesCommon in advanced Stages
    • 82. 8383 Hemolytic AnemiaHemolytic Anemia Sickle Cell Disease - TREATMENTSickle Cell Disease - TREATMENT  TreatmentTreatment  CHEST SYNDROMECHEST SYNDROME – Supportive, Conservative & ExpectantSupportive, Conservative & Expectant – Folate Supplementation DailyFolate Supplementation Daily – Opiod AnalgesicsOpiod Analgesics – Oxygen / HyperbaricOxygen / Hyperbaric – Correct DehydrationCorrect Dehydration – Hypertransfusion in CrisisHypertransfusion in Crisis – Hydrea- reduce ulcers, transfusion, crisesHydrea- reduce ulcers, transfusion, crises
    • 83. 8484 Case 5Case 5  36 YO female presents with history of URI36 YO female presents with history of URI symptoms, ear ache, fever.symptoms, ear ache, fever.  Unremarkable past medical historyUnremarkable past medical history  WBC 11 K, HGB 5 g, PLT 202,000WBC 11 K, HGB 5 g, PLT 202,000  What is the next step……What is the next step……
    • 84. 8585 Case 5Case 5  Iron studies are normal except for ferritinIron studies are normal except for ferritin 988988  B12/Folate are normalB12/Folate are normal  Additional laboratory data requestedAdditional laboratory data requested
    • 85. 8686 Case 5Case 5  Iron studies are normal except for ferritinIron studies are normal except for ferritin 988988  B12/Folate are normalB12/Folate are normal  Peripheral SmearPeripheral Smear  Additional laboratory data requestedAdditional laboratory data requested  LDH 1000, Haptoglobin 5, T.Bili 3, ReticLDH 1000, Haptoglobin 5, T.Bili 3, Retic 12%12%
    • 86. 8787 Hemolytic AnemiaHemolytic Anemia Increased RI, LDH, Indirect Bilirubin Decreased Haptoglobin Urine Hemoglobin- severe cases Direct Antiglobulin test Indirect Antiglobulin test Peripheral Smear
    • 87. 8888 Hemolytic AnemiaHemolytic Anemia AcquiredAcquired TypeType MechanismMechanism Disease StatesDisease States Diagnostic testsDiagnostic tests ImmuneImmune mediatedmediated Antibodies toAntibodies to RBC surfaceRBC surface antigensantigens Drugs,Drugs, Malignancy,Malignancy, AIHAAIHA SpherocytesSpherocytes +DAT+DAT MicroangiopathiMicroangiopathi cc Destruction ofDestruction of RBC inRBC in circulationcirculation TTP, HUS, DIC,TTP, HUS, DIC, Pre-eclampsia,Pre-eclampsia, Prosthetic valvesProsthetic valves SchistocytesSchistocytes InfectiousInfectious Malaria, Babesia,Malaria, Babesia, ClostridiaClostridia BartonellaBartonella Positive bloodPositive blood culturescultures
    • 88. 8989 Hemolytic AnemiaHemolytic Anemia ImmuneImmune  Antibodies to Red Cell or Drug InteractionAntibodies to Red Cell or Drug Interaction  Direct Coombs – Detects IgA/G orDirect Coombs – Detects IgA/G or Complement (C3)Complement (C3)  Indirect Coombs – Detects Antibody inIndirect Coombs – Detects Antibody in Serum of Recipient Against DonorSerum of Recipient Against Donor
    • 89. 9090 Hemolytic AnemiaHemolytic Anemia Immune MediatedImmune Mediated
    • 90. 9191 Hemolytic AnemiaHemolytic Anemia Alloantibody ImmuneAlloantibody Immune  Transfusion ReactionsTransfusion Reactions – Recipient Antibody to Donor AntigenRecipient Antibody to Donor Antigen – Increased Risk with TransfusionsIncreased Risk with Transfusions – Single Donor Donation DecreasesSingle Donor Donation Decreases  Erythroblastosis Fetalis – IgG-Anti-RhErythroblastosis Fetalis – IgG-Anti-Rh – RhRh-- Mother Carrying RhMother Carrying Rh++ FetusFetus – RhoGam (IgM-Anti-Rh) at Delivery/MiscarryRhoGam (IgM-Anti-Rh) at Delivery/Miscarry
    • 91. 9292 Hemolytic AnemiaHemolytic Anemia AutoimmuneAutoimmune  Warm Antibody – IgG orWarm Antibody – IgG or < IgA< IgA – Inefficient CInefficient C33 & C& C44 FixationFixation – Active at 37Active at 37oo C, NonagglutinatingC, Nonagglutinating – Evan’s Syndrome- associated thrombocytopeniaEvan’s Syndrome- associated thrombocytopenia – Symptoms: Inc RI, SM, SpherocytosisSymptoms: Inc RI, SM, Spherocytosis – Destruction in SpleenDestruction in Spleen – Idiopathic 20%Idiopathic 20%  CLL 20%, Lymphoma 10%, Misc. 10%CLL 20%, Lymphoma 10%, Misc. 10%  Collagen Vascular 15%, Thyroid Disease 10%Collagen Vascular 15%, Thyroid Disease 10%  GI Diseases (UC) 10%GI Diseases (UC) 10% – TreatmentTreatment  Steroids, Immunosuppression, SplenectomySteroids, Immunosuppression, Splenectomy
    • 92. 9393 Case 5Case 5  36 YO female presents with history of URI36 YO female presents with history of URI symptoms, ear ache, fever.symptoms, ear ache, fever.  Unremarkable past medical historyUnremarkable past medical history  WBC 11 K, HGB 5 g, PLT 202,000WBC 11 K, HGB 5 g, PLT 202,000
    • 93. 9494 Hemolytic AnemiaHemolytic Anemia AutoimmuneAutoimmune  Cold Antibody – IgMCold Antibody – IgM – Efficient Complement Fixation (C3)Efficient Complement Fixation (C3) – Active at 4Active at 4oo C, Agglutinate; Dissociate at 32C, Agglutinate; Dissociate at 32oo CC – Destruction in Liver, IntravascularDestruction in Liver, Intravascular  Mycoplasma (5-10 days post recovery),viralMycoplasma (5-10 days post recovery),viral illnessesillnesses  Lymphoproliferative, Often ChronicLymphoproliferative, Often Chronic  MGUSMGUS – TreatmentTreatment  Acute - Usually Self Limited, Warm EnvironmentAcute - Usually Self Limited, Warm Environment  Chronic – Steroids, Splenectomy not Helpful;Chronic – Steroids, Splenectomy not Helpful; ImmuneImmune SuppressionSuppression
    • 94. 9595 Hemolytic AnemiaHemolytic Anemia Acquired – DICAcquired – DIC MicroangiopathicMicroangiopathic Disseminated Intravascular Coagulation (DIC)Disseminated Intravascular Coagulation (DIC)  Obstetrical, Bacterial Sepsis, Carcinoma,Obstetrical, Bacterial Sepsis, Carcinoma, TraumaTrauma  Diffuse Microthrombi Followed byDiffuse Microthrombi Followed by Fibrinolysis Consuming Coagulant ProteinsFibrinolysis Consuming Coagulant Proteins  Extensive Hemorrhage, Thrombocytopenia,Extensive Hemorrhage, Thrombocytopenia, Fragmented RBC’s (Schistocytes),Fragmented RBC’s (Schistocytes), ↑↑PT/PTT,PT/PTT, ↑↑Fibrin Split ProductsFibrin Split Products (FSP), Mod. Hemolysis(FSP), Mod. Hemolysis  Severe disease usually with low PlasmaSevere disease usually with low Plasma Fibrinogen LevelFibrinogen Level  TREATMENT: Underlying DisorderTREATMENT: Underlying Disorder
    • 95. 9696 Hemolytic AnemiaHemolytic Anemia HereditaryHereditary TypeType MechanismMechanism TriggersTriggers DiagnosticDiagnostic teststests Hemoglobin-Hemoglobin- opathiesopathies ThalassemiaThalassemia Sickle CellSickle Cell DiseaseDisease -- HemoglobinHemoglobin electrophoresiselectrophoresis MembraneMembrane dysfunctiondysfunction HereditaryHereditary Spherocytosis,Spherocytosis, ElliptocytosisElliptocytosis -- Spherocytes,Spherocytes, Family history,Family history, negative DATnegative DAT EnzymeEnzyme mediatedmediated G6PDG6PD DeficiencyDeficiency Infections,Infections, Drugs, FavaDrugs, Fava beansbeans Abn G6PDAbn G6PD activityactivity
    • 96. 9797 Hemolytic AnemiaHemolytic Anemia Microangiopathic – TTPMicroangiopathic – TTP Thrombotic Thrombocytopenic PurpuraThrombotic Thrombocytopenic Purpura (TTP)(TTP)  Etiology Unclear; Immunologic, MicroaneurysmEtiology Unclear; Immunologic, Microaneurysm  Anemia with Fragmented RBC’s,Anemia with Fragmented RBC’s, ↑↑Retics,Retics, Moderate Thrombocytopenia, Jaundice, PetechiaeModerate Thrombocytopenia, Jaundice, Petechiae < ITP< ITP  PT, PTT, Fibrinogen, FSP usually near NLPT, PTT, Fibrinogen, FSP usually near NL  Fever, Abdominal Pain, ArthralgiasFever, Abdominal Pain, Arthralgias  Bleeding Unusual; Course Days to WeeksBleeding Unusual; Course Days to Weeks  Death Due to Renal Failure, Cerebral IschemiaDeath Due to Renal Failure, Cerebral Ischemia  Plasmaphoresis, SteroidsPlasmaphoresis, Steroids
    • 97. 9898 Transfusion ReactionsTransfusion Reactions TypeType OnsetOnset LaboratoryLaboratory TreatmentsTreatments Acute hemolyticAcute hemolytic Within hoursWithin hours + DAT+ DAT IVF, StopIVF, Stop transfusiontransfusion Delayed hemolyticDelayed hemolytic 2-12 days2-12 days + DAT (Also+ DAT (Also Indirect +)Indirect +) IVFIVF Febrile nonhemolyticFebrile nonhemolytic Within hoursWithin hours - DATDAT SupportiveSupportive AnaphylacticAnaphylactic WithinWithin minutesminutes IgA deficiencyIgA deficiency EpinephrineEpinephrine PosttransfusionPosttransfusion PurpuraPurpura 5-12 days5-12 days Seen with pltSeen with plt transfusiontransfusion IVIGIVIG UrticarialUrticarial WithinWithin minutesminutes - DATDAT DiphenhydramineDiphenhydramine Can continue TxCan continue Tx
    • 98. 9999 Hemolytic AnemiaHemolytic Anemia Microangiopathic – TTPMicroangiopathic – TTP Thrombotic Thrombocytopenic PurpuraThrombotic Thrombocytopenic Purpura (TTP)(TTP) Pentad: FAT-RNsPentad: FAT-RNs 40% Present with Pentad40% Present with Pentad 30% of patients will relapse30% of patients will relapse
    • 99. 100100 Hemolytic AnemiaHemolytic Anemia Microangiopathic – HUSMicroangiopathic – HUS Hemolytic Uremic Syndrome (HUS)Hemolytic Uremic Syndrome (HUS)  ASSOCIATED WITH E.COLI: O-157-H7ASSOCIATED WITH E.COLI: O-157-H7 infectioninfection (5-10% of infections)(5-10% of infections)  Intracorpuscular Defect Acquired in Stem CellsIntracorpuscular Defect Acquired in Stem Cells  Viral Prodrome, Young ChildrenViral Prodrome, Young Children  Acute Hemolytic Anemia, ThrombocytopenicAcute Hemolytic Anemia, Thrombocytopenic Purpura, Oliguria, Venous ThrombosisPurpura, Oliguria, Venous Thrombosis  Blood Smear & Coagulation Studies Similar ITPBlood Smear & Coagulation Studies Similar ITP  Neurologic Deficits UncommonNeurologic Deficits Uncommon  Dialysis, TransfusionDialysis, Transfusion  Mortality 5% to 20%Mortality 5% to 20%
    • 100. 101101
    • 101. 102102 REFERENCESREFERENCES References for Hematology lecture dated 9/25/08References for Hematology lecture dated 9/25/08 1.1. Myelodysplasia,Myelodysplasia, Blood, 1 August 2008, Vol. 112, No. 3, pp. 479.Blood, 1 August 2008, Vol. 112, No. 3, pp. 479. 2.2. BMJ 1998 / B12 DeficiencyBMJ 1998 / B12 Deficiency 3.3. Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood.Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood. 2006;107:3481–34852006;107:3481–3485 4.4. Silverman LR, McKenzie DR, Peterson BL, et al; Cancer and Leukemia Group B. FurtherSilverman LR, McKenzie DR, Peterson BL, et al; Cancer and Leukemia Group B. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921,analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol. 2006;24:3895–3903.and 9221 by the Cancer and Leukemia Group B. J Clin Oncol. 2006;24:3895–3903. 5.5. Kantarjian H, Gandhi V, Cortes J, et al. Phase 2 clinical and pharmacologic study of clofarabineKantarjian H, Gandhi V, Cortes J, et al. Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood. 2003;102:2379.in patients with refractory or relapsed acute leukemia. Blood. 2003;102:2379. 6.6. Faderl S, Gandhi V, O’Brien S, et al. Results of a phase 1–2 study of clofarabine in combinationFaderl S, Gandhi V, O’Brien S, et al. Results of a phase 1–2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood. 2005;105:940with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood. 2005;105:940 7.7. Burnett AK, Mohite U. Treatment of older patients with acute myeloid leukemia—new agents.Burnett AK, Mohite U. Treatment of older patients with acute myeloid leukemia—new agents. Semin Hematol. 2006;43:96–106.Semin Hematol. 2006;43:96–106. 8.8. Greenberg et al. International Scoring System for Evaluating Prognosis in Myelodysplastic Syndromes.Greenberg et al. International Scoring System for Evaluating Prognosis in Myelodysplastic Syndromes. Blood 1997;89:2079-2088.Blood 1997;89:2079-2088. 9.9. Silverman LR, Demakos EP, Peterson BL, et al (2002). "Randomized controlled trial ofSilverman LR, Demakos EP, Peterson BL, et al (2002). "Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemiaazacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B". J. Clin. Oncol.group B". J. Clin. Oncol. 2020 (10): 2429–40.(10): 2429–40.
    • 102. 103103 MalariaMalaria  Clinical ManifestationClinical Manifestation – 1 to 6 weeks after Innoculation1 to 6 weeks after Innoculation – P. vivax & P. ovale Recurrent 6 – 12 MonthsP. vivax & P. ovale Recurrent 6 – 12 Months – Chills, Fever, Myalgia, Splenomegaly, Anemia;Chills, Fever, Myalgia, Splenomegaly, Anemia; Leukocytosis RareLeukocytosis Rare – P. falciparum – Encephalitis, ARDSP. falciparum – Encephalitis, ARDS – Blackwater Fever – Massive Immune Hemolysis, RenalBlackwater Fever – Massive Immune Hemolysis, Renal FailureFailure  TreatmentTreatment – P. falciparum - Chloroquine Resistant; Quinine &P. falciparum - Chloroquine Resistant; Quinine & DoxycyclineDoxycycline – Others - Chloroquine ResponsiveOthers - Chloroquine Responsive – P. vivax & P. ovale; Add PrimaquineP. vivax & P. ovale; Add Primaquine  ProphylaxisProphylaxis – Chloroquine, Mefloquine– Chloroquine, Mefloquine
    • 103. 104104 Hemolytic AnemiaHemolytic Anemia Infectious - BabesiosisInfectious - Babesiosis  Malaria-Like Intraerythrocyctic ParasiteMalaria-Like Intraerythrocyctic Parasite  Eastern and Western Seaboard,Eastern and Western Seaboard,  Ixodidae Ticks; Rodents, PetsIxodidae Ticks; Rodents, Pets  Symptoms: Febrile Hemolytic AnemiaSymptoms: Febrile Hemolytic Anemia Incubation 1-3 weeksIncubation 1-3 weeks Flu like Symptoms, Myalgias, Dark UrineFlu like Symptoms, Myalgias, Dark Urine Asplenic individuals can have overwhelmingAsplenic individuals can have overwhelming diseasedisease Often co-infection with Borrelia burgdoferiOften co-infection with Borrelia burgdoferi
    • 104. 105105 Hemolytic AnemiaHemolytic Anemia Infectious - BabesiosisInfectious - Babesiosis  Diagnosis – Blood SmearsDiagnosis – Blood Smears – Similar to P Falciparum (Malaria) but theseSimilar to P Falciparum (Malaria) but these organisms produce no pigment.organisms produce no pigment. – ““Maltese Cross”Maltese Cross”  Therapy – Clindamycin & QuinineTherapy – Clindamycin & Quinine  Exchange Transfusion when SevereExchange Transfusion when Severe DiseaseDisease
    • 105. 106106
    • 106. 107107 Hemolytic AnemiaHemolytic Anemia CongenitalCongenital DAT negativeDAT negative  Membrane AbnormalitiesMembrane Abnormalities – Hereditary SpherocytosisHereditary Spherocytosis  HemoglobinopathiesHemoglobinopathies – Sickle Cell AnemiaSickle Cell Anemia – Hemoglobin C & SC DiseaseHemoglobin C & SC Disease – ThalassemiaThalassemia – Defective MetabolismDefective Metabolism – Glucose-6-phosphate Dehydrogenase DeficiencyGlucose-6-phosphate Dehydrogenase Deficiency
    • 107. 108108 Hemolytic AnemiaHemolytic Anemia Membrane AbnormalityMembrane Abnormality  Hereditary SpherocytosisHereditary Spherocytosis – Common Hemoglobinopathy in WhitesCommon Hemoglobinopathy in Whites – Defective Fragile Red Cell MembraneDefective Fragile Red Cell Membrane ;; SpherocytesSpherocytes – Hemolysis in Spleen; Splenomegaly,Hemolysis in Spleen; Splenomegaly, CommonCommon SkinSkin Ulcers Over AnklesUlcers Over Ankles – Mildly Reduced HgB,Mildly Reduced HgB, Increased Retics.Increased Retics. – Occasional Jaundice, +Gallstones, Anemia is mild toOccasional Jaundice, +Gallstones, Anemia is mild to severe, Increased MCHC, Aplastic Crisis in Viralsevere, Increased MCHC, Aplastic Crisis in Viral Infection orInfection or ↓↓FolateFolate – Splenectomy Curative (Don’t forget vaccinations!)Splenectomy Curative (Don’t forget vaccinations!) – Lifelong FolateLifelong Folate
    • 108. 109109
    • 109. 110110 Hemolytic AnemiaHemolytic Anemia Acquired NonimmuneAcquired Nonimmune Paroxysmal Nocturnal HemoglobinuriaParoxysmal Nocturnal Hemoglobinuria Acquired stem cell disorderAcquired stem cell disorder Susceptible to complement due to two missingSusceptible to complement due to two missing membrane components of the complementmembrane components of the complement system.system. Look for Specific assays for CD 55 and CD59 byLook for Specific assays for CD 55 and CD59 by Flow CytometryFlow Cytometry Complication: ThrombosisComplication: Thrombosis Treatment: Steroids, Transfusions, Iron and folateTreatment: Steroids, Transfusions, Iron and folate replacementreplacement
    • 110. 111111 Hemolytic AnemiaHemolytic Anemia Enzyme DeficienciesEnzyme Deficiencies  Glucose-6-Phosphate DehydrogenaseGlucose-6-Phosphate Dehydrogenase ↑↑ Glutathione-SH (in a series of biochem rxns)Glutathione-SH (in a series of biochem rxns) – GSH Protects Oxidation Cysteine in Cell Wall,GSH Protects Oxidation Cysteine in Cell Wall, Oxidation MethHgB (FeOxidation MethHgB (Fe3+3+ →→ FeFe2+2+ )) – X - Linked, > 250 VariantsX - Linked, > 250 Variants – Acute Hemolysis 2-4 days after drug exposureAcute Hemolysis 2-4 days after drug exposure – American Blacks – African Variant (AAmerican Blacks – African Variant (A-- ))  13% Males; 20% Female Carriers, Variable Affect13% Males; 20% Female Carriers, Variable Affect  Self-Limited; Retics NL G-6-PD ActivitySelf-Limited; Retics NL G-6-PD Activity  May Confer Malarial ProtectionMay Confer Malarial Protection – Italian/Greek – Mediterranean, More SevereItalian/Greek – Mediterranean, More Severe
    • 111. 112112
    • 112. 113113
    • 113. 114114
    • 114. 115115 Hemolytic AnemiaHemolytic Anemia G6-PD Deficiency – What causes aG6-PD Deficiency – What causes a crisis?crisis?  Oxidative Drug-Induced HemolysisOxidative Drug-Induced Hemolysis – Sulfonamides, Dapsone; NitrofurantoinSulfonamides, Dapsone; Nitrofurantoin – Antimalarials; Primaquine, ChloroquineAntimalarials; Primaquine, Chloroquine – Vitamin K (Water Soluble), ProbenecidVitamin K (Water Soluble), Probenecid – Occasional - Infection, Diabetic KetoacidosisOccasional - Infection, Diabetic Ketoacidosis  Mediterranean VariantMediterranean Variant – Quinine, Quinidine; AspirinQuinine, Quinidine; Aspirin – Favism – Exposure to Fava Bean or PollenFavism – Exposure to Fava Bean or Pollen
    • 115. 116116 Hemolytic AnemiaHemolytic Anemia G6-PD DeficiencyG6-PD Deficiency  Laboratory StudiesLaboratory Studies – Heinz Bodies (Precipitated GS-SG HgB)Heinz Bodies (Precipitated GS-SG HgB) – Bite cellsBite cells – NL 50% Enzyme Decline in 120d RBC LifeNL 50% Enzyme Decline in 120d RBC Life  Black Variant (ABlack Variant (A-- );); ↓↓RBC Survival, w/o AnemiaRBC Survival, w/o Anemia  Mediterranean;Mediterranean; ↓↓↓↓Survival, Anemia w/o ExposureSurvival, Anemia w/o Exposure  G6PD enzyme normal with active hemolysisG6PD enzyme normal with active hemolysis – Acute PhaseAcute Phase  ↓↓RBC,RBC, ≅≅ 25% in A25% in A-- ,, > Mediterranean> Mediterranean  ↑↑Plasma HgB,Plasma HgB, ↑↑Uncong. Billi.,Uncong. Billi., ↓↓HaptoglobinHaptoglobin  ± Hemoglobinuria± Hemoglobinuria  Heinz Bodies Cleared After Day 1Heinz Bodies Cleared After Day 1 →→ Bite CellsBite Cells
    • 116. 117117 Hemolytic AnemiaHemolytic Anemia G6-PD DeficiencyG6-PD Deficiency  Treatment – Maintain HydrationTreatment – Maintain Hydration – Black Variant Self-LimitedBlack Variant Self-Limited – MediterraneanMediterranean  Splenectomy not EffectiveSplenectomy not Effective  RBC Transfusion Rarely IndicatedRBC Transfusion Rarely Indicated – PreventionPrevention  Screening - Avoid Oxidant DrugsScreening - Avoid Oxidant Drugs  Prompt Treatment InfectionPrompt Treatment Infection
    • 117. 118118 Other AnemiasOther Anemias Bloom’s Syndrome: AR, Ashkenazi Jews,Bloom’s Syndrome: AR, Ashkenazi Jews, Mild anemia, stunted growth,Mild anemia, stunted growth, Photosensitivity, Mental Retardation,Photosensitivity, Mental Retardation, Facial erythema, Infertility (men)Facial erythema, Infertility (men) Dyskeratosis congenita: Marrow aplasia,Dyskeratosis congenita: Marrow aplasia, Dystrophic nails, Skin hyperpigmentation,Dystrophic nails, Skin hyperpigmentation, Leukoplakia, Continuous lacrimation,Leukoplakia, Continuous lacrimation, Testicular atrophyTesticular atrophy
    • 118. 119119 Acute Intermittent PorphyriaAcute Intermittent Porphyria AD, presents in adulthoodAD, presents in adulthood Defect of porphobiligen deaminase activity,Defect of porphobiligen deaminase activity, accumulate Aminolevulinic acid andaccumulate Aminolevulinic acid and porphobilinogen in urineporphobilinogen in urine Symptoms: Abdominal pain, Autonomic (HTN,Symptoms: Abdominal pain, Autonomic (HTN, Tachycardia) and Peripheral Neuropathy,Tachycardia) and Peripheral Neuropathy, Hyponatremia, MS changes, Psychosis, Seizures,Hyponatremia, MS changes, Psychosis, Seizures, (No Skin changes like other porphyrias)(No Skin changes like other porphyrias) Treatment: High carb diet, IV Glucose, HematinTreatment: High carb diet, IV Glucose, Hematin
    • 119. 120120 Myeloproliferative DisordersMyeloproliferative Disorders Polycythemia Vera Low EPO, Inc RBC Mass, SM.Treat w/Phlebotomy, Hydrea, ASA Symptoms: HA, Visual Changes, Fatigue, Pruritus, Epistaxis, DVT, High B12 levels If Hct >54- rule out secondary causes- Hypoxia, Carboxyhem, Tobacco, EPO tumors). SHOULD GET BM BIOPSY Myelofibrosis Essential Thrombocythemia CML
    • 120. 121121 MYELODYSPLASTIC DISORDERSMYELODYSPLASTIC DISORDERS MDS- Refractory anemia, RA with ringedMDS- Refractory anemia, RA with ringed sideroblasts, RA with excess blasts, RA withsideroblasts, RA with excess blasts, RA with excess blasts in transformation, CMMOLexcess blasts in transformation, CMMOL Causes: Environmental exposures, postCauses: Environmental exposures, post chemotherapy, Aplastic anemia, Fanconi’s anemiachemotherapy, Aplastic anemia, Fanconi’s anemia Symptoms: of Anemia, SM, increased MCV,Symptoms: of Anemia, SM, increased MCV, Hyposegmented PMNs (Pelger Huet anomaly)Hyposegmented PMNs (Pelger Huet anomaly) Treatment: SCT, Growth factors, Chemotherapy,Treatment: SCT, Growth factors, Chemotherapy, TransfusionsTransfusions
    • 121. 122122 Leukemia/LymphomaLeukemia/Lymphoma CLLCLL CMLCML AMLAML ALLALL Non-Hodgkins LymphomaNon-Hodgkins Lymphoma Hodgkins LymphomaHodgkins Lymphoma
    • 122. 123123 CHRONIC LYMPHOCYTIC LEUKEMIACHRONIC LYMPHOCYTIC LEUKEMIA  Most common form of Leukemia in USMost common form of Leukemia in US  Usually seen in pts > 50 yrs oldUsually seen in pts > 50 yrs old  Most pts are asymptomatic at presentationMost pts are asymptomatic at presentation  Diagnosis made by flow cytometryDiagnosis made by flow cytometry  Abnormal cells resemble mature smallAbnormal cells resemble mature small lymphocyteslymphocytes  Symptoms: LA, SM, Anemia, ThrombocytopeniaSymptoms: LA, SM, Anemia, Thrombocytopenia  Associated with Autoimmune disordersAssociated with Autoimmune disorders  Median Survival > 10 yearsMedian Survival > 10 years
    • 123. 124124 CHRONIC LYMPHOCYTIC LEUKEMIACHRONIC LYMPHOCYTIC LEUKEMIA Infections and Indications for RxInfections and Indications for Rx  Hypogammoglobulinemia- Can give IVIGHypogammoglobulinemia- Can give IVIG – Staph PneumoniaeStaph Pneumoniae – Staph AureusStaph Aureus – Hemophilus influenzaHemophilus influenza  Indications for TreatmentIndications for Treatment – Anemia Hb < 10Anemia Hb < 10 – Thrombocytopenia Platelets < 100,000Thrombocytopenia Platelets < 100,000 – Constitutional SymptomsConstitutional Symptoms – Bulky LymphadenopathyBulky Lymphadenopathy – Richter’s TranformationRichter’s Tranformation
    • 124. 125125 CHRONIC MYELOGENOUS LEUKEMIACHRONIC MYELOGENOUS LEUKEMIA  15 to 20 percent of cases of leukemia in adults15 to 20 percent of cases of leukemia in adults  Annual incidence of 1 to 2 cases per 100,000Annual incidence of 1 to 2 cases per 100,000  Male predominanceMale predominance  Median age at presentation- 50 yearsMedian age at presentation- 50 years  Uncontrolled production of maturingUncontrolled production of maturing granulocytes, predominantly neutrophils, butgranulocytes, predominantly neutrophils, but also eosinophils and basophils.also eosinophils and basophils.  Three phases: Chronic phase (85% atThree phases: Chronic phase (85% at Diagnosis), Accelerated phase, Blast crisis.Diagnosis), Accelerated phase, Blast crisis.
    • 125. 126126 CHRONIC MYELOGENOUS LEUKEMIACHRONIC MYELOGENOUS LEUKEMIA
    • 126. 127127 CHRONIC MYELOGENOUS LEUKEMIACHRONIC MYELOGENOUS LEUKEMIA Symptoms:Symptoms: SM (60%), leukocytosis, thrombocytosis, BlastSM (60%), leukocytosis, thrombocytosis, Blast crisis- fever, night sweats, bone pain,crisis- fever, night sweats, bone pain, ecchymosesecchymoses Diagnosis:Diagnosis: Philadelphia chromosome (9;22) translocationPhiladelphia chromosome (9;22) translocation Treatment:Treatment: Tyrosine kinase inhibitors (Imatinib, Desatinib)Tyrosine kinase inhibitors (Imatinib, Desatinib) HydroxyureaHydroxyurea Interferon Alpha with or without cytarabineInterferon Alpha with or without cytarabine Stem Cell TransplantStem Cell Transplant
    • 127. 128128 CHRONIC LYMPHOCYTIC LEUKEMIACHRONIC LYMPHOCYTIC LEUKEMIA  Most common form of Leukemia in USMost common form of Leukemia in US  Usually seen in pts > 50 yrs oldUsually seen in pts > 50 yrs old  Most pts are asymptomatic at presentationMost pts are asymptomatic at presentation  Diagnosis made by flow cytometryDiagnosis made by flow cytometry  Abnormal cells resemble mature smallAbnormal cells resemble mature small lymphocyteslymphocytes  Symptoms: LA, SM, Anemia, ThrombocytopeniaSymptoms: LA, SM, Anemia, Thrombocytopenia  Associated with Autoimmune disordersAssociated with Autoimmune disorders  Median Survival > 10 yearsMedian Survival > 10 years
    • 128. 129129 AMLAML Definition, Manifestations, OutcomeDefinition, Manifestations, Outcome  Uncontrolled clonal proliferation andUncontrolled clonal proliferation and accumulation of neoplastic hematopoieticaccumulation of neoplastic hematopoietic precursorsprecursors  Inhibition of normal hematopoiesisInhibition of normal hematopoiesis  Defective maturationDefective maturation  MultilineageMultilineage  Extramedullary diseaseExtramedullary disease  Outcome has improved in younger adults, butOutcome has improved in younger adults, but much less so for older adultsmuch less so for older adults
    • 129. 130130 FAB ClassificationFAB Classification FABFAB SubtypeSubtype MorphologyMorphology FrequencyFrequency (%)(%) M0M0 Agranular myeloblastsAgranular myeloblasts 2-32-3 M1M1 Acute myeloblastic leukemiaAcute myeloblastic leukemia without maturationwithout maturation 2020 M2M2 Acute myeloblastic leukemiaAcute myeloblastic leukemia with maturationwith maturation 25 – 3025 – 30 M3M3 Acute promyelocytic leukemiaAcute promyelocytic leukemia 8 – 158 – 15 M4M4 Acute myelomonocyticAcute myelomonocytic leukemialeukemia 20 – 2520 – 25 Bennett et al, Br J Haematol, 1976
    • 130. 131131 FAB Classification FABFAB SubtypeSubtype MorphologyMorphology FrequencyFrequency (%)(%) M4E0M4E0 Myelomonoblasts with abnMyelomonoblasts with abn eoseos 55 M5M5 Acute monocytic leukemiaAcute monocytic leukemia monoblasts, promonocytesmonoblasts, promonocytes or monocytes comprise 80%or monocytes comprise 80% of nonerythroidsof nonerythroids 1010 M6M6 ErythroleukemiaErythroleukemia >50% of nucleated cells>50% of nucleated cells erythroiderythroid 55 M7M7 Acute megakaryocyticAcute megakaryocytic leukemialeukemia 1-31-3 Bennett et al, Br J Haematol, 1979
    • 131. 132132 Leukemic Myeloblast Auer Rod in Leukemic Myeloblast
    • 132. 133133 M4 M5
    • 133. 134134 M6
    • 134. 135135 AML- Acute Myelogenous LeukemiaAML- Acute Myelogenous Leukemia Risk factorsRisk factors Ionizing radiationIonizing radiation Chemical exposure: benzeneChemical exposure: benzene Previous chemotherapy:Previous chemotherapy: Melphalan, Cyclophosphamide, EtoposideMelphalan, Cyclophosphamide, Etoposide Genetic factors:Genetic factors: Downs syndrome, Klinefelter’s, Fanconi’s anemiaDowns syndrome, Klinefelter’s, Fanconi’s anemia MDSMDS
    • 135. 136136 AML- Acute Myelogenous LeukemiaAML- Acute Myelogenous Leukemia PrognosisPrognosis AgeAge Performance statusPerformance status Secondary AMLSecondary AML Previous chemotherapyPrevious chemotherapy WBC >20,000/WBC >20,000/µµLL
    • 136. 137137 1)Good prognosis features:1)Good prognosis features: cytogenetic interpretation (t15:17, t8:21 or i16)cytogenetic interpretation (t15:17, t8:21 or i16) 60% of patients are cured with multiple cycles of high dose60% of patients are cured with multiple cycles of high dose AraCAraC 2)For patients with normal cytogenetics (intermediate risk)2)For patients with normal cytogenetics (intermediate risk) approximately 70% achieve a complete remission andapproximately 70% achieve a complete remission and 40% of complete responders (i.e. 28% overall) are cured.40% of complete responders (i.e. 28% overall) are cured. 3)Poor prognostic features for AML include WBC>10,0003)Poor prognostic features for AML include WBC>10,000 or platelets <40,000.or platelets <40,000. -CALGB AML Study (>1200 patients)-CALGB AML Study (>1200 patients) 1)1)5-year survival for good risk cytogenetics= 55%.5-year survival for good risk cytogenetics= 55%. 2)2)5-year survival for intermediate risk= 24%.5-year survival for intermediate risk= 24%. 3)3)5-year survival for poor risk= 5%.5-year survival for poor risk= 5%.
    • 137. 138138 Clinical PresentationClinical Presentation Fatigue, dyspnea, pallorFatigue, dyspnea, pallor Petechiae, hematoma, bleedingPetechiae, hematoma, bleeding Recurrent infectionsRecurrent infections Not common to see splenomegalyNot common to see splenomegaly Leptomeningeal involvementLeptomeningeal involvement Neurologic abnormalities- may be signal ofNeurologic abnormalities- may be signal of intracranial bleedintracranial bleed Tumor lysis syndromeTumor lysis syndrome
    • 138. 139139 Major ClinicalMajor Clinical FeaturesFeatures  Incidence/PrevalenceIncidence/Prevalence Estimated new cases in US in 2002: 10,600Estimated new cases in US in 2002: 10,600 80% >15 years old; median age 70 years80% >15 years old; median age 70 years Estimated deaths in US in 2002: 7,400Estimated deaths in US in 2002: 7,400 Mortality in US = 7/100,000/yearMortality in US = 7/100,000/year  PancytopeniaPancytopenia  Extramedullary diseaseExtramedullary disease Skin, gingiva – M5Skin, gingiva – M5 CNS – M5, ? Increased in M4EOCNS – M5, ? Increased in M4EO Orbit – M2 with t(8;21) and CD56 expressionOrbit – M2 with t(8;21) and CD56 expression
    • 139. 140140 Major Clinical FeaturesMajor Clinical Features  HyperleukocytosisHyperleukocytosis – microgranular APL, monocytic differentiationmicrogranular APL, monocytic differentiation – 11q23 and inv(16)(p13;q22)11q23 and inv(16)(p13;q22) – >100,000 myeloblasts/>100,000 myeloblasts/µµLL – leukostasis (obstruction, vascular injury,leukostasis (obstruction, vascular injury, hypoxemia)hypoxemia) – leukaphoresis, hydroxyurea, RT, chemotherapyleukaphoresis, hydroxyurea, RT, chemotherapy  Coagulation abnormalitiesCoagulation abnormalities – abn plt functionabn plt function – consumption: APL > M5, M4consumption: APL > M5, M4  Metabolic abnormalitiesMetabolic abnormalities – tumor lysis syndrometumor lysis syndrome – renal tubular dysfunctionrenal tubular dysfunction  Typhlitis (mimics appendicitis)Typhlitis (mimics appendicitis)
    • 140. 141141 Chloroma Gingival Hyperplasia in M5
    • 141. 142142 DiagnosisDiagnosis Peripheral smearPeripheral smear Identification of myeloblastsIdentification of myeloblasts Bone Marrow BiopsyBone Marrow Biopsy CBC: WBC can be high or lowCBC: WBC can be high or low Blast count high or lowBlast count high or low ThrombocytopeniaThrombocytopenia AnemiaAnemia Increased LDH, Uric Acid, K, PO4Increased LDH, Uric Acid, K, PO4
    • 142. 143143 Common Induction RegimenCommon Induction Regimen  Daunorubicin 45-60 mg/mDaunorubicin 45-60 mg/m22 /d IV x 3 days/d IV x 3 days  Cytarabine 100 mg/mCytarabine 100 mg/m22 /d CI x 7 days/d CI x 7 days
    • 143. 144144 Tumor Lysis SyndromeTumor Lysis Syndrome Rapid cell turnoverRapid cell turnover Prevent with Fluids, Allopurinol, SodiumPrevent with Fluids, Allopurinol, Sodium BicarbonateBicarbonate TestTest ResultResult Uric AcidUric Acid IncreasedIncreased PotassiumPotassium IncreasedIncreased PhosphatePhosphate IncreasedIncreased CalciumCalcium DecreasedDecreased
    • 144. 145145 PLASMA CELL DISORDERSPLASMA CELL DISORDERS Multiple MyelomaMultiple Myeloma PlasmacytomaPlasmacytoma MGUS (Monoclonal Gammopathy ofMGUS (Monoclonal Gammopathy of Undetermined Significance)Undetermined Significance) POEMS (Polyneuropathy w/Organomegaly,POEMS (Polyneuropathy w/Organomegaly, Endocrinopathy, M-Protein production, and SkinEndocrinopathy, M-Protein production, and Skin changes)changes) Waldenstrom’s MacroglobulinemiaWaldenstrom’s Macroglobulinemia Amyloidosis (ASSOCIATED WITH FACTOR XAmyloidosis (ASSOCIATED WITH FACTOR X DEFICIENCY) types- AA, AL, Familial, Dx:DEFICIENCY) types- AA, AL, Familial, Dx: Fibers stain with Congo Red- Apple greenFibers stain with Congo Red- Apple green BirefringenceBirefringence CryoglobulinemiaCryoglobulinemia
    • 145. 146146 PLASMA CELL DISORDERSPLASMA CELL DISORDERS If Suspected:If Suspected: 1.1. Quantitate Immunoglobulin production-Quantitate Immunoglobulin production- SPEP, SIFE, UPEP, UIFESPEP, SIFE, UPEP, UIFE 2.2. BM BiopsyBM Biopsy 3.3. Skeletal survey, Abdominal Fat PadSkeletal survey, Abdominal Fat Pad Biopsy if MM present (r/o Amyloid)Biopsy if MM present (r/o Amyloid)
    • 146. 147147 MULTIPLE MYELOMAMULTIPLE MYELOMA  Second most common hematologic malignancySecond most common hematologic malignancy  More common in African AmericansMore common in African Americans Associated withAssociated with  Monoclonal SpikeMonoclonal Spike  Lytic Lesions – increased risk of fracture, Cord CompressionLytic Lesions – increased risk of fracture, Cord Compression  Renal insufficiencyRenal insufficiency  Bence Jones ProteinuriaBence Jones Proteinuria  HypercalcemiaHypercalcemia  HyperviscosityHyperviscosity  Peripheral Smear: Rouleaux FormationPeripheral Smear: Rouleaux Formation  Increased Risk of Bacterial InfectionsIncreased Risk of Bacterial Infections Treat with Stem Cell Transplant, Thalidomide, ThalidomideTreat with Stem Cell Transplant, Thalidomide, Thalidomide derivatives, Melphalan, Steroids, Bisphosphonates (watchderivatives, Melphalan, Steroids, Bisphosphonates (watch for osteonecrosis of jaw)for osteonecrosis of jaw)
    • 147. 148148 MULTIPLE MYELOMAMULTIPLE MYELOMA
    • 148. 149149 MM – Monoclonal BandMM – Monoclonal Band
    • 149. 150150 Multiple MyelomaMultiple Myeloma MajorMajor CriteriaCriteria Dx madeDx made with 1Mwith 1M +1m or 3m+1m or 3m 1. Plasmacytoma1. Plasmacytoma 2. BM with >30%2. BM with >30% Plasma cellsPlasma cells 3. M protein3. M protein IgG >3.5 g/dLIgG >3.5 g/dL IgA >2.0 g/dLIgA >2.0 g/dL minorminor criteriacriteria 1.1. BM with >10-30%BM with >10-30% Plasma cellsPlasma cells 2. M protein less than2. M protein less than aboveabove 3. Lytic bone lesion3. Lytic bone lesion 4. Decreased4. Decreased
    • 150. 151151 Multiple MyelomaMultiple Myeloma Lytic lesionsLytic lesions
    • 151. 152152 Severe aplastic anemiaSevere aplastic anemia  Disease of bone marrow – etiology eitherDisease of bone marrow – etiology either toxin, genetic, or autoimmunetoxin, genetic, or autoimmune  Incidence: 3 per million per yearIncidence: 3 per million per year  Genetic include Fanconi anemia –Genetic include Fanconi anemia – accounts for 20%accounts for 20%  Radiation, chemicals, or viruses for toxinRadiation, chemicals, or viruses for toxin (Benzene, Radiation, Parvo B19,(Benzene, Radiation, Parvo B19, Hepatitis)Hepatitis)
    • 152. 153153 Treatment of SAATreatment of SAA  Bone Marrow Transplant – if matchedBone Marrow Transplant – if matched related donor around 70-85% cure andrelated donor around 70-85% cure and little chance of leukemia.little chance of leukemia.  Immunosuppressive therapy –Immunosuppressive therapy – cyclosporin, antithymocyte globulin, andcyclosporin, antithymocyte globulin, and prednisoneprednisone  May add erythropoietin, and NeupogenMay add erythropoietin, and Neupogen  Supportive with transfusion and chelationSupportive with transfusion and chelation
    • 153. 154154 Thalassemia ScreeningThalassemia Screening > 78 > 27 A+A2 < 3% < 78 < 27 A+F(0.1-7%) + A2 > 3.5% β-THAL Carrier MCV Fl MCH pg Hb pattern

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