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Anemia.ppt - Anemia Evaluation

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  • Examination of smear bya physician who is aware of pt’s clinical condition is very useful. Even highly skilled lab technitians could overlook subtle changes. Indices are machine generated by averaging analysis.
  • Mention on PLT on oil emersion view 7-20. Check for clumping when low PLT (EDTA induced clumping).
  • Ferritin sen=90% spec=80%
  • Insufficient production of protoporphyrin to utilize the iron or unavailability of ferrous iron for insertion into protoporphyrin
  • Three part (B12; B12 + IF; Antibiotic)
  • Ruloux in MM Auer rods in AML

Anemia.ppt - Anemia Evaluation Anemia.ppt - Anemia Evaluation Presentation Transcript

  • Systematic Approach in Anemia Evaluation and Review of Peripheral Smears Jun W. Kim, MD Family Medicine Residency Dewitt Army Community Hospital
  • Objective
    • Recognize abnormal peripheral blood smear
    • Review differentials through systematic approach
  • Approach to Dx
    • Hx- age, duration, onset, subjacent illness, blood loss (GI, menstruation, surgery…), diet, medications, toxic exposure, occupation, Family Hx, Social Hx
    • PE- complete exam including skin (jaundice, petechiae), HEENT, Abdomen (hepatosplenomegally), lymphatics, rectal, and pelvic
  • Basic Labs to Start
    • Repeat CBC w/ manual differential
    • (WBC, RBC, HCT, HGB, PLT, indices- MCH, MCHC, MCV, RDW)
    • Peripheral Smear
    • Reticulocyte count
  • Reticulocyte count
    • Retic count = % immature RBC
    • Normal 0.5-1.5% (for non-anemic)
    • <1% Inadequate production
    • >=1% Increased production (? adequacy)
  • Reticulocyte Correction
    • %Retic count frequently overestimates
    • Retic count should be compared to non-anemic RBC count to assess adequacy of response
    • Corrected Retic count = %Retic X HCT/45
  • Reticulocyte Production Index
    • Correction for left shift – Retic lifespan is increased in blood
    • RPI = % Retic X Hct/45 X 1/CF
    • Hct Correction factor (CF)
    • 40-45 1.0
    • 35-39 1.5
    • 25-34 2.0
    • 15-24 2.5
    • Normal RPI = 1 (for non-anemic pt)
    • RPI < 2 : hypoproliferative
    • RPI >=2 : hyperproliferative
  • Retic Production Index
    • Hypoproliferative
    • - Iron def. anemia
    • - B12/folate def.
    • - Chronic disease
    • - Sideroblastic anemia
    • - Aplastic anemia
    • - Myeloproliferative
    • Hyperproliferative
    • - Hemolytic disease
    • - Hemoglobinopathy (including thalassemia)
  • Peripheral smear
    • Optimal area for review
    • RBC morphology, WBC differential, PLT (clumping?)
  • RBC morphology
    • 7-9  m with 1/3 central palor
    • Lifespan of 110-120 days
    • About the size of nucleus of normal lymphocyte
    • Poikilocytosis & Anisocytosis
  • Basophilic stippling
    • Precipitated RNA
    • lead or heavy metal poisoning
    • ETOH abuse
    • Hemolytic anemia
  • Burr cells
    • Altered lipid in cell membrane
    • artifact
    • Uremia
    • Renal failure
    • gastric CA
    • transfused old blood
  • Elliptocytes/ovalocytes
    • Abnormal cytoskeletal proteins
    • Hereditary elliptocytosis
  • Howell Jolly body
    • Nuclear remnant - DNA
    • hemolytic anemia
    • absent or hypofunction spleen
  • Schistocyte/helmet cells
    • Fragmented (mechanical or phagocytosis)
    • DIC
    • TTP
    • HUS
    • Vasculitis
    • prosthetic heart valve
    • severe burns
  • Sickle cells
    • Molecular aggregation of Hgb-S
    • SS, SC, S-thal
    • rarely S-trait
  • NRBC
    • Common in newborn
    • severe degree of hemolysis
  • Spherocyte
    • Absent central palor
    • look smaller
    • Hereditary spherocytosis
    • immune hemolytic anemia
  • Stomatocyte
    • Mouth like
    • Membrane defect
    • Smear artifact
    • Hereditary stomatocytosis
    • Liver disease
  • Target cells
    • Increased redundancy of membrane
    • hemoglobinopathies
    • thalassemia
    • liver disease
  • Tear drop cells
    • Distorted drop shaped
    • Smear artifact
    • myelofibrosis
    • promyeloblastic leukemia
    • space occupying lesions of marrow
  • Differentials
    • H&P
    • Indices (MCV, MCHC, RDW)
    • RBC Morphology
    • Retic response
    • Other labs as needed
  • Anemia Differential Dx by Flow Chart MCV/smear Micro Normo Macro Iron panel Retic Low Retic High High Low Iron/B12/Folate *Occult Blood Loss Yes No Coombs (+) Coombs (-) Go to *Occult Blood Loss B12/Folate B12 Low Folate/Low Normal MMA/Homocysteine MMA high – B12 Low Homocysteine high – Folate Low Normal – Go to ** **Normal Bone Marrow Bx Anemia of Chronic Dis.
  • First use size ( MCV ) to sort the Differential Dx MCV Micro Normo Macro
  • Microcytic anemia
    • Get Iron panel- serum iron, TIBC, ferritin
  • Iron def. Anemia
    • Low Retic count
    • High RDW
    • Due to chronic blood loss
    • Diet deficiency
  • Thalassemia
    • Normal to inc. RPI
    • Normal RDW
    • Target cells
    • Mentzer index <13
    • =MCV/RBC
    • Youden’s index - using RDW & Mentzer index
    • - sensitivity = 82%
    • - specificity = 80%
    • confirm w/ Hgb electrophoresis
  • Thalassemia continues
    • Alpha-thalassemia
    • SE Asia & Africa
    • aaaa - normal
    • aaaa^ - silent carrier
    • aaa^a^ - trait (mild)
    • aa^a^a^ - HbH (Bart) hemolytic disease
    • a^a^a^a^ - hydrops fetalis (stillborn)
    • Beta-thalassemia
    • Mediterranean
    • Beta-thal minor
    • one beta gene,
    • increased HbA2/HbF
    • Beta-thal major
    • 2 beta genes,
    • severe, failure to thrive, sig HbF
  • Sideroblastic anemia
    • Accumulation of mitochondrial iron in erythroblasts     
    • Hereditary
    • Drugs - INH, lead, zinc, alcohol, chloramphenicol, cycloserine, plavix
    • Hypothermia
    • Confirm w/ BM Bx
  • Sample question #1
    • Anemia of chronic disease is due to inadequate production of, or poor response to, which one of the following?
    • A. Iron
    • B. Folate
    • C. Erythropoietin
    • D. Ferritin
    • E. Hemosiderin
    AFP, Nov. 15, 2000
  • Anemia of chronic disease
    • Infections: TB, SBE, osteo, chronic UTI or pyelo, fungal
    • Malignancy: mets, leukemia, lymphoma, myeloma
    • Chronic inflammatory disorders: RA, SLE, Sarcoid, collagen vascular disease, polymyalgia rheumatica, chronic hepatitis, decubitus ulcer
  • Macrocytic anemia Macro RPI >= 2 RPI < 2 Check Occult Blood Loss Check B12 and folate No Yes Coombs’ test
  • Macrocytic: RPI < 2 B12/Folate B12 Low Normal Folate Low MMA High MMA Homocysteine Normal Homocysteine High Consider Liver, Renal, Thyroid, Alcohol, Chronic dis. Consider Bone Marrow Bx
  • Macrocytic: RPI < 2 Megaloblastic Anemia
    • B12
    • Inadequate absorption
    • Synthesized by bacteria
    • Meat, fish, dairy (strict vegans)
    • Absorbed as B12-IF complex in ileum (gastrectomy)
    • Ca++ and pH dependant (PPI)
    • Folate
    • Inadequate intake
    • Synthesized by plants and micro-organism
    • Green leafy vege’s
    • Fruits
    • Absorbed in jejunum
  • Sample question #2
    • Which of the following tests can be useful in determining if an elderly patient has folate deficiency?
    • A. RBC folate concentration
    • B. Serum homocysteine level
    • C. Serum ferritin level
    • D. Serum methylmalonic acid level
    AFP, Oct. 1, 2000
  • Macrocytic: RPI < 2 Megaloblastic Anemia
    • Smear
    • Macro-ovalocytic
    • Polychromasia
    • Hypersegmented neutrophil
    • Other Labs
    • Homocysteine – Folate def.
    • Methylmalonic acid – B12 def.
    • Intrinsic Factor Ab test – very specific for pernicious anemia but only 50% sensitive
    • Parietal cell AB test – quite sensitive (90%) but not specific
    • Schilling test
  • Macrocytic: RPI < 2 Non-megaloblastic
    • Consider Liver, Renal, Endocrine (thyroid), alcohol, drugs
    • Consider anemia of chronic disease
    • Get Bone Marrow Biopsy
    • Myelodysplastic
    • Myeloproliferative - Leukemia, Lymphoma, Multiple Myeloma
  • Macrocytic: RPI < 2 continues Aplastic Anemia
    • Fanconi anemia – congenital
    • Direct stem cell destruction – external radiation
    • Drugs - chloramphenicol , gold, sulfonamides, felbamate
    • Other Toxins - Solvents, degreasing agents, pesticides
    • Viral infection - parvovirus B19, HIV, other
    • Idiopathic
  • Macrocytic: RPI >= 2 Occult Blood Loss? Yes No Investigate source Coombs’ (DAT) Check for Hemolysis Peripheral smear
  • Sample question #3
    • Of the following laboratory results, which one does not occur in hemolytic anemia?
    • Reticulocytosis
    • Increased unconjugated bilirubin
    • Increased haptoglobin
    • Increased LDH
    • Hemosiderinuria
    AFP, June 1, 2004
  • Macrocytic: RPI >= 2 Hemolytic Anemia
    • Other Lab Characteristics
    • RBC morphology
    • Serum haptoglobin
    • Serum LDH
    • Unconjugated bilirubin
    • Hemoglobinuria
    • Hemosiderinuria
  • Macrocytic: RPI >= 2 Hemolytic Anemia Coombs’ (DAT) Positive Negative Immune Hemolysis Drug related Hemolysis Transfusion, Infection, Cancer Hemoglobinopathy, G6PD, PK, Spherocytosis, Eliptocytosis, PNH, TTP, DIC
  • Coombs’ positive with Spherocytes Autoimmune hemolytic anemia
    • Warm AIHA
    • Abrupt onset
    • IgG
    • Anti-Rh, e, C, c, LW, U
    • Jaundice
    • Splenomegaly
    • SLE, CLL, Lymphoma
    • Drugs: methyl-dopa, mefenamic acid, cimetidine, cefazolin
    • Cold AIHA
    • Insidious onset
    • IgM, complement
    • Anti-I, I, Pr
    • Cold agglutinin titer
    • Absent jaundice
    • Mycoplasma
    • Virus
  • Coombs’ positive with Spherocytes Other immune hemolytic anemia
    • Alloantibody hemolytic anemia
    • Transfusion reaction
    • Feto-maternal incompatibility (Kleihauer-Betke test)
    • Drug related Hemolytic anemia
    • Toxic immune complex (drug+Ab+C3)
    • - Quinine, Quinidine, Rifampin, INH, Sulfonamides,
    • Tetracyclin
    • Hapten formation (anti-IgG)
    • - PCN, methicillin, ampicillin
  • Coombs’ Negative Hemolytic anemia
    • Episodic - G6PD def., PNH
    • Hemoglobinopathy
    • - Sickle, crystals or target cells
    • Elliptocytosis
    • Spherocytosis
    • DIC, TTP
  • Coombs’ Negative Hemolytic Anemia Membrane Defects
    • Spherocytosis
    • Common among Northern European
    • Autosomal dominant
    • Decreased spectrin
    • Osmotic fragility test
    • Autohemolysis test
    • Elliptocytosis
    • 90% with no clinically significant hemolysis
    • Abnormal membrane protein
  • Coombs’ Negative Hemolytic Anemia Deficiency of RBC Enzymes
    • Pyruvate Kinase Def.
    • Severe anemia in newborns
    • Adults symptomatic
    • Jaundice
    • Splenomegaly
    • Fluorescent screening test
    • Quantitative test
    • G6PD Def.
    • X-linked
    • Mediterranean, African American, and Asian
    • Oxidant drugs – ASA, quinine, primaquine, chloroquine, sulfacetamide, sulfamethoxazole, nitrofurantoin, chloramphenicol, procainamide, quinidine
    • Infections
    • Quantitative test
  • Coombs’ Negative Hemolytic Anemia Hemoglobinopathy
    • HbS disease
    • Valine substitution for Glutamic acid at the 6 th position of b-chain
    • Sickle crises
    • Severe anemia
    • Screening test - Na Metabisulfite solubility
    • Hgb electrophoresis
  • Coombs’ Negative Hemolytic Anemia Hemoglobinopathy continues
    • HbC disease
    • Mild hemolysis
    • Splenomegaly
    • Lysine substitution
    • HbC crystals “bar of gold”
    • Hgb electrophoresis
    • HbSC disease
    • Sickle and SC crystals “Washington monument”
    • Less crises
    • More retinopathy/aseptic necrosis
  • Coombs’ Negative Hemolytic Anemia P aroxysmal N octurnal H emoglobinuria
    • Rare chronic condition
    • Recurrent abdominal pain, vomiting, headaches, eye pain, thrombophlebitis
    • Episodic Hgb in urine, Hemosiderinuria
    • Abnormal cell membrane - increased lysis by complement
    • Screening - Sucrose hemolysis test
    • Confirm - Acid hemolysis test (Ham’s test)
  • Coombs’ Negative Hemolytic Anemia Fragmented RBC’s & Thrombocytopenia
    • TTP-HUS
    • Thrombocytopenia
    • Microangiopathic hemolytic anemia
    • Neurologic symptoms and signs
    • Renal failure
    • Fever
    • Idiopathic - 37 %
    • Drug-associated - 13 %
    • Autoimmune disease - 13 %
    • Sepsis - 9 %
    • Pregnancy - 7 %
    • Bloody diarrhea - 6 %
    • Hematopoietic cell
    • transplantation - 4 %
    • DIC
    • Depletion of clotting factor
    • (TTP – normal)
    • Thrombocytopenia
    • Bleeding (64%)
    • Renal dysfunction (25%)
    • Hepatic dysfunction (19%)
    • Respiratory dysfunction (16%)
    • Shock (14%)
    • Thromboemboli (7%)
    • Central nervous system involvement (2%)
    • Sepsis, trauma, malignancy
  • TTP-HUS / DIC
  • Normocytic Anemia Hyperproliferative (RPI >= 2)
    • Use same flow chart as macrocytic hyperproliferative
    Occult Blood Loss? Yes No Investigate source Coombs’ (DAT) Check for Hemolysis Peripheral smear
  • Normocytic Anemia Hypoproliferative (RPI < 2)
    • 1. Get iron panel (ferritin)/B12/folate
    • - some clue from RBC indices to check early disease, high RDW, peripheral smear.
    • 2. Consider liver, renal, drugs, toxin, endocrine (thyroid), and anemia of chronic disease.
    • 3. Get BM bx
    • - Leukopenia, thrombocytopenia, CRI < 0.1
    • - Aplastic anemia/pancytopenia
    • - Abnormal (immature) cells on smear
  • Questions?