Evaluation of Anemia Md. Shafiqul Bari Associate professor (Medicine) SOMC
Definition Anemia is operationally defined as a reduction in one or more of the major RBC measurements Hemoglobin concentration Hematocrit or RBC count
WHO criteria Hemoglobin level <13 g/dl in men and <12 g/dl in women
It is a clinical sign of disease Almost always a secondary disorder Need to look for the underlying cause!
Objectives of evaluation Two main objectives First, it is essential to determine the degree of disability Second, as much information as possible about the likely cause of the anemia There is no place for the blind treatment of anemia without first establishing the cause
Clinical assessment History?Acute blood loss/chronic blood loss?anorexia and weight loss Chronic inflammation, infection, malignancy or CKD?dark urine intravascular hemolysis
?bleeding manifestations aplastic anemia or acute leukemia?fever leukemia, lymphoma, aplastic anemia, chronic inflammation, infection, malignancy?drug /toxin history: drug/toxin induced
Physical findings?koilonychia IDA?mild jaundice hemolytic anemia?htn CKD?Anemia with glossitis IDA, megaloblastic anemia
?lymphadenopathy leukemia, lymphoma, malignancy, inflammation or infection?anemia with bony tenderness acute leukemia or MM?features of PN vit B12 deficiency
Haematological 3 primary measures RCC Hb PCV or haematocrit RBC indices Lab evaluation MCV, MCH, MCHC & RDW Reticulocyte count Blood smear
The Three Primary Measures Measurement Normal Range A. RBC count (RCC) 5 million 4 to 5.7 B. Hemoglobin 15 g% 12 to 17 C. Hematocrit (PCV) 45 38 to 50 A x 3 = B x 3 = C - This is the rule of thumb
PCV or Hematocrit 57% Plasma 1% Buffy coat WBC & platelets 42% Hct (PCV)
The Three Derived Indicies Measurement Range Normal A. RCC 5 million 4 to 5.7 B. Hemoglobin 15 g% 12 to 17 C. Hematocrit 45 % 38 to 50 MCV C A x 10 = 90 fl MCH B A x 10 = 30 pg MCHC (%) B C x 100 = 33%
MCV MCV is average size of RBC If 80-100 fl, normal range, RBCs considered normocytic If < 80 fl are microcytic If > 100 fl are macrocytic Not reliable when have marked anisocytosis 14
Inflammation Thal trait Iron deficiency Myelodysplasia Hemolysis Normal Pernicious anemia Aplastic anemia 50 70 90 110 130 MCV
MCH MCH is average weight of hemoglobin per RBC. MCH: 30 ± 3 pg - normal 16
MCHC MCHC is average hemoglobin concentration per RBC MCHC: 33 ± 2% - normal If MCHC is normal, cell described as normochromic If MCHC is less than normal, cell described as hypochromic There are no hyperchromic RBCs 17
RDW Most automated instruments now provide an RBC Distribution Width (RDW) An index of RBC size variation May be used to quantitate the amount of anisocytosis on peripheral blood smear Normal range is 11.5% to 14.5% for both men and women 18
Reticulocytes Reticulin - insoluble ribosomal RNA Present after extrusion of nucleus until degradation of rrna. Retics normally spend 3.5 days in marrow, 1 day in blood Reticulocytes demonstrated by Crystal Violet stain of blood smear (most labs now use flourescent dye and automated cell counter)
Reticulocyte count - 9%, Hb - 7.5 gm%, hematocrit 23% Correction #1 for anemia: This correction produces the corrected reticulocyte count = RC x pts Hb or Hct/expected Hb or Hct = 9 x (7.5/15) [or x (23/45)]= 4.5%
Correction #2 for longer life of prematurely released reticulocytes in the blood:this correction produces the RPI RPI= corrected reticulocyte count/correction factor= 4.5/2=2.25 CF: Hct 41-50 (1), 30-40 (1.5), 20-29 (2), 10-19 (2.5)
An approach to anemia is based on asking 3 main questions: 1. Reticulocyte count? (Bone marrow function) 2. MCV? 3. Involvement of additional lineages?
Differential diagnosis guided by retic index and MCV Hyporegenerative Microcytic Macrocytic Normocytic Hyperregenerative
Microcytic, hyporegenerative anemia Microcytosis implies defective hemoglobin production Iron deficiency (R/O GI bleeding!) Thalassemia Inflammation Sideroblastic anemia (myelodysplasia, lead poisoning etc)
Macrocytic, hyporegenerative anemia Megaloblastic: B12/folate deficiency Myelodysplastic syndrome Drug-induced Non-megaloblastic: Liver disease Alcohol Hypothyroidism
Normocytic, hyporegenerative anemia Marrow disorders Aplastic anemia Pure red cell aplasia Myelophthisic state Myelodysplasia Leukemia Low EPO state Uremia, inflammation, endocrinopathy, HIV infection, etc
Hyperregenerative anemia Blood loss Hemolysis Immune Mechanical/microangiopathic Hereditary (hemoglobinopathy, membrane defect, enzyme deficiency) Acquired membrane defect (PNH, spur cells) Infection (malaria, Clostridia, babesiosis)
Additional lineage(s) involvement: Leukopenia Aplastic anemia Malignancy Chemotherapy Hypersplenism Drug-related Megaloblastic anemia
Thrombocytopenia Aplastic anemia Malignancy Chemotherapy Hypersplenism Drug-related Megaloblastic anemia TTP DIC
Lab assessment of microcytic anemia Test Fe Defic Anemia of inflammation Thal Ferritin Low* NL/high NL Serum Fe Low Low NL TIBC High NL/low* NL Retic index NL/low NL/low NL/high *best discriminators of Fe defic vs anemia of inflammation
Hemolytic anemia laboratory evaluation Blood smear (fragments, spherocytes, sickle cells, malaria, etc) Nonspecific indicators of hemolysis: LDH, bilirubin Direct Coombs test Warm antibody = IgG C3 Cold antibody = C3 only (cold agglutinin) Indicators of intravascular hemolysis: haptoglobin, urine hemosiderin, plasma or urine hemoglobin Other: Hgb electrophoresis, rbc enzyme levels, G6PD, osmotic fragility, PNH testing etc
Indications for BM biopsy Retic index not appropriately increased No evidence of iron/b-12/folate deficiency, renal failure, endocrinopathy, inflammation or other low EPO state Poor response to EPO, iron or vitamin replacement WBC/plts/diff abnormal, monoclonal gammopathy, or other peripheral blood evidence of marrow disorder Would you treat leukemia/mds or other neoplastic disorder if you found it?
Other investigations History & examination findings Results of primary investigations
CONCLUSION If Hb% is low Do not start on Iron straight away Ask for RCC, Hematocrit Derive MCV, MCH, MCHC Order for Reticulocyte count Is RPI < 2 % or > 2% Thoroughly look for blood loss acute / chronic / occult Is it hyporegenarative or hyperregenarative anemia? If hypo regenerative Microcytic, normocytic or Macrocytic? (MCV, RDW)
If microcytic IDA or others Sr Ferritin TIBC, BM Iron If macrocytic Megaloblastic (B12, FA) or Normoblastic BM If normocytic Anemia of chr. Disease Liver, CKD, Ca or aplastic anemia Peripheral smear study for RBC size, shape, colouration etc. If retic. count is - HA work up; Hb EP, spl. tests