Differential diagnosis of anemia

"Courage is the price that life exacts for granting peace. The soul that knows it not, knows no release from little things." - Amelia Earhart Anemia – A discussion with Pathologist Dr. Venkatesh M. Shashidhar Senior Lecturer in Pathology Fiji School of Medicine Blood Smear - Normal White Blood Cells: RBC disorders (Anemias) : “Anemia is decreased red cell mass affecting tissue oxygenation” * Low Hb <13.5 (males), <11.5 (females)  Onset, chronicity, presentation & pattern.  Congenital disorders:  Membrane, Hb & enzyme disorders.  Acquired disorders: production  Increased loss  Decreased Congenital RBC Disorders: 1. (Hemolysis) Membrane Disorders:  Spherocytosis, Elliptocytosis 1 2 3 2. Hemoglobin Disorders:   Hemoglobinopathies - Sickle cell, HbC etc. Thalassemia Syndromes - , ,  G6PD, PK deficiency 3. Enzyme disorders:  Her. Spherocytosis: Sickle Cells ß Thalassemia Major: G6PD Deficiency Anemia: Acquired RBC disorders : (Deficiency, Marrow disorder, Blood loss & Hemolytic)  Decreased Production: anemias Iron, B12, Folate etc.  Aplastic, Hypoplastic anemias  Marrow disease, malignancy, radiation  Increased  Blood  Deficiency loss/destruction: loss anemias - parasites, bleeding  Hemolytic anemias - Autoimmune (cold & warm antibody) mechanical, drugs & toxins. Iron Deficiency Anemia: Megaloblastic Anemia : Anemia - Differential diagnosis Anemia with Low MCV (Microcytic Hypochromic) – when MCV <80fl.  Anemia - Many weeks after Iron store depletion.  <6micron diameter – IDA (moderate in others)  RDW – Red cell Distribution Width - IDA  Microcytes Low MCV and Low Retics* Differential diagnosis  Iron deficiency  Sideroblastic anemia  Thalassemia trait  Anemia of chronic disease  Laboratory evaluation  Iron, iron-binding capacity, and ferritin  Blood smear - Target cells, stippling, etc.  Hb electrophoresis for Thalassemia  Bone marrow iron stores, ring sideroblasts  Iron Deficiency Anemia: Iron Deficiency Anemia: Iron Deficiency Anemia: High MCV and Low Retics Differential diagnosis Megaloblastic anemia  Vitamin B12 deficiency  Folate deficiency  Myelodysplastic syndrome  Drug-induced anemia  Nonmegaloblastic anemia  Liver disease  Hypothyroidism  Reticulocytosis  High MCV and Low Retics Laboratory evaluation  Serum vitamin B12, RBC folate  Examination of peripheral smear for  hypersegmented neutrophils, giant platelets  Thyroid function tests,  Liver function tests  Bone marrow aspirate for evaluation for myelodysplastic features 20353-Meg.An 20353-Meg.An Megaloblastic Anemia: Normal MCV and Low Retics Differential diagnosis  Primary bone marrow failure  Aplastic anemia  Constitutional red cell aplasia (Diamond- Blackfan)  Acquired red cell aplasia  Myelophthisis  Secondary  Uremia  Endocrinology  Human bone marrow failure immunodeficiency virus infection  Anemia of chronic disease Normal MCV and Low Retics Laboratory evaluation  Iron, iron-binding capacity, and ferritin  Blood smear for marrow disorders: ‘teardrop’  Serum creatinine, thyroid function tests, liver function tests, cortisol levels if appropriate Erythropoietin level  Bone marrow aspirate and biopsy. Bone Marrow Cellularity Anemia with high Retics blood loss, Splenic sequestration  Hemolysis hemolytic anemia  Mechanical hemolysis Valve, Microangiopathic(DIC)  Hereditary hemolytic anemia  Acquired membrane defects: PNH  Infection-related hemolysis: Clostridia, malaria.  Immune  Acute Anemia with high Retics Laboratory evaluation  Blood smear –RBC Morphology  Urinary hemosiderin,  Direct and indirect Coombs test  Cold agglutinin titer  Appropriate further tests as indicated by  Hemoglobin electrophoresis,  G6PD, PK, Osmotic Fragility, sucrose lysis test,  bacterial cultures/ smear for parasites. Anemia Problem cases Polychromasia - Hemolytic An. Problem Cases cases - Not fully evolved  Mixed conditions – nutritional deficiency  Chronic  Early disorders + nutritional deficiency  Nutritional + bleeding – more  Other diseases/Factors – Infections, deficiency, anemia with nutrophilia.  Megaloblastic IDA on Treatment : Clinical History Fiji Indian female  Progressive Weakness, fainting attacks since few months.  Had blood transfusion for severe anemia a month ago.  Hypertensive on Methyldopa.  WBC count 166,000, MCV 110, >80% lymphs  60Year Blood Film: High WBC Blood Film: Lymphoid cells Smear cells (Fragile) Bone Marrow Biopsy: • Highly cellular marrow Clinical History Year Fiji Indian Male  Anemia chronic.  Bilateral arthralgia, Moderate Lymph-node enlargement and Hepatosplenomegaly  6x2cm Bilateral tumor over outer aspect of thighs.  Hb 11gm, PLT- 400,000, very high WBC count 256,000.  27 Left thigh Blood Film: • High WBC • Myeloid cells • Mature Neutrophils • Platelets Bone Marrow Trephine Biopsy • Highly cellular Diagnosis this case the diagnosis remains uncertain.  The high white cell count with mature-looking cells and the highly cellular bone-marrow suggest that his might be a myeloproliferative disorder, however it doesn’t fit exactly into any of these diseases.  The masses over the hips probably represent sites of extramedullary haematopoesis.  In Case - Severe Anemia Indian Female  Presented with Congestive cardiac failure  Hb 4gm, MCV 136 fl  ? B12 deficiency  Not a vegetarian, gastroscopy normal  Blood smear and Bone marrow.  70year Blood Film Small lymphocyte Macrocytic RBC (oval) Bone Marrow Giant Metamyelocyte Diseases do not read books….! Reference range – not normal values….! Complete Picture…! C.B.C / FBC / Hemogram - 15±2.5, 14 ±2.5 - g/dl  PCV - 0.47 ±0.07, 0.42 ±0.05 - l/l (%)  Haematocrit,  Haemoglobin effective RBC volume - better count - 5.5 ±1, 4.8 ± 1 x1012/l  MCHC - Hb/PCV - 30-36 - g/dl  Hb  RBC synthesis within RBC  MCH - Hb/RBC - 29.5 ± 2.5 pg/l Hb in RBC  Average  MCV - PCV/RBC 85 ± 8 - fl Microcytic Anemia (IDA) Macrocytic Anemia (Meg.): Thalassemia Trait: “The real art of conversation is not only to say the right thing at the right place but to leave unsaid, the wrong thing at the tempting moment…!” -- Dorothy Nevill