"I am careful not to confuse excellence with perfection' Excellence is what I can reach for Perfecti

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"I am careful not to confuse excellence with
perfection. Excellence is what I can reach
forPerfection is God's business Michael J.
Fox
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HEMATOLOGY Part-I RBC disorders

• Dr. Venkatesh M. Shashidhar
• Senior Lecturer in Pathology
• Fiji School of Medicine

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Introduction

• Yolk sac Placenta ? Liver Spleen ? B.marrow.
• Haemopoietic marrow ? fatty marrow.
• RE system can take over hemopoiesis.
• 50 fat in adult marrow.
• Stem cell ? Progenitor cells ? Mature cells
• Growth factors Erythropoietin, thyroxine,
  Androgens.
• Iron, Vit B12, Folate, Zinc, Vit-C, B6, E,
  thiamine, riboflavin, other metals, aminoacids

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Introduction

• low O2 ? Kidney ? Erythropoietin ?
  Erythropoiesis.
• 1 blast ? 16 RBC, 1 week, 1-2 day in spleen ?
  mature
• Hb formation and DNA essential for maturation.
• Immature RBC RNA/DNA remnant polychr.. lt2
• RBC cannot use oxygen only glycolysis why?

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Haemopoiesis
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Bone Marrow Cellularity
Normal Hypercellular Hypocellular
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Erythropoiesis
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C.B.C

• Haemoglobin - 152.5, 14 2.5 - g/dl
• PCV - 0.47 0.07, 0.42 0.05 - l/l ()
• Haematocrit, effective RBC volume - better
• RBC count - 5.5 1, 4.8 1 x1012/l
• MCHC - Hb/PCV - 30-36 - g/dl
• Hb synthesis within RBC
• MCH - Hb/RBC - 29.5 2.5 pg/l
• Average Hb in RBC
• MCV - PCV/RBC 85 8 - fl

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Blood Smear - Normal
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White Blood Cells
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RBC disorders (Anemias)
Anemia is decreased red cell mass affecting
tissue oxygenation Low Hb lt13.5 (males), lt11.5
(females) Polycythemia ? High Hb.
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Anemia Classification

• Acquired
• Decreased production
• Increased loss
• Congenital
• Increased loss/Hemolytic

• Decreased production
• Nutritional
• Marrow suppression
• Marrow infiltration
• Increased loss
• Blood loss
• Hemolytic
• Immune
• Non immune

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Acquired RBC disorders

• Decreased Production
• Aplastic, Hypoplastic anemias
• Deficiency anemias Iron, B12, Folate etc.
• Lack of erythropoiesis - Kidney disease
• Marrow disease, malignancy, radiation
• Increased loss/destruction
• Blood loss anemias - parasites, bleeding
• Hemolytic anemias - Autoimmune (cold warm
  antibody) mechanical, drugs toxins.

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Iron Deficiency Anemia

• Most abundant metal but most common deficiency..!
• Common in developing world,
• Worm infestation, chronic blood loss, poor diet.

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Low HbAnemia MCV
Low microcytic
Normal normocytic
High macrocytic
Measure Ferritin
Measure B12 folate
Normal/high
Low
Low Megaloblastic anemia
Normal
Anemia of chronic disease/ Congenital Hb dis.
Iron def Anemia
Reticulocyte count
Anemia of chronic disease Renal failure Marrow
failure
high
low
Hemolytic anemia or blood loss
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Iron Metabolism

• Limited absorption and no excretory mech.
• Recycling of iron dead cells to new cells
• 1mg/day ? 3-6G body ? 1mg/day
• 10 of the 10 to 20 mg of dietary iron.
• Iron is absorbed in Jejunum.
• Stored as Ferritin Hemosiderin.
• Laboratory tests
• Serum iron(1mg/l)
• Serum iron binding capacity (3mg)
• Serum ferritin (gt20ug)

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IDA - Etiology

• Blood loss bleeding, parasites
• Poor diet malnutrition (greens meat)
• Increased need Pregnancy, children

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IDA - Pathogenesis

• Decreased Iron stores
• Decreased Hb Synthesis
• Delayed maturation of erythroblasts (cytopl)
• Decreased cell size (microcytes)
• Decreased hb content (hypochromia)
• Decreased RBC number
• Anemia.

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Microcytic Anemia (IDA)
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Clinical Features

• Anemia
• Pallor, Weakness, Lethargy
• Breathlessness on exertion
• Palpitations may lead to heart failure - edema
• IDA
• Angular cheilosis, atrophic glossitis,
• dysphagia, koilonychia, gastric atrophy.

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Angular cheilitis Glossitis
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Iron Deficiency Anemia
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IDA on Treatment
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Megaloblastic anemia

• Vitamin B12/Folic acid deficiency
• Second most common type of anemia.
• Multi System disease All organs with increased
  cell division.
• Macrocytic anemia, pancytopenia.
• Pernicious anaemia
• autoimmune, Gastric atrophy, VitB12 def.

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Megaloblastic anemia - Etiology

• Malnutrition
• Intrinsic factor Ab - Pernicious anemia
• Gastrectomy, Ileal resection
• Inflammatory bowel disease
• Malabsorption syndromes - Sprue
• Blind loop syndrome

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Megalobl - Pathogenesis

• Decreased Vit B12 / Folate
• Decreased DNA Synthesis
• Delayed maturation of erythroblasts (Nucleus)
• Increased cell size (macrocytes)
• Normal hb content (Normochromia)
• Decreased RBC number
• Decreased WBC number (pancytopenia)
• Anemia Pancytopenia.

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Macrocytic Anemia (Meg.)
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Megaloblastic Anemia
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CWM-20353-Meg.An
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CWM- ?
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CWM - ?
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Hemolytic Anemia - Types

• Immune lysis
• Warm Cold Ab types.
• Mechanical Damage
• Microangiopathy (DIC), prosthesis, march
• Hereditary Defects
• Membrane, Hb Enzyme defect
• Infection induced
• Clostridia, malaria, septicemia

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Clinical Features

• Pallor mild mucosal
• Jaundice - Mild fluctuating
• Splenomegaly
• No bile in urine (dark on standing-UBG)
• Pigment gall stones in chronic forms
• Crisis aplastic, hemolytic, vascular
• Ankle ulcers

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Polychromasia - Hemolytic An.
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CBC Analyzer Report
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Congenital RBC Disorders

• Membrane Disorders
• Spherocytosis, Elliptocytosis
• Hemoglobin Disorders
• Hemoglobinopathies - Sickle cell, HbC etc.
• Thalassemia Syndromes - ?, ?, ?
• Enzyme disorders
• G6PD, PK deficiency

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Thalassemia Trait
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Thalassemia Major
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Blood Smear Interpretation
Normal Micro/hypo Macro Target Sphero Heinz
body Schistocyte nRBC Polychrom Teardrop
A B C D E F G H I J
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Basophilic Stippling
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Polychromasia - Hemolytic An.
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ß Thalassemia Major
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Sickle Cell Disease
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Microangiopathy / DIC
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Her. Spherocytosis /AIHA
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Cold Hemagglutinin Disease
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Anemia with 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

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Anemia with High MCV, Low Retics

• Differential diagnosis
• Megaloblastic anemia
• B12, Folate deficiency
• Myelodysplastic syndrome
• Nonmegaloblastic anemia
• Liver disease , Hypothyroidism
• Laboratory evaluation
• Serum B12, RBC folate levels.
• Examination of peripheral smear
• Bone marrow examination.

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Anemia with Normal MCV,Low Retics

• Differential diagnosis
• Primary bone marrow failure
• Aplastic anemia, drugs, chemotherapy
• Secondary bone marrow failure
• Uremia, Endocrine disorders, AIDS,
• Anemia of chronic disease
• Laboratory evaluation
• Blood smear Iron, TIBC, Ferritin.
• Bone marrow smear and iron stores
• Kidney, Thyroid liver function tests, Cortisol
  levels
• Erythropoietin level

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Anemia with high Retics - Hemolysis

• Differential diagnosis
• Immune Warm Cold Ab, Auto Allo immune
• Mechanical - Valve, Microangiopathy (DIC)
• Hereditary hemolytic anemias Hb, Enzyme mem
• Infection-related hemolysis Clostridia, malaria.
• Laboratory evaluation
• Blood smear morphology, nRBC, Parasites, Retics.
• Evidence of Hemolysis Bilirubin, Haptoglobin,
• Direct and indirect Coombs test
• Hemoglobin electrophoresis, G6PD screen etc.

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Causes of High Hct/polycythemia

• Relative or spurious erythrocytosis
• Hemoconcentration secondary to dehydration
• (diarrhea, diaphoresis, diuretics, deprivation
  of water, emesis, ethanol, etc.)
• Absolute erythrocytosis (True )
• Tissue hypoxia - High altitude, Pumonary disease,
  respiratory def. Right to left cardiac shunts,
  Carbon monoxide intoxication, High
  oxygen-affinity Hb.
• High EPO - Renal disease, Tumors eg. HCC.
• Androgen therapy
• Primary - Polycythemia vera