Overview of Anemia

           Resident Haematology           Aga Khan University Hospital

       Dr. Adnan Qureshi

Red Cell Production (Erythropoiesis)
Kidney Bone Marrow
Multi-potent stem cell Erythroid stem cell

Epo Oxygen sensor

3-4 days

Blood vessel

Peripheral blood
RBC survival 100-120 days


Definition Understanding anemia
• Condition - a secondary manifestation of another disease

• Impaired red cell production • Increased rate of destruction • Blood loss


Classification of Anemia
Different modes of classification  Clinical findings
• Acute / Chronic • Hereditary / Acquired
 

Red cell size
• Determined by MCV

Red cell kinetics
• Determined by reticulocyte count


Anemia - Causes

Blood loss • Acute • Chronic Increased destruction • Intrinsic
– Membrane disorders: HS, HE … – Enzyme deficiencies: G6PD, PK … – Disorder of hemoglobin synthesis: Hemoglobinopathies, PNH …

Impaired production
• • • • • • • • Aplastic anemia PRCA Anemia of Chronic disease Anemia of renal failure Anemia of endocrine disorders Iron deficiency anemia Megaloblastic anemia Etc….

• Extrinsic
– Antibody mediated – Mechanical trauma: MAHA, TTP, DIC – Infections: malaria – Sequestration  

Laboratory Evaluation of Anemia

Commonly ordered test
• CBC • Peripheral film

Supplementary test (depending upon the initial findings)
• • • • • Retic count Coomb’s test HB elctrophoresis G6PD Bone marrow

Reticulocyte Count
 

Relative reticulocyte count
• Percent of all RBC

Corrected reticulocyte count
• Retic % x Pt. Hct Normal Hct

Absolute reticulocyte count
• Relative reticulocyte count x RBC count

Reticulocyte production index (RPI)


Classification of Anemia Based on RBC Size
Microcytic < 76fl Normocytic 76-96 fl Macrocytic > 96 fl


Hypochromic Microcytic Anemia:

• Iron deficiency • Thalassemia • Lead toxicity • Sideroblastic anemia • Long standing anemia of chronic disease


Causes of Iron Deficiency
Iron deficiency is a symptom, not a disease

Increased iron requirements
• Blood loss
– Gastrointestinal tract – Genitourinary tract – Blood donation

Inadequate iron supply
• Insufficient dietary iron • Impaired iron absorption
– Gastric surgery – Intestinal malabsorption – Celiac disease

• Pregnancy and lactation


Iron Deficiency Anemia

Iron profile
• Serum Iron • TIBC • Serum Ferritin • Transferrin Saturation Low Raised Low Low


Thalassemia: Impaired Globin Gene Production
Hgb A tetramer

α globin

β globin

β globin

α globin



Decreased production of normal globin chains
∀ α thalassemia - deficiency of α gene(s) ∀ β thalassemia - deficiency of β gene(s)


Alpha Thalassemia: Clinical Features

Absence of 1-2 alpha chains
• Common • Asymptomatic • Does not require therapy

α2 α2

α1 α1

α2 α1



α2 α2

α1 α1

Absence of 3 alpha chains (Hgb H disease)
• Microcytic anemia (Hgb 7-10) • Splenomegaly

α2 α2 α1 α1

Absence of 4 alpha chains
• Hydrops fetalis (non-viable)

α2 α2 α1 α1

Alpha Thalassemia: Laboratory Findings
Hemoglobin α Chains Hgb (g/dl) αα/αα αα/-α α-/α- or --/αα --/-α --/- 

MCV (fl)

Analysis Normal

Normal 12-14 11-13 7-10 75-85 70-75 50-60 -


Normal Normal with Hgb Barts (γ4); Hgb H (β4) - small Normal with Hgb Barts (γ4); Hgb H (β4) - large Not viable

Beta Thalassemia
Clinical Syndrome
Minor (Trait) Intermedia Major (Cooleys)

β/β+ or β/β° β+/β+ β+/β° or β°/β°

Hgb (g/dl)
10-13 7-9 <7

Hgb Analysis
↑ Hgb A2, ↑ Hgb F ↑ Hgb A2, ↑↑ Hgb F ↑ Hgb A2, ↑↑↑ Hgb F


Normocytic Anemia with Low Retic Count

Decreased stimulation of RBC production in bone marrow
• Anemia of chronic disease • Chronic renal insufficiency

Isolated decrease in RBC precursors (red cell aplasia)  Bone marrow damage

• • • •

Aplastic anemia Fibrosis Stem cell damage Infiltration with tumor/infection

Disorder of hematopoeisis
• Myelodysplasia/sideroblastic anemia

Anemia of Chronic Disease

Associated conditions
• Infections
– Viral, bacterial, TB, parasitic, fungal

• Autoimmune diseases
– RA, SLE, sarcoidosis, IBD, vasculitis

• Cancer

• • • • WBC and platelet counts are normal Anemia of variable severity (mild-severe) Low erythropoietin level Low reticulocyte count

Normocytic Anemia with High Reticulocyte Count

General principles
• Bleeding may have similar lab findings as hemolysis • High reticulocyte count may lead to macrocytosis • Classification
– Hereditary vs. acquired – Extravascular vs. intravascular – Immune vs. nonimmune


Hemolytic Anemia with Extravascular Hemolysis

Extravascular (reticuloendothelial system)
• Hereditary
– Hemoglobinopathies (sickle cell anemia) – Enzymopathies (G6PD deficiency) – Membrane defects (hereditary spherocytosis)

• Acquired
– Immune mediated
 Autoimmune  Spur

hemolytic anemia

– Nonimmune mediated
cell hemolytic anemia


Sickle Cell Disease

Mutation in beta globin (β6 Glu Val) Inherited as autosomal recessive Protection against malaria


Glucose-6-Phosphate Dehydrogenase Deficiency
 

G-6-PD - reduces NADP/oxidizes glucose-6-phosphate
• Detoxifies free radicals and peroxides

Sex-linked disorder  Effects > 200 million people  Hemolytic anemia occurs in the presence of stress (infection or drugs)
• African form - mild hemolysis • Mediterranean form - more severe
– Unique sensitivity to fava beans

Hereditary Spherocytosis
 

Autosomal dominant disorder Abnormality in RBC membrane protein Clinical and laboratory findings
• Splenomegaly • Chronic hemolytic anemia • Spherocytes on peripheral smear • Increased osmotic fragility

Acquired Hemolytic Diseases
 

Immune mediated hemolytic anemia Non-immune mediated


Autoimmune Hemolytic Anemia

Warm antibodies (IgG-mediated)
• Primary • Secondary
– Lymphoproliferative disease – Connective tissue disease – Infectious disease

• Drug-induced

Laboratory testing
• Normocytic/macrocytic anemia • Peripheral smear – spherocytosis • Coomb’s test - positive  

Anti-Globulin (Coombs) Testing
Direct antiglobulin testing

Patients RBCs

Anti-C3d Anti-IgG


Hemolytic Anemia with Intravascular Hemolysis

Mechanical damage (Microangiopathic hemolytic anemia) Chemical damage (Burns) Infection (Malaria) Transfusion reaction (ABO incompatibility)

  


Differential Diagnosis of Microangiopathic Hemolytic Anemia
      

Thrombotic thrombocytopenic purpura (TTP) Hemolytic uremic syndrome (HUS) Disseminated intravascular coagulation (DIC) Vasculitis Malignant hypertension Metastatic neoplasm with vascular invasion Preeclampsia/HELLP syndrome of pregnancy

Macrocytic Anemia with Low Reticulocyte Count

Megaloblastic anemia
• Vitamin B12 deficiency • Folate deficiency

Nonmegaloblastic macrocytic anemia
• • • • Liver disease Hypothyroidism Drug-induced (DNA synthesis block) Myelodysplastic syndrome

Morphology ….


























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