Académique Documents
Professionnel Documents
Culture Documents
Dr. Adnan Qureshi
Resident Haematology
Aga Khan University Hospital
Red Cell Production (Erythropoiesis)
Kidney Bone Marrow Multi-potent
stem cell
Erythroid
Epo stem cell
Oxygen
sensor
3-4
days
Blood vessel
Peripheral
blood
RBC survival
100-120 days
Anemia
Definition
Understanding anemia
• Condition - a secondary manifestation of another disease
Causes
• 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 Impaired production
• Acute • Aplastic anemia
• Chronic • PRCA
• Anemia of Chronic disease
Increased destruction
• Anemia of renal failure
• Intrinsic
• Anemia of endocrine disorders
– Membrane disorders: HS, HE …
• Iron deficiency anemia
– Enzyme deficiencies: G6PD, PK …
• Megaloblastic anemia
– Disorder of hemoglobin synthesis:
• Etc….
Hemoglobinopathies, PNH …
• 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
MCV
Hypochromic Microcytic Anemia:
Causes:
• 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 Inadequate iron supply
• Blood loss • Insufficient dietary iron
– Gastrointestinal tract • Impaired iron absorption
– Genitourinary tract – Gastric surgery
– Blood donation – Intestinal malabsorption
• Pregnancy and lactation – Celiac disease
Iron Deficiency Anemia
Iron profile
• Serum Iron Low
• TIBC Raised
Thalassemia: Impaired Globin Gene
Production
Hgb A tetramer
α globin β globin
β globin α globin
Thalassemia
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 X
α2 α1 α2 α1 X
α2 α1
• Splenomegaly
Absence of 4 alpha chains XX
α2 α1
• Hydrops fetalis (non-viable) XX
α2 α1
Alpha Thalassemia: Laboratory Findings
Hemoglobin
α Chains Hgb (g/dl) MCV (fl) Analysis
Beta Thalassemia
Clinical Hgb
Syndrome Genotype Hgb (g/dl) Analysis
Minor (Trait) β/β+ or β/β° 10-13 ↑ 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
Characteristics
• 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 hemolytic anemia
– Nonimmune mediated
Spur cell hemolytic anemia
Sickle Cell Disease
Mutation in beta globin
(β6 Glu Val)
Inherited as autosomal
recessive
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
+
Anti-C3d
Patients RBCs Anti-IgG
Hemolytic Anemia with Intravascular
Hemolysis
Mechanical damage (Microangiopathic hemolytic
anemia)
Infection (Malaria)
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
Morphology ….
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