Haematopoiesis & Approach to anaemia
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    Haematopoiesis & Approach to anaemia Haematopoiesis & Approach to anaemia Presentation Transcript

    • Haematopoiesis& Approach to Anaemia
      Dr (Brig) YD Singh
      MBBS, MD, FIACM, DIT
      Professor (Internal Medicine)
      SKN Medical College & Gen Hospital
      Pune 411 041
    • Haematopoiesis (1)
      Process by which formed elements of blood
      Produced & Regulated through series of steps
      Pluripotent haematopoietic stem cell
      Capable of producing red cells,
      All classes of granulocytes, monocytes, platelets
      Mechanism to become committed to a given lineage
      Not fully known
      24-Sep-11
      Dr (Brig) YD Singh
    • Haematopoiesis (2)
      Following lineage commitment
      Haematopoietic progenitor & precursor cells
      Come under regulatory influence of growth factors and hormones.
      For red cell production
      Erythropoietin (EPO) is regulatory hormone
      EPO is required for Maintenance of
      Committed Erythroid progenitor cells
      In absence of EPO hormone
      Undergo programmed cell death (apoptosis)
      24-Sep-11
      Dr (Brig) YD Singh
    • Factors Regulating RBCProduction
      24-Sep-11
      Dr (Brig) YD Singh
      Regulated process of RBC production is Erythropoiesis
    • RBC Characteristics
      Mature red cell is 8 micron in diameter
      Anucleate , Biconcave & discoid in shape
      Extremely pliable
      Needs to traverse microcirculation easily
      Membrane integrity maintained by
      Intracellular generation of ATP
      Average RBC lives 100–120 day
      1% of all circulating RBC daily replaced
      Erythron:Organ for red cell production
      Pool of marrow erythroid precursor cells & large mass of mature circulating RBCs
      24-Sep-11
      Dr (Brig) YD Singh
    • RBCs : Normal Indices
      Mean cell volume (MCV)
      (Haematocrit x10) / (RBC count x 106) =90 ± 8 fL
      Mean Cell Haemoglobin (MCH)
      (Hb x 10) / (red cell count x 106) = 30 ± 3 pg
      Mean cell Hb concentration (MCHC)
      (Hb x 10) / hematocrit or MCH/MCV = 33 ± 2%
      24-Sep-11
      Dr (Brig) YD Singh
    • Leukocytes
      All Leukocytes derived from
      Common Stem cell in Bone marrow
      3/4th of nucleated cells of bone marrow
      Committed to production of Leukocytes
      Mediate Inflammatory / Immune Responses
      Include Neutrophils, T & B Lymphocytes
      Natural Killer (NK) cells, Monocytes
      Eosinophils & Basophils
      These cells have specific functions
      Antibody production by B Lymphocytes
      Destruction of bacteria by Neutrophils
      24-Sep-11
      Dr (Brig) YD Singh
    • Granulocytes Development (1)
      24-Sep-11
      Dr (Brig) YD Singh
    • Granulocytes Development (2)
      24-Sep-11
      Dr (Brig) YD Singh
    • Neutrophils
      24-Sep-11
      Dr (Brig) YD Singh
      Neutrophil band with Döhle body
      Normal Neutrophil
    • 24-Sep-11
      Dr (Brig) YD Singh
      Eosinophil
      Large bright orange granules
      usually bilobed Nucleus
      Basophil
      Large purple-black granules
      fill the cell & obscure nucleus
    • Normal Bone Marrow
      24-Sep-11
      Dr (Brig) YD Singh
      Low Power View
    • Bone marrow
      24-Sep-11
      Dr (Brig) YD Singh
      Normoblast
      with dividing Nucleus
      Eosinophil Cell
      Fat Cell
      Erythrocyte Cell
      Normoblast Cell
      Myelocyte dividing
      Myelocyte Cell
      Myelocyte Cell
      Fat Cell
      Fat Cell
    • Bone Marrow: Erythroid Hyperplasia
      24-Sep-11
      Dr (Brig) YD Singh
    • Bone Marrow: Myeloid Hyperplasia
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Introduction
      Serum Hblevel or haematocrit < expected value for age & sex
      WHO criteria
      Adult men
      Blood Hbconcentration <13 g/dLor
      Hematocrit <39%
      Adult women
      Blood Hbconcentration <12 g/dL) or
      Hematocrit <37%
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Types
      Iron-Deficiency Anemia
      Vitamin B12 Deficiency Anemia
      Folate-Deficiency Anemia
      Anemia of Chronic Disease
      Haemolytic Anaemia
      AplasticAnemia
      Myelodysplastic Syndromes
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Mechanisms
      3 major physiologic mechanisms of anemia
      Marrow production defects (Hypoproliferation)
      Reflects absolute or relative marrow failure
      Erythroid marrow not proliferated appropriately
      Can result from
      Marrow damage
      Iron deficiency
      Inadequate erythropoietin stimulation
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Mechanisms
      Ineffective erythropoiesis (RBC maturation defects)
      Nuclear maturation defects associated with macrocytosis & abnormal marrow development
      Cytoplasmic maturation defects associated with microcytosis and hypochromia, usually from defects in hemoglobin synthesis
      Decreased erythrocyte survival: blood loss or hemolysis
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Symptoms & Signs (1)
      Often recognized by abnormal results on screening lab tests
      Signs and symptoms depend on
      Level of anaemia
      Time course over which it developed
      Acute onset Anaemia
      Chronic Anaemia
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Symptoms & Signs (2)
      Acute anaemia (nearly always due to blood loss or haemoptysis)
      If Loss of 10–15% of total blood volume
      Hypotension
      Decreased organ perfusion
      Loss of >30% of blood volume
      Postural hypotension
      Tachycardia
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Symptoms & Signs (3)
      Loss of >40% of blood volume
      Hypovolemic shock
      Confusion
      Dyspnoea
      Diaphoresis
      Hypotension
      Tachycardia
      Haemolytic Anaemia
      Presentation depends on mechanism that leads to RBC destruction
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Symptoms & Signs (3)
      Chronic or progressive anaemia
      Presentation depends on age of patient
      Adequacy of blood supply to critical organs
      Possible Symptom / Sign
      Fatigue and Loss of stamina
      Breathlessness (specially on exertion)
      Pale skin and mucous membranes (Pallor)
      Palpitation (Tachycardia, after physical exertion)
      Forceful heartbeat (Heaving Apex beat)
      High Volume pulse & Systolic flow murmur
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Symptoms & Signs (4)
      In patients with coronary artery disease
      Anginal episodes may appear or
      Increase in frequency and severity
      In patients with carotid artery disease
      Light-headedness
      Dizziness may develop
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: DD (1)
      Hypoproliferativeanaemias(75% of cases)
      Marrow damage
      Infiltration/fibrosis
      Aplasia
      Iron deficiency (mild to moderate)
      Decreased stimulation
      Inflammation
      Metabolic defect (Hypothyroidism)
      Renal disease
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: DD (2)
      Maturation disorder
      Cytoplasmic defects
      Iron deficiency (severe)
      Thalassemia
      Sideroblastic
      Nuclear defects
      Folate deficiency , Vitamin B 12 deficiency
      Drug toxicity
      Methotrexate & Alkylating agents
      Alcohol
      Refractory anemia
      Myelodysplasia
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: DD (3)
      Haemolysis / Haemorrhage
      Blood loss
      Intravascular haemolysis
      Metabolic defect
      Membrane abnormality
      Haemoglobinopathy
      Autoimmune defect
      Fragmentation haemolysis
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Diagnostic Approach (1)
      02 questions need to be answered:
      Type of Anaemia & Cause of Anaemia
      Careful history
      Nutritional history
      Related to diet, drugs or alcohol
      Family history of anaemia (Genetic)
      Geographic backgrounds and ethnic origins
      G 6 PD deficiency
      Haemoglobinopathies
      Middle Eastern, Mediterranean, or African origin
      Exposure to toxic agents or drugs
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Diagnostic Approach (2)
      Physical examination
      May provide clues to mechanisms / cause of anaemia
      Infection
      Blood in the stool
      Splenomegaly & Lymphadenopathy
      Petechiae suggest platelet dysfunction.
      Laboratory assessment
      Including review of past laboratory measurements to determine time of onset
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Diagnostic Approach (3)
      Physiologic classification / Type of anaemia
      Reticulocyte index <2.5 & Normocytic, Normochromic anaemia
      Hypoproliferative
      Marrow damage:
      Infiltration / fibrosis
      Aplasia
      Decreased stimulation:
      Inflammation
      Metabolic defect
      Renal disease
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Diagnostic Approach (4)
      Reticulocyte index <2.5 & microcytic or macrocyticanemia
      Maturation disorder
      Cytoplasmic defects:
      Iron deficiency,
      Thalassemia, Sideroblastic
      Nuclear defects:
      Folate deficiency
      Vitamin B deficiency
      Drug toxicity
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Diagnostic Approach (5)
      Reticulocyte index ≥2.5
      Haemolysis / Haemorrhage
      Blood loss
      Intravascular haemolysis
      Metabolic defect
      Membrane abnormality
      Haemoglobinopathy
      Autoimmune defect
      24-Sep-11
      Dr (Brig) YD Singh
    • AnaemiaAlgorithm
      24-Sep-11
      Dr (Brig) YD Singh
    • Normal Blood Smear (Wright’s stain)
      24-Sep-11
      Dr (Brig) YD Singh
      Normal RBCs, single Neutrophil & few platelets seen
    • Reticulocytes (Supravital Stain)
      24-Sep-11
      Dr (Brig) YD Singh
      Reticulocyte count is key to initial classification of anemia
      Reticulocytes are RBCs recently released from marrow
    • Severe Iron Def Anaemia(Wright’s stain)
      24-Sep-11
      Dr (Brig) YD Singh
      Microcytic & Hypochromic RBCs smaller than nucleus of a
      Lymphocyte + marked variation in size (Anisocytosis) &
      shape (Poikilocytosis)
    • Macrocytosis
      24-Sep-11
      Dr (Brig) YD Singh
      RBCs larger than small Lymphocyte & well haemoglobinized. Macrocytes are oval-shaped (Macroovalocytes)
    • Howell-Jolly bodies
      24-Sep-11
      Dr (Brig) YD Singh
      In absence of functional spleen, nuclear remnants are not expelled from RBCs & remain as small homogeneously staining blue inclusions on Wright stain
    • Red cell changes in myelofibrosis
      24-Sep-11
      Dr (Brig) YD Singh
      A Teardrop-shaped RBC & a Nucleated RBC is seen. These forms are seen in Myelofibrosis with Extramedullary Haematopoiesis
    • Red cell changes in Thalassemia & Liver disease
      24-Sep-11
      Dr (Brig) YD Singh
      Target cells have a bull’s-eye appearance & are seen in Thalassemia & Liver disease
    • Red cell changes in Sickle Cell Disease
      24-Sep-11
      Dr (Brig) YD Singh
      Sickle shaped cells are seen in Sickle Cell disease
    • Anaemia: Lab Tests
      CBC
      Erythrocyte count
      Haemoglobin & Haematocrit
      Reticulocyte count
      Erythrocyte indices
      Mean cell volume (MCV)
      Mean cell haemoglobin
      Mean cell haemoglobin concentration
      Leukocyte count
      Cell differential
      Nuclear segmentation of Neutrophils
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia: Lab Tests
      Platelet count
      Cell morphology
      Cell size
      Anisocytosis (variations in cell size)
      Poikilocytosis (variations in cell shape)
      Polychromasia
      Iron supply studies
      Serum iron
      Total iron-binding capacity (TIBC)
      Serum ferritin, marrow iron stain
      24-Sep-11
      Dr (Brig) YD Singh
    • Hypoproliferative Anaemia: Key Tests
      Serum iron & iron-binding capacity
      Serum ferritin, to assess iron stores
      Evaluation of renal & thyroid function
      Marrow biopsy or aspirate
      Detect marrow damage or infiltrative disease
      Anemia of chronic inflammation shows
      Low serum iron & Normal or low TIBC
      Low percent transferrin saturation
      Normal or high serum ferritin
      24-Sep-11
      Dr (Brig) YD Singh
    • Hypoproliferative Anaemia: Key Tests
      Mild to moderate iron deficiency anaemia:
      Low serum iron level & High TIBC
      Low percent transferrin saturation
      Low serum ferritin level
      Marrow damage by drug, infiltrative disease (Leukaemia / Lymphoma / Aplasia)
      Peripheral blood and
      Bone marrow morphology
      Infiltrative disease or fibrosis
      Marrow biopsy will likely be required
      24-Sep-11
      Dr (Brig) YD Singh
    • Maturation disorders Anemia: Tests
      Vitamin B12
      Folate
      Serum iron and iron-binding capacity
      Serum ferritin to assess iron stores
      Haemoglobin electrophoresis
      24-Sep-11
      Dr (Brig) YD Singh
    • Haemolytic Anemia: Tests
      Haemoglobin electrophoresis
      Screen for red cell enzymes
      Direct or indirect anti-globulin test
      Cold agglutinin titre
      24-Sep-11
      Dr (Brig) YD Singh
    • Anaemia Classification
      Based on defect in RBC production
      Marrow production defects: Hypo-proliferation
      Maturation defects: Ineffective Erythropoiesis
      Decreased survival: Blood Loss / Haemolysis
      Classification by MCV
      Microcytic: MCV <80 fL
      Normocytic: MCV 80–100 fL
      Macrocytic: MCV >100 fL
      24-Sep-11
      Dr (Brig) YD Singh
    • Complications: Anaemia
      High-output Cardiac Failure
      End-organ ischemia or infarct
      Myocardial infarction
      Stroke
      Hypovolumic shock
      Death
      24-Sep-11
      Dr (Brig) YD Singh
    • Management Pearls: Anaemia
      Anaemia may be Multi-factorial
      Finding one cause does not mean that no other forms of anaemia are present
      Iron deficiency may occur with folate / B12 def
      Producing Dimorphic anaemia
      Iron deficiency often means
      Occult blood loss
      Worms infestation
      Nutritional
      24-Sep-11
      Dr (Brig) YD Singh
    • Treatment Approach: Anaemia
      Mild to Mod Anaemia
      Initiate treatment when sp diagnosis is made
      Selection of treatment
      Determined by cause of anaemia
      Cause may be multi-factorial
      Evaluate iron status before starting treatment
      Rarely anaemia may be so severe
      RBC transfusions required before specific diagnosis is made
      24-Sep-11
      Dr (Brig) YD Singh