Anaemia

Anaemia is defined as a decrease in red cell mass as evidenced by low haemoglobin concentration in blood below the reference range for a given age or sex in a given population or geographic location. WHO gives the reference value for Hb <13g/dL in adult males and <12g/dL for adult females as criteria for anemia. Most patients do not need to be transfused. Chronic anemia is particularly well-tolerated, and iron supplements safely and cost-effectively raise the hemoglobin in IDA. It is still very important to ESTABLISH THE CAUSE in patients with anemia.

Classification of Anaemia

HemorrhageAcute LossTrauma
Chronic LossUpper and Lower GI bleed, Menorrhagia, Hematuria
HemolysisInherited Hemolytic AnemiaMembranopathies, Enzymopathies, Hemoglobinopathies
Acquired Hemolytic AnaemiaAlloimmune, Autoimmune, TTP, HUS, Malaria
Diminished ErythropoiesisMicrocytic AnaemiaDefective Heme synthesis, Defective Globin Chain
Macrocytic AnaemiaMegaloblastic and Non-megaloblastic macrocytic anemias
  • Indications for blood transfusion in anaemia
    • Hb < 7 g/dL (especially in acute anemia)
    • Symptomatic Anaemia
    • Comorbidities e.d. Ischemic Heart Disease
  • Treatment of severe anemia with heart failure
    • Transfuse with caution to restore Hb to safe levels of 6-8 g/dL
    • IV/PO Furosemide 40mg
    • Check for signs of worsening congestion (JVP, basal crackles). If present, stop and treat.
  • Signs and symptoms of anaemia
    • Fatigue, weakness, pallor, breathlessness
    • Pallor: Seen on mucous membranes and conjunctivae
    • Jaundice: seen in haemolytic anaemia
    • Pica: Craving for ice or dirt. Seen in IDA
    • Features of a hyperdynamic state
      • Bounding pulses
      • Tachycardia/palpitations
      • Flow murmur
      • Pulsatile sound in the ear
      • Possibly heart failure (anaemia-induced heart failure)
    • Features of extramedullary haematopoiesis
      • Hepatosplenomegaly
      • Paravertebral mass
      • Widening of diploic spaces of the skull
  • Laboratory Investigations for patients with anaemia
    • To establish that there is anaemia
      • Complete blood count for Hemoglobin and Hematocrit
    • To classify the anaemia
      • Red cell indices (MCV, MCH, MCHC) and Peripheral blood film
      • Size: Normocytic, Microcytic, Macrocytic
      • Degree of haemoglobinization: normochromic, hypochromic
      • Shape e.g. Poikilocytes
    • To establish the cause of anaemia
      • Decreased Erythropoiesis
        • Bone marrow aspirate or Trephine Biopsy: for bone marrow failure
        • Iron, Folate and B12 levels: for hematinic deficiency
      • Excessive loss or destruction
        • Urinalysis and Serum study (Bilirubin, Haptoglobin, LDH) for hemolytic anaemia
        • Stool for ova and cysts
        • Gastroscopy and Colonoscopy

Causes of anemia according to morphology

Normocytic anaemiaAcute blood loss, Anaemia of chronic disease, Bone marrow fialure, Renal failure, Hypothyroidism, Hemolysis, Pregnancy
Macrocytic anemiaB12 and folate deficiency, Alcohol excess, Reticulocytosis, Cytotoxics, Myelodysplasti syndrome, Hypothyroidism
Microcytic anemiaIron deficiency anemia, Thalassemia, Sideroblastic anemia
  • Oxygen-Hemoglobin dissociation curve ****
    • Describes the Oxygen carrying capacity of Haemoglobin at different PO2
    • Co-operativity – binding of one O2 molecule facilitates the second molecule binding
    • P50 is 26.6mmHg (PO2 at which Hb is half saturated with O2)
    • Normal position depends on: 2,3-DPG concentration, H+ concentration, CO2, Hb structure
    • Right shift (decreased affinity): High 2,3-DPG, H+, CO2, HbS (Also BAT ACE)
    • Left shift (Increased affinity): Low 2,3-DPG, HbF
  • Stages of erythropoiesis and morphology of precursors
    • In Bone marrow
      • Hematopoietic stem cell: round, non-adherent, with a rounded nucleus and low cytoplasm-to-nucleus ratio, resemble lymphocytes
      • Proerythroblast: Large cells, basophilic cytoplasm, Large nucleus
      • Erythroblast: basophilic cytoplasm, Smaller nucleus, no nucleoli
      • Normoblast: acidophilic cytoplasm, compact nucleus
      • Reticulocyte: acidophilic cytoplasm, granules composed of cytoplasmic ribosomal RNA
    • In blood
      • Reticulocytes
      • Erythrocyte: Eosinophilic, biconcave shape, central pallor no more than 2/3 of diameter, diameter of 7um
  • Causes of anaemia of diminished erythropoiesis
    • Inherited genetic defects
      • Defects leading to stem cell depletion
        • Fanconi anaemia
        • Telomerase deficiency
      • Defects affecting erythroblast maturation: Thalassemia syndromes
    • Nutritional deficiencies
      • Deficiencies affecting DNA synthesis:
        • B12 deficiency
        • Folate deficiencies
      • Deficiencies affecting haemoglobin synthesis
        • Iron deficiency
    • Erythropoietin deficiency
      • Renal failure
      • Anaemia of chronic inflammation
    • Immune-mediated injury of progenitors
      • Aplastic anaemia
      • Pure red cell aplasia
    • Inflammation-mediated iron sequestration
      • Anaemia of chronic inflammation
    • Primary hematopoietic neoplasm
      • Acute and Chronic leukaemias
      • Myelodysplastic syndrome
      • Myeloproliferative neoplasms
    • Space-occupying marrow lesions
      • Metastatic neoplasm
      • Granulomatous disease
    • Infections of red cell progenitors
      • Parvovirus B19 infection
    • Unknown mechanisms
      • Endocrine disorders
      • Hepatocellular liver disease