Hematology

• Hematopoiesis

  The process of blood cell formation
• Erythropoietin (EPO)

  • Synthesized from peritubular interstitial fibroblast (cortex and outer medulla)
• Supravital stains for reticulocyte identification

  New methylene blue/Brilliant cresyl blue
• Anemia

  Hb < 13 g/dL (male), Hb < 12 g/dL (female), Hb < 11 g/dL (pregnancy), Hb < 10 g/dL (CKD)
• Reticulocyte count

  Measured in %, Corrected retic count = Retic count x (Hb of the patient/desired Hb)
• Needs evaluation: Hb > 16.5 g/dL (male), Hb > 16 g/dL (female)
• Blood cells formed from hematopoietic stem cells

  • RBC
  • Platelet
  • Neutrophil
  • Eosinophil
  • Basophil
  • Monocyte → Macrophage (tissues)
  • B Lymphocytes
  • T Lymphocytes
  • NK Cells
• Desired Hb: 15 g/dL (male), 13 g/dL (female)
• Reticulocyte Production Index (RPI)

  Best indicator of bone marrow response
• Mean Corpuscular Volume (MCV)

  Average volume of an RBC, Normal range: 80 - 100 fL
• Hypoproliferative anemia

  • Symptoms duration: 2-3 months, RPI < 2.5, MCV normal to low
• Causes of hypoproliferative anemia

  • Iron deficiency anemia
  • Megaloblastic anemia (vitamin B12, folate deficiency)
  • Non megaloblastic macrocytic anemia
  • Anemia of chronic disease
  • Sideroblastic anemia
  • Thalassemia trait/thalassemia minor
• Hypoproliferative anemia

  RPI < 2.5
• Hyperproliferative anemia

  RPI > 2.5
• RPI

  Corrected Retic count/2
• Macrocytosis

  MCV > 100
• Types of macrocytic anemia

  • Megaloblastic
  • Non megaloblastic
• RPI < 2.5

  Normal/decreased MCV
• Increased MCV

  Macrocytosis
• Causes of macrocytic anemia with RPI < 2.5

  • Iron deficiency anemia
  • Anemia of chronic disease
  • Sideroblastic anemia
  • Thalassemia trait
• Heme iron

  Fe2+ state, Transported via heme transporter
• Non-heme iron

  Fe3+ state, Transported via Divalent Metal Transporter (DMT-1)
• 2/3rd of dietary iron is heme iron, 1/3rd is non-heme iron
• Iron stores detection

  Prussian blue (mainly hemosiderin)
• Iron stores in the body

  • Bone marrow
  • Macrophage
  • Liver
  • Brain
  • Duodenal enterocytes
• Iron indices

  • Serum ferritin
  • Serum iron
  • TIBC (Total iron binding capacity)
  • TSAT (Transferrin Saturation)
• Serum ferritin

  Reflects iron stores in the body, Earliest marker of Fe deficiency anemia, High S. ferritin (acute phase reactant) cannot rule out Fe deficiency
• Serum iron

  Amount of transferrin bound Fe in circulation
• TIBC

  Indirect measurement of S. Transferrin
• TSAT

  TSAT = (S. Fe/TIBC) x 100, Around 33% or 1/3rd of TIBC
• Iron stored inside the cell

  Fe3+ state, Ferritin (major), Hemosiderin (minor: Macrophages)
• Iron transport

  1. Iron in Fe2+ state transported out via ferroportin

  2. Hephaestin in basolateral membrane converts Fe2+ → Fe3+

  3. Fe3+ binds to transferrin (transport form)

  4. Fe3+-transferrin complex

  5. Marrow → Soluble transferrin receptors: Bind Fe-transferrin complex

  6. Transferrin released into circulation

  7. Fe3+ taken up for erythropoiesis
• In brain, conversion of Fe2+ → Fe3+ is done by ceruloplasmin
• Earliest marker of Fe deficiency: S. Ferritin, Most specific & sensitive marker: Soluble Transferrin Receptor assay (STFR) or log ferritin
• Free erythrocyte protoporphyrin: Lack of Fe to bind to protoporphyrin
• Clinical features of iron deficiency anemia

  • Fatigue
  • Tiredness
  • Palpitation
  • Pallor on examination
  • PICA symptoms (especially pagophagia)
  • Restless leg syndrome
  • Epithelial changes (nails, tongue, mouth, hypopharynx, stomach)
  • Growth related issues
  • Neuropsychiatric issues in growing child
  • Hair loss
• Anemia in males usually evaluated with colonoscopy and upper GI endoscopy to rule out GI bleed
• Anti-Ttg ab, anti-endomysial ab used to detect celiac disease
• EPO therapy should be started only after replenishing iron stores
• Causes of iron deficiency anemia

  • Menstrual loss (mainly in females)
  • GI blood loss unless proved otherwise
  • Celiac disease: Malabsorption
  • CKD on erythropoietin therapy (with EPO resistance)
  • Nutritional deficiency