Delta Sem (6) - Hematology Lecture (1) - Erythropoiesis & Anemia

Hematology

• Hematology covers erythropoiesis and anemia.

Hematopoiesis

• The process of blood cell formation.
• Erythropoiesis is the formation of red blood cells.
• Leucopoiesis is the formation of white blood cells.
• Megakaryopoiesis is the formation of platelets.

Erythropoiesis

• New red blood cells formation
• Involves a gradual decrease in cell size
• Causes condensation and eventual expulsion of the nucleus
• Leads to increase in hemoglobin production

Normal Adult Red Cell Values

• Hemoglobin for adult males is 14-16 g/dl
• Hemoglobin for adult females is 13-15 g/dl
• PCV/HCT for adult males is 40-52%
• PCV/HCT for adult females is 36-48%
• Red cell count for adult males is 4.5-6.5 x10^12/l
• Red cell count for adult females is 3.9-5.6 x10^12/l
• Mean corpuscular volume is 80-95 fL
• Mean corpuscular hemoglobin 27-34 pg
• MCHC 30-35 g/dL
• Reticulocyte count of 50-150 x10^9/L

Anemia

• Reduction in hemoglobin concentration
• Reduction in red blood cells and hematocrit values below normal for age and sex
• Hemoglobin for adult males is less than 130 g/L
• Hemoglobin for adult females is less than 120 g/L
• Anemia is a sign of a disease process rather than a disease

Etiological Classification of Anemia

• Decreased Bone Marrow function may cause aplastic anemia.
• Bone marrow infiltration may cause leukemia or lymphoma.
• Deficiency in substances essential for hematopoiesis causes deficiency anemia
• Iron deficiency anemia
• Megaloblastic anemia is due to vitamin B12 and folic acid deficiency.
• Excessive red blood cell loss causes Hemorrhagic anemia or Hemolytic anemia.
• Chronic disorders cause anemia.
• Endocrinal disorders cause anemia.
• Renal failure cause anemia.
• Liver disease anemia.
• The reticulocyte count assesses red blood cell regeneration, hyporegenerative Regenerative anemia helps to identify.

Morphological Classification of Anemia

• Microcytic anemia has a decreased MCV of less than 80 fL
• Microcytic anemia has aMCH of less than 27 pg
• Microcytic anemia has a MCHC of less than 30 g/dl
• Microcytic anemia includes iron deficiency anemia, thalassemia, lead poisoning, sideroblastic anemia, and anemia of chronic disease.
• Macrocytic anemia has MCV higher than 95-100 fL
• Macrocytic anemia is megaloblastic when caused by Vitamin B12 or folic acid deficiency
• Macrocytic anemia is non-megaloblastic when caused by alcohol, pregnancy, liver diseases, smoking, and reticulocytosis.
• Mean Corpuscular Volume (MCV) is the size of red blood cells.
• Mean Corpuscular Hemoglobin (MCH) is the hemoglobin concentration inside red blood cells.

BM Proliferative Response

• Hypo-proliferative anemia (aregenerative) are due to Bone Marrow failure/Aplastic anemia, Myelodysplasia, Anemia of chronic disease, and Megaloblastic anemia.
• Hyperproliferative is regenerative and is due to Hemorrhage, or Hemolysis.
• Reflected by Reticulocytes' count (RC) = (Normal = 0.5-2.5%)

Clinical Manifestations of Anemia

• Reflects diminished oxygen supply to the tissues.
• Depends on speed of onset, severity of anemia, age of patient, and underlying diseases, especially cardiovascular diseases

Anemia Symptoms

• Lack of concentration, headache, tinnitus, and blurring of vision.
• Low COP symptoms, exertional dyspnea and palpitation, angina and intermittent claudication, and symptoms of heart failure
• Bone ache, and fatigability.
• Menstrual disturbance and decreased libido.
• Polyuria.

Anemia Signs

• Detected in palm and palmer creases, nail bed, tongue and inner conjunctiva
• Pallor may also arise from infective endocarditis, MI, and myxedema.
• Tachycardia, hemic murmur, collapsing pulse, capillary pulsation, and congestive heart failure.
• Increased capillary permeability, and HF.
• Koilonychia (spoon nails) and angular stomatitis indicate IDA.
• Jaundice indicates hemolytic and megaloblastic anemias.
• Bone deformity and mongoloid facies indicate thalassemia.
• Leg ulcer indicates sickle cell anemia.
• Purpura and infection suggests decreased Bone Marrow
• Beefy red tongue may indicate megaloblastic anemia
• Pain and paresthesia indicates B12 deficiency.

Laboratory Investigations

• Red blood cells are normocytic, microcytic, or macrocytic.
• Decreased White blood cells and platelets in pancytopenia.
• Pancytopenia indicates aplastic anemia, hypersplenism, myelofibrosis, a leukemic leukemia, BM infiltration, megaloblastic anemia, PNH, or SLE.
• Bone marrow exam tests for Bone Marrow Failure, leukemia, and infiltration.
• Increased Reticulocyte Count indicates Hemolytic anemia or Hemorrhagic anemia.
• Decreased Reticulocyte Count indicates Bone marrow Failure or infiltration.

Microcytic Anemia Investigations

• Check serum iron, serum ferritin and TIBC.
• Perform Hemoglobin Electrophoresis.
• In IDA, serum iron and serum ferritin are decreased, while TIBC is increased
• In Anemia of chronic disease, serum iron is decreased, serum ferritin may be normal or increased, and TIBC is decreased
• In Thalassemia, serum iron, serum ferritin and TIBC are all normal
• In Sideroblastic Anemia, serum iron and serum ferritin are increased, while TIBC is normal

Normocytic Anemia Investigations

• Increased Reticulocytes indicates hemolytic & hemorrhagic
• Decreased Reticulocytes indicates Bone Marrow failure
• Decreased cellularity and Increased fatty spaces in Aplastic Anemia
• Serum bilirubin, urine urobilinogen, and fecal stercobilinogen are increased; serum haptaglobin is decreased and reticulocytosis, and Bone Marrow Analysis erythroid hyperplasia are present

Hemolytic Anemia Investigations

• Perform a Hemoglobin electrophoresis to test for hemoglobinopathies.
• Perform a sickling test to test for sickle anemia.
• Test with osmotic fragility for spherocytosis.
• Enzyme assay for GP6D
• Direct coomb's test for autoimmune hemolytic anemia
• Ham’s test and flow cytometry → PNH (hemolysis of RBCs at low pH serum).
• For Macrocytic Anemia serum Folate and B12 level should be checked.

Microcytic Hypochromic Anemia

• Most common cause of anemia
• Most important cause of microcytic hypochromic anemia.
• Majority affected are young children, adolescent girls, and women.
• Iron is absorbed in the duodenum.

Etiology of IDA Include

• Low iron diet, such as in young children and those with restricted diets (vegetarian, vegan)
• Chronic External blood loss, such as menstrual blood loss in post-menarchal adolescents and gastrointestinal blood loss in adolescent and adult males.
• Blood donation.
• Malabsorption, such as Gastrointestinal conditions (Crohn’s disease, tropical sprue and celiac disease) in recurrent, refractory, persistent cases, or Iron refractory iron deficiency anemia (IRIDA).

Clinical Presentation of IDA Include

• General symptoms & signs of anemia, painless glossitis, angular stomatitis, and pica
• Brittle, ridge or spoon nails (koilonychia) and dysphagia as a result of pharyngeal webs (Paterson-Kelly or Plummer-Vinson syndrome).
• Koilonychia and Angular cheilosis
• Paterson-Kelly (plummer – Vinson syndrome: barium swallow x-ray showing filling defect due to post-cricoid web

Diagnosing Ida

• Positive clinical history
• Full blood count indicates Microcytic anemia
• Blood film indicates microcytosis, hypochromia, pencil cells, anisopoikilocytosis
• Reticulocyte count is decreased in relation to anemia
• Iron studies includes low serum iron, increased TIBC, low transferrin saturation
• Low ferritin is always consistent with iron deficiency
• Investigate cause with and occult blood test, test for Helicobacter pylori, and do Radiology of pelviabdominal US or CT.
• Endoscopy, and Upper & lower GIT endoscopy
• If present symptoms and history are inconsistent / normal iron panel, consider other causes of microcytic anemia.

Treating IDA

• Address underlying etiology
• Increase iron-rich diet, such as meat, liver, beans (black beans or lentils)
• Minimize blood loss with Hormonal therapy or treatment of underlying uterine disorder
• Oral iron therapy with Ferrous sulfate (iron salt) for better absorption, Ferrous fumarate, or Ferrous gluconate.
• Parenteral iron administered via Ferric hydroxide and Iron dextran
• Not considered standard of care for majority of patients, used in patients with chronic kidney diagnosis, With intolerance to oral iron, With malabsorption, With persistent IDA despite oral iron therapy, For severe cases.

Etiology of Refractory IDA

• Incorrect diagnosis
• Persistence of etiology → Ongoing blood loss
• Insufficient iron dose
• Non-adherence
• Malabsorption → Inflammation/underlying GI condition
• Some genetic mutations that cause resistance in iron absorption.

Take Home Message for Anemia And IDA

• There are different types and different classifications of anemia
• Not every microcytic anemia is IDA
• Perform the full investigations mainly Iron profile to confirm the diagnosis
• If proved IDA, search for the cause and give proper therapy