Introduction to Anemia, Hereditary Spherocytosis & G6PD

Flashcards about Anemia, Hereditary Spherocytosis & G6PD

What is Hemoglobin (Hb)?

Iron-containing, oxygen transport protein found in red blood cells; less indicates anemia, more indicates polycythemia.

What is Mean Corpuscular Volume (MCV)?

Average size of RBCs; normal (normocytic) is 80-100 fL, smaller (microcytic) is

What is Mean Corpuscular Hemoglobin (MCH)?

Average content of Hb per RBC; can be normal (normochromic) or reduced (hypochromic).

What is Mean Corpuscular Hemoglobin Concentration (MCHC)?

Concentration of Hb in each volume of RBC; very low in iron deficiency anemia, very high may indicate spherocytosis.

What is Hematocrit (Hct)?

Volume percentage of RBCs in blood.

What is Reticulocyte count?

Percentage of young, immature red blood cells (reticulocytes) in the blood; normal is 0.5% to 1.5%.

What is Red Cell Distribution Width (RDW)?

Coefficient of variation of MCV, indicates how similar or different the RBCs are in size; higher the variation, higher the RDW.

What defines Anemia?

Decreased level of Hemoglobin, Hematocrit, or RBC count, leading to reduced oxygen-carrying capacity of the blood and tissue hypoxia.

What are the clinical features of Anemia?

Pallor (conjunctiva, palms, and face), weakness, malaise, easy fatigability, dyspnea, angina pectoris (rarely), headache, dimness of vision, and faintness.

How is Anemia Classified?

Based on morphology (normocytic, microcytic, macrocytic) and based on pathophysiology.

Describe a Normal RBC in Morphological Classification

Biconcave shape with central pallor, no nucleus or organelles for more Hb and surface area, deformable for passage through small capillaries.

What causes Macrocytic Anemia?

Impaired DNA synthesis but normal RNA synthesis, nutritional deficiencies (B12, Folic Acid), alcohol use, hypothyroidism.

What causes Microcytic Anemia?

Hb synthesis is affected, less Hb production, smaller size of RBC, iron deficiency, thalassemia, sideroblastic anemia, anemia of chronic disease.

What causes Normocytic Anemia?

Signal for erythropoiesis reduced, not enough space for erythropoiesis, acute blood loss, liver disease, hereditary spherocytosis, early stage of iron deficiency anemia, reticulocytosis, sickle cell disease, primary bone marrow disease, Glucose 6 phosphate dehydrogenase deficiency (G6PD).

What are the causes of Blood Loss?

Acute loss (trauma) or chronic loss (gastrointestinal cancers, menorrhagia).

What are the causes of Decreased Production in Anemia?

Defective stem cells, no space in bone marrow, lack of raw materials for RBC production.

What are the causes of Hemolytic Anemias?

Membrane defects (Hereditary spherocytosis), Enzyme defects (G6PD deficiency), Hemoglobin defects (Sickle cell anemia, Thalassemia), Complement mediated lysis (Paroxysmal nocturnal hemoglobinuria), Autoantibodies against RBC antigens (Autoimmune hemolytic anemias), Mechanical damage to RBCs (Micro and Macroangiopathic hemolytic anemias).

What are the effects of Acute Blood Loss?

Decreased blood pressure, RAAS activation, water entering intravascular system, hemodilution, profound anemia, kidney releases EPO.

What are the effects of Chronic Blood Loss?

Rate of loss exceeds marrow regenerative capacity, iron reserves depleted, iron deficiency anemia appears, common in gastric bleeds, peptic ulcer disease, diverticulosis, cancers in GIT.

What are the Common Features in Hemolytic Anemias?

Shortened red cell life span, elevated erythropoietin levels, compensatory increase in erythropoiesis, accumulation of hemoglobin degradation products (bilirubin).

When are RBCs more prone to destruction by splenic macrophages in Extravascular Hemolysis?

RBCs are less deformable or have been rendered 'foreign' by antibody coating.

What causes RBCs to die within the vessels in Intravascular Hemolysis?

Mechanical injury to RBC, complement fixation, toxic injury, intracellular parasites.

What occurs during Intravascular Hemolysis?

Free hemoglobin released, bound by haptoglobin, serum haptoglobin levels reduced, free Hb becomes brown methemoglobin and is excreted in urine, hemosiderin accumulates within tubular cells.

What is the Laboratory Evidence of Hemolytic Anemia?

Normochromic normocytic anemia, polychromasia, erythroid hyperplasia, elevated bilirubin, LDH, decreased haptoglobin, free hemoglobin level, hemosiderinuria, hemoglobinuria.

What is Hereditary Spherocytosis?

Inherited disorder caused by intrinsic defects in the red cell membrane skeleton, RBCs become spheroid in shape, less deformable, and are destroyed in the spleen, average RBC lifespan is 10-20 days.

What is the Pathogenesis of Hereditary Spherocytosis?

Reduced RBC membrane stability, loss of small fragments during shearing, RBCs become spherical, splenic sinusoids difficult to traverse, phagocytosis by macrophages, splenomegaly, increased MCHC.

What are the Clinical Features of Hereditary Spherocytosis?

Anemia, Splenomegaly, Jaundice, Increased reticulocytes, LDH, Family history, Intercurrent infections with Parvovirus B19.

What are the Hematological Findings in Hereditary Spherocytosis?

Normocytic normochromic RBCs, Spherocytes, Polychromatophilic cells, Howell Jolly bodies, MCHC high, Positive Osmotic Fragility Test, Negative Coombs test.

What is G6PD Deficiency?

Deficient or impaired enzyme function, abnormalities in hexose monophosphate shunt or glutathione metabolism, reduced ability of red cells to protect against oxidative injuries.

ETIOPATHOGENESIS of G6PD

Glucose 6 phosphate dehydrogenase deficiency, X linked recessive inheritance, absence renders RBC sensitive to oxidative stress.

What are the Hemolysis in G6PD Deficiency?

Significant membrane damage in RBCs leads to intravascular hemolysis or less membrane damage can result in spherocytes and extravascular hemolysis.

What are patterns of presentation for G6PD Deficiency?

Acute hemolysis after exposure to oxidant stress (infections, drugs, fava beans), neonatal jaundice, recovery phase with reticulocytosis, intermittent hemolytic episodes.

How is G6PD Deficiency Diagnosed and what Lab Findings?

Clinical history, CBC, evidence of hemolysis, peripheral blood findings (Normocytic normochromic anemia, Heinz bodies, Polychromatic cells, Bite cells), G6PD enzyme assay.

What you should know about G6PD Deficiency

the Mediterranean variant is more severe vs African variant , avoid G6PD enzyme assay is conducted immediately after a hemolytic episode