RBC disorders 1 Flashcards
Anemia
Reduction, below normal limits, of total circulating red cell mass.
Clinical symptoms of anemia
• Easy fatigability and loss of energy
• Headaches
• Fainting or dizziness
• Shortness of breath
• Palpitations
Severe anemia: Angina ,CHF , confusion
Clinical signs of anemia
-Pallor
-Hemic murmurs
-Increased pulse rate and respiratory rate which can increase stroke volume and eventually (if severe) can lead to high output cardiac failure
Anemia can be classified based on:
1) The morphological changes in RBCs
2) The pathophysiological mechanisms causing the anemia
Morphological Classification of Anemia
-Normochromic/hypochromic
-macrocytic/normocytic/microcytic
-based on cell shape
Microcytic Hypochromic anemias
-iron deficiency
-anemia of chronic disease
-lead poisoning
-thalassemia
Normochromic Normocytic anemia
-acute blood cell
-hemolytic anemia
-anemia of chronic disease
Normochromic Macrocytic anemia
-folate deficiency
-B12 deficiency
Classification of Anemia According to Underlying Mechanism
-accelerated RBC loss / destruction
-impaired RBC production
What is the immediate concern with anemia caused by acute bleeding
Hypovolemia
-it is a normocytic normochromic anemia
Anemia caused by chronic blood loss
-Rate of loss > RBC regeneration
-iron stores are gradually depleted
-no risk of hypovolemia
-microcytic hypochromic anemia
Hemolytic anemias common features
- Shortened RBC life span( below 120 days) - Increase in erythropoietin & erythropoiesis - Accumulation of Hb breakdown products
Classification of hemolytic anemias
1) By site: intravascular or extravascular
2) By cause: intrinsic or extrinsic (to RBCs)
Intravascular Hemolysis:
-Mechanical injury to RBCs
-complement fixation
-infections
-no organomegaly
Extravascular Hemolysis
– Caused by defects that increase the destruction of RBCs by the phagocytes in the spleen
• RBCs rendered “less deformable”
• RBCs rendered “foreign” usually by immune
mechanism (antibody coating)
– Associated with Splenomegaly
Laboratory Evidence of Hemolytic Anemia- peripheral blood
– Normochromic normocytic anemia, with polychromasia ±
nucleated RBCs.
Laboratory Evidence of Hemolytic Anemia-bone marrow
– Show erythroid hyperplasia leads to RBC
production(↑Reticulocytes)
Laboratory Evidence of Hemolytic Anemia-Plasma/serum: RBC breakdown
-Increased Bilirubin (unconjugated )
-increased LDH
-absent haltoglobin
-increased free Hb (intravascular )
-, Hemoglobinuria (intravascular hemolysis/ negative in extravascular )
Intrinsic RBC Defects
-hereditary
– Membrane defect: Hereditary Spherocytosis
– Enzyme defect: G-6-PD deficiency, Paroxysmal nocturnal hemoglobinuria (PNH) – Acquired
– Hemoglobin defect: Sickle cell disease, Thalassemi
Extrinsic Defects
-Acquired
– Immune mediated damage: autoimmune diseases,drugs-associated, transfusion reaction.
– Nonimmune damage: mechanical trauma, infections,chemicals, hypersplenism
Hereditary Spherocytosis
- inherited abnormalities in critical proteins in the RBC membrane skeleton
• The RBCs become spheroid in shape, less deformable, and are destroyed in the spleen
• Average RBC lifespan is10-20 days
What proteins are affected in hereditary spherocytosis
-ankyrin , band 3 , spectrin and band 4.2
Pathogenesis of Hereditary Spherocytosis(extravascular)
Reduced RBC membrane stability→loss of small fragments during normal shearing stresses in the blood circulation→RBCs become increasingly more spherical→unable to traverse the splenic sinusoids→phagocytosis and destruction by splenic macrophages (spleen usually enlarged)
Hereditary Spherocytosis: Clinical Features
-Anemia
-splenomegaly
-jaundice
Hereditary Spherocytosis: Diagnosis and Lab Findings
-family evidence
-hemolysis
-Normochromicnormocyticanemia
• Spherocytes
• Polychromaticcells±nucleated RBCs
• Howell-Jolly bodies
-increase in MCHC
Osmotic fragility test for hereditary spherocytosis
– This test confirm the presence of spherocytes
– Spherocytic RBCs lyse prematurely (compared to normal RBCs), when exposed to increasingly hypotonic salt solutions
Coombs test fir hereditary spherocytosis
– Spherocytes can also be seen
– Autoimmune hemolytic anemias(+ve coombs test)
– A Negative Coombs test will confirm the diagnosis of Hereditary spherocytosis
G6PD A- variant:
– Present in ~ 10% of the American Blacks
– Characterized by normal enzyme activity but a decreased half-life
G6PD Mediterranean variant
– Mostly seen in Middle Eastern populations
– Thought to be due to natural selection
-half live severely reduced
G6PD Deficiency: Pathophysiology
-Abnormal enzyme variants are misfolded and are thus susceptible to proteolytic degradation
-mature RBCs have no nucleus
-enzyme activity is decreased
-Heinz bodies (intravascular)
-bite cells (extravascular)
How are Heinz bodies formed
G6PD deficient RBCs, exposed to a high level of oxidants→oxidation of sulfhydryl groups (SH groups) on globin chains of Hb→denatured and formed membrane bound precipitate
How are bite cells foremen
If membrane damage is severe, intravascular hemolysis occurs. Less affected RBCs traverse the spleen where macrophages “bite” out the inclusions→bite cells.
-These abnormal RBCs are eventually removed by the spleen (extravascular hemolysis)
G6PD Deficiency: Clinical Presentation
-G6PD deficiency is an X-linked recessive disorder (mostly affect Males)
-neonatal jaundice
-Chronic low-grade hemolytic anemia
G6PD Deficiency: Diagnosis and Lab Findings
+/- Hemoglobinemia,& Hemoglobinuria ↑Reticulocytes,
-LDH,
-Free Hb
-Absent Haptoglobin
