Hemolytic Anemia Flashcards
Hemolytic Anemia Classification System
Extravascular: within macrophages in spleen, liver, and bone marrow; this is how RBCs die normally
Intravascular: within the blood stream and leave substances that are not supposed to be in the blood; abnormal
Intrinsic: RBC issues stem from hereditary causes such as abnormal Hb, enzyme defects, membrane abnormalities
Extrinsic: RBC issues stem from outside processes such as immunologic, mechanical factors, infections/toxins, liver disease, and hypersplenism
Mechanisms of Extravascular Hemolysis
Abnormal environment: infections, medication, immunologic process
RBC membrane abnormalities
RBC metabolic defects
Abnormalities in Hb structrure
Mechanisms of Intravascular Hemolysis
- mechanical damage to RBCs:
a. fibrin present in vessel lumen (DIC or vasculitis)
b. physical trauma of RBCs (prosthetic valves)
c. thermal injury from burns - Infection (malaria) or toxins (poisonous snakes)
- complement mediated: cold agglutinins, incompatible RBCs transfusions, paroxysmal nocturnal hemoglobinuria
Pathogenesis of Intravascular Hemolysis
Hb released binds to haptoglobin to decrease serum level of haptoglobin, but when binding capacity is exceeded the free Hb is filtered in the kidneys, thus turning the urine red
Hb can be detected in tubular cells and can be microscopically, but cannot see RBCs
Hemosiderin can be seen in the urine because product from Hb = positive for iron stains of urinary sediment
Intrinsic - Hereditary RBC Disorders
Abnormal Hb: sickle cell disease and thalassaemias
Membrane abnormalities: spherocytosis, elliptocytosis
Enzyme defects: G-6-PD
Extrinsic - Acquired Hemolytic States
Autoimmune hemolytic anemia
Malaria
Microangiopathic hemolytic anemia
Hemolytic Anemia: Labs
CBC Reticulocyte count (increases) Erythropoietin Peripheral smears (increased RBC fragments) Bone marrow aspirate and biopsy
Intravascular Hemolysis: Labs
decreased serum haptoglobin level \+ Free Hb in plasma \+ Hemoglobinuria \+ iron stain in urinary sediment Presence of plasma or urine hemoglobin Detection of hemosiderin in renal tubular cells in the urinary sediment
Extravascular Hemolysis: Labs
Coombs test: Igs and Complement on RBC surface
Hb electrophoresis for hemoglobinopathies
These tests detect Hb and complement (Ab) in RBC surfaces or Hb electrophoresis
Peripheral Smear Findings
RBC morphological abnormalities: sickle cells, bite cells, schistocytes, spherocytes.
RBCs agglutination (increased Ig, parasites)
Erythrophagocytosis
Polychromasia- increased number of RBCs
Bone Marrow: hyperplasia of erythroid progenitors
Hemolytic Anemia: Dx
Compensatory production Reticulocyte index > 3 Absolute count is > 100,000/ mm3 Indirect bilirubin is elevated LDH may be elevated Serum haptoglobin diminished
Intravascular Urine and plasma Hb Iron stains of urinary sediment Extravascular Coombs tests Hb electrophoresis
Hereditary Spherocytosis
Autosomal inherited disorder
Intrinsic defects in RBCs membrane: spheroid RBCs (less deformable), which cause destruction especially in spleen
1/5000 in northern Europe
Reduced membrane stability
Beneficial effect of splenectomy (treatment)
Hereditary Spherocytosis Protein Defects
Defects in the RBC cytoskeleton that cause the cell to assume a spherical shape caused by a defect in the expression of spectrin, ankyrin, band 3, and protein 4.2
Hereditary Spherocytosis: Symptoms and Histology
Distinctive: Spherocytes, small and hyperchromic (lack central paleness).
Reticulocytosis
B.M. erythroid hyperplasia
Hemosiderosis
Mild jaundice
Cholelithiasis in 50% of the affected adults
Moderate splenomegaly (erythrophagocytosis)
Osmotic Fragility Test
Get RBCs from venipuncture and expose to different concentrations of sodium chloride from 0-1%
The volume to area ratio is higher in spherocytosis
Fragility is increased in these cells because in normal RBCs in 1%, which is the normal concentration of NaCl in the blood, so at 0.5% it will lyse, but as concentrations become closer to 1% (normal in body) then the cells will be less likely to lyse. In spherocytosis cells, the cells are more fragile and so they lyse between 1% and 0.5% because they cannot handle the concentration difference as much, so they lyse sooner than 0.5%
Herediary Spherocytosis - Diagnosis
Osmotic fragility test- initial
Molecular studies of ankyrin gene - confirms dx
G6PD
Impaired enzyme function reduce the ability of RBCs to protect against oxidative stress/injury causing acute episodic intra/extravascular hemolysis
Leads to anemia, hemoglobinemia, hemoglobinuria
Lysis is self limited
Prevalent in areas where malaria is endemic
Increases Hb presence in blood and urine
Hb oxidation causes denaturation in globin chains, which precipitate in the cytoplasm creating Heinz bodies and induces hemolysis
Presence of Howell-Jolly bodies, Heinz bodies, and bite cells
RBC Extrinsic Defects
Immune hemolytic anemia:RBC covered with Ig and/or C3
Non immune hemolytic anemia:RBC trauma
Immune Hemolytic Anemia
Ab and can be classified by warm or cold Ab depending on which temperature the Ab are functional; intra or extravascularly
Lysis occurs at warm temperatures (37/98.9) with IgG involvement, splenic macrophages recognize Fc receptors, but 50% idiopathic
Lysis occurs at cold temperatures (4/39.2) with IgG or IgM involvement, idiopathic or viral (EBV), or Ab against Ag system on RBC
The Antiglobin Test
The Antiglobulin test (Coomb’s test) is used to distinguish immune from nonimmune – mediated hemolysis.
The Coomb’s reagent – Antibodies that recognize either the Fc portion of human Ig or C3d
Diagnostic for: hemolytic disease of the newborn acquired autoimmune hemolytic anemia transfusion reaction RBC sensitization caused by drugs
Positive Test: When blood precipitates because RBC have the Ab on the surface and make net and precipitate
Fetal Hemolytic Disorder
Mother becomes sensitive to Ag that are present in fetus, especially with negative Rh factor and the baby has a positive Rh factor and then the mother IgG crosses the placenta and destroys the RBCs of the fetus even within the bone marrow and also destroys hepatocytes which decreases albumin and oncotic pressure and causes edema within the fetus and the fetus cannot survive = hydrops fetalis
Hypersplenism Anemia
Anemia secondary to spleen enlargement
Increased RBC sequestration in the spleen/enhanced phagocytosis by macrophages
Causes of hypersplenism: portal hypertension, collagen vascular disease, RA
Blood picture is that of pancytopenia (deficiency of all blood cells including RBCs, WBCs, and platelets)
Overall Hemolysis Lab Test Results
LDH – elevated. Bilirubin – elevated (mostly indirect). Haptoglobin – decreased. Peripheral smear – spherocytes, schistocytes bite cells, sickle cells, present. Reticulocyte count – markedly elevated
