11. Hemolytic and Intrinsic Anemia Flashcards
*** Classification of Hemolytic Anemias
Intrinsic Defects -
Extrinsic Defects- Outside the body “attacks” the cells
Hemolytic Anemia
-RBCs have a shortened life span and hemolyze before 120 days.
Extravascular Hemolysis
- break down of red blood cells outside of the blood vessels
Intravascular Hemolysis
- break down of red blood cells inside the blood vessels
- doesn’t happen too often
**Increased extravascular hemolysis
Liver becomes overwhelmed with the amount of billirubin…
*** Increased intravascular hemolysis
look up in book :(
Tests Reflecting Increased RBC destruction
Intravascular
- Hemoglobinuria, hemoglobinemia, hemosiderinuria
- Decreased haptoglobin
- Increased LDH
- Increased serum bilirubin
- Increased retics
Pyruvate Kinase Deficiency
- most common enzyme deficiency in the Embden-meyerhof pathway
- autosomal recessive
- results in decreased ability to generate ATP
- Affects ability to maintain osmotic gradient
- Results in accumulation of 2,3-DPG (decreases the affinity for oxygen to bind to hemoglobin)
- Clinical - variable anemia, chronic hemolysis, splenomegaly, gallstones
Pyruvate Kinase Deficiency - Lab Values
- Normocytic, normochromic anemia
- increased Reticulocytes (even more post-splenectomy)
- Smear - increased polychromasia, anisocytosis, nRBC
- Increased bilirubin, decreased haptoglobin
- Diagnostic test - PK screen, PK assay (flourescent spot test)
Heinz bodies / Bite cells
- denatured hemoglobin in RBCs
- results from oxidation
- cells containing theses are destroyed by the spleen
G6PD Deficiency
- X-linked recessive
- inability to protect against oxidative stress
- Clinically asymptomatic until oxidative stress
- During hemolytic episodes, may experience hemoglobinuria and jaundice
- There are variants of G6PD ( Type A -/+ Type B -/+)
G6PD Laboratory Values
- Normocytic, normochromic anemia
- Smear - Increased poly, poik, bite or helmet cells** (halmark)
- Increased bilirubin, decreased haptoglobin
- Heinz body prep - stain with supravital stain, not specific for G6PD
- Diagnostic test - G6PD screen or assay (fluoresce if present)
RBC Membrane
- Semi-permeable lipid bi-layer supported by a protein cytoskeleton
- Chemically - 40% lipid, 52% protein, 8% carbohydrate
- Glycophorin: principal RBC glycoprotein, location of RBC antigens
- Spectrin: major cytoskeletal protein (along with ankyrin)
Hereditary Spherocytosis
- autosomal dominant but can be from a new mutation
- Membrane defect resulting in loss of surface area of RBC membrane
- Spectrin, ankyrin deficiency
- Cells demonstrate increased osmotic fragility
- Clinical - anemia, jaundice, splenomegaly
- Frequent gallstones due to increased bilirubin in bile
- Treatment - splenectomy
Hereditary Spherocytosis Laboratory Values
- Increased MCHC (no central palor)
- Smear - spherocytes, increased poly
- Increased reticulocytes
- Abnormal osmotic fragility test
- RBC membrane studies
Hereditary Elliptocytosis
- autosomal dominant
- Characterized by large numbers of elliptical cells
- Functional defect of spectrin is suspected
- Not usually symptomatic
Hereditary Elliptocytosis Laboratory Values
- Normal RBC indices
- Smear - greater than 30% elliptical cells
Hereditary pyropoikilocytosis
- Thermal instability of RBC
- Severe hemolytic disease
- Smear: microspherocytosis, micropoikilocytosis, fragments (very bizzar looking)
Hereditary Stomatocytosis
- autosomal dominant
- Alteration in RBC permeability of cations
- Results in RBC swelling
- Variable hemolytic anemia
- Smear: stomatocytes (mouth cells)
Hereditary Xerocytosis
- autosomal dominant
- Alteration in RBC permeability of cations
- Results in RBC dehydration
- Cells not sequestered in the spleen
- Smear: RBCs with condensed hemoglobin pockets
Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Acquired stem cell disorder – affect RBC, WBC and platelets
E- pisodic hemolysis, hemoglobinuria and thrombosis - Pancytopenia
- Cells lack CD 55 and 59 which normally protect the cells from lysis by complement
- All cells show an increased susceptibility to lysis by complement
PNH Lab Findings
- Anemia
- Hemoglobinuria, hemosiderinuria
- Decreased haptoglobin; increased plasma hemoglobin
- Direct anti-globulin test (Coombs test) is negative
- Positive Sucrose Hemolysis Test
- Positive Acidified Serum Lysis Test
- Decreased expression of CD 55 and CD 59
Sucrose Hemolysis test
Hypotonic solution; PNH affected patients’ red cells lyse
Acidified Serum Lysis (Ham’s Test)
Needed for lysis:
- PNH cells
- complement
- acid conditions
