Chapter 9 - Hemolytic Anemias

Define intracorpuscular and extracorpuscular RBC defects relating to hemolytic anemia classification

Intracorpuscular (intrinsic abnormalities)

• hereditary

  • defects in membrane, enzyme defects, hemoglobinopathies, thalassemia syndromes

• acquired

  • paroxysmal nocturnal hemoglobinuria (PNH)

Extracorpuscular (extrinsic abnormalities)

• acquired

  • immune hemolytic anemias, infections, exposure, micro/macroangiopathic hemolytic anemias, hypersplenism, general systemic disorders

Contrast lab tests that reflect increased RBC destruction from those that reflect RBC production

increased RBC destruction

• serum unconjugated (indirect) bilirubin

• serum haptoglobin

• lactate dehydrogenase (LDH)

RBC production

• Reticulocyte production index (RPI)

• RNA staining

Calculate a reticulocyte production index

corrects the hematocrit to a normal value of 45% and considers the maturation time of the reticulocyte at a particular hematocrit (approximately 1.0 day at a hematocrit of 45%, 1.5 days at 35%, 2.0 days at 25%, and 2.5 days at 15%).

RPI = % Reticulocytes / Reticulocyte maturation time x HCT % / 45%

RPI > 2.5 = hemolysis

Outline the approach and laboratory tests to classify the cause of red cell hemolysis

Coombs test (DAT test)

• pos = immunohemolytic anemias

• neg

  • smear-positive

  • smear-negative/nonspecific

  • → RBC morphology → diagnoses

Detail the structure of the red cell membrane

outer = hydrophilic = glycolipids, glycoproteins, proteins

middle = hydrophobic = phospholipids (fluidity)

inner = hydrophilic = proteins (AE1, integral, stability)

Spectrin = major skeletal protein

Ankyrin = major linker protein

Identify the molecular and red cell membrane defects associated with hereditary spherocytosis

Molecular

• decreased amounts of spectrin, ankyrin, AE1, or protein 4.2

RBC membrane

• spherocytes

• MCV usually normal

Recognize abnormal laboratory results associated with hereditary spherocytosis

spherocytes on peripheral smear

Vertical vs. Horizontal interactions red cell membranes

Vertical

• membrane and bilayer

• HS

• spectrin-ankyrin-AE1 interactions

Horizontal

• membrane skeleton

• spectrin-actin-protein 4.1R

• skeletal destabilization, HE, HPP

Name the functional abnormalities affecting membrane skeleton proteins in hereditary elliptocytosis and ovalocytosis

Identify the abnormalities that cause the severe fragmentation and microsphercytosis characteristics of hereditary pyropoikilocytosis

Recall lab findings associated with hereditary elliptocytosis disorders

Elliptical RBC

List disorders of red cell hydration and membrane cation permeability

mild