Normocytic Anemias with Predominant Extravascular Hemolysis Flashcards
What is hereditary spherocytosis? Describe the pathophysiology. What type of anemia does this cause?
Inherited defect in RBC cytoskeleton tethering proteins (ankyrin, spectrin or band 3.1). Membrane blebs lost over time resulting in a decreased amount of membrane and the inability to form the biconcave shape. RBCs form sphere shape which are consumed by splenic macrophages. Extravascular hemolysis normocytic anemia.
What are the clinical and laboratory findings associated with spherocytosis?
Spherocytes with loss of central pallor, Increased RDW, Increased mean corpuscular Hb conc, splenomegaly, jaundice w/ unconjugated bilirubin, increased risk for bilirubin gallstones
How is spherocytosis Dx?
Osmotic fragility test (hypotonic solution). Spherocytes are fragile and will lyse in hypotonic solution.
What is the Tx for spherocytosis induced extravascular hemolysis normocytic anemia? What are hematological findings after Tx?
Splenectomy. Spherocytes persist and Howell-Jolly bodies (fragments of nuclear material in RBCs) emerge on blood smear (spleen normally clears out RBCs containing DNA).
What is sickle cell anemia?
Autosomal recessive mutation in the beta chain of hemoglobin; hydrophilic glutamic acid is replaced with hydrophobic valine
In what population is sickle cell anemia 10%? Why?
Individuals of African descent, protective role against Plasmodium falciparum malaria
Physiologically, when does sickle cell diease arise? What is the prevalence of the sickle Hb in the RBCs?
When two beta genes are mutated resulting in 90% of HbS in RBCs
Describe the RBC sickling process. What are 3 risk factors for sickling?
HbS polymerizes when deoxygenated resulting in needle like structure. 1) Hypoxemia 2) Dehydration 3) Acidosis
What type of Hb protects against sickling? What drug increases this particular Hb?
HbF, hydroxyurea increases levels of HbF
Describe how how sickling and desickling results in RBC membrane complications.
Primarily Extravasc hemolysis: Reticuloendothelial system removes RBCs with damaged membranes resulting in typical extravasc hemolysis Syx and lab findings; Intravasc hemolysis: RBCs with damaged membranes dehydrate and lyse resulting in decreased available haptoglobin and target cells.
What is the body’s response to the extra in intravascular hemolysis? What type of infection could have devastating consequences on a patient with sickle cell disease?
Massive erythroid hyperplasia: Hemtopoiesis into skull (crewcut xray pattern) and facial bones (chipmunk facies), Extramedullary hematopoiesis with hepatomegaly, and risk of aplastic crisis with parvovirus B19 infection.
What are the consequences of irreversible RBC sickling?
Dactylitis, Autosplenectomy, Acute chest syndrome
