RBC Disorders - Hemolytic Anemia

Question 1

Hereditary spherocytosis

Answer 1

Extravascular hemolysis
Due to defect in proteins interacting w RBC membrane skeleton and plasma membrane
Ankyrin, band 3, protein 4.2, spectrin
Result: small, round (not discs) RBCs w less surface area and no central pallor –> premature removal by spleen –> anemia
Splenomegaly, aplastic crisis (parvovirus B19 infection)
Osmotic fragility test +
Normal-v MCV w abundance of cells
^MCHC (smaller, more concentrated), ^RDW
Tx: splenectomy

Question 2

Sickle cell anemia

Answer 2

HbS point mutation: glutamic acid (hydrophilic) replaced w valine (hydrophobic)
Causes extra and intravascular hemolysis
Pathogenesis: low O2, high altitude, or acidosis precipitates sickling (deoxygenated HbS polymerizes) –> anemia and vaso-occlusive disease
Newborns initially asymptomatic bc ^HbF and vHbS
Heterozygotes (trait) have resistance to falciparum malaria
8% African Americans carry HbS allele
Sickle cells = crescent shaped RBCs
Crew cut skull on x-ray due to marrow expansion from ^ erythropoiesis (also in thalassemia!)

Complications:

• aplastic crisis (due to parvovirus B19)
• autosplenectomy (Howell-Jolly bodies) –> ^ risk of infection by encapsulated bacteria (e.g. S. pneumonia) - most common cause of death in kids
• Splenic infarct/ sequestration crisis
• Salmonella osteomyelitis
• Painful crisis (vaso-occlusive): dactylics, priapism, acute chest syndrome (most common cause of death in adults), avascular necrosis, stroke
• Renal papillary necrosis: (v PO2 in papilla) and microhematuria (medullary infarcts)

Diagnosis: hemoglobin on electrophoresis
Tx: hydroxyurea (^HbF), hydration

Question 3

G6PD deficiency

Answer 3

Most common enzymatic disorder of RBCs
Causes extra and intravascular hemolysis
X-linked recessive
Defect in G6PD –> v glutathione (neutralizes H2O2) –> ^ RBC susceptibility to oxidative stress –> hemolytic anemia following oxidative stress (e.g. sulfa drugs, antimalarials, infection, fave beans)
African variant - mildly reduced half-life of G6PD –> mild intravascular hemolysis
Mediterranean variant - markedly reduced half-life –> severe intravascular hemolysis
Carrier protected against falciparum malaria
Back pain, hemoglobinuria a few days after the oxidative stress.
Labs: RBCs w Heinz bodies and bite cells - oxidative stress precipitates Hb as Heinz bodies, which are removed from RBCs by splenic macrophages –> bite cells

Question 4

Pyruvate Kinase deficiency

Answer 4

Autosomal recessive.
Defects in pyruvate kinase –> v ATP –> rigid RBCs –> extravascular hemolysis.
Hemolytic anemia in newborn.
Echinocytes “Burr” cells.

Question 5

HbC disease

Answer 5

Glutamic acid to ly-C-ine mutation in B-globin.
Causes extravascular hemolysis.
HbSC (1 of each mutant gene) milder than HbSS.
Labs (homozygotes): Hb Crystals inside RBCs and target cells.

Question 6

Paroxysmal nocturnal hemoglobinuria

Answer 6

^ complement-mediated intravascular RBC lysis

Acquired mutation in a hematopoietic stem cell –> absent GPI anchor –> DAF protective protein not secured to cell membrane –> cell susceptible to damage by complement.

^acute leukemias.
Triad: Coombs (-) hemolytic anemia, pancytopenia, venous thrombosis.
Labs: CD55/59 (-) RBCs on flow cytometry.
Tx: eculizumab (terminal complement inhibitor)

Question 7

Autoimmune hemolytic anemia

Answer 7

Antibody-mediated (IgG or IgM) destruction of RBCs.

WARM: IgG - chronic anemia w SLE, CLL, certain drugs (a-methyldopa, penicillin, cephalosporins) - extravascular hemolysis

COLD: IgM and complement - acute anemia triggered by cold w CLL, mycoplasma pneumonia, mononucleosis - intravascular hemolysis - RBC agglutinates may cause painful blue fingers and toes w cold exposure.

Often idiopathic.
Spherocytes

Coombs +
Direct Coombs test: anti-Ig antibody added to pt’s blood and RBCs agglutinate if RBCs are coated w Ig.
Indirect Coombs test: normal RBCs added to pt’s serum and if it has anti-RBC surface Ig, RBCs agglutinate when anti-Ig antibody is added.

Question 8

Microangiopathic anemia

Answer 8

RBCs are damaged when passing through obstructed or narrowed vessel lumina.

DIC, TTP/HUS, SLE, malignant HTN.

Schistocytes due to mechanical destruction of RBCs.

Question 9

Macroangiopathic anemia

Answer 9

Prosthetic heart valves and aortic stenosis may cause hemolytic anemia due to secondary mechanical destruction of RBCs/

Schistocytes