7 - Hemolytic Anemia

When would free Hb be released into the bloodstream, and why is too much dangerous?

• Intravascular hemolysis

• Scavenges nitric oxide and causes vasoconstriction and is toxic to tubular cells of kidney(Can lead to AKI via ischemia or direct toxic damage)

Trace intravascular hemolysis pathway:

• RBC lyses in vessel → Hb released → Hb binds haptoglobin → Complex taken up by liver and broken down to iron and heme → Heme becomes bilirubin → If there is excess free Hb it goes to the kidney where it’s reabsorbed, but if there’s too much, it comes out in urine → Hemoglobinuria

Trace extravascular hemolysis pathway:

• RBC eaten in spleen → heme becomes biliverdin then unconjugated bilirubin → conjugated by liver → secreted as bile → most excreted as feces, some reabsorbed to continue the cycle → If there’s too much, they become gallstones

What values can we pretty much always expect to see go up or down in hemolytic anemia?

Goes up: Total bilirubin, polychromasia

Goes down: Haptoglobin, Hct, Hb

Why do we not see urinary bilirubin?

• Unconjugated bilirubin can’t cross glomerulus

G6PD Deficiency

• Clinical presentation and cause

• Mechanism

• Lab results

• Blood smear

• Acute hemolytic anemia due to fava beans, infection, or drugs(triggers that introduce ROS)

• Missing Glucose 6 Phosphatase Dehydrogenase enzyme

• Hb and Hct down, MCV can be higher because of reticulocytes

• Normochromic Normocytic RBCs with anisocytosis, poikilocytosis, bite cells, eccentrocytes, Hb leakage cells, ghost cells, polychromasia, Heinz body

Why can a G6PD enzyme activity test right after an acute episode be normal?

Because the G6PD deficient cells are destroyed, the remaining reticulocytes skew the result upward

Hereditary Spherocytosis

• Clinical presentation and cause

• Mechanism

• Lab results

• Blood smear

• Due to vertical proteins of RBC deficiency(Ankyrin, band 3, spectrin) causing a weak membrane and reducing surface area to volume ratio and it bunches up into a sphere → These spherocytes are not flexible and get stuck in the spleen → Spleen takes a bite or destroy them completely → Spherocytosis and anemia

• MCHC>35(because cell loses volume but not Hb concentration), increased osmotic fragility, low Hb, low Hct

• Spherocytes, polychromoasia

AIHA

• Clinical presentation and cause

• Mechanism

• Lab results

• Blood smear

• Anemia symptoms, jaundice, some splenomegaly due to autoimmune attack

• IgG coats RBC → spleen recognises via Fc receptors → EVH, surviving cells become microspherocytes. 1/3 activate complement → Kupffer cells (EVH) or MAC formation if complement pathway goes fully (IVH)

• Hb and Hct down, raised bilirubin, raised LDH, low haptoglobin, raised reticulocytes

• Spherocytes, polychromasia. DAT positive for IgG

AIHA (Cold)

• Clinical presentation and cause

• Mechanism

• Lab results

• Blood smear

• Anemia symptoms, jaundice, some splenomegaly due to autoimmune attack that happens especially in cold weather

• IgM causes autoagglutination + fixes complement 100% → C3b → Kupffer cells (EVH) or MAC (IVH). IgM dissociates at 37°C leaving C3d on RBC surface

• Hb and Hct down, MCV falsely elevated due to autoagglutination, raised reticulocytes

• Autoagglutination on smear, polychromasia. DAT positive for complement (C3d) only

Paroxysmal nocturnal hemoglobinuria

• Clinical presentation and cause

• Mechanism

• Lab results

• Blood smear

• Dark urine that’s worse in the morning due to a acquired somatic mutation of GPI anchor molecule

• Loss of GPI anchor → CD55 and CD59 absent from RBC surface → complement runs to completion unopposed → MAC → IVH. No splenic/hepatic involvement

• Hb and Hct down, raised reticulocytes, elevated MCV and RDW as a result. Iron deficiency can develop from chronic urinary iron loss

• Normochromic normocytic with polychromasia. Hypochromic microcytic if IDA develops. No spherocytes, no agglutination