H e m o l y t i c A n e m i a
Causes
Inherited
1. Defects in red blood cell membrane
2. Enzyme deficiencies
3. Defects in globin structure/synthesis
Acquired
3. Infection-related
• Protozoa (e.g., malaria, babesia)
• Bacteria (e.g., clostridia, typhoid fever)
Clinical Features
Chronic hemolytic anemias
• Usually congenital
• Sometimes well-compensated (bone marrow increases red cell production
to offset the hemolysis), with few symptoms (until a crisis happens).
• Crises (due to fragile equilibrium between red cell destruction and bone
marrow compensation)
• Usually precipitated by infection (especially common: parvovirus B19).
• Parvovirus attacks red cells; the already maxed-out bone marrow
cannot compensate!
• Splenomegaly
• Jaundice (increased unconjugated bilirubin)
• Gallstones (unclear pathophysiologic reasons)
Acute hemolytic anemias
• (usually acquired)
• Aching back, abdominal, and/or limb pain.
• Headache, malaise, fever.
• Pallor, jaundice, tachycardia.
Laboratory Findings
Signs of excessive red cell destruction
• Hemoglobinemia/hemoglobinuria (when hemolysis is intravascular, or so
brisk extravascularly that macrophages cannot keep up).
• Increased serum unconjugated bilirubin (unless liver can keep up with
excretion!).
• Decreased free haptoglobin (a protein that binds free Hgb).
• Increased lactate dehydrogenase (LDH) (a red cell enzyme).
• Decreased red cell lifespan (label cells with Chromium,
measure t ; rarely done because expensive, time-consuming).
Signs of accelerated erythropoiesis: reticulocytosis
1. Reticulocyte count = percentage of red blood cells that are reticulocytes
• normal = 1-3%
• This is just a raw measurement of how many reticulocytes there are.
It doesn't take into account things like the patient's hemoglobin, or
the presence of shift reticulocytes (see below)
• To be more precise, you need to do some calculations (below)
to account for these conditions.
2. "Corrected" reticulocyte count = reticulocyte % x Hgb/15
• This formula takes into account the patient's hemoglobin
(at lower hemoglobin, should have more retics!).
3. "Reticulocyte production index" = (reticulocyte %/reticulocyte maturation
time) x Hgb/15.
• This formula takes into account the fact that when the blood is 
desperate for red cells, the bone marrow starts pushing out very
young, not-quite-mature reticulocytes into the blood (these are called
"shift" reticulocytes).
• Because they are not as far along in development as normal
reticulocytes when they are kicked out into the blood, it takes
a little extra time in the blood before these shift reticulocytes are
fully mature.
• A rough measure of this extra time is the reticulocyte maturation time.
Normally (at Hgb of about 15), it takes 1 day for reticulocytes to
mature in the blood into red cells.
at Hgb of 12, it takes 1.5 days for (shift) reticulocytes to mature
at Hgb of 8, it takes 2 days for (shift) reticulocytes to mature
at Hgb of 5, it takes 2.5 days for (shift) reticulocytes to mature
Morphology
• Most cases of hemolytic anemia are normochromic and normocytic
• Spherocytes are always present, no matter what's causing the hemolysis
• Other more specialized poikilocytes:
• Target cells (seen frequently in thalassemia and hemoglobinopathies)
• Elliptocytes (seen frequently in hereditary elliptocytosis)
• Sickle cells (seen in sickle cell anemia)
• Schistocytes, helmet cells, other fragmented red cells
(seen in microangiopathic hemolytic anemia)
• Signs of increased erythropoiesis:
• Polychromatophilia (or, if stained with supravital stain, reticulocytosis)
• Basophilic stippling (RNA remnants not yet removed from cell)
• Nucleated red blood cells (bone marrow hurrying to get red cells out
as quickly as possible)
Important Lab Test
• Also called the Coomb's test.
• Mix patient's red cells with anti-IgG and anti-IgM antibodies.
• If the red cells are coated with antibodies (as they are in some immune
processes, see later), the anti-IgG or anti-IgM will attach to those antibodies,
bridging the red cells and making them clump together.
• So, a positive result (red cell clumping) means the patient's red cells are
coated with antibodies, and the hemolysis is probably immune-related.
Diagnosis
1. Is there hemolysis? Look for:
• Signs of increased red cell destruction
• Signs of increased erythropoiesis (if hemolysis has been around
long enough)
2. What's causing the hemolysis? Using the history, DAT, and blood smear,
you can catogerize patients into 5 groups:
• Patients with known exposure to infectious or chemical agents.
• Patients with positive DAT (diagnosis: immune-related hemolytic anemia).
• Patients with negative DAT but lots of spherocytes (probable diagnosis:
hereditary spherocytosis).
• Patients with negative DAT and other specific, morphologic
abnormalities (e.g., sickle cells).
• Patients with negative DAT and no specific morphologic abnormalities
(do Hgb electrophoresis).
