PATH - Normocytic (80-100fL), normochromic anemia

Question 1

Intravascular hemolysis

Answer 1

DEC haptoglobin
INC LDH
schistocytes
INC reticulocytes on blood smear

hemoglobinuria, hemosiderinuria, and urobilinogen in urine. May also see INC unconjugated
bilirubin.

Notable causes are mechanical hemolysis (eg, prosthetic valve), paroxysmal nocturnal hemoglobinuria, microangiopathic hemolytic anemias

Question 2

Extravascular hemolysis

Answer 2

macrophages in spleen clear RBCs
Spherocytes in peripheral smear
urobilinogen in urine

INC LDH
INC unconjugated bilirubin–>jaundice

Question 3

Anemia of chronic disease

Answer 3

Nonhemolytic, normocytic anemia

Inflammation–>INC hepcidin–>DEC release of iron from
macrophages and DEC iron absorption from gut.

DEC iron
INC TIBC
INC ferritin

Associated with conditions such as rheumatoid
arthritis, SLE, neoplastic disorders, and chronic kidney disease.

TX: EPO

Question 4

Aplastic anemia

Answer 4

Nonhemolytic, normocytic anemia

Caused by failure or destruction of myeloid stem cells due to:
-Radiation and drugs
ƒ-Viral agents (parvovirus B19, EBV, HIV, hepatitis viruses)
ƒ-Fanconi anemia
ƒ-Idiopathic (immune mediated, 1° stem cell
defect); may follow *acute hepatitis

DEC reticulocyte count
INC EPO

Symptoms: fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infection

Pancytopenia characterized by severe anemia,
leukopenia, and thrombocytopenia

Question 5

Hereditary spherocytosis

Answer 5

Intrinsic hemolytic anemia

*Extravascular hemolysis due to defect in proteins interacting with RBC membrane skeleton and plasma membrane

Results in small, round RBCs with less surface area and no central pallor (INC MCHC)–>premature removal by spleen

Splenomegaly, aplastic crisis (parvovirus B19 infection)

osmotic fragility test ⊕. Normal to DEC MCV with abundance of cells

TX: splenectomy

Question 6

G6PD deficiency

Answer 6

Intrinsic hemolytic anemia

X-linked recessive

Most common enzymatic disorder of RBCs

*Causes extravascular and intravascular hemolysis.

Defect in G6PD–>DEC glutathione–>INC RBC
susceptibility to oxidant stress

Hemolytic anemia following oxidant stress (eg, sulfa
drugs, antimalarials, infections, *fava beans).

Back pain, hemoglobinuria a few days after oxidant stress

Labs: blood smear shows RBCs with *Heinz bodies and *bite cells

“*Stress makes me eat *bites of *fava beans with *Heinz ketchup.”

Question 7

Pyruvate kinase deficiency

Answer 7

Intrinsic hemolytic anemia

Autosomal recessive

Hemolytic anemia in a *newborn

Defect in *pyruvate kinase–>DEC ATP–>rigid RBCs–>extravascular hemolysis

Question 8

HbC disease

Answer 8

Intrinsic hemolytic anemia

*Glutamic acid–to-lysine mutation in β-globin.

Causes *extravascular hemolysis.

Labs (homozygotes): blood smear shows hemoglobin *crystals inside RBCs and *target cells.

Question 9

Paroxysmal nocturnal

hemoglobinuria

Answer 9

Intrinsic hemolytic anemia

Triad: Coombs ⊝ hemolytic anemia, pancytopenia, and venous thrombosis.

Labs: CD55/59 ⊝ RBCs

Acquired mutation in a *hematopoietic stem cell.

INC incidence of acute leukemias.

TX: eculizumab

Question 10

Sickle cell anemia

Answer 10

Intrinsic hemolytic anemia

Autosomal Recessive

*HbS point mutation causes a single amino acid replacement in β chain (substitution of *glutamic acid with valine).

low O2, high altitude, or acidosis precipitates sickling (deoxygenated HbS
polymerizes)–>anemia and faso-vaso-occlusive disease.

Causes extravascular and intravascular hemolysis

Newborns are initially asymptomatic because of
INC HbF and DEC HbS.

Heterozygotes (sickle cell trait) also have *resistance to malaria.

• Sickle cells are crescent-shaped RBCs
• “Crew cut” on skull x-ray due to marrow expansion from  erythropoiesis (also seen in
  thalassemia) .

Complications:
-Aplastic crisis
-Autosplenectomy (Howell-Jolly bodies)
-Splenic infarct/sequestration crisis.
ƒ-Salmonella osteomyelitis.
ƒ-Painful crises (vaso-occlusive): dactylitis, priapism,
acute chest syndrome, avascular necrosis, stroke.
ƒ-Renal papillary necrosis and
microhematuria (medullary infarcts).

Diagnosis: hemoglobin electrophoresis

TX: hydroxyurea ( HbF), hydration

Question 11

Autoimmune hemolytic anemia

Answer 11

Extrinsic hemolytic anemia

Warm (IgG)—chronic anemia seen in SLE and CLL and with certain drugs (α-methyldopa)
(“warm weather is *Great”).

Cold (*IgM and complement)—acute anemia triggered by cold; seen in CLL,
*Mycoplasma pneumonia infections, and infectious Mononucleosis
(“cold weather is MMMiserable”).
-RBC agglutinates may
cause painful, blue fingers and toes *with cold
exposure

Autoimmune hemolytic anemias are usually
Coombs⊕

Question 12

Microangiopathic anemia

Answer 12

Extrinsic hemolytic anemia

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

Seen in DIC, TTP/HUS, SLE, and malignant hypertension.

*Schistocytes (eg, “helmet cells”) are seen on
peripheral blood smear

Question 13

Macroangiopathic anemia

Answer 13

Extrinsic hemolytic anemia

*Prosthetic heart valves and *aortic stenosis may
also cause hemolytic anemia 2° to mechanical
destruction of RBCs

*Schistocytes on peripheral blood smear.

Question 14

Infections

Answer 14

Extrinsic hemolytic anemia

INC destruction of RBCs (eg, malaria, Babesia).