STEPTRACKERHEMATOLOGY | PATHOLOGY | HIGH-YIELD REVIEW

Hemolysis Basics & Hereditary Spherocytosis

Where red cells are destroyed — in the spleen or inside vessels — and the classic membrane defect that makes them spheres.

FOCUS ON
Know the two hemolysis patterns. Extravascular (spleen): jaundice, splenomegaly, gallstones. Intravascular: haptoglobin very low, hemoglobinuria, hemosiderinuria. For HS: spherocytes, ↑ MCHC, negative Coombs, abnormal EMA binding test, and splenectomy as the fix.
TOPIC
DETAIL
MECHANISM
CLUE
Extravascular hemolysis
spleen and liver
Macrophages engulf abnormal RBCs; heme → unconjugated bilirubin.
↑ LDH, ↑ indirect bilirubin, ↑ urine urobilinogen, mild ↓ haptoglobin
Jaundice, splenomegaly, pigment gallstones
Intravascular hemolysis
inside vessels
RBCs lyse in circulation; free Hb binds haptoglobin, then spills into urine.
Haptoglobin very low, hemoglobinemia, hemoglobinuria, hemosiderinuria later
PNH, G6PD crisis, MAHA, ABO mismatch, mechanical valves, malaria, cold AIHA
Intrinsic vs extrinsic
classification
Intrinsic: the RBC is defective. Extrinsic: the environment destroys a normal RBC.
Intrinsic: membrane (HS, PNH), enzyme (G6PD, PK), Hb (sickle, thal) · extrinsic: immune, MAHA, infection, mechanical, hypersplenism
Intrinsic defects are usually inherited (except PNH)
HS — defect
Ankyrin, spectrin, band 3 or protein 4.2 — the proteins tying the membrane to the cytoskeleton. Usually autosomal dominant.
Membrane lost in blebs → smaller surface area → sphere
Northern European ancestry most common
HS — labs
Spherocytes (no central pallor), ↑ MCHC, ↑ RDW, ↑ reticulocytes; MCV normal or low.
Coombs negative; ↓ eosin-5-maleimide (EMA) binding; ↑ osmotic fragility
EMA flow test preferred
HS — clinical
Anemia, jaundice, splenomegaly; neonatal jaundice; pigment (calcium bilirubinate) gallstones in childhood.
Spheres trapped in splenic cords and eaten
Parvovirus B19 → aplastic crisis
HS — treatment
Splenectomy for moderate–severe disease; folate.
Anemia resolves; spherocytes remain; Howell-Jolly bodies appear
Vaccinate for encapsulated organisms first
Hereditary elliptocytosis
Spectrin defect in horizontal links → oval cells.
Usually mild or none
Elliptocytes on smear

Mechanism — how a sphere is born and destroyed

Membrane protein defectAnkyrin, spectrin, band 3
→
Membrane lostBlebs shed
→
SpherocyteLow surface : volume
→
Trapped in spleenCan't deform
→
PhagocytosedExtravascular hemolysis

Losing membrane while keeping hemoglobin makes the cell dense — that is why MCHC rises.

Intravascular vs extravascular

FEATURE
EXTRAVASCULAR
INTRAVASCULAR
Site
Spleen, liver macrophages
Inside blood vessels
Haptoglobin
Mildly ↓
Markedly ↓ / absent
Urine
↑ urobilinogen
Hemoglobin, then hemosiderin
Spleen
Enlarged
Usually normal
Late effect
Pigment gallstones
Iron deficiency from urinary loss
Examples
HS, warm AIHA, sickle cell, PK deficiency
PNH, G6PD crisis, ABO reaction, MAHA, valves

How it's tested

COMMON CONFUSIONSpherocytes appear in HS and in warm autoimmune hemolytic anemia. The direct Coombs test separates them: negative in HS, positive in AIHA.
THE TRAPA child with HS suddenly has a very low Hb with no reticulocytes. That is a parvovirus B19 aplastic crisis, not worse hemolysis.
YOUR APPROACHConfirm hemolysis (LDH, bilirubin, haptoglobin, retic) → decide where it happens → smear + Coombs → name the defect.

If you see… think…

Anemic, jaundiced child with big spleen, spherocytes, ↑ MCHC, Coombs ⁻ → hereditary spherocytosis
Teen with HS and right-upper-quadrant pain → pigment gallstones
HS with sudden severe anemia and reticulocytes near zero → parvovirus B19
Howell-Jolly bodies after HS splenectomy → asplenia
Spherocytes + positive direct Coombs → warm AIHA, not HS
Absent haptoglobin + hemoglobinuria → intravascular hemolysis
Mechanical aortic valve + schistocytes → mechanical intravascular hemolysis
Reduced EMA binding on flow cytometry → HS
Chronic intravascular hemolysis with microcytosis → iron lost in urine