STEPTRACKERHEMATOLOGY | PATHOLOGY + BIOCHEMISTRY | HIGH-YIELD REVIEW

G6PD, PK Deficiency & PNH

Enzyme defects that leave red cells defenseless against oxidants or short of ATP — and the acquired stem-cell defect that exposes them to complement.

FOCUS ON
G6PD: X-linked, episodic hemolysis after oxidant triggers, Heinz bodies and bite cells. PK: chronic hemolysis from birth with echinocytes. PNH: acquired loss of CD55/CD59 → complement lysis, dark morning urine and thrombosis at odd sites.
TOPIC
DETAIL
MECHANISM
CLUE
G6PD — defect
X-linked recessive
↓ G6PD → ↓ NADPH → ↓ reduced glutathione.
Oxidants denature Hb into Heinz bodies; splenic macrophages bite them out → bite cells
Mostly men; protects against malaria
G6PD — triggers
Infection (most common), fava beans, drugs: primaquine, dapsone, sulfonamides, nitrofurantoin, rasburicase, methylene blue.
Acute, episodic, largely intravascular hemolysis
African (milder) vs Mediterranean (severe) variants
G6PD — testing
Heinz bodies on supravital (crystal violet) stain; bite cells on smear.
Enzyme level can look normal during a crisis — the oldest, most deficient cells are already gone
Retest weeks later
PK deficiency — defect
autosomal recessive
No pyruvate kinase → glycolysis yields little ATP → rigid RBCs.
Chronic extravascular hemolysis; ↑ 2,3-BPG shifts O₂ curve right
Anemia is better tolerated than the Hb suggests
PK deficiency — clinical
Hemolytic anemia from the newborn period; jaundice, splenomegaly.
Echinocytes (burr cells) on smear
Transfusion; splenectomy helps some
PNH — defect
acquired
PIGA mutation in a hematopoietic stem cell → no GPI anchor.
Loss of CD55 (DAF) and CD59 (MIRL) → complement lyses RBCs
Affects all blood lines
PNH — clinical
Episodic dark urine (classically in the morning), fatigue, pancytopenia; thrombosis — hepatic vein (Budd-Chiari), portal, cerebral veins.
Thrombosis is the leading cause of death
Linked to aplastic anemia; can evolve to AML
PNH — diagnosis & treatment
Flow cytometry: absent CD55/CD59 (FLAER).
Eculizumab or ravulizumab (C5 blockers)
Vaccinate against meningococcus first

Mechanism — two kinds of failure

Glucose-6-P
→
G6PDMakes NADPH
→
Glutathione reduced
→
H₂O₂ neutralizedIf not: Heinz bodies
PIGA mutation
→
No GPI anchor
→
No CD55/CD59
→
MAC lyses RBCs+ platelet activation → clots

Side by side

FEATURE
G6PD
PK
PNH
Inheritance
X-linked
AR
Acquired
Pattern
Episodic
Chronic
Episodic + chronic
Site
Mainly intravascular
Extravascular
Intravascular
Smear
Heinz bodies, bite cells
Echinocytes
Often unremarkable
Test
G6PD assay (after crisis)
PK assay
Flow: CD55/CD59
Treatment
Avoid triggers
Transfusion, splenectomy
C5 inhibitor

How it's tested

COMMON CONFUSIONG6PD crises follow a trigger; PK deficiency is steady and lifelong. PNH is the only one acquired in adulthood.
THE TRAPA young adult with hemolysis, pancytopenia and a hepatic vein thrombosis has PNH. Unusual-site clots plus hemolysis should make you order flow cytometry.
YOUR APPROACHHemolysis + trigger + bite cells → G6PD. Hemolysis since birth + echinocytes → PK. Hemolysis + clots + cytopenias → PNH.

If you see… think…

Man on primaquine or dapsone, sudden dark urine, bite cells → G6PD deficiency
Mediterranean boy with hemolysis after fava beans → G6PD (severe variant)
Heinz bodies on supravital stain → oxidized hemoglobin
Normal G6PD level during the attack → retest later
Newborn with chronic hemolysis and burr cells → PK deficiency
Dark morning urine + pancytopenia + Budd-Chiari → PNH
Absent CD55/CD59 on flow cytometry → PNH
Starting eculizumab → meningococcal vaccine
Hemolysis after rasburicase for tumor lysis → G6PD deficiency