Hemolytic Anemias: Membrane and Enzyme Disorders

Comprehensive vocabulary flashcards covering major hereditary hemolytic anemias, including membrane defects (Spherocytosis, Elliptocytosis, Stomatocytosis), enzyme deficiencies (G6PD, PK), and hemoglobinopathies (Sickle Cell Anemia).

Hereditary Spherocytosis (HS)

A heterogeneous group of hemolytic anemias caused by defects in proteins that disrupt the vertical interactions between transmembrane proteins and the underlying protein cytoskeleton.

HS Prevalence

Affects $1$ in $2000$ to $3000$ ($5000$) individuals of northern European ancestry; according to Steninger, the rate is $1$ in $5000$ individuals.

ANK1

The gene involved in Hereditary Spherocytosis that codes for the cytoskeletal protein ankyrin.

SPTA1 and SPTB

Genes that code for alpha-spectrin and beta-spectrin, respectively, which are essential cytoskeletal proteins for maintaining the RBC biconcave shape.

EPB42

The gene that codes for protein $4.2$, a cytoskeletal protein involved in the pathogenesis of Hereditary Spherocytosis.

SCL4A1

The gene that codes for the transmembrane protein band $3$, which anchors the cell membrane to the underlying cytoskeleton.

Osmotic Fragility Test (OFT)

A test that demonstrates increased RBC fragility in specimens with decreased surface area-to-volume ratios, showing increased hemolysis of spherocytes when exposed to hypotonic solutions.

Eosin-5'-maleimide (EMA) binding test

A sensitive flow cytometry-based test for confirming HS that quantifies the band $3$ complex and shows decreased fluorescence in affected patients.

Direct Antiglobulin Test (DAT)

A test used to differentiate HS from immune-mediated hemolytic anemias; a negative result is expected in HS, while a positive result indicates immune disorders.

Hereditary Elliptocytosis (HE)

Also known as Hereditary Ovalocytosis, it is a genetically inherited RBC membrane disorder marked by elliptical or oval-shaped RBCs due to mutations in proteins such as spectrin, protein $4.1$, and actin.

Hereditary Pyropoikilocytosis (HPP)

An autosomal recessive, severe variant of HE characterized by a blood smear that resembles heat-damaged cells with poikilocytes, microspherocytes, and fragments.

Southeast Asian Ovalocytosis (SAO)

An autosomal dominant variant of HE caused by a $27$-bp deletion in $SLC4A1$ (band $3$), showing ovalocytes with ridges and providing protection against malaria.

Overhydrated Hereditary Stomatocytosis (OHS)

A condition where RBCs are excessively permeable to sodium and potassium, leading to a net increase in cellular cation concentration and cell swelling.

Dehydrated Hereditary Stomatocytosis (DHS)

Also known as Hereditary Xerocytosis, it is characterized by excessive potassium leakage and water loss, resulting in dehydrated, spiculated cells ($\text{xerocytes}$).

PIEZO1

The gene associated with Dehydrated Hereditary Stomatocytosis, located at $16q23-q24$.

Glucose-6-phosphate dehydrogenase (G6PD)

A protein in RBCs responsible for the pentose phosphate pathway, which protects cells from oxidative damage by maintaining levels of reduced glutathione ($GSH$).

Heinz bodies

Clumps of damaged or altered hemoglobin inside red blood cells, representing the first signs of oxidative damage in G6PD deficiency.

Bite cells

Abnormal RBCs formed when the spleen removes Heinz bodies, leaving characteristic "bite-like" marks on the cell membrane.

Fluorescent spot test

A screening tool for G6PD activity that detects NADPH fluorescence under UV light; no fluorescence indicates a G6PD deficiency.

Pyruvate Kinase (PK) Deficiency

A rare autosomal recessive disorder caused by a mutation in the $PKLR$ gene ($\text{chromosome 1q21}$), leading to ATP depletion and impaired RBC membrane function.

Echinocytes

Also known as burr cells or spiny cells, these appear on a peripheral blood smear in Pyruvate Kinase Deficiency due to ATP depletion and sodium-potassium pump failure.

Sickle Cell Anemia (SCA)

A chronic hemolytic anemia caused by a point mutation in the $\beta$-globin gene ($HBB$, $\text{chromosome 11}$) where glutamic acid ($GAG$) is substituted with valine ($GTG$) at position $6$.

Hb S polymerization

The process where deoxygenated Hemoglobin S forms long, rigid, helical polymers that distort red blood cells into a sickle shape.

Vaso-occlusive crises

The hallmark symptom of sickle cell anemia where sickle-shaped RBCs block blood vessels, causing oxygen deprivation and severe pain.

Sickle Cell Dactylitis

Also known as Hand-foot syndrome, it is often the first sign of SCA in children under $3$, causing painful swelling in the hands and feet.

Hemoglobin Solubility Test

A common screening test that uses sodium hydrosulfite and saponin; a turbid solution indicates the presence of deoxygenated $Hb\,S$ tactoids.

Isoelectric focusing (IEF)

A complex and expensive confirmatory method for hemoglobin identification that separates molecules along a pH gradient until they reach their isoelectric point.