Anemias: Hemolytic - Lecture 6

A set of 100 flashcards covering hemolytic anemias, including membrane defects, enzymopathies, and immune/non-immune extrinsic mechanisms based on Chapters 21-23.

Hereditary spherocytosis (HS)

An RBC membrane abnormality caused by a primary mutation in proteins that disrupt vertical membrane interactions, such as spectrin, ankyrin, or band 3.

Vertical membrane interactions

The structural interactions disrupted in HS, leading to loss of membrane and a decreased surface area-to-volume ratio.

Clinical triad of HS

Anemia, jaundice, and splenomegaly, sometimes accompanied by gallstones.

HS Diagnostic MCHC

Establishing a diagnosis of HS often involves finding a mean cell hemoglobin concentration (MCHC) greater than $36\,g/L$.

DAT in HS

The Direct Antiglobulin Test (DAT) is negative in hereditary spherocytosis, helping to differentiate it from immune-mediated spherocytosis.

Normal Osmotic Fragility (OF)

Normal biconcave RBCs show initial hemolysis at $0.45\%\,NaCl$ and complete hemolysis between $0.35\%$ and $0.30\%\,NaCl$.

HS Osmotic Fragility

In HS, the curve shifts to the left with increased osmotic fragility, where initial hemolysis starts at $>0.5\%\,NaCl$.

Thalassemia Osmotic Fragility

In target cells of thalassemia, the curve is shifted to the right, indicating decreased osmotic fragility.

Eosin-5′-maleimide (EMA) binding

A fluorescent dye test that binds to band 3, Rh, RhAg, and CD47 in the RBC membrane; fluorescence is decreased in HS.

Autohemolysis test

A test where RBCs and serum are incubated for $48$ hours; HS RBCs show $10\%$ to $50\%$ hemolysis which corrects with the addition of glucose.

Polychromasia

A peripheral blood film finding in HS and other hemolytic anemias indicating the presence of reticulocytes.

Hereditary Elliptocytosis (HE)

An RBC membrane abnormality caused by mutations in proteins (alpha-Spectrin, beta-Spectrin, or protein 4.1) that disrupt horizontal linkages in the cytoskeleton.

Hereditary Pyropoikilocytosis (HPP)

A rare subtype of HE characterized by severe anemia and extreme poikilocytosis with fragmentation, similar to thermal burns.

HPP MCV

The Mean Corpuscular Volume in HPP is very low, ranging from $50$ to $65\,fL$ due to RBC fragments.

HPP Thermal Sensitivity

RBCs in the HPP phenotype fragment after incubation at $41^{\circ}C$ to $45^{\circ}C$.

Normal RBC Thermal Stability

Normal RBCs do not begin to fragment until reaching a temperature of $49^{\circ}C$.

Hereditary stomatocytosis

A defect in membrane cation permeability causing the cell to swell (overhydrate) with low intracellular $K$ and high intracellular $Na$.

Stomatocytes

RBCs seen on a PBS (typically $5\%$ to $50\%$) in hereditary stomatocytosis, often accompanied by macrocytes with an MCV of $110$ to $150\,fL$.

Paroxysmal Nocturnal Hemoglobinuria (PNH)

A rare chronic hemolytic anemia due to mutations in genes encoding CD55 (DAF) and CD59 (MIRL).

CD55

Also known as Decay Accelerating Factor (DAF), one of the markers lacking in PNH cells.

CD59

Also known as Membrane Inhibitor of Reactive Lysis (MIRL), which protects RBCs from complement lysis.

RBC I phenotype (PNH)

PNH RBCs with normal marker levels and little or no complement-mediated hemolysis.

RBC II phenotype (PNH)

PNH RBCs with partial deficiency of CD55 and CD59 that are relatively resistant to complement-mediated hemolysis.

RBC III phenotype (PNH)

PNH RBCs with no CD55 and CD59 proteins, making them highly sensitive to spontaneous lysis by complement.

G6PD deficiency inheritance

An RBC enzymopathy that is inherited in an X-linked pattern.

Class I G6PD deficiency

A severe deficiency with $<1\%$ enzyme activity, resulting in chronic hereditary nonspherocytic hemolytic anemia.

Class II G6PD deficiency

A severe deficiency ($<10\%$ activity) associated with episodic acute hemolytic anemia from infections, drugs, or fava beans; not self-limited.

Class III G6PD deficiency

A mild to moderate deficiency ($10\%$ to $60\%$ activity) with self-limited episodic acute hemolytic anemia.

Class IV G6PD deficiency

A variant with mildly deficient to normal enzyme activity ($60\%$ to $150\%$) and no clinical manifestations.

Class V G6PD deficiency

A variant with increased enzyme activity ($>150\%$) and no clinical manifestations.

Hexose monophosphate shunt

The metabolic pathway where G6PD plays a critical role; its deficiency leads to Heinz body formation.

Heinz bodies

Denatured hemoglobin inclusions seen in G6PD deficiency; they are detected and confirmed using special stains.

Favism

A clinical syndrome of G6PD deficiency induced by the ingestion of fava beans.

Bite cells

RBC fragments formed when the spleen removes Heinz bodies; commonly seen in G6PD deficiency.

Pyruvate kinase (PK) deficiency

The second most common cause of enzyme-deficient hemolytic anemia, presenting with chronic hemolysis and Burr cells.

Burr cells

RBC morphology specifically associated with Pyruvate kinase (PK) deficiency on a peripheral blood smear.

MAHA (Microangiopathic Hemolytic Anemia)

A group of hemolytic anemias caused by abnormalities in the microvasculature, including TTP, HUS, and DIC.

TTP (Thrombotic thrombocytopenic purpura)

A condition characterized by abrupt MAHA, severe thrombocytopenia, and markedly elevated serum LD activity.

ADAMTS13

A protease involved in the pathogenesis of TTP; its deficiency involves Von Willebrand factor abnormalities.

Childhood HUS

Hemolytic-uremic syndrome in children often caused by specific microorganisms or toxins.

Malaria vector

The female Anopheles mosquito, which transfers the parasite from mosquito to human.

Infective stage of Malaria

The sporozoite, which is injected into the human by the mosquito during a blood meal.

Exoerythrocytic cycle

The stage of the malarial life cycle that occurs within the human liver cells.

Erythrocytic cycle

The stage of the malarial life cycle where the parasite infects and ruptures human RBCs.

Trophozoite (Ring stage)

An immature stage of the malarial parasite seen within RBCs during the blood cycle.

Schizont

A mature stage of the malarial parasite that eventually ruptures to release more parasites.

Gametocytes

The sexual stages of the malarial parasite (macrogametocyte and microgametocyte) that are ingested by the mosquito.

Babesia

An intracellular tick-borne parasite often identified as B. microti in humans.

Ixodes scapularis

The tick vector responsible for transmitting Babesia to humans.

Babesiosis diagnosis

Includes detection of the parasite on PBS, PCR-based methods, or indirect immunofluorescent antibody assay for IgG and IgM.

Immune Hemolytic Anemia (IHA)

RBC destruction caused by antibodies, which can be autoantibodies or alloantibodies.

WAIHA (Warm-reactive AIHA)

The most common AIHA ($>85\%$ of cases), mediated by IgG antibodies that typically cause EV hemolysis.

CAIHA (Cold-reactive AIHA)

AIHA mediated by IgM autoantibodies that bind to RBCs at cold temperatures ($30^{\circ}C$) and activate complement.

PCH (Paroxysmal Cold Hemoglobinuria)

An acute form of cold-reactive HA, often secondary to viral infections in children, involving the anti-P autoantibody.

Donath-Landsteiner (DL) antibody

The alternate name for the biphasic IgG hemolysin found in Paroxysmal Cold Hemoglobinuria.

Biphasic IgG

The characteristic of the anti-P antibody in PCH; it binds in the cold and causes full complement lysis at $37^{\circ}C$.

Alloimmune Hemolytic Anemia

Hemolysis caused by antibodies against foreign RBC antigens, such as those from a transfusion or a fetus.

Immediate transfusion reaction

A reaction occurring when a patient receives incompatible RBCs (e.g., group A receives group B), resulting in IV hemolysis.

Delayed transfusion reaction

A reaction occurring, for example, when an Rh- patient receives Rh+ RBCs, resulting in EV hemolysis.

HDFN (Hemolytic Disease of the Fetus and Newborn)

An alloimmune condition where maternal IgG (e.g., anti-Rh) crosses the placenta and lyses fetal RBCs.

Hydrops fetalis

A severe consequence of untreated HDFN caused by severe hemolytic anemia in the fetus.

Haptoglobin

A serum protein that decreases during hemolytic events as it binds free hemoglobin.

Lactate dehydrogenase (LDH)

An enzyme that increases in the serum as a result of RBC destruction.

Indirect bilirubin

The form of bilirubin that increases during hemolytic anemia due to the breakdown of hemoglobin.

Schistocytes

Fragmented RBCs commonly observed in MAHA (TTP/HUS) and severe G6PD deficiency.

Spherocytes

Small, dense RBCs lacking central pallor, typical of HS and warm-reactive AIHA.

Elliptocytes

Oval or cigar-shaped RBCs characteristic of Hereditary Elliptocytosis.

Helmet cells

A specific type of RBC fragment (schistocyte) seen in cases of fragmentation hemolysis like MAHA or G6PD deficiency.

Anisocytosis

A variation in RBC size, often quantified by the RDW (Red Cell Distribution Width).

Poikilocytosis

A general term for variations in RBC shape on a peripheral blood smear.

Erythrophagocytosis

The process of phagocytes engulfing RBCs, sometimes observed in immune hemolytic anemias.

Hemoglobinemia

The presence of free hemoglobin in the blood plasma, an indicator of intravascular hemolysis.

Hemoglobinuria

The presence of hemoglobin in the urine, which can turn the urine dark red or gross red.

Gilbert's syndrome

A condition mentioned in Case 1 that causes jaundice, which can be confused with or concurrent with HS.

Splenomegaly

Enlargement of the spleen, a common physical finding in many hemolytic anemias like HS and G6PD deficiency.

MCHC in AIHA

Mean cell hemoglobin concentration can be increased ($>36.0\,g/dL$) in AIHA due to the presence of spherocytes.

Reticulocyte count in hemolysis

A measure of RBC production that is typically increased (e.g., $14.3\%$ in Case 1) as the bone marrow compensates for hemolysis.

Bilirubin (Direct vs. Total)

In hemolytic cases, total bilirubin increases significantly, primarily driven by the indirect (unconjugated) fraction.

Toxic granulation

A finding in neutrophils often associated with infection or severe stress, noted in the G6PD case study.

Veil or blister cells

Specific RBC morphology where membrane appears clear at the edge, seen in G6PD deficiency.

Pre-warming EDTA blood

A procedure ($37^{\circ}C$ for $15$ min) required for CAIHA samples to correct falsely decreased RBC counts and increased MCV from agglutination.

Auto anti-I

The common specificity of the IgM autoantibody involved in cold-reactive AIHA.

Anti-Rh IgG

The antibody produced by an Rh- mother that can cross the placenta and cause HDFN in an Rh+ fetus.

Intracellular infectious agents

Pathogens like Malaria and Babesia that live inside the RBC and cause hemolytic anemia.

Sporogonic cycle

The sexual phase of the malaria life cycle occurring within the mosquito.

Plasmodium falciparum

One of the four listed species of malaria that cause hemolytic anemia in humans.

Plasmodium vivax

A species of malarial parasite mentioned in the life cycle diagrams.

Plasmodium malariae

A species of malaria that infects humans.

Plasmodium ovale

One of the specified species of malaria causing human disease.

SDS-PAGE analysis of membrane proteins

A specialized laboratory test used for atypical cases of HS to analyze membrane protein composition.

Hyperchromic (hyperdense) RBCs

RBCs that appear darker and lack central pallor on a smear, often synonymous with spherocytes in HS.

Extrinsic defects

Hemolytic anemias caused by factors outside the RBC, classified into immune and non-immune mechanisms.

Traumatic cardiac hemolytic anemia

A non-immune extrinsic hemolytic anemia caused by mechanical trauma to RBCs, often from prosthetic heart valves.

Exercise-induced hemoglobinuria

A form of non-immune extrinsic hemolytic anemia associated with physical exertion.

Alloantibody

An antibody produced against an antigen found in another individual of the same species.

Agglutination on PBS

A finding typical of cold-reactive antibodies where RBCs clump together.

DAT detecting C3d

In CAIHA and PCH, the DAT often detects these complement components remaining on the RBC surface.

Hemosiderinuria

The presence of hemosiderin in the urine, a sign of chronic intravascular hemolysis.

Ankurin mutation

One of the specific primary protein defects that can cause Hereditary Spherocytosis.

Band 3 mutation

A mutation in this membrane protein can disrupt vertical interactions in HS or be the target for EMA binding.