Part 3: RBC Membrane Defects

Hereditary spherocytosis

True increase in MCHC (between 35 and 38 g/dL)

31 to 37 g/dL

Normal range for MCHC

Splenectomy

This procedure is beneficial for px with hereditary spherocytosis

Hereditary Pyropoikilocytosis

The only autosomal recessive RBC Membrane defect

Southeast Asian ovalocytosis

Hereditary Spherocytosis is also known as

Overhydrated hereditary stomatocytosis

The deficient protein of this RBC membrane defect is the Rh-associated protein (RHAG)

Dehydrated hereditary stomatocytosis (Hereditary Xerocytosis)

The deficient protein of this RBC membrane defect is the Piezo-type mechanosensitive ion channel component 1

Hereditary Xerocytosis

This is the most common form of stomatocytosis

elevated

The RBC count, hemoglobin and hematocrit values are ______in people living at a higher altitude over what they would be at sea level

GLUT-1

Glucose penetrates the RBC with no energy expenditure via _____

2

How many does EMP pathway produced?

Embden-Meyerhof Pathway

Major glycolytic pathway; helps in modulating the amount of 2,3-BPG generated

Autosomal recessive

Inheritance pattern of PK deficieny

Pyruvate Kinase Deficiency

Most common enzyme deficiency of the EMP and is the most common form of hereditary nonspherocytic hemolytic anemia

Acanthocytes and burr celll

Possible PBS findings in PK deficiency

Autohemolysis test and PK fluorescent spot test

Recommended screening test for PK deficiency

Quantitative PK Assay

Confirmatory test for PK deficiency

Pentose Phosphate Pathway

HMP shunt is also known as

HMP Shunt

Aerobically converts glucose to pentose and produces NADPH, preventing the denaturation of the globin by oxidation.

X-linked recessive

Inheritance pattern of G6PD deficiency

G6PD deficiency

Most common enzyme deficiency in the pentose phosphate pathway and is also known as the most common RBC enzyme defect worldwide

Heinz bodies and bite cells

Possible PBS findings in G6PD deficiency

Class II

Cass of G6PD deficiency variants by WHO associated with favism (fava beans)

Soya, fava beans, legumes, naphthalene

Some of the foods/ chemicals that may cause hemolysis in G6PD deficiency px

Cytochrome b5 reductase

Methemoglobin reductase is also known as

Methemoglobin Reductase Pathway

Maintains iron in the heme (Hb) in its reduced state (ferrous)

Rapoport-Luebering Shunt

Pathway responsible for the production of 2,3-BPG

Bohr Effect

A shift to the curve due to an alteration in pH (or hydrogen ion concentration)

Haldane Effect

depicts the occurrence by which the binding of O2 to the Hgb promotes the release of CO2

Anisocytosis

Increased no. of red cells with variation in size

Macrocytes

Associated with impaired DNA synthesis

Microcytes

Associated with defective hemoglobin formation

cell size

X-axis represents the ______

no. of cells

Y-axis represents the ______

MCV and RDW

Two parameters calculated from RBC histogram

36 fL and 360 fL

Instruments used in RBC histogram count those cells with volume sizes between ________

right

if the RBCs are macrocytic, the curve will shift to the

left

if the RBCs are microcytic, the curve will shift to the

RDW

A calculated index (from the RBC histogram) given by hematology analyzers to help identify anisocytosis and provide information about its degree.

11.5-14.5%

RDW-CV Reference range (adult)

39-46 fL

RDW-SD Reference Range (adult)

RDW-CV

Earliest method provided by the hematology analyzers to measure red cell variations. It is dependent on the width of the distribution curve and the MCV

RDW-SD

A better and more reliable measure of erythrocyte variability. The width of the curve is measured at the point that is 20% above the baseline and not influenced by the MCV

Anemia of chronic inflammation (ACI)

Anemia of chronic inflammation or IDA: Decreased MCV, Normal RDW

Iron Deficiency Anemia

Anemia of chronic inflammation or IDA: Decreased MCV, Increased RDW (anisocytosis)

G6PD deficiency

G6PD deficiency or Sickle Cell Anemia: Normal MCV, Increased RDW (anisocytosis)

Sickle Cell Anemia

G6PD deficiency or Sickle Cell Anemia: Normal MCV, Normal RDW

Liver Disease

Liver Disease or Megaloblastic Anemia: Increased MCV, Normal RDW

Megaloblastic Anemia

Liver Disease or Megaloblastic Anemia: Increased MCV, Increased RDW (anisocytosis)

1/3 of the diameter

Normally, RBCs have a central pallor approximately ________

Anisochromia

The occurrence of hypochromic cells and a normochromic cells in the same blood smear; general term for a variation in the normal coloration

Hypochromic cells

Cells with a central pallor >1/3 of the diameter

1+

Grading of hypochromia: ½ of the diameter

2+

Grading of hypochromia: 2/3 of the diameter

3+

Grading of hypochromia:3/4 of the diameter

4+

Thin rim of hemoglobin

Anulocyte/Pessary cell/ Ghost cell

RBC with a thin rim of hemoglobin and and a large, clear center

Hyperchromic cells

RBC cells that lack central pallor even though they lie in a desirable area for evaluation

Jaundice

Anemia

Splenomegaly

3 Clinical Manifestations of HS

Polychromatophilic erythrocytes or Diffusely Basophilic Erythrocytes

Larger than normal Red cells with bluish tinge (Wright’s stain)

Residual RNA

The bluish tinge of polychromatophilic erythrocytes is due to the ________

Slight

Polychromasia: 1%

1+

Polychromasia: 3%

2+

Polychromasia: 5%

3+

Polychromasia: 10%

4+

Polychromasia: >11%

Poikilocytosis

Increased number of red cells with variation in shape

Spherocyte

Almost spherical in shape and lacks the central pallor

Spherocyte

Poikilocyte associated with burns, ABO HDN, and autoimmune hemolytic anemia

Mouth cell

Stomatocyte is also known as ______

Stomatocyte

Elongated RBCs with a slit-like central pallor

Stomatocyte

Poikilocyte associated with Rh deficiency syndrome, alcoholism, electrolyte imbalance and Hereditary Xerocytosis

Hereditary Xerocytosis

also known as Dehydrated Hereditary Xerocytosis is the most common form of stomatocytosis

Xerocyte

A dehydrated form of a stomatocyte. It appears to have puddled at one end (half-light, half-dark)

Thorn cell or spurr cell

Acanthocyte is also known as

Acanthocyte

RBCs with irregularly spiculated surface

Bassen-Kornzweig Syndrome

Abetalipoproteinemia is also known as

Abetalipoproteinemia

Characterized by defective Apo B synthesis

Acanthocyte

Poikilocyte associated with McLeod Syndrome

Acanthocyte and Echinocyte

Poikilocytes associated with renal insufficiency (uremia)

Southeast Asian Ovalocytosis

Ovalocytosis is also known as

Elliptocyte

Cigar-shaped or hotdog shaped RBC

Thalassemia

Also known as Mediterranean Anemia

Burr cell

Echinocyte is also known as

Dacryocyte

Poikilocyte associated with PMF( Primary Myelofibrosis)

Dacryocyte

Pear-shaped or teardrop shaped RBCs, aka teardrop cells

Schistocyte

Poikilocyte characterized by fragmented RBCs

Schicstocyte

Poikilocyte associated with patients with artificial valves, uremia, severe burns, HUS, DIC

MAHAs

Group of disorders characterized by RBC fragmentation and thrombocytopenia

Helmet cell

A type of schistocyte that may appear in MAHA

DIC

It is also known as defibrination syndrome; a generalized over-activation of the coagulation and fibrinolytic systems

APL (Acute Promyelocytic Leukemia)

What leukemia can cause DIC?

Drepanocyte

Sickle cell/ Meniscocyte is also known as

Drepanocyte

Sickle or crescent shaped RBCs

ISC (irreversible Sickle Cells)

Form of drepanocyte that is crescent-shaped and when reoxygenated, they fragment

Oat-shaped cells

Form of drepanocyte with less pronounced projections and when reoxygenated, they return to the original, biconcave disk shape

Target cell

Also known as platycyte, Greek Helmet cell, Mexican hat cell, Leptocyte

Target celll

RBCs which show centrally stained area with a thin outer rim of hemoglobin

Target cell

Poikilocyte associated with LCAT

bell-shaped

Codocytes are RBCs with an increased cell membrane-to-volume ratio and appear ______in Electron Microscopy