Intrinsic Hemolytic Anemias

What is an intrinsic hemolytic anemia?

Defect in the red blood cell itself

What is an extrinsic hemolytic anemia?

An acquired defect that allows external factors to alter existing red blood cells

What are Heinz Bodies?

Excess hemoglobin chains that precipitate out into cytoplasm of rbc and can be viewed using supravital stains

What is Thalasemmia?

Loss of either alpha or beta hemoglobin chains causing decreased synthesis of hemoglobin

What is beta thalassemia?

Mutation of one or both genes leading to decreased beta chain production and an excess of alpha chains

What is beta thal minor?

One normal gene is inherited while the other is an altered or deleted gene

How is beta thal minor denoted?

B/B+ or B/B0

What is an alpha thal minor?

Deletion of two genes leading to minor anemia

How is alpha thal minor denoted?

aa/_ or a _ /a _

What is alpha thal intermedia (Hemoglobin H)

Deletion of three genes causing HbH

How is alpha thal intermedia denoted?

a _ / _ _

What is the PBS, CBCD and iron studies of thalassemia/

Low MCV, high RDW, poikilocytosis, normal plt and wbc morphs, normal iron studies

What is the bone marrow of thalassemia?

Increased iron stores, decreased M:E (erythroid hyperplasia)

What confirmatory testing can be used for thalassemia?

HPLC and Hgb electrophoresis

What is Hemoglobin S?

A hemoglobin variant that is hydrophobic when unbound to oxygen and will polymerize other HbS to form stacks and eventually the sickle shape

What amino acid substitution causes HbS?

Glutamic acid is replaced by Valine at the 6th position

What are the four conditions that favour HbS polymerization?

Low O2, low pH, increased 2-3BPG, cell dehydration

Why does IVH and EVH happen with HbS?

IVH: They have increased fragility and may rupture inside capillaries

EVH: spleen is working hard to remove all the sickled red blood cells

What is the difference between Sickle Cell trait and Sickle Cell Disease

Trait only inherits one HbS and has malarial resistance while Disease inherits both HbS

What is the substitution causing Hemoglobin E?

Glutamic acid is replaced by lysine at the 6th position on beta chain. It polymerizes similar to HbS and forms short and fat crystals, spheros, schistos, and targets are seen

What is the substituion causing Hemoglobin E?

Lysine replaced with glutamic acid at the 26th position of b chain but it does not cause polymerization

What can be seen in the PBS of HbE?

Microcytic and target cells

What substitution causes Hemoglobin M>

Proximal or distal tyrosine replaced with tyrosine on affected hemoglobin chain forming methemoglobin

What is the significance of methemoglobin formation?

Iron is in its ferric state and have decreased affinity for O2 causing cyanotic state to patient

What is G6PD?

An enzyme in the Embden-Meyerhof pathway that reduces NADP to NADPH with NADPH reducing glutathione to help prevent oxidative damage

Why is glutathione needed to prevent oxidative damage?

Cells cannot utilize hexose monophosphate shunt to break down H2O2 causing damage to hemoglobin

What can be seen in the PBS of G6PD deficieny?

Bite cells and schistocytes since the spleen is working hard to remove inclusion in cells. Heinz bodies will precipitate out from hemoglobin

What is the inheritance of G6PD deficienct?

X-linked inheritance

What is Pyruvate Kinase?

An enzyme in the last step of Embden-Myer pathway to help generate ATP

What is the significance if ATP is not generated?

RBC will have membrane permeability causinh K and H2O to leak out, it becomes rigid and less deformable causing early removal from cirulation

What can be seen on the PBS and symptoms of PK deficiency?

Reticulocytotic, anemia, enlarged spleen, jaundice

What is the inheritance for PK deficiency?

Autosomal recessive pattern

Integral proteins/Transmembrane proteins provide (vertical/horizontal) structure while peripheral proteins provide (vertical/horizontal) structure

Vertical, horizontal

What is the inheritance and defects of Hereditary Elliptocytosis?

Autosomal dominant with defects in spectrin and protein 4.1

What happens to rbc in Hereditary Elliptocytosis?

Lack of horizontal structure does not allow the rbc to shift back into its biconcave shape as it passes through the vasculature leading to its elongated shape

Are rbc removed by IVH or EVH in HE?

EVH since they become trapped in the spleen

What is the defect causing Hereditary Spherocytosis?

Defects in vertical proteins such as ankyrin, protein 4.2, band 3, and spectrin

What is seen in the PBS of HS?

Spherocytes since rbc lose lipid membrane causing decreased SA:V, and it is removed through EVH

What is Hereditary Acanthocytosis?

Autosomal recessive disease caused by mutations in microsomal triglyceride transfer (MTP) protein leading to decreased cholesterol and increased sphingomyelin in the plasma

What is Paroxysmal Nocturnal Hemoglobinura?

Acquired stem cell mutation forming rbc without GPI anchored proteins such as CD55 and 59

Why are CD55 and CD59 essential?

CD55 prevents lysis from c3 and c5 convertase while CD59 prevents MAC formation. Without them, rbc are prone to spontaneous complement