Enzyme deficiency

Globin abnormality

PNH

Mechanical

Infection

Chemical and physical agents

Antibody-mediated

Most common and most severe hemoglobinopathy.

Valine replaces glutamine at the 6th position of the beta globin chain (α2β2 6Glu > Val).

When oxygen is released from the molecule, a conformational change happens which results in polymerization of hemoglobin molecules, leading to the formation of tactoids or crystals, creating a sickle cell appearance.

Glutamine is replaced by lysine at the 6th position of the beta globin chain

Associated with mild hemolytic anemia, but typically not as severe as Hemoglobin S.

Crystals caused by this are hexagonal in appearance.

with a characteristic “Washington monument” appearance, found protruding the RBC membrane

with a characteristic “Bar of gold” appearance, found within the RBC membrane.

A mutation in the beta globin gene where glutamic acid is replaced by lysine at the 26th position

It is the decrease or total absence of the synthesis of one or more globin chains.

Also known as: Hereditary Leptocytosis, Mediterranean Anemia

Common clinical findings: pallor, jaundice, splenomegaly, skeletal deformities.

Typically caused by a deletion of one, two, three or all four alpha globin genes.

Caused by mutations that affect the beta globin gene complex

have the following physical characteristics: 1. Frontal bossing 2. Cheekbone and upper jaw prominence 3. “Hair on end” appearance of the skill in radiographs 4. Iron accumulation in various organs

Which of the following forms of alpha thalassemia is Asymptomatic?

(-α/αα); this indicates that only one is absent; the other three are still NORMAL.

Mild hypochromic, microcytic anemia is often associated with which form of a-thalassemia?

(-- /αα) or (-α/-α); indicates 2 deletion in either one or both pairs.

(--/-α) ; 3 deletion

β4 ; tetrads of beta chain is often seen in..

Microcytic, hypochromic anemia is often associated with...

Present in adults

Most severe form of alpha thalassemia.

Hydrops fetalis syndrome (--/--)

γ4 tetrads of gamma chain is often seen in which form of a-thalassemia?

(βsilent/β) one silent; other is NORMAL

Which form of beta thalassemia is often asymptomatic; and has normal hematologic parameters?

Which form of beta thalassemia often presents with mild hypochromic, microcytic anemia?

a.k.a. β-Thalassemia minor

(β+ /β) or (β0 /β) one NORMAL while other one is affected. or one absent and other one is NORMAL

a.k.a. Cooley’s anemia

β+ /β+ both affected

β+ /β0 one affected, other is absent

β0 /β0 both absent

Most severe form of Beta thalassemia.

Transfusion-dependent.

βsilent/βsilent both silent

β+ / βsilent one affected, other is silent

β0 / βsilent one absent, other is silent

Which of the following forms of beta thalassemia presents with moderate clinical symptoms, and is transfusion independent?

(Heme synthesis pathway)

Hereditary and acquired diseases in which enzymes of the heme synthetic pathway are missing or impaired.

When an enzyme in heme synthesis is missing, the products from earlier stages in the pathway accumulate in cells that actively produce heme, such as erythrocytes and hepatocytes. The excess porphyrins leak from the cells as they age or die and may be excreted in urine or feces, which allows diagnosis.

Problem with iron metabolism, iron incorporation with protoporphyrin.

Acquired or inherited.

can be categorized as both an acquired porphyria and acquired sideroblastic anemia.

It affects two steps of porphyrin synthesis: (1) ALA to PBG (by ALA dehydratase). (2) Incorporation of iron to protoporphyrin IX by ferrochelatase or heme synthase.

a. Acquired Ø Usually due to repeat transfusions. b. Hereditary (Hemochromatosis)

The most common form of hereditary nonspherocytic hemolytic anemia (HNSHA).

Poikilocyte often associated in this condition is burr cell.

The most common enzyme deficiency in the Embden-Meyerhof pathway

Most common RBC enzymopathy.

2nd most common hereditary nonspherocytic hemolytic anemia (HNSHA)

- Characteristic inclusion: Heinz bodies

- Confers protection against infection with: P. falciparum

- The 3rd most common RBC enzyme deficiency that causes HNSHA

- The deficient enzyme is needed for the degradation and elimination of rRNA in reticulocytes.

Characteristic inclusion: coarse Basophilic stippling

Mutation in proteins involved in vertical membrane interactions

Mutation in proteins involved in horizontal membrane interactions

Mutation in band 3 protein; typically carried by Diego blood group antigen.

Overhydrated Stomatocytosis

Dehydrated stomatocytosis

Caused by damage in microvessels, leading to mechanical fragmentation of red blood cells.

Associated conditions: TTP, HUS, HELLP syndrome, DIC

Caused by damage in larger vessels, often due to mechanical stress from structural abnormalities.

Common causes: Traumatic cardiac hemolytic anemia (prosthetic heart valve), Exerciseinduced hemoglobinuria

Causes maltese-cross formation

Caused by Clostridium perfringens

A.k.a. Carrion disease

Disease caused by Bartonella bacilliformis

The bacteria produces a protein called deformin that forms pits or invaginations in the RBC membrane.

WAIHA

HDFN

Elevated total red cell mass, elevated EPO

Normal total red cell mass, but increased HCT due to decreased plasma.

Diminished plasma volume is associated with..

Spurious polycythemia is often associated with?

Secondayr polycythemia, genetic polycythemia, primary marrow disorder such as polycythemia vera all belongs to?

HTR

PCH

CAD