Thalassemia

eta thalassemia is attributed to a wide variety of genotypes including

B+/B+, B0/B+, or B0/B

The genotypes associated with beta thalassemia minor are

B0/B or B+/B.

he different genotypes associated with beta thalassemia major are

B0/B0, B0/B+, or B+/B+

levels for anemia? Beta thal minima: beta thal minor: beta thal intermid: beta thal major:

Beta thal minima: absent beta thal minor: Mild to absent beta thal intermid:Moderate beta thal major:Severe

hemoglobin levels Beta thal minima: beta thal minor: beta thal intermid: beta thal major:

Beta thal minima:Normal beta thal minor:Decreased to normal beta thal intermid:Decreased beta thal major:Marked decrease

RBC count Beta thal minima: beta thal minor: beta thal intermid: beta thal major:

Beta thal minima:Normal beta thal minor:Increased beta thal intermid:Decreased to normal beta thal major:Decreased

MCV Beta thal minima: beta thal minor: beta thal intermid: beta thal major:

Beta thal minima:Slight to no decrease beta thal minor:Marked decrease beta thal intermid:Marked decrease beta thal major:Marked decrease

Which hemoglobin(s) can be decreased in alpha thalassemia?

A, A2, and F

--/-α

Alpha Thalassemia Intermedia, Hemoglobin H disease

(--/--

Alpha Thalassemia Major

--/αα

Alpha Thalassemia Minor - Heterozygous one parent contributes a normal gene while the other one a gene with both alpha chain gene loci deleted

all the alpha thalassemia syndromes which can display Bart's Hemoglobin on alkaline electrophoresis.

Alpha thalassemia major Alpha thalassemia intermedia

Which chromosome demonstrates a partial or full gene loci deletion in various forms of beta thalassemia?

Chromosome 11

Hb electrophoresis of beta thalassemia intermedia

Decreased amount of Hb A Variable amount of Hb A2 Hb F is usually increased

Hb electrophoresis of beta thalassemia minor

Decreased amount of Hb A Variable amounts of Hb A2 and Hb F

symptoms are mild to moderate depending on the severity of the disease and can include mild, hypochromic anemia, slight hepatomegaly and/or splenomegaly and occasional bone changes due to the erythroid hyperplasia.

Delta-beta thalassemia

normal adult amount of Hb A, Hb A2, Hb F

Hb A - 95-98% Hb A2 - 1.5-3.7% Hb F - <2% (Neonates have 1-2% Bart's Hemoglobin (gamma chain tetramers). Hb H inclusions are rarely seen. Bone marrow is also normal.)

alpha thalassemia minor amount of Hb A, Hb A2, Hb F amounts

Hb A - 95-98% Hb A2 - 1.5-3.7% Hb F - <2% (Neonates have 5-15% Bart's Hemoglobin (gamma chain tetramers). Hb H inclusions are rarely seen. Bone marrow demonstrates erythroid hyperplasia.)

alpha thalassemia major Hb A, Hb Barts, Hb Portland amounts

Hb A - absent Hb Bart's - 80-90% Hb Portland - 0-20% Bone marrow demonstrates marked erythroid hyperplasia.

hemoglobin levels for delta-beta thalassemia minor

Hb A and A2 will both be decreased and Hb F will be increased.

Which abnormal hemoglobins may be formed in alpha thalassemia?

Hb Bart's Hb H

In what order do normal and abnormal hemoglobins migrate in alkaline electrophoresis (from cathode to anode)?

Hb C migrates with Hb A2 near the cathode. Hb S lies between Hb A2 and Hb F. Hb H and Bart's hemoglobin are unstable and very fast moving, placing them past Hb A and near the anode with Hb H being the fastest of the two.

Which hemoglobin will be increased in delta-beta thalassemia?

Hb F

in Chromosome 11 Delta-Beta Thalassemia Major only ____ can be made

Hb F

alpha thalassemia intermedia Hb A, Hb A2, Hb F, Hb H amounts

HbA - decreased HbA2 - decreased HbF - normal to decreased Hb H - 2-40% (beta chain tetramers) (Neonates: 10-40% Bart's (gamma chain tetramers), Hb H inclusions are frequently seen. Bone marrow demonstrates erythroid hyperplasia.)

Infants born with alpha thalassemia intermedia appear normal at birth but often develop _____ and ____ by the end of their first year

anemia, splenomegaly

A decrease in the rate of production of beta chains due to a partial or total deletion of loci from chromosome 11 that code for the beta chain.

beta thalassemia

Growth and development in children with this disorder can usually be considered normal and most patients have a normal life span; however, some patients have facial bone deformity and/or splenomegaly. Hemoglobin levels are usually decreased with a disproportionately high red blood cell count.

beta thalassemia intermedia

rarely have physical signs or symptoms caused by this disorder and usually do not require any treatment. Hemoglobin levels may be slightly decreased but with little clinical consequence. A person with ____________ has a normal life expectancy.

beta thalassemia minor

normal vs abnormal hemoglobin electrophoresis

cathode(-) -----> anode(+_ normal: HbA2 HbF HbA abnormal: HbC HbS Bart's HbH

Chromosome __ is affected by beta, delta, epsilon, and gamma thalassemia

chromosome 11

chromosome __ affected by alpha and zeta thalassemia

chromosome 16

Decreases in both Hb A and A2 and an increase in Hb F correlates with

delta-beta thalassemia minor.

hemoglobin A production of silent carrier

full potential, 95-98%

In alpha thalassemia, the body can produce excess ______ as a compensatory mechanism.

gamma chains

Which hemoglobin moves the fastest in electrophoresis?

hemoglobin A migrates the fastest, followed by hemoglobin F. Hemoglobin A2 moves only slightly from the point of origin near the cathode.

gamma chain tetramers in the unborn child

hemoglobin Bart's

Delta-beta thalassemia patients have increased

hemoglobin F level

beta chain tetramers in adults.

hemoglobin H

three of four gene loci deleted

hemoglobin H disease

-α/-α

homozygous state Alpha Thalassemia Minor This is an identical inheritance from both mother and father, defined as homozygous.

all four gene loci deleted

homozygous state, alpha thalassemia major, hydrops fetalis

Persons with alpha thalassemia intermedia usually have a _______ levels of lactate dehydrogenase (LD). This LD is of red blood cell origin, which leaks in to the plasma during hemolysis.

increase

Persons with beta thalassemia major usually have__________ bilirubin level.

increased

iron stain of bone marrow smear from alpha thalassemia can show

increased levels of hemosiderin. Sideroblasts are present along with an occasional ringed sideroblast

Persons with beta thalassemia may have a slightly_____ level of serum iron with a slightly________ iron binding capacity.

increased, decreased

Persons with alpha thalassemia intermedia usually have a________ bilirubin level, because of ongoing hemolysis. This bilirubin is typically

increased, the unconjugated fraction of bilirubin.

Hemoglobin H bodies can directly alter the

integrity of the RBC membrane

excess free alpha chains in produced in beta thalassemia form insoluble precipitates within

red blood cells, causing hemolytic anemia

In the genotypic notation of beta thalassemia, a "+" represents a ______ in beta chain production whereas a "0" represents a ________ of a locus.

reduction, complete deletion

In alpha thalassemia, haptoglobin levels are

remain normal or only slightly decreased, even during hemolytic events. The reason for this is that haptoglobin functions by binding the alpha chain portion of hemoglobin. With the absence of these chains in alpha thalassemia major and intermedia, haptoglobin cannot bind free hemoglobin. Therefore it is not consumed as it would be in other types of hemolytic anemia.

Upon analysis using Brilliant Cresyl Blue stain, RNA present in _________ will appear as darker inclusions. These RNA inclusions are fewer in number than Hemoglobin H bodies, and are only seen in

reticulocytes

Individuals with alpha thalassemia, especially Hb H disease, may have a slightly increased level of ____ with slightly decreased _______. Transferrin saturation is usually _____

serum iron, iron binding capacity, increased

one of four gene loci deleted

silent carrier

RBC morphology of alpha thalassemia intermedia

slight hypochromic microcytosis with codocytes (target cells), schistocytes, and basophilic stippling. Reticulocytes are moderately increased.

RBC morphology of alpha thalassemia major

slight hypochromic microcytosis with codocytes, schistocytes, nucleated RBCs. Reticulocytes are increased.

Excess beta chains of alpha thalassemia intermidia that remain unpaired form ______ chains called____

tetramers beta , Hemoglobin H

two of four gene loci deleted

thalassemia minor

A cell stained with brilliant cresyl blue in which unstable hemoglobin is not present or has not yet precipitated will appear

to have a smooth surface with no inclusions

The genotypic system classifies the beta thalassemias based on their

zygosity (heterozygous vs. homozygous) as well as degree of the mutation (partial vs. full)

The notation for the normal number of alpha loci is

αα/αα

When three gene loci of alpha chains are deleted (--/-α) or inactive, how much of Hemoglobin A is made?

70-90%

The amount of Hb A produced by this normal gene is

95-98 %.

Homozygous minor

A patient with alpha thalassemia, who is African American, most likely has which form of the disorder?

Which two of the following beta thalassemia forms are associated with the genotype B0/B+?

Beta thalassemia intermedia Beta thalassemia major

Children with this disease usually develop clinical signs during their first year of life. They appear to be malnourished and may exhibit abdominal girth expansion. They show bone marrow expansion and skeletal deformations, which are a result of increased erythropoiesis due to low hemoglobin levels. A common finding is facial bone changes caused by this bone marrow expansion (sometimes referred to as Mongoloid facial features).

Beta thalassemia major

clinical signs include frequent infections, hepatomegaly, splenomegaly, gall stones, leg ulcers, iron toxicity, and poor growth and sexual development. In addition, cardiac failure

Beta thalassemia major

This condition results in a range in beta chain synthesis from 10 - 50%.

Beta thalassemia minor (one gene mutation or deletion)

Hemoglobin H, consisting of beta chain tetramers, is an unstable hemoglobin which forms precipitates just below the red blood cell membrane. This precipitated hemoglobin inclusion can be observed when red blood cells are stained with

Brilliant Cresyl Blue (BCB).

Beta thalassemia minima is genotypically denoted as

Bsc/B, for silent carrier

Beta thalassemia major is also referred to as

Cooley's anemia

A hemoglobin F concentration of 100% may be seen in which beta thalassemia?

Delta-beta thalassemia major

which hemoglobins are typically increased in beta thalassemia?

F and A2 respectively

Delta-Beta Thalassemia is most common in persons from

Greece, Africa, and Italy.

plasma protein responsible for binding free hemoglobin during episodes of hemolysis

Haptoglobin

With the exception of beta thalassemia minima, which hemoglobin is decreased in beta thalassemia?

Hb A

regions of the world where severe forms of beta thalassemia occur more frequently

Italy, Algeria, Greece, Saudi Arabia, and southeast Asia. Individuals of African descent have a higher frequency of milder forms of beta thalassemia than individuals in other regions

RBC morphology of beta thalassemia intermedia

Marked hypochromia and microcytosis Codocytes (target cells) Possible basophilic stippling Nucleated RBCs are usually not present

RBC morphology of beta thalassemia minor

Marked hypochromia and microcytosis Codocytes (target cells) Possible basophilic stippling Nucleated RBCs are usually not present

RBC morphology of beta thalassemia major

Marked hypochromia and microcytosis Codocytes (target cells) Schistocytes Ovalocytes Basophilic stippling Polychromasia Nucleated RBCs

Which of the following is NOT decreased in beta thalassemia major: Mean corpuscular hemoglobin concentration (MCHC) Mean corpuscular volume (MCV) Red cell distribution width (RDW) Red blood cell (RBC) count

RDW is increased (not decreased) in beta thalassemia major due to anisocytosis and poikilocytosis

Hb electrophoresis of beta thalassemia major

Severly decreased amount of Hb A Variable amount of Hb A2 Usually an increased amount of Hb F

-α/αα

Silent Carrier

Any ethnic group can have occurrences of hemoglobin H disease; but it is most often seen in

Southeast Asia, the Middle East and the Mediterranean islands.

Ethnic groups most commonly associated with infant alpha thalassemia

Southeast Asian and occasionally Mediterranean decent.

hemoglobin synthesis disorder in which there exists a defect in the rate of production of one or more of the globin chains. This defect results from either a heterozygous or homozygous deletion or inactivation of a globin chain gene.

Thalassemia