Clinical Compendium 262-267

Front 1

Where is thalassemia most prevalent?

Back 1

Mediterranean, Africa, Southeast Asia. Parallels the prevalence of malaria.

Front 2

On what genes are the α- and β- genes located?

Back 2

α-genes are located on chromosome 16.
β-genes are located on chromosome 11p15.5.

Front 3

How many copies of the β gene are on each chromosome?

Back 3

One, for a total of two productive genes in normal cells.

Front 4

How many copies of the α gene are on each chromosome?

Back 4

Two, for a total of four α chain producing gene loci in each normal cell.

Front 5

What type of mutations are most common in β-thalassemia?

Back 5

Point mutations

Front 6

What type of mutations are most common in α-thalassemia?

Back 6

Large deletions

Front 7

What is the most common genotype in African Americans with thalassemia?

Back 7

(-α/). The is a genotype in which chromosome 16 has one normal and one deleted α gene.

Front 8

What are the typical CBC findings in thalassemias?

Back 8

Elevated RBC count (>5.5 x 10^12 in men, >5.0 x 10^12 in women)
Low MCV (65-75 fL in α-thal; 55-65 fL in β-thal)
Low hematocrit
Normal to slightly elevated RDW

Front 9

What MCV/RBC count favors thalassemia?

Back 9

An MCV/RBC count ratio < 13 favors thalassemia, while a ratio > 15 favors iron deficiency.

Front 10

What are typical peripheral smear findings in thalassemia?

Back 10

Microcytic hypochromic anemia with occasional target cells (more in β-thal) and basophilic stippling.

Front 11

In what populations is α-thalassemia most common?

Back 11

Sub-saharan Africans and southeast Asians. The α thal 1 gene is prevalent only in Asians, and it is they who are at risk for the very severe kinds of α-thalassemia (Hg Bart and Hg H diseases). The α thal 2 gene is most prevalent in blacks.

Front 12

What type of symptoms do persons with single gene deletion α-thalassemia have?

Back 12

None. They are entirely asyptomatic, have normal CBC, and normal electrophoresis.

Front 13

Persons with α-thalassemia trait (2 gene deletions) manifest what clinically?

Back 13

A CBC with thalassemic indices and electrophoresis with normal A and A2 bands. A2 is not increased. In the absence of iron deficiency, this can be interpreted as consistent with α-thal trait.

Front 14

In what populations β-thalassemia most common?

Back 14

Mediterranean populations.

Front 15

At what age do manifestations of β-thalassemia become evident?

Back 15

6 to 9 months.

Front 16

Beta thal minor typically result from inheritance of how many abnormal β genes?

Back 16

One. Either β+ or β⁰.

Front 17

What is the most common electrophoretic pattern in beta thal minor?

Back 17

High HbA2 (over 2.5%, usually 4-8%and normal HbF. The second most common shows a normal A2. This is due to simultaneous iron deficiency, and may be erroneously interpreted as consistent with α-thalassemia.

Front 18

In δ-β thal (deletion of both the δ and β genes), what is the electrophoretic pattern?

Back 18

Normal A2 and elevated HbF (5-20%).

Front 19

In heterozygous Hb Lepore (fusion of δ and β), what is the electrophoretic pattern?

Back 19

Normal A2, slightly elevated HbF, and a band in the S region comprising 6-15% (Hb Lepore).

Front 20

Beta thal major results from inheritance of how many abnormal genes?

Back 20

Two, such as β⁰ β⁰, β+med β+med, or β⁰ β+med.

Front 21

What is the most common cause of death in childhood in patients with beta thal major?

Back 21

Individuals are not anemic at birth but develop anemia within one year. The most common cause of death in childhood is infection.

Front 22

What is the electrophoretic pattern in beta thal major?

Back 22

Increased HbF (50-95%), normal to elevated A2, and little to no HbA.

Front 23

What is the clinically distinguishing factor between beta thal intermidia and beta thal major?

Back 23

Beta thal major is transfusion dependent.

Front 24

Warm autoimmune hemolytic anemia is usually mediated by what type of antibody?

Back 24

A warm-reacting IgG antibody.

Front 25

In warm autoimmune hemolytic anemia, does the responsible antibody usually have a broad or narrow reactivity with red cell antigens?

Back 25

Usually a broad reactivity, especially Rh antigens. Uncommonly, the antibody has a narrow specificity; eg, for a specific Rh antigen, Kell, Kidd, etc.

Front 26

What is the crucial test in diagnosing autoimmune hemolytic anemia?

Back 26

The DAT (antiglobulin test, Coombs test). It is positive in nearly all cases of warm autoimmune hemolytic anemia.

Front 27

What type of reactivity can be seen in the DAT test in a patient with warm autoimmune hemolytic anemia?

Back 27

Usually polyspecific and anti-IgG reagents, sometimes with both anti-IgG and anti-C3, and uncommonly with anti-C3 only. Infrequently, the DAT may be falsely negative, due to very rapid intravascular destruction of RBCs or very low titer Ab.

Front 28

How are cells destroyed in warm autoimmune hemolytic anemia?

Back 28

The Ab binds to Ags on the red cell surface. In most cases, the bound Ab acts as an opsonin that provoked RBC destruction by splenic macrophages (extravascular hemolysis). In this instance, some escape and are seen on smear as spherocytes. In other cases, the Ab activates complement and results in either intravascular hemolysis (through formation of the MAC), or opsonization (cascade arrested at C3b).

Front 29

How do patients with warm autoimmune hemolytic anemia present?

Back 29

Patients present with variable severity. Some have abrupt onset and severe symptomatic anemia, while others have a chronic low grade hemolysis.

Front 30

Is warm autoimmune hemolytic anemia a primary or secondary disease?

Back 30

Can be both. Secondary comprises about 70% of cases, and occurs in hematolymphoid neoplasms, inherited autoimmunity (common variable immunodeficiency, IgA deficiency, Bruton’s), collagen vascular disease, thymoma). Stem cell transplantation has also been associated.

Front 31

What type of antibodies are cold agglutinins?

Back 31

IgM

Front 32

What is the specificity of cold agglutinins?

Back 32

Cold agglutinins are IgM antibodies with specificity that is most commonly anti-I. Others include anti-i, anti-H, anti-Pr, and anti-IH.

Front 33

What are the most important laboratory features in predicting pathogenicity of cold agglutinins?

Back 33

Titer and thermal range (thermal amplitude).

Front 34

At what temperature do nonpathologic cold agglutinins react?

Back 34

Nonpathologic cold agglutinins react most strongly at 4⁰ C, but have variably wide thermal amplitudes and may react at up to 22⁰C.

Front 35

What is the titer of most nonpathologic cold agglutinins?

Back 35

The titer of benign cold agglutinins is usually <64 at 4⁰C.

Front 36

What is the only reliable CBC index in the presence of cold agglutinins?

Back 36

Hemoglobin.

Front 37

At what temperature do pathologic cold agglutinins react?

Back 37

They are reactive over a broad range, up to 32-37⁰C and cause spontaneous autoagglutination in anticoagulated blood at room temperature.

Front 38

What is the titer of pathologic cold agglutinins?

Back 38

The titer is often >1000 at 4⁰C.

Front 39

What is the predominant clinical scenario in idiopathic cold autoimmune hemolytic anemia?

Back 39

A chronic condition found predominantly older individuals complaining of acrocyanosis and Reynaud phenomenon with a moderate hemolytic anemia.

Front 40

What is the clinical scenario in secondary cold autoimmune hemolytic anemia?

Back 40

A transient condition often associated with infection. M pneumonia infection is associated with anti-I, and EBV-associated infectious mononucleosis is associated with anti-i.