37 Pure Red Cell Aplasia

Question 1

The diagnosis applied to isolated anemia secondary to failure of erythropoiesis

Answer 1

Pure red cell aplasia

Historical names for pure red cell aplasia include erythroblast hypoplasia, erythroblastopenia, red cell agenesis, hypoplastic anemia, and aregenerative anemia.

Question 2

Cardinal findings of Pure red cell aplasia

Answer 2

• Low hemoglobin level
• Reticulocytopenia
• Absent or extremely infrequent marrow erythroid precursors

Question 3

Constitutional PRCA

A disease of ribosomal biogenesis

Answer 3

Diamond-Blackfan anemia

Question 4

Gene abnormality in Diamond-Blackfan anemia

Answer 4

Chromosome 19q13
Ribosomal protein S19 (RPS19) gene

Question 5

Genotype and phenotype correlation in Diamond-Blackfan anemia

Answer 5

GATA1 and TSR2: X-linked
RPL11: thumb abnormalities
RPL5: thumb, craniofacial, and heart defects
RPS28 and TSR2: mandibulofacial dysostosis

Question 6

The major defect in the erythropoietin-independent erythropoiesis in Diamond-Blackfan anemia

Answer 6

Late stage of erythropoietin-dependent erythroid cell expansion and maturation

Compatible with the classic findings of macrocytosis and increased hemoglobin F expression

Question 7

Most frequent clinical feature in Diamond-Blackfan anemia

Answer 7

Craniofacial dysmorphism: “tow-colored hair, snub nose, wide set eyes, thick upper lips, and an intelligent expression”

Question 8

TRUE OR FALSE

Untreated inherited pure red cell aplasia is fatal; death results from severe anemia and congestive heart failure.

Answer 8

TRUE

Untreated inherited pure red cell aplasia is fatal; death results from severe anemia and congestive heart failure.

Question 9

Management of Diamond-Blackfan anemia

Answer 9

Transfusions, glucocorticoids, and allogeneic stem cell transplantation (curative)

Question 10

Predictors of glucocorticoid responsiveness

Answer 10

Older age at presentation, a family history, and a normal platelet count

Question 11

The difference of temporary failure of erythropoiesis from pure red cell aplasia

Answer 11

• Spontaneous resolution of symptoms and of the laboratory findings of normocytic and normochromic anemia
• Marrow erythroid hypoplasia, usually over the course of a few weeks

Question 12

Causes of temporary failure of erythropoiesis

Answer 12

(1) by acute primate erythroparvovirus 1 (B19 parvovirus) infection, typically in the context of underlying hemolytic disease (called transient aplastic crisis);

(2) in normal children, usually after an infection by another (unknown) childhood virus (transient erythroblastopenia of childhood);

(3) as a drug reaction

Question 13

Transient aplastic crisis also was noted as a complication of ____________ disease

Answer 13

Sickle cell disease

Question 14

In transient aplastic crisis, marrow examination showed decrease or absence of erythroid precursor cells, and often___________________

Answer 14

Giant erythroblasts

Question 15

A small DNA virus, commonly infects humans; tropic for erythroid progenitor cells

Answer 15

B19 parvovirus

Question 16

The receptor for entry of ParvoB19 into the cell

Answer 16

Surface P antigen or globoside

The virus is tropic for erythroid progenitor cells

Question 17

Symptoms and signs of a typical “slapped cheek” cutaneous eruption and arthralgia or arthritis

IgM antibody is present in the blood, and virus levels are either low or undetectable

Answer 17

Fifth disease

In contrast, in transient aplastic crisis, high concentrations of virus are present in the circulation, and fifth disease does not develop in patients.

Question 18

TRUE OR FALSE

Transient aplastic crisis associated with sickle disease has a higher frequency of fever, pain, acute chest syndrome, and acute splenic sequestration syndrome.

Answer 18

TRUE

Transient aplastic crisis associated with sickle disease has a higher frequency of fever, pain, acute chest syndrome, and acute splenic sequestration syndrome.

Question 19

TRUE OR FALSE

The etiology of transient erythroblastopenia of childhood is not understood.

Answer 19

TRUE

The etiology of transient erythroblastopenia of childhood is not understood.

Question 20

Typically occurs in younger patients who are chronically anemic as a result of hereditary spherocytosis, sickle cell disease, or another hemolytic anemia.

Answer 20

Transient aplastic crisis

Question 21

Presents as an acute anemia in a previously well child

Most common cause of acquired red cell aplasia in pediatric patients

B19 parvovirus is not the etiology

Answer 21

Transient erythroblastopenia of childhood

Question 22

How to distinguish transient erythroblastopenia of childhood in contrast to inherited red cell aplasia

Answer 22

Transient erythroblastopenia of childhood :
* Age at presentation is older
* No family history
* Physical anomalies are absent
* Syndrome resolves spontaneously
* Erythrocyte adenosine deaminase levels are normal
* Red cells do not show “stress” patterns of fetal hemoglobin and i antigen (red cell antigen expressed primarily on fetal erythrocytes) expression

(but transient erythroblastopenia of childhood may be familial and can occur simultaneously in siblings)

Question 23

Transient aplastic crisis resolves as neutralizing antibodies to B19 parvovirus are made, usually within _______ weeks of infection.

Answer 23

1–2 weeks

Meanwhile, transient erythroblastopenia of childhood typically terminates after a few weeks, but anemia may sometimes persist for months.

Question 24

The mechanism of red cell failure in acquired pure red cell aplasia

Answer 24

• T-cell–mediated autoimmune destruction and
• Persistent B19 parvovirus infection

Suppression of erythropoiesis by T cells may be more common than antibody inhibition as a mechanism of erythropoietic failure

Question 25

TRUE OR FALSE

Persistence of B19 parvovirus infection occurs in the setting of immunodeficiency, most commonly caused by chemotherapeutic and immunosuppressive drugs, human immunodeficiency virus 1 infection, and occasionally Nezelof syndrome’s subtle immunologic abnormalities.

Answer 25

TRUE

Persistence of B19 parvovirus infection occurs in the setting of immunodeficiency, most commonly caused by chemotherapeutic and immunosuppressive drugs, human immunodeficiency virus 1 infection, and occasionally Nezelof syndrome’s subtle immunologic abnormalities.

Question 26

Genetic defects can lead to failure of erythropoiesis

Red cell aplasia occasionally can be the first or the major manifestation of a myelodysplastic syndrome.

Answer 26

N-RAS
Loss of the RPS14 gene in 5q− deletions

Question 27

May predict responsiveness to immunosuppressive treatment

Answer 27

Erythroid colony assays

Question 28

Thymomas are frequently associated with autoimmune disease, ____________most prominently, and with marrow failure syndromes

Answer 28

Myasthenia gravis

In a patient with acquired pure red cell aplasia, a thymoma should be sought by chest imaging, including computed tomographic scan.

Question 29

BMA finding in persistent parvovirus infection

Answer 29

Giant pronormoblasts

But such typical cells may not be observed

Question 30

Typically, oral prednisone 1–2 mg/kg per day is given first, and about ________ of patients improve.

Answer 30

Half

Higher response rates have been cited for cyclosporine, and some experts (and the author) advocate using this drug first.

Question 31

Preferred in red cell aplasia associated with LGL

Answer 31

Azathioprine and cyclophosphamide

Question 32

Most effective drug to treat pure red cell aplasia associated with thymoma

Answer 32

Cyclosporine

A thymoma should be excised to prevent local spread of a malignant tumor, but thymectomy does not necessarily improve marrow function.

Question 33

TRUE OR FALSE

Red cell aplasia is an indication for stem cell transplantation because the anemia usually can’t be managed with less drastic approaches.

Answer 33

FALSE

Red cell aplasia is rarely an indication for stem cell transplantation because the anemia usually can be managed with less drastic approaches.

Despite early favorable case reports, androgens, erythropoietin, and splenectomy are not routinely used to treat pure red cell aplasia.

Question 34

An excellent source of B19 parvovirus neutralizing antibodies present in a large proportion of the normal population

Answer 34

Immunoglobulin

0.4 g/kg per day for 5–10 days