37 Pure Red Cell Aplasia Flashcards
The diagnosis applied to isolated anemia secondary to failure of erythropoiesis
Pure red cell aplasia
Historical names for pure red cell aplasia include erythroblast hypoplasia, erythroblastopenia, red cell agenesis, hypoplastic anemia, and aregenerative anemia.
Cardinal findings of Pure red cell aplasia
- Low hemoglobin level
- Reticulocytopenia
- Absent or extremely infrequent marrow erythroid precursors
Constitutional PRCA
A disease of ribosomal biogenesis
Diamond-Blackfan anemia
Gene abnormality in Diamond-Blackfan anemia
Chromosome 19q13
Ribosomal protein S19 (RPS19) gene
Genotype and phenotype correlation in Diamond-Blackfan anemia
GATA1 and TSR2: X-linked
RPL11: thumb abnormalities
RPL5: thumb, craniofacial, and heart defects
RPS28 and TSR2: mandibulofacial dysostosis
The major defect in the erythropoietin-independent erythropoiesis in Diamond-Blackfan anemia
Late stage of erythropoietin-dependent erythroid cell expansion and maturation
Compatible with the classic findings of macrocytosis and increased hemoglobin F expression
Most frequent clinical feature in Diamond-Blackfan anemia
Craniofacial dysmorphism: “tow-colored hair, snub nose, wide set eyes, thick upper lips, and an intelligent expression”
TRUE OR FALSE
Untreated inherited pure red cell aplasia is fatal; death results from severe anemia and congestive heart failure.
TRUE
Untreated inherited pure red cell aplasia is fatal; death results from severe anemia and congestive heart failure.
Management of Diamond-Blackfan anemia
Transfusions, glucocorticoids, and allogeneic stem cell transplantation (curative)
Predictors of glucocorticoid responsiveness
Older age at presentation, a family history, and a normal platelet count
The difference of temporary failure of erythropoiesis from pure red cell aplasia
- 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
Causes of temporary failure of erythropoiesis
(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
Transient aplastic crisis also was noted as a complication of ____________ disease
Sickle cell disease
In transient aplastic crisis, marrow examination showed decrease or absence of erythroid precursor cells, and often___________________
Giant erythroblasts
A small DNA virus, commonly infects humans; tropic for erythroid progenitor cells
B19 parvovirus
The receptor for entry of ParvoB19 into the cell
Surface P antigen or globoside
The virus is tropic for erythroid progenitor cells
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
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.
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.
TRUE
Transient aplastic crisis associated with sickle disease has a higher frequency of fever, pain, acute chest syndrome, and acute splenic sequestration syndrome.
TRUE OR FALSE
The etiology of transient erythroblastopenia of childhood is not understood.
TRUE
The etiology of transient erythroblastopenia of childhood is not understood.
Typically occurs in younger patients who are chronically anemic as a result of hereditary spherocytosis, sickle cell disease, or another hemolytic anemia.
Transient aplastic crisis
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
Transient erythroblastopenia of childhood
How to distinguish transient erythroblastopenia of childhood in contrast to inherited red cell aplasia
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)
Transient aplastic crisis resolves as neutralizing antibodies to B19 parvovirus are made, usually within _______ weeks of infection.
1–2 weeks
Meanwhile, transient erythroblastopenia of childhood typically terminates after a few weeks, but anemia may sometimes persist for months.
The mechanism of red cell failure in acquired pure red cell aplasia
- 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
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.
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.
Genetic defects can lead to failure of erythropoiesis
Red cell aplasia occasionally can be the first or the major manifestation of a myelodysplastic syndrome.
N-RAS
Loss of the RPS14 gene in 5q− deletions
May predict responsiveness to immunosuppressive treatment
Erythroid colony assays
Thymomas are frequently associated with autoimmune disease, ____________most prominently, and with marrow failure syndromes
Myasthenia gravis
In a patient with acquired pure red cell aplasia, a thymoma should be sought by chest imaging, including computed tomographic scan.
BMA finding in persistent parvovirus infection
Giant pronormoblasts
But such typical cells may not be observed
Typically, oral prednisone 1–2 mg/kg per day is given first, and about ________ of patients improve.
Half
Higher response rates have been cited for cyclosporine, and some experts (and the author) advocate using this drug first.
Preferred in red cell aplasia associated with LGL
Azathioprine and cyclophosphamide
Most effective drug to treat pure red cell aplasia associated with thymoma
Cyclosporine
A thymoma should be excised to prevent local spread of a malignant tumor, but thymectomy does not necessarily improve marrow function.
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.
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.
An excellent source of B19 parvovirus neutralizing antibodies present in a large proportion of the normal population
Immunoglobulin
0.4 g/kg per day for 5–10 days
