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Dr. Andrew Rynne

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Article Home Children's Health Anemia Congenital Pure Red Cell

Anemia Congenital Pure Red Cell

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Pure red cell aplasia (PRCA) describes a condition in which RBC precursors in bone marrow are nearly absent, while megakaryocytes and WBC precursors are usually present at normal levels. Pure red cell aplasia exists in several forms, and the most common form is an acute self-limited condition. Congenital pure red cell aplasia is a lifelong disorder, and it is associated with physical abnormalities. Acquired pure red cell aplasia is often chronic and is associated with underlying disorders such as thymomas and autoimmune diseases.

Clinical types

  • Acute pure red cell aplasia
  • Chronic pure red cell aplasia-Congenital
  • Chronic pure red cell aplasia-Acquired

Causes

The etiology of pure red cell aplasia is diverse and is different for the acute self-limited, the acquired chronic (sustained), and the congenital chronic forms of pure red cell aplasia.

Acute self-limited pure red cell aplasia

  • Respiratory infections, gastroenteritis, primary atypical pneumonia, infectious mononucleosis, mumps, and viral hepatitis may trigger pure red cell aplasia.
  •  Most cases of acute transient pure red cell aplasia are caused by parvovirus B19 infection.
  • Parvovirus B19 can cross the placenta in infected women and can destroy erythroid cells in the fetus; in some cases, the virus can induce spontaneous abortion.
  • Drugs- Phenytoin, Carbamazepine, Sodium Valproate, Azathioprine, Chloramphenicol, Procainamide, and Isoniazid

Acquired chronic pure red cell aplasia

Congenital chronic pure red cell aplasia (ie, Diamond-Blackfan syndrome)

  • Approximately 90% of cases are sporadic, and one suggestion is that the sporadic cases are caused by in utero damage to erythroid stem cells.
  • In 10% of patients, a dominant, or more rarely recessive, familial pattern has been observed.

Clinical features

Anemia is the primary problem in pure red cell aplasia. The degree of anemia can range from subclinical to severe.

Acute self-limited pure red cell aplasia

  • Mumps, infectious mononucleosis, and viral hepatitis often precede the development of acute pure red cell aplasia.
  • Evidence of a recent viral infection (eg, a rash, jaundice in viral hepatitis, splenomegaly in infectious mononucleosis, enlarged parotid glands in mumps) may be present.
  • In patients with acute pure red cell aplasia who have hemolytic disorders, anemia can be severe because virtually no production of erythrocytes occurs to compensate for hemolysis. This is known as an aplastic crisis.

Acquired chronic (ie, sustained) pure red cell aplasia

  • Autoimmune disorders may be associated with arthritis.
  • Thymomas are rarely large enough to be detected during the physical examination.
  • Lymphadenopathy and splenomegaly may indicate the presence of an underlying lymphoproliferative disorder or systemic lupus erythematosus.

Congenital pure red cell aplasia

  • Some, but not all, cases of congenital pure red cell aplasia are associated with severe anemias.
  • More than one third of patients have malformations or mental retardation.
  • In addition to anemia, approximately one third of patients develop physical abnormalities, most often involving the head, upper limbs, thumbs, urogenital system, or cardiovascular system.
  • Growth retardation and unusual thumb formation can occur. However, these physical deformities are less severe than in Fanconi syndrome.
  • Anemia is not often observed during the early neonatal period, but pallor, weakness, and dyspnea attributable to the anemia develop during the first year of life.
  • Thymomas have not been found in these patients.

Tests and diagnosis

Basis studies

  • CBC count
  • Platelet count
  • Differential count
  • RBC indices
  • Reticulocyte count
  • Lactate dehydrogenase level
  • Indirect bilirubin level
  • Serum haptoglobin level

In acute pure red cell aplasia, rule out the following:

  • Parvovirus B19 infection (Sensitive techniques utilizing immunofluorescence (IF) staining and increased viral DNA production by dot blot hybridization and quantitative PCR have been recently reported to be effective in the detection of Parvovirus B19 infection
  • Atypical mycoplasmal pneumonia
  • Infectious mononucleosis
  • Mumps
  • Viral hepatitis

In acquired chronic pure red cell aplasia, rule out the following:

  • HIV infection
  • Thymomas
  • Chronic active hepatitis
  • Systemic lupus erythematosus
  • Autoimmune disorders (direct Coombs test)
  • Collagen-vascular disorders
  • Pregnancy
  • Chest radiography or CT scan to rule out thymoma
  • Bone marrow aspiration and biopsy are indicated to confirm the diagnosis.

For congenital pure red cell aplasia, obtain the following:

  • Fetal Hgb and erythrocyte adenine deaminase levels
  • Serum folate and vitamin B-12 levels
  • Genetic testing
  • Peripheral smear results - Can show megaloblastic changes

Treatment

Common to all forms is the treatment of anemia. Adequate Hgb levels should be maintained with transfusion therapy. Folic acid and multivitamins have been recommended.

Acute self-limited pure red cell aplasia

  • Discontinue offending drugs and treatment of associated infections or other illness.
  • Transfusion therapy is not usually indicated because of the self-limited nature of acute pure red cell aplasia.
  • Transfusions may be indicated in patients with hemolytic anemias who develop pure red cell aplasia.

Acquired chronic (sustained) pure red cell aplasia

  • The underlying disorder (eg, thyomoma, systemic lupus erythematosus [SLE], collagen-vascular disease, lymphoproliferative disorder) should be treated.
  • Corticosteroids can be effective, but a high dosage is often required, and the adverse effects frequently preclude using these agents. Prednisone can induce remission in approximately 45% of cases.
  • The next level of treatment is with cytotoxic or immunosuppressive drugs. Cyclophosphamide, 6-mercaptopurine, Azathioprine, and cyclosporine have all been used.
  • Patients refractory to corticosteroids and immunosuppressive are treated with monoclonal antibodies- Alemtuzumab, Rituximab
  • Autologous and nonmyeloablative allogeneic peripheral stem cell transplantation have been used and may be considered in patients who are refractory to other therapy.
  • Donor lymphocyte infusions have been used for refractory pure red cell aplasia relapsing after both autologous and nonmyeloablative allogeneic peripheral stem cell transplantation.
  • Antithymic or antilymphocyte serum has been effective. Several patients have responded to plasmapheresis or lymphocytapheresis.

Congenital pure red cell aplasia

  • Treatment is complicated because this condition is a lifelong disorder, and the consequences of treatment can have devastating effects on growth and sexual maturity.
  • Transfusion is an integral modality in treating congenital pure red cell aplasia.
  • Two units of blood every 2 weeks is usually sufficient.
  • Aggressive chelation using deferrioxamine (ie, desferrioxamine) infusions are critical to avoid hemosiderosis because transfusion therapy is usually started at a young age.
  • Corticosteroids are also a principal therapeutic option, and this therapy is believed to allow the abnormal stem cells in patients with congenital pure red cell aplasia to become more sensitive to growth factors. High doses of prednisone (ie, 1-2 mg/kg) are needed but should not be continued for more than 4-6 weeks. If prednisone therapy fails, a trial of high-dose methylprednisolone can be tried.
  • Danazol and other androgens can be used in refractory cases, but these agents may be contraindicated in prepubertal children.

Surgical care

  • Thymectomy may be indicated for the treatment of acquired chronic pure red cell aplasia
  • Splenectomy is not indicated unless hypersplenism can be documented to interfere with the treatment of pure red cell aplasia.

Prognosis

Because most cases of pure red cell aplasia are the acute self-limited form of pure red cell aplasia, morbidity and mortality from pure red cell aplasia are not significant.

The mortality rate for acquired chronic pure red cell aplasia and for congenital pure red cell aplasia is expected to be slightly greater than that for the acute form of pure red cell aplasia