Pure red cell aplasia
Synonyms and keywords: Pure red cell aplasia; Erythroblastopenia.

# Overview
Pure red cell aplasia was first discovered by Paul Kaznelson in 1922. Pure red cell aplasia may be classified into primary (idiopathic) PRCA and acquired red cell aplasia. It is thought that acquired pure red cell aplasia is the result of profound anemia due to severe reduction in number of RBC in peripheral blood and absence of erythroid precursors, proerythroblast in the bone marrow.  Causes include autoimmune disease, thymoma, viral infections, lymphoproliferative disorders, idiopathic, drugs, ABO- incompatible hematopoietic cell transplantation, Anti- erythropoietin antibodies. Pure red cell aplasia must be differentiated from transient erythroblastopenia of childhood, Diamond-Blackfan anemia (DBA) and aplastic anemia. The incidence of Diamond-Blackfan anemia (DBA) is approximately 6.6 per 100,000 individuals in Europe. Pure red cell aplasia due to Diamond-Blackfan anemia (DBA) affects men and women equally. Common risk factor in the development of pure red cell aplasia include strong family history. If left untreated, 14% of patients with pure red cell aplasia may have spontaneously remitting disease. Pure red cell aplasia due to parvovirus infection usually resolve within 2-3 weeks. Common complications of pure red cell aplasia include infection due to side effects of some treatments. Prognosis is generally good. Diagnostic study of choice include complete blood count, peripheral smear, reticulocyte count, hepatic function test, renal function test, bone marrow aspiration and biopsy. Common symptoms of pure red cell aplasia include fatigue and lethargy. Laboratory findings consistent with the diagnosis of pure red cell aplasia include normocytic, normochromic anemia, very low or zero reticulocyte percentage and an absolute reticulocyte count <10,000/microL, normal white blood cell and platelets. An x-ray may be helpful in the diagnosis of thymoma and other neoplasms. Medical therapy include red blood cell transfusion in symptomatic anemia, cessation of offending drugs, Intravenous immune globulin (IVIG) in resistant pure red cell aplasia, Immunosuppressive therapy in idiopathic pure red cell aplasia. Surgery is usually reserved for patients with thymoma.

# Historical Perspective
- Pure red cell aplasia was first discovered by Paul Kaznelson in 1922.
- A congenital form of PRCA was described by Diamond and Blackfan in 1938.

# Classification
There is no established system for the classification of pure red cell aplasia (PRCA). However it may be classified into primary (idiopathic) PRCA and acquired red cell aplasia. Diamond-Blackfan anemia (DBA) is a congenital form of red cell aplasia. Based on the duration of symptoms, pure red cell aplasia may be classified as either acute or chronic.

# Pathophysiology
- It is thought that acquired pure red cell aplasia is the result of profound anemia due to severe reduction in number of RBC in peripheral blood and absence of erythroid precursors, proerythroblast in the bone marrow.
- The numbers of white blood cells and platelets are normal.
- In autoimmune disorders, IgG fraction in serum inhibit the growth of normal erythroid progenitors.
- In some cases of autoimmune PRCA, T lymphocytes suppress erythropoiesis.

# Causes
- Autoimmune disease
Autoimmune hemolytic anemia
Systemic lupus erythematosus
Rheumatoid arthritis
- Autoimmune hemolytic anemia
- Systemic lupus erythematosus
- Rheumatoid arthritis
- Thymoma
- Viral infections
HIV
Herpes
Parvovirus B19 (Fifth disease)
Hepatitis such as hepatitis C
- HIV
- Herpes
- Parvovirus B19 (Fifth disease)
- Hepatitis such as hepatitis C
- Lymphoproliferative disorders
T-cell large granular lymphocyte leukemia, especially in china 
Chronic lymphocytic leukemia
Hodgkin lymphoma
Non-Hodgkin lymphoma
- T-cell large granular lymphocyte leukemia, especially in china 
- Chronic lymphocytic leukemia
- Hodgkin lymphoma
- Non-Hodgkin lymphoma
- Myeloid malignancies such as chronic myeloid leukemia
- Myelodysplastic syndrome
- Idiopathic
- Drugs 
Phenytoin
Chloramphenicol
Azathioprine
Isoniazid
Valproic acid
Erythropoietin
Trimethoprim-sulfamethoxazole
Zidovudine
Chlorpropamide
- Phenytoin
- Chloramphenicol
- Azathioprine
- Isoniazid
- Valproic acid
- Erythropoietin
- Trimethoprim-sulfamethoxazole
- Zidovudine
- Chlorpropamide
- ABO- incompatible hematopoietic cell transplantation
- Anti-erythropoietin antibodies due to treatment with recombinant human erythropoietin
- Plasma cell disorders
- Pregnancy

# Differentiating Pure Red Cell Aplasia from Other Diseases
Pure red cell aplasia must be differentiated from transient erythroblastopenia of childhood, Diamond-Blackfan anemia (DBA) and Aplastic anemia:
- Transient erythroblastopenia of childhood: It is self-limited condition during first years of life.
- Diamond-Blackfan anemia (DBA): congenital form of red cell aplasia. It is associated with some malignancies and it does not respond to prednisone.
- Aplastic anemia: It affects other bone marrow cells as well.

# Epidemiology and Demographics
- The incidence of Diamond-Blackfan anemia (DBA) is approximately 6.6 per 100,000 individuals in Europe. Pure red cell aplasia due to Diamond-Blackfan anemia (DBA) affects men and women equally and there is no racial predilection to this disease.
- The acquired form of pure red cell aplasia can presents as an acute self-limited disease predominantly in children or chronic illness that is more seen in adults.
- The incidence of thymoma in patients with pure red cell aplasia is about 5%.

# Risk Factors
Common risk factor in the development of pure red cell aplasia include strong family history.

# Screening
There is insufficient evidence to recommend routine screening for pure red cell aplasia.

# Natural History, Complications, and Prognosis
- If left untreated, 14% of patients with pure red cell aplasia may have spontaneously remitting disease.
- Pure red cell aplasia due to parvovirus infection usually resolve within 2-3 weeks. 
- Common complications of pure red cell aplasia include infection due to side effects of some treatments such as glucocorticoids and cyclophosphamide.
- Prognosis is generally good. In one study in 1984, survival in idiopathic pure red cell aplasia was more than 10 years, but only four years in pure red cell aplasia secondary to leukemia and lymphoma.

# Diagnosis

## Diagnostic Study of Choice
- Complete blood count, peripheral smear, reticulocyte count
- Hepatic function test
- Renal function test
- Bone marrow aspiration and biopsy

## History and Symptoms
Common symptoms of pure red cell aplasia include fatigue and lethargy.

## Physical Examination
Common physical examination findings of pure red cell aplasia include fast heart beat and pale apperance.

## Laboratory Findings
Laboratory findings consistent with the diagnosis of pure red cell aplasia include:
- Normocytic, normochromic anemia; rarely, macrocytic anemia may be seen
- Very low or zero reticulocyte percentage and an absolute reticulocyte count <10,000/microL
- Normal white blood cell
- Normal platelet counts
- Bone marrow biopsy: normal myelopoiesis, lymphopoiesis, and megakaryocytopoiesis, but few erythroid precursors

## Electrocardiogram
There are no ECG findings associated with pure red cell aplasia.

## X-ray
An x-ray may be helpful in the diagnosis of thymoma and other neoplasms.

## Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with pure red cell aplasia.

## CT scan
Chest CT scan may be helpful in the diagnosis of thymoma and other neoplasms.

## MRI
Chest MRI may be helpful in the diagnosis of thymoma and other neoplasms.

## Imaging Findings
There are no other imaging findings associated with pure red cell aplasia.

## Other Diagnostic Studies
- Viral studies for hepatitis C and parvovirus B19
- Autoimmune antibody studies
- Karyotype
- T cell receptor clonality studies
- Peripheral blood immunophenotyping

# Treatment

## Medical Therapy
- Symptomatic anemia: Red blood cell transfusions
- Cessation of offending drugs
- Investigation for associated condition
- Self limited if due to ABO incompatible hematopoietic cell transplantation
- Intravenous immune globulin (IVIG): Single infusion 400 mg/kg over 2-3 hours if spontaneous resolution does not occur during 2-3 weeks. IVIG, 400 mg/kg daily for five day can be considered in resistant pure red cell aplasia.
- Immunosuppressive therapy in idiopathic pure red cell aplasia such as:
Glucocorticoids: Prednisone, oral dose ( 60 mg/day in divided doses ). It is considerd as a initial treatment.
Glucocorticoids plus cyclosporine: If no response to glucocorticoids occur after one to two months. Cyclosporine oral dosage can be considered 200 to 600 mg/day.
Glucocorticoids plus cyclophosphamide: Cyclophosphamide oral dosage can be considered 2 to 3 mg/kg per day.
- Glucocorticoids: Prednisone, oral dose ( 60 mg/day in divided doses ). It is considerd as a initial treatment.
- Glucocorticoids plus cyclosporine: If no response to glucocorticoids occur after one to two months. Cyclosporine oral dosage can be considered 200 to 600 mg/day.
- Glucocorticoids plus cyclophosphamide: Cyclophosphamide oral dosage can be considered 2 to 3 mg/kg per day.
- Refractory cases:
Azathioprine (2 to 3 mg/kg per day)
Antilymphocyte globulin
Antithymocyte globulin
Rituximab: Anti-CD20 monoclonal antibody 
Alemtuzumab: Anti-CD52 monoclonal antibody
Daclizumab: Anti-interleukin monoclonal receptor antibody 
- Azathioprine (2 to 3 mg/kg per day)
- Antilymphocyte globulin
- Antithymocyte globulin
- Rituximab: Anti-CD20 monoclonal antibody 
- Alemtuzumab: Anti-CD52 monoclonal antibody
- Daclizumab: Anti-interleukin monoclonal receptor antibody 

## Surgery
Thymectomy: Surgery is usually reserved for patients with thymoma. 

## Primary Prevention
There are no established measures for the primary prevention of pure red cell aplasia.

## Secondary Prevention
There are no established measures for the secondary prevention of pure red cell aplasia.