Overview

Pure Red Cell Aplasia (PRCA) is a rare blood disorder characterised by severe anaemia due to low counts of erythrocytes - red blood cells (RBCs) - in your body and little to no erythroblasts (RBC precursors) present in the bone marrow. It can be caused by a variety of factors and you may be more susceptible to it if you suffer from Diamond-Blackfan anaemia. Different treatments are available depending on the individual cause of this condition, and cyclosporine can be used as an immunosuppressive treatment in most cases. If you want to find out more about PCRA and how it can be treated with cyclosporine, the information below may give you some clarity.¹

Causes of PRCA

There are two types of PRCA inherited and acquired. Inherited PRCA comes in the form of a congenital genetic disorder called Diamond-Blackfan syndrome. It is most commonly caused by genetic mutations in mitochondrial genes which manifests as anaemia due to low erythrocyte precursors and bone abnormalities from early childhood years.² 

Acquired PRCA is a form of this disease caused by underlying medical conditions or treatments. It is further divided into primary acquired PRCA and secondary acquired PRCA. 

Primary acquired PRCA is considered an autoimmune disease, meaning that your immune system prevents the healthy formation of RBCs. This type of PRCA manifests as a result of unspecified autoimmune disorders.^1,3 

Secondary acquired PRCA arises due to known conditions or medication which may include:

• Autoimmune diseases e.g. lupus erythematosus
• Lymphoproliferative disorders
• Blood cancers (leukemias)
• Infections caused by viruses e.g. parvovirus B19
• Infections caused by bacteria e.g. tuberculosis
• The presence of cancerous in the body e.g. thymoma
• Treatment with recombinant erythropoietin (rhEPO)
• Other medication e.g. diphenylhydantoin (anti-seizure medication)
• Deficiency in vitamin B2 (riboflavin)
• Being pregnant¹

Symptoms of PRCA

All PRCA is characterised by anaemia, hence you may experience symptoms typical for anaemia such as:

• Overall fatigue
• Decreased ability to do physical exercise
• Pale appearance
• Heart palpitations
• Feeling you’re about to faint or fainting

The symptoms experienced are not specific to PRCA. You may also suffer from these symptoms associated with other underlying conditions that caused the PRCA.¹

PRCA diagnosis

Diagnosis of PRCA starts with blood tests:

• Full blood count including the percentage of each blood cell type (differential)
• Erythropoietin level test (measures hormone crucial for RBCs’ production)
• Blood type and crossmatch (this will help determine donor blood compatibility with yours, especially when transfusion is needed for severe anaemia)¹

If your results show that you have anaemia and low levels of RBCs’ precursors with normal levels of white blood cells and platelets, your doctor will do further tests to rule out other diseases and confirm PRCA diagnosis. They may include:

• Peripheral blood tests which can detect underlying conditions/states:
  • Antibodies indicating autoimmune conditions
  • The presence of viruses that suggest viral infections
  • The presence of abnormal T-cells (T-cell gene rearrangement test)
  • Pregnancy (test to exclude pregnancy-related transient PRCA) if you’re assigned female at birth individual

• Blood flow cytometry to test for cancerous cell clones
• Plasma cell disease tests
• Bone-marrow tests such as aspiration or biopsy
• Tests for high levels of iron (iron overload)
• Diamond-Blackfan diagnosis tests¹

Available treatments for PRCA

The treatment for PRCA will depend on the cause of your PRCA. However, there is some overlap in available therapies. For congenital PRCA (Diamond-Blackfan syndrome) the standard treatment/management is:

• Corticosteroids (these have anti-inflammatory and immunosuppressive effects)
• Stem cell transplantation
• Blood transfusion
• Immunosuppressive drugs

As various underlying conditions can cause acquired PRCA there is a range of therapies available depending on each specific case. PRCA caused by:

• Autoimmune diseases - treatment with immunosuppressive agents such as cyclosporine, corticosteroids, cytotoxic agents, stem cell transplant, and plasmapheresis
• Lymphoproliferative disorders - treatment as above, and Rituximab shown to be especially effective
• Infections caused by viruses e.g. Parvovirus B19 - treatment with immunoglobulins
• Cancerous growth e.g. Thymoma - treatment with cyclosporine
• Medication e.g. recombinant erythropoietin (rhEPO) - treatment with cyclosporine, corticosteroids¹
• Being pregnant - treatment with blood transfusion only or with corticosteroid administration⁴

Treatment with cyclosporine

About cyclosporine

Cyclosporine is one of the main forms of treatment for PRCA. It is an immunosuppressive compound usually used for patients with transplant rejection issues but also those with autoimmune diseases. Typically, it works by suppressing the type of T-cells which in autoimmune disorders “attack” bone marrow red blood cells. Hence, when these “attacking” T-cells are suppressed, red blood cells in the bone marrow can start growing and multiplying and in turn stop the anaemia.⁵

Cyclosporine for inherited PRCA

In terms of Diamond-Blackfan-related PRCA, cyclosporine therapy has not shown any promising results. Hence, other forms of treatment are now used instead such as glucocorticoids and red blood cell transfusions.¹

Cyclosporine for acquired PRCA

Cyclosporine has been shown to be most effective in treating primary acquired PRCA. It is also used as a treatment for PRCA caused by other conditions.¹

Cyclosporine for autoimmunity-related PRCA

In secondary acquired PRCA due to known autoimmune conditions, cyclosporine is used along with corticosteroids. The recommended dose is 6mg/kg of body mass, daily until resolved.³

Cyclosporine for thymoma-related PRCA

In PCRA caused by thymoma, cyclosporine was shown to be effective and no return of the disease was seen. Thymoma-related anaemia is also treated with corticosteroids, but the best effects in patients are seen with cyclosporine treatment with a dose of 4.6mg/kg of body mass.⁶

Cyclosporine for rhEPO-induced PRCA and maintenance 

Even though it is a rare condition, cyclosporine is also the first choice for the treatment of PRCA that has arisen due to rhEPO antibodies, often supplemented by corticosteroids. Cyclosporine therapy is also usually required as a maintenance treatment in most cases of PRCA to prevent the disease from coming back.¹

Side effects of cyclosporine

As with any medication, cyclosporine may cause some side effects such as:

• Arrhythmia
• Hypertension
• Decreased filtrating ability of the kidneys (dose and length of treatment-dependant)
• Endocrine conditions
• Metabolic disorders
• Seizures and other involuntary contractions

Additionally, treatment with cyclosporine as well as corticosteroids may lead to a condition called bone marrow suppression (myelosuppression). This means that your bone marrow may be producing blood cells at a lower rate, making you more susceptible to infections as your immune system would be weakened.¹

Cyclosporine may interact with other medications that you may be taking and it may not be suitable if you suffer from certain conditions such as infections, asthma or kidney issues. If you suffer from psoriasis and take cyclosporine there is also an Increased risk of lymphoproliferative and skin malignancies. Hence it is crucial that you discuss any already ongoing conditions and treatments with your doctor, to avoid adverse effects.⁵

FAQs

How long is it safe to take cyclosporine?

This will largely depend on the severity of the condition and how quickly the effect will take. As a rule of thumb, a patient can take cyclosporine as long as required for the PRCA to be gone. However, if there are severe side effects that outweigh the benefits of the treatment, your doctor may advise you to stop the treatment.

What not to eat while on cyclosporine?

Some research shows that grapefruit and pomelo juice may interact with cyclosporine. Therefore, you may want to avoid eating these fruits and/or drinking their juices while undergoing cyclosporine treatment.⁷

Can cyclosporine cause anaemia?

Although the research is limited, it has been shown that cyclosporine may induce anaemia in rodents. Nevertheless, considering that PRCA patients already suffer from anaemia, cyclosporine-related anaemia may be masked.⁸

Does cyclosporine affect mood?

Some animal studies show that rodents treated with cyclosporine exhibit symptoms similar to human anxiety and depression. This could be due to the drug’s neurotoxic effect. However, there is no available research regarding this in human patients.^{9, 10}

Summary

Pure red cell aplasia (PRCA) is a form of anaemia, occurring due to low red blood cell (RBC) count. There are two main types of PRCA, “inherited” - caused by the congenital disease Diamond-Blackfan anaemia and “acquired” - caused by various underlying conditions. Symptoms include fatigue and a pale appearance. PRCA is mainly diagnosed through a variety of blood tests that help determine the underlying cause. There are different treatment options available depending on the condition that caused the PRCA. The treatment options may include cyclosporine, other immunosuppressants and corticosteroids. 

Cyclosporine is a medication of choice for acquired PRCA and is also used as a maintenance treatment. However, it has not been found to be effective for Diamond-Blackfan-related PRCA. It is important to note that cyclosporine may induce various side effects, interact with other medications and be unsuitable for patients with certain conditions.