Pure red cell aplasia: causes, diagnosis and treatment

Red blood cells are made in the bone marrow from precursor cells. In pure red cell aplasia those precursors are specifically lost or blocked, while the production of white blood cells and platelets carries on normally. The MSD Manual (professional edition) describes it as a disorder of erythroid precursors that results in an isolated normocytic anaemia, in which white cells and platelets are not affected.

A published case report describes PRCA as a rare disorder and one cause of severe normochromic normocytic anaemia, which can be congenital or acquired. The congenital form, Diamond-Blackfan anaemia, is covered separately in the MSD Manual. This page concentrates on acquired PRCA.

The MSD Manual says symptoms are generally mild and related to the degree of anaemia or the underlying disorder, and onset is usually insidious, often over weeks or months. They include fatigue, lethargy, decreased exercise tolerance and pallor. In the case report an elderly patient presented with fatigue, dizziness, syncope and skin itchiness.

Because the anaemia comes on gradually, many people adjust without noticing. Anyone with persistent tiredness, breathlessness on exertion, looking pale or fainting should see a GP for a full blood count.

Severe anaemia can cause chest pain, marked breathlessness at rest, fainting or a very fast heartbeat. These need emergency assessment: call 999 or go to A&E. Anyone known to have PRCA who develops fever or signs of infection, particularly while on immunosuppressive medicines, should seek same-day advice from their haematology team or NHS 111.

The MSD Manual says PRCA is most often due to an inappropriate immune response causing suppression of red cell production. It lists causes including the following.

• ABO-mismatched bone marrow transplant.

• Autoimmune and connective tissue diseases such as systemic lupus erythematosus and rheumatoid arthritis.

• Medicines, including some tranquilisers, antiseizure medicines, recombinant erythropoietin and immune checkpoint inhibitors.

• HIV infection.

• Lymphoproliferative diseases, such as chronic lymphocytic leukaemia, large granular lymphocyte leukaemia, lymphomas and myeloma.

• Parvovirus B19, particularly in immunocompromised people.

• Pregnancy, riboflavin deficiency, solid tumours, thymomas and toxins.

The MSD Manual lists a complete blood count with reticulocyte count, bone marrow examination, a blood film looking for large granular lymphocytes and sometimes flow cytometry and T-cell gene rearrangement testing. PRCA shows a normocytic anaemia with normal white cell and platelet counts and decreased reticulocytes; the marrow shows an arrest of red cell maturation. A chest CT is indicated to look for a thymoma if no other cause is found.

The case report illustrates how thorough the search can be: flow cytometry, T-cell receptor gene rearrangement and PET/CT were used to establish that the cause was an autoimmune disorder rather than a malignancy.

Treatment depends on the cause. The MSD Manual says some people undergo spontaneous remission if the causative medicine is stopped, after delivery if pregnancy is the cause, or after an ABO-incompatible transplant. PRCA has been successfully managed with immunosuppressants such as prednisone, ciclosporin and cyclophosphamide, especially when an autoimmune mechanism is suspected. PRCA secondary to parvovirus infection is treated with intravenous immune globulin, and thymectomy is done for thymoma-associated PRCA, though most patients improve but are not always cured and require immunosuppressive agents.

The case report notes that its patient was sensitive to ciclosporin despite earlier reports that people with clonal T-cell receptor rearrangement may respond poorly. Your haematology team will advise whether supportive measures such as transfusion are needed while treatment takes effect, and anyone on immunosuppression needs monitoring for infection and drug side effects.

On the NHS, anaemia found by the GP leads to blood tests and haematology referral where a bone marrow examination is considered. Care for PRCA is delivered by haematology teams, sometimes with rheumatology, immunology or thoracic surgery depending on the cause.

A private haematologist can arrange tests quickly, though bone marrow biopsy and long-term immunosuppression monitoring should be coordinated with your NHS team. We could not find a UK patient information page for PRCA, so this guide draws on a professional reference and published case reports.