Pure red cell aplasia: when only the red cells fail

When only the red cells are missing from the count

Pure red cell aplasia, usually shortened to PRCA, is one of the less familiar ways the bone marrow can fail. The blood test that prompts a closer look often shows low haemoglobin, with white cell and platelet counts that sit where they should. That pattern is the first clue that the marrow has stopped making red cells while the rest of its output carries on.

This page covers what PRCA is, its main causes, how it differs from aplastic anaemia (spelled aplastic anemia in US sources), and what treatment usually involves. The causes range from an immune reaction and a viral infection to a rare inherited syndrome, and the approach depends heavily on which one is behind it.

Because PRCA is rare, much of what is known comes from case series and retrospective studies rather than large trials. The StatPearls review on the condition says as much, so the patterns described here are best read as guides rather than firm rules.

Only the red cell line is affected

The bone marrow builds red cells, white cells and platelets from the same pool of stem cells. In PRCA the fault sits in the red cell line. Few or no red cell precursors, called erythroblasts, are present, so the body makes fewer red cells. Erythropoietin, the hormone that drives red cell production, is usually raised as the body tries to compensate, according to NORD.

The anaemia is typically normocytic and normochromic. The red cells that do get through look normal in size and colour. What stands out is the shortage of young cells, which shows up as a markedly low reticulocyte count.

Aplastic anaemia works differently. The marrow fails to produce red cells, white cells and platelets, which is why it is usually described as a failure across all three lines. Our guide to aplastic anaemia covers that picture in more depth, and the table below sets the two conditions side by side.

Pure red cell aplasia and aplastic anaemia compared

The two conditions can look alike at first, because both cause anaemia and tiredness. The features below are the ones that tend to tell them apart.

What causes pure red cell aplasia

PRCA is usually grouped as acquired or inherited. Acquired forms can appear in adulthood or later childhood. Sometimes no trigger is ever found, and this is called primary or idiopathic PRCA. When a specific cause is identified, the condition is described as secondary.

Acquired causes

The cause most consistently linked to PRCA is a tumour of the thymus gland, called a thymoma. Autoimmune conditions such as systemic lupus erythematosus and rheumatoid arthritis are also associated, as are some lymphoid cancers. Large granular lymphocytic leukaemia is one of the more common links, while chronic lymphocytic leukaemia is the lymphoproliferative disorder most often connected with the condition.

Infection matters too. Parvovirus B19 is the most common viral cause. In people with normal immunity, antibodies usually clear the virus within one to two weeks, so the red cell shutdown is brief. In people who cannot mount an antibody response, the infection can persist and keep damaging red cell precursors.

Some medicines are also implicated. Drugs linked to PRCA include phenytoin, azathioprine, allopurinol, isoniazid and rifampin, among others. The drug most commonly linked is recombinant human erythropoietin, a manufactured form of the hormone. Antibodies that target the protein part of the drug have mostly appeared in people on dialysis, according to the StatPearls review.

The inherited form

Diamond-Blackfan anaemia is the inherited form, and it is the one most often studied. It usually becomes apparent during the first year of life. Most cases involve mutations in genes that make ribosomal proteins, the parts of the cell that build proteins. The condition affects approximately 5 to 7 newborn babies per million, according to MedlinePlus. Many people with it also have physical differences, such as a small head or thumb abnormalities, and some have milder forms that appear later in childhood or adulthood.

Symptoms and what the tests show

Nothing about the symptoms is unique to PRCA. People usually feel the anaemia first, as fatigue, reduced tolerance for exercise, palpitations and pallor. In someone whose heart is already under strain, the lower oxygen levels can bring on light-headedness or fainting. The history often offers the first clue to the cause, so a recent medicine, a pregnancy or a known autoimmune condition is worth mentioning at the first appointment.

A full blood count typically shows low haemoglobin with normal white cell and platelet counts, and a markedly reduced reticulocyte count. Erythropoietin levels are usually high. The bone marrow examination is often the decisive step. In autoimmune PRCA, erythroblasts make up less than 1% of the cells counted, in an otherwise normal-looking marrow.

Further tests look for the trigger. These include antibody tests for autoimmune disease, viral studies including parvovirus B19, flow cytometry to rule out a clonal blood cancer, and immunoglobulin tests for plasma cell disorders. Your haematology team will decide which of these apply to you.

How pure red cell aplasia is treated

Treatment works on two fronts. The first is to find and treat the cause. If a medicine is the trigger, stopping it is often the most important step. Where a thymoma is present, surgical removal of the thymus gland often brings about remission, according to NORD. Parvovirus-related transient PRCA is self-limited. In persistent infection, intravenous immunoglobulin corrected the anaemia in 93% of patients in the reviewed series, although up to 42% relapsed within about four months.

The second front is immune suppression for the immune-mediated forms. Corticosteroids were the first drugs to help, and they still have a role, but many people relapse once the dose is reduced. Ciclosporin (cyclosporine in US sources) is now often the first choice in adults, with response rates reported as high as 75%. Cytotoxic drugs such as cyclophosphamide are used when people do not respond to ciclosporin, and cyclophosphamide is especially useful for large granular lymphocytic leukaemia. Antithymocyte globulin, rituximab and intravenous immunoglobulin have also been used, with antithymocyte globulin reported to produce a response in about half of cases.

Supportive care runs alongside all of this. Red cell transfusions keep haemoglobin steady while treatment takes effect, and erythropoiesis-stimulating agents and iron are sometimes added. More detail on transfusions is in our page on blood and platelet transfusions.

Living with a condition that turns everyday tiredness into a constant companion can be wearing in ways a blood count does not capture. The weeks of waiting for a diagnosis can be hard on families too, and those feelings are a normal part of the picture.

Inherited PRCA is handled differently. In children with Diamond-Blackfan anaemia, corticosteroids, transfusion and stem cell transplant are the main approaches, as the StatPearls review describes. Shwachman-Diamond syndrome is a separate inherited marrow condition and has its own page.

A red-cells-only pattern is worth chasing

When the red cells are the only line that fails, the pattern narrows the search, and a cause is often identifiable. Treating that cause, whether by stopping a medicine, removing a thymoma or clearing an infection, is the first step. Where no cause emerges, immune suppression and supportive care can often hold the red cell count steady, although relapse is possible. The wider picture of inherited and acquired forms is set out in acquired vs inherited bone marrow failure.