Pure Red Cell Aplasia (PRCA)

What is pure red cell aplasia?

Bone marrow makes three main cell lines: red blood cells, white blood cells and platelets. In PRCA, only the red cell line fails. The earliest red cell precursors, called erythroblasts, are absent or nearly so, while the other lines are spared. That distinguishes it from aplastic anemia, where all three lines fail.

Because red cells live about 120 days, hemoglobin falls slowly, by roughly 1 g/dL a week, so symptoms usually appear over weeks.

Types and causes

Congenital PRCA

Diamond-Blackfan anemia is an inherited form that appears in infancy, often with physical differences such as thumb abnormalities or short stature.

Acquired PRCA

In young children, transient erythroblastopenia of childhood is a temporary, usually post-viral form that recovers within weeks without treatment.

In healthy people, parvovirus B19 (the cause of "fifth disease") stops red cell production for only about a week, which goes unnoticed. In people with sickle cell disease or other conditions that shorten red cell life, the same pause causes a sudden severe drop called an aplastic crisis.

Symptoms

The symptoms are those of anemia:

• Tiredness and weakness
• Pale skin, lips and inner eyelids
• Shortness of breath on exertion
• Fast or pounding heartbeat
• Dizziness, headaches
• Chest pain in people with heart disease

Fever, bleeding, frequent infections or enlarged lymph nodes are not part of PRCA itself and suggest an underlying blood cancer or a different marrow problem.

How PRCA is diagnosed

1. Complete blood count: low hemoglobin, usually with normal-sized red cells, and normal white cells and platelets.
2. Reticulocyte count: very low, typically under 1%. This is the key clue that the marrow is not responding.
3. Bone marrow biopsy: confirms the near-absence of erythroid precursors with otherwise normal marrow. In parvovirus infection, giant early red cell precursors (pronormoblasts) may be seen.
4. Parvovirus B19 PCR on blood or marrow.
5. CT scan of the chest to look for a thymoma.
6. Flow cytometry and T-cell receptor studies for LGL leukemia and other lymphoid disorders.
7. Autoimmune tests, HIV testing, medication review, and anti-EPO antibody testing if on epoetin.

Treatment

Support

• Red cell transfusions to relieve symptoms, given as needed.
• Iron chelation to remove excess iron if many transfusions are needed, since each unit adds iron that the body cannot excrete. See iron overload.

Treating the cause

• Stop any suspect medicine, including epoetin if anti-EPO antibodies are found.
• Thymectomy (removal of the thymoma); anemia does not always improve afterward and immune treatment is often still needed.
• IVIG (intravenous immunoglobulin) for persistent parvovirus infection, plus reducing immune suppression when possible.
• Treatment of LGL leukemia or lymphoma.

Immune-suppressing therapy

For autoimmune PRCA or when the cause cannot be removed:

• Cyclosporine, with or without corticosteroids, is the most widely used first treatment and leads to recovery in a majority of people.
• Corticosteroids alone help some.
• Other options: cyclophosphamide, rituximab, antithymocyte globulin, sirolimus, and more recent targeted agents for resistant cases.

Response, when it happens, is seen as a rising reticulocyte count within weeks, followed by rising hemoglobin.

Outlook

Outcomes vary by cause. Drug-induced and parvovirus-related PRCA often resolve once the trigger is removed. Idiopathic PRCA responds well to immune suppression in most people, but relapses are common when treatment stops, so some need long-term maintenance therapy. Long-term transfusion dependence carries a risk of iron overload, which must be managed.

Frequently asked questions

What is pure red cell aplasia?

It is a rare condition in which the bone marrow stops making red blood cells, while white cells and platelets are produced normally. The result is severe anemia with very few young red cells in the blood. It can be inherited or acquired from immune, viral, drug or cancer-related causes.

What causes pure red cell aplasia?

Acquired PRCA is most often autoimmune with no clear trigger. Recognized causes include thymoma, large granular lymphocytic leukemia and other blood cancers, lupus, chronic parvovirus B19 infection in people with weak immunity, certain medicines, and antibodies against epoetin injections.

How is pure red cell aplasia different from aplastic anemia?

In PRCA only red blood cell production fails. In aplastic anemia the whole bone marrow fails, so white cells and platelets are also low, causing infections and bleeding as well as anemia. The two are distinguished with a blood count and bone marrow biopsy.

Can pure red cell aplasia be cured?

Often, yes. When a cause such as a drug, parvovirus infection or thymoma is treated, red cell production can return. Most people with autoimmune PRCA respond to cyclosporine or steroids, though relapses are common and some need long-term treatment.