Pure Red Cell Aplasia

Pure red cell aplasia is a rare blood disorder where your bone marrow stops making the normal number of red blood cells, leading to severe anemia that can leave you feeling exhausted and short of breath.

Table of contents

• What is Pure Red Cell Aplasia?
• Types of Pure Red Cell Aplasia
• What Causes This Condition?
• Signs and Symptoms
• How Doctors Diagnose PRCA
• Treatment Options
• What to Expect

What is Pure Red Cell Aplasia?

Pure red cell aplasia (PRCA) is a rare blood disorder that happens when your bone marrow (the soft, spongy tissue inside your bones) doesn’t produce the normal number of red blood cells.^[1] Red blood cells are essential because they carry oxygen to your tissues and organs throughout your body.^[2]

erythroblastopenia

• Bone marrow

When your red blood cell supply drops below normal levels, you have anemia. With anemia, you don’t have enough healthy red blood cells to deliver oxygen where it’s needed in your body.^[2] The condition is characterized by normocytic, normochromic anemia, which means the red blood cells that are present are normal in size and color, but there are simply too few of them.^[1]

What makes PRCA distinct from other blood disorders like aplastic anemia is that it only affects red blood cells. Your white blood cells and platelets remain at normal levels and function properly.^[3] This is important because white blood cells help fight infections and platelets help your blood clot.

PRCA was first described by Kaznelson in 1922. The inherited form of the condition, called Diamond-Blackfan anemia, was described by Joseph in 1936 and later by Diamond and Blackfan in 1938.^[1]

Types of Pure Red Cell Aplasia

There are three main types of PRCA, each with different characteristics and patterns of occurrence.^[3]

Acquired Pure Red Cell Aplasia is a very rare condition that usually affects adults. It is characterized by an absence of red cell precursors (immature red blood cells called reticulocytes) in the bone marrow and a low red blood cell count. The amounts of white blood cells and platelets remain normal.^[3]

Transient or Acute Self-limited PRCA is the most common type of PRCA. It is identical to acquired PRCA except that, at some point, it simply goes away on its own. Transient PRCA is usually triggered by a virus or drug. In most cases, when the virus clears or the responsible drugs are eliminated, the PRCA will disappear. This is most dangerous to patients who already have chronic conditions affecting their red blood cells. Patients with otherwise normal functioning bone marrow may even recover without having known they had it.^[3]

Inherited or Congenital Pure Red Cell Aplasia, also known as Diamond-Blackfan anemia, is a genetic condition usually diagnosed during the first two years of life. About half of patients also have physical malformations or developmental delays. Only several hundred cases have been reported worldwide. The severity of the disease varies by patient.^[3]

What Causes This Condition?

Pure red cell aplasia has several different causes. The cause of most cases of PRCA is thought to be autoimmune in nature. This means doctors think it is caused by a mistaken attack by the patient’s own immune cells on blood-forming stem cells.^[3]

People who develop PRCA often have underlying medical conditions. It may also be a side effect of medications.^[2] People can inherit PRCA or develop it because they have certain medical conditions.

Autoimmune diseases are a common cause. Conditions like systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease are examples of autoimmune diseases that may cause PRCA.^[2]

Blood cancers are another important cause. Chronic lymphocytic leukemia (CLL) and large granular lymphocytic leukemia (LGL) are two of the most common blood cancers linked to PRCA.^[2]

Cancerous tumors can also trigger PRCA. Thymoma (thymic carcinoma) is the most common cancerous tumor linked to pure red cell aplasia.^[2] The association of PRCA with thymoma led to the discovery of the autoimmune mechanisms producing this rare disease.^[1]

Viral infections are a common cause. Parvovirus B19 infection is a particularly common cause of PRCA. It affects people who have weak immune systems or other underlying conditions that affect their bone marrow. This virus attacks stem cells in your bone marrow that are intended to become red blood cells. Other infections include human immunodeficiency virus (HIV), Epstein-Barr virus, and all types of hepatitis.^[2] PRCA has been the object of much laboratory research due to its association with parvovirus B19 in patients with sickle cell disease.^[1]

Bacterial infections may also cause PRCA. Group C streptococcus, tuberculosis, and bacterial sepsis may cause PRCA.^[2]

Medication is another potential cause. Many different medications are linked to PRCA. For example, erythrocyte-stimulating agents (ESA) may cause PRCA. ESAs are medications designed to help your body produce more red blood cells.^[2]

Pregnancy can sometimes trigger PRCA. Some people develop PRCA during pregnancy. The condition goes away after giving birth.^[2]

In many cases, the cause of the condition is unknown and is called idiopathic.^[7]

Signs and Symptoms

By definition, all PRCA patients have anemia. The symptoms you experience are related to having too few red blood cells in your body.^[3] The bone marrow fails to produce mature red blood cells, leading to symptoms such as fatigue, weakness, pallor, and shortness of breath.^[1]

Common symptoms of PRCA include:^[2]

• Fatigue (feeling extremely tired)
• Difficulty breathing (dyspnea), especially during physical activity or exertion
• Dizziness
• Skin that’s paler than usual
• Headaches
• Pulsatile tinnitus (ringing in the ears that matches your heartbeat)
• Angina (chest pain)

Acquired PRCA can be caused by an underlying condition that may add other symptoms beyond those caused by anemia itself.^[3]

How Doctors Diagnose PRCA

PRCA diagnosis can be challenging due to its rarity, diverse presentations, and possible causes. Despite the difficulties, healthcare providers can effectively diagnose this condition by systematically evaluating the patient’s medical history, conducting appropriate tests, and ruling out other potential causes of anemia.^[1]

When you come in for your first appointment, your provider will want to know all about your symptoms, how long you’ve had them, if they’re getting worse, and how they’re affecting your life. You’ll also have a physical exam.^[2]

Providers diagnose this condition by doing blood tests and imaging tests. Tests and tools doctors use to diagnose PRCA include:^[2][3]

• Complete blood count (CBC), including a count of white blood cell types. This test looks at the total number and type of blood cells in your blood
• Reticulocyte count to determine blood levels of young red blood cells
• Peripheral blood smear, which allows doctors to examine your blood cells under a microscope
• Parvovirus B19 test to check for viral infection
• Computed tomography (CT) scan to look for tumors or other abnormalities
• Bone marrow aspiration or bone marrow biopsy. This is one of the most important tests because it allows doctors to examine your bone marrow directly to see if red blood cell precursors are present

The characteristics of PRCA found during testing include severe anemia, a reticulocyte count less than 1%, the presence of less than 0.5% mature red blood cell precursors in the bone marrow, and bone marrow that is otherwise normal in most cases.^[5]

Treatment Options

Treatment varies based on what caused you to develop PRCA. The treatment of PRCA aims to address the underlying cause of the condition and relieve the associated signs and symptoms.^[3] As a consequence, treatment of PRCA is diverse and strictly dependent on the presented clinical scenario.^[7]

The initial treatment plan should include transfusions for patients who are severely anemic and have cardiorespiratory failure. Anemia is more severe in patients with pure red cell aplasia who have ongoing breakdown of red blood cells.^[13]

Medications that could cause PRCA should be discontinued. Infections should be treated. PRCA due to medication or infections is usually reversible within a few months, if not earlier.^[13]

Treatment options include:^[2]

Immunosuppressants: These medications help control your immune system. Common medications for PRCA include cyclosporine (Gengraf®, Neoral® or Sandimmune®) and corticosteroids (prednisone). You may need to stay in the hospital during treatment and you may need more than one treatment. Idiopathic PRCA due to autoimmunity should be initially treated with corticosteroids. A response is expected within 4-6 weeks in about 45% of patients.^[13] Other immunosuppressive agents used in PRCA include cyclophosphamide, 6-mercaptopurine, azathioprine, and cyclosporine.^[13]

Blood transfusion: Receiving donor blood followed by treatment to remove excess iron that could damage your organs. Iron chelation should be considered in patients who have had multiple transfusions and have evidence of iron overload.^[13]

Surgery: If a thymus tumor causes PRCA, surgeons may remove your thymus (thymectomy) to prevent the tumor from spreading. About 30% of patients with thymomas respond to thymectomy.^[13]

High-dose intravenous immunoglobulin therapy should be considered for parvovirus B19 infections.^[13] For cases related to B19 parvovirus, administration of commercial immunoglobulin can treat or cure parvovirus by replacing neutralizing antibodies.^[6]

Underlying conditions should be treated. These conditions include a thymoma, blood cancers such as T-cell large granular lymphocyte leukemia, solid tumors, and systemic lupus erythematosus.^[13]

Other treatment options that have been used include rituximab, which has been reported to be effective in managing PRCA, and antithymocyte globulin (ATG). Plasmapheresis has been used to remove autoantibodies. Several patients have responded to plasmapheresis or lymphocytapheresis.^[6][13]

Autologous and nonmyeloablative allogeneic peripheral stem cell transplantation have been used, especially in patients whose disease is refractory to therapy.^[13]

Children with PRCA should be observed and not aggressively treated to avoid corticosteroid-related growth retardation. This caution is feasible since PRCA in children is often transient and reversible. However, transfusion should be administered if indicated.^[13]

What to Expect

Prognosis can vary depending on the underlying cause and how well the patient responds to treatment.^[1]

The life expectancy of patients with idiopathic PRCA is about 1-2 decades. The survival of patients with congenital PRCA is limited. The lifespan of patients with secondary PRCA depends on the course of the underlying disorder.^[5]

During treatment, patients typically receive a median of two different therapies to achieve remission. Frequently used therapy includes calcineurin-inhibitors with a steroid taper, which yields a first-line overall response rate of 76%.^[11]

Most effective therapies are directed against T-cell-mediated immunity, and therapeutic choices need to account for associated conditions that may help in choosing alternative salvage agents.^[11]