What is Pure Red Cell Aplasia?
Pure red cell aplasia (PRCA) is a rare disease causing anemia, or low red blood cell count, due to interference with the process of creating red blood cells, known as erythropoiesis. PRCA leads to anemia where the size and hemoglobin content of the red blood cells remains normal, but there is an associated decrease in the number of young red blood cells, known as reticulocytes, and very few immature red blood cells are found in the bone marrow. Unlike aplastic anemia, where all blood cells are affected, PRCA only affects red blood cells, leaving normal numbers and types of platelets and white blood cells.
The disease was first identified in 1922 by Kaznelson, and a hereditary version, called Diamond-Blackfan syndrome, was described in the 1930s. The association of PRCA with abnormal growths in the thymus gland, or thymoma, led to the discovery of autoimmunity – in other words, the body attacking its own cells – as a cause of this disease. PRCA is also linked with parvovirus B19 infections in patients with another red blood cell disorder, sickle cell disease. However, because the disease is quite rare, it is hard to run large clinical trials, so the best treatment approaches often rely on looking back at patient outcomes from older treatment methods and anecdotal reports.
All blood cells originate from a common type of stem cell. Astonishingly, from a pool of just 100,000 of these stem cells, hundreds of billions of blood cells can be made every day. Stem cells can make more of themselves, as well as transforming into specific types of cells as needed, maintaining the supply of blood cells.
Blood cells start to appear in the embryo during the third week of development. By the third month, the stem cells move from the yolk sac to the liver, which is the primary producer of blood cells until birth. By the fourth month, bone marrow starts to be populated by these cells. At birth, all marrow sites are making blood cells, taking over from the liver. Up until puberty, the marrow remains fully active, but by adulthood, half of the marrow becomes fatty and inactive. The only active sites left are found in the skull, vertebrae, sternum, ribs, pelvis, and near the ends of the large long bones in the arms and legs.
Blood cells all start from a specific type of stem cell which can transform into either a myeloid or lymphoid stem cell. Some of these cells, under the influence of specific growth factors, become a common precursor for red cells, platelet-forming cells, and cells which can lead to an allergic response. Another factor, erythropoietin (EPO), encourages these common cells to evolve into young red cells, which then mature into normal red blood cells. Red blood cells contain hemoglobin, a molecule which binds to oxygen and delivers it to all the tissues of our body.
What Causes Pure Red Cell Aplasia?
Pure red cell aplasia (PRCA) is a condition that affects the body’s ability to produce red blood cells. It can be inherited at birth or it can develop later in life. Diamond-Blackfan syndrome is a type of PRCA that kids often inherit.
On the other hand, the kind of PRCA that develops later in life can be caused by several issues.
Some of them are:
– Autoimmune disorders, where the body’s immune system attacks its own cells. These can include conditions like lupus, rheumatoid arthritis, and inflammatory bowel disease.
– Certain types of cancer like leukemias, lymphomas, and specific solid tumors including thymoma (a tumor in the thymus gland), and cancers of the breast, bile duct, stomach, lung, thyroid, and kidney.
– Transplants of stem cells that don’t match certain important blood group systems.
– Infections from various viruses like Parvovirus B19, HIV, different hepatitis viruses, or bacteria including streptococcus or tuberculosis.
– The use of certain medications, with a drug called recombinant human EPO being a common one linked to PRCA.
– During pregnancy or due to a deficiency of a vitamin called riboflavin.
– As yet unknown causes.
It is vital to find out the root cause of PRCA, as this will determine how it needs to be treated. Many times, addressing the underlying issue or stopping the use of a particular medication can improve or even solve PRCA. However, it might be necessary to continue monitoring the condition and treating it, to avoid complications and keep blood counts stable.
Risk Factors and Frequency for Pure Red Cell Aplasia
Pure Red Cell Aplasia (PRCA) is a rare disorder and there’s not much data on how often it occurs in the general population. That said, a variation of it called Diamond-Blackfan syndrome is slightly more common, affecting roughly 5 to 7 out of every 1 million babies born. According to a UK health registry:
- About 67% of people diagnosed with this condition have larger than normal red blood cells.
- About 13% were already anemic when they were born.
- Almost 73% show symptoms by the time they’re 3 months old.
Signs and Symptoms of Pure Red Cell Aplasia
Pure red cell aplasia (PRCA) often begins with signs of anemia such as constantly feeling tired, being unable to exercise for long, experiencing heart palpitations, and in more severe cases, fainting. Additionally, the presence of certain conditions like a recent drug reaction, pregnancy, or an autoimmune disorder could suggest a person has PRCA.
Upon physical examination, patients with PRCA usually look pale. The skin should be carefully examined for red skin infections or the sign of a recent infection by the parvovirus B19. In children, this condition is known for causing a bright red rash on the face and a net-like rash on the body. Other symptoms might include swollen glands, an enlarged liver or spleen, and sore joints. Although none of these symptoms confirm PRCA, they can provide important insights into the cause.
- Tiredness
- Decreased ability to exercise
- Heart palpitations
- Fainting (in severe cases)
- Pale appearance
- Red skin infections or recent parvovirus B19 infection
- Swollen lymph nodes
- Enlarged liver or spleen
- Sore joints
Diamond-Blackfan syndrome, a type of PRCA, can show physical abnormalities in around 40% of infants suffering from it. These can include unusual features of the head and face, abnormal thumbs, short height, problems with the urinary or reproductive organs, a webbed neck, and issues with bones and the heart. Children with Diamond-Blackfan syndrome often have a distinct appearance with light-colored hair, a snub nose, eyes that are farther apart than usual, fuller upper lips, and a bright expression. They can also have an unusual instability in the joints of the thumb.
Testing for Pure Red Cell Aplasia
When you have low red blood cell counts but normal white cell and platelet counts, it may suggest a condition called Pure Red Cell Aplasia (PRCA). Identifying PRCA usually starts with a review of a blood sample, followed by tests to determine how severe your anemia is and find out the exact cause.
These tests include:
1. Complete blood count with differential – this test checks different components of your blood. Low amounts of hemoglobin and hematocrit, along with healthy numbers of white cells and platelets and a significantly reduced reticulocyte (young red blood cells) count, strongly support a diagnosis of PRCA.
2. EPO level – EPO is a hormone that stimulates the production of red blood cells. High EPO levels usually go along with anemia.
3. Type and cross – this is done in preparation for a red blood cell transfusion if needed.
After these, your doctor will order tests to find out what is causing your PRCA:
Tests to check for autoimmune disease – These search for antibodies (proteins your immune system uses to fight infections) that could be causing your body to incorrectly attack its own cells.
Viral studies – Checking for certain types of viral infection, such as Parvovirus B19, hepatitis A, B, C, and E, HIV, EBV, CMV, and HTLV-1, which could be causing PRCA.
Flow cytometry of peripheral blood cells – This test checks for abnormal cells that could indicate a cancerous condition.
There are also tests that can detect a bone marrow disorder, and a pregnancy test may also be carried out.
Sometimes, testing for iron overload might be needed:
This involves checking your level of ferritin (a protein that stores iron in your body), which increases as you have more transfusions. They’ll also check your iron level and total iron-binding capacity. If you’ve had too many transfusions, these will both be too high.
A liver and kidney function test may also be required, as these organs can be affected by excessive iron in the body.
There is another condition, the Diamond-Blackfan syndrome, which is associated with unusual activity in a certain enzyme in your red cells. Very few labs can carry out this test, and it must be done on a fresh blood sample from a patient who hasn’t recently had a blood transfusion. Only one lab in the US performs this test.
Treatment Options for Pure Red Cell Aplasia
The management of Pure Red Cell Aplasia (PRCA), a condition affecting red blood cell production, varies depending on whether it’s congenital or acquired. Congenital PRCA is present at birth and is due to genetic causes that cannot be corrected, but some patients can undergo a special treatment called hematopoietic stem cell transplantation (HSCT, a procedure to replace damaged bone marrow with healthy cells). Acquired PRCA on the other hand, often has an identifiable source which can be easier to treat.
Treatments for the condition generally aim at managing symptoms of anemia (low red blood cell count) and maintaining stable hemoglobin (protein in red blood cells that carries oxygen) levels. Supportive care often includes blood transfusions and iron supplementation. Regular checkups are necessary to assess progress, manage complications, and adjust treatments if necessary.
There are different types of PRCA, including untreated congenital PRCA, congenital PRCA and various types of acquired PRCA. Each type needs specific treatment options that often include blood transfusions and the use of medication like corticosteroids. Steroids are typically used for children with DBA, but its long-term use can lead to side effects such as growth problems, facial changes, potential risks of diabetes and high blood pressure, and increased risk of eye conditions like cataracts. Thus, it is essential to start steroid therapy early and give live vaccines before starting therapy.
Acquired PRCA can also be treated with measures such as blood transfusions and EPO-stimulating agents (drugs that prompt the bone marrow to produce more red blood cells). Some treatments, including intravenous immunoglobulin (IVIG) or rituximab, aim to suppress the abnormal immune response causing the disease.
If PRCA results from parvovirus B-19 infection, treatment involves managing the infection and maintaining the body’s immune response. In usual cases, the immune system can control the infection with the development of immunity within two weeks. However, some patients may need treatment with IVIG.
For thymoma-associated PRCA (thymomas are tumors in the thymus) the recommended treatment is cyclosporine, another type of immunosuppressant medication. This type of PRCA can also occur after stem cell transplants. To manage this, adjustments to the immunosuppressant regime, introducing donor-leukocyte (white blood cell) infusion, and rituximab, an anti-CD20, have been used.
Lastly, it’s important to prevent iron overload from chronic blood transfusions – a common complication in PRCA. To address this, medications known as iron chelators may be used to remove the excess iron from the body. Among such medications are Deferoxamine, Deferasirox, and Deferiprone. Early detection and treatment of iron overload are crucial to prevent further complications.
What else can Pure Red Cell Aplasia be?
When a patient comes in with symptoms of anemia and reticulocytopenia, the doctor needs to check for a condition called PRCA. The low count of reticulocytes, a type of blood cell, sets PRCA apart from hemolytic anemia, a condition where the body destroys red blood cells faster than it can make them. A good patient history and smart use of tests can help the doctor figure out what is causing the patient’s anemia.
Different versions of PRCA can be identified based on their causes, and can also be distinguished from other conditions based on how they present in a patient.
- Diamond Blackfan syndrome often comes with abnormalities of the face and thumbs. Not every patient will have these symptoms, though. High levels of fetal hemoglobin, increased activity of a red blood cell enzyme, and a particular gene mutation helps confirm this diagnosis. The doctor also has to rule out Fanconi anemia, which affects the bone marrow, using specific genetic tests and stress markers.
- TEC recovers on its own. This condition can present right at birth or later in life. Differentiating TEBI, a variation of TEC, from inherited PRCA in babies can be hard due to similar timings of onset. But, TEBI is more likely if the patient recovers spontaneously than if they are dealing with congenital PRCA.
- It’s tough to separate inherited PRCA from the acquired type when the condition first shows up in adulthood.
When the patient is also dealing with neutropenia, a lack of an immune cell type, the physician should rule out aplastic anemia and acute lymphoblastic leukemia. A bone marrow examination can be a big help in clearing up this uncertainty.
What to expect with Pure Red Cell Aplasia
The outcome prognosis of PRCA, a type of anemia where the body stops producing red blood cells, can vary depending on several factors. These can include the underlying cause of the condition, how severe the condition is, the age the patient was at onset, and how well they respond to treatment. Those patients who react positively to immune-suppressing therapy have a good chance of going into remission and maintaining stable blood cell counts. However, some patients may not respond to treatment, or their disease may come back after initial remission.
Inherited PRCA patients who have a positive response to steroid treatment, meaning their body accepts the treatment well and they can eventually stop using it, generally live a normal life span. However, patients who don’t respond to steroid treatment and need chronic blood transfusions may suffer from organ damage due to overload of iron. These patients usually live between 30 to 40 years. Patients who get HSCT (a treatment that transplants healthy cells into your body) at a younger age generally have better outcomes than those who get the treatment at an older age after receiving chronic blood transfusions.
In the case of Acquired PRCA (a type gotten after birth, not due to genetic inheritance), a Japanese study found that these patients live significantly shorter overall lives than average. The lifespan of patients with different causes of PRCA, such as LGL (when the body makes too many of a certain type of white blood cell), thymoma (a type of tumor), and idiopathic PRCA (with unknown causes), do not have significantly different life spans from each other.
Most deaths in PRCA patients are due to infections and organ failure, not worsening of the underlying disease. This points out the importance of closely watching patients for any signs of complications, like infections from a suppressed immune system and iron overload resulting from repeated blood transfusions. Regular use of a medication called cyclosporine needs to be maintained for most patients to prevent the disease from returning. Patients who respond well to steroid treatment usually live around 12 years. On the other hand, a study showed that almost all patients who responded well to cyclosporine A remained alive after a follow-up of 14 years.
In conclusion, the outlook for PRCA can greatly depend on personal factors. Constant monitoring and regular follow-up visits to the doctor are crucial to detect any complications or return of the disease early and adjust treatment as needed.
Possible Complications When Diagnosed with Pure Red Cell Aplasia
Children diagnosed with DBA, or Diamond Blackfan Anemia, have a higher risk of getting cancer than children their age in the general population. Even though this risk is not as high as in children with Fanconi anemia, it’s still considerable. The chances of getting both solid and liquid forms of cancer are higher in kids with DBA. The most common blood cancer seen in these children is Acute myeloid leukemia, while the most frequently found solid organ tumor is osteogenic sarcoma.
Problems from chronic anemia like reduced growth rate, delayed psychomotor development, and increased heart strain are also associated with DBA. Severe anemia can cause a condition where the heart has to work harder to supply blood, which can lead to heart failure in individuals with existing heart conditions.
Pregnancy in women with anemia can also involve complications. Early labor, babies born with a lower than average weight and risk of mother or baby mortality increase with anemic conditions. Chronic tiredness and lower quality of life are also common symptoms of anemia.
- Higher risk of cancer
- Slow growth rate
- Delayed development
- Inreased heart strain
- Potential heart failure in individuals with heart conditions
- Pregnancy complications
- Chronic fatigue
- Lower quality of life
Some DBA patients with PRCA, or Pure Red Cell Aplasia, who regularly receive blood transfusions may amass excessive iron in their bodies which can be harmful. Using immunosuppressive therapy drugs like cyclosporine or steroids for a long time can suppress bone marrow function, making patients susceptible to infections. Using corticosteroids, whether as short, high-dose or long term therapy, is associated with a range of negative side effects.
Preventing Pure Red Cell Aplasia
There are several steps that can potentially help prevent Pure Red Cell Aplasia (PRCA), a condition where your body doesn’t produce enough red blood cells, or reduce the complications related to this condition:
1. If your family is affected by hereditary PRCA, it’s important to consider genetic counseling. This can provide you with useful information about genetic risks and potential management strategies.
2. You can help avoid infections, which might increase your PRCA risk, by frequently washing your hands, maintaining good cleanliness habits, and keeping a safe distance from people with contagious illnesses.
3. Engaging in healthy lifestyle habits can also minimize your exposure to harmful toxins that might cause PRCA. This includes eating a balanced diet, avoiding areas with poor air quality, not smoking, and limiting alcohol consumption.
4. For individuals with hereditary PRCA, having a procedure called a hematopoietic stem cell transplant (HSCT) early on could help avoid complications linked to long-term immune suppressing treatments and routine blood transfusions.
5. Regular follow-up appointments with your doctor can help prevent complications arising from any underlying conditions and side effects from treatments.
It’s important to understand that PRCA often recurs and usually requires ongoing treatment. If you notice any new symptoms, whether they are from the treatment or the condition itself, you should seek medical help right away.
