Anemia is the most common blood disorder associated with lupus – affecting over 50% of all those diagnosed.  So, if you have lupus, it is a good idea to review the latest information regarding the symptoms, causes and treatment options for the various forms of anemia.

• Introduction
• Symptoms
• Types of Anemia and Causes
• Tests and Diagnoses
• Treatments
• Prevention
• In Conclusion

Introduction

Anemia is generally defined as the lack of sufficient red blood cells (RBC’s) to adequately carry oxygen to all parts of the body. However, there are a number of reasons for having too few RBC’s, and so there are just as many types of anemia to consider.  Before exploring these individually, it helps to have a brief overview of how red blood cells are produced in the body in the first place and why we need them.

All red blood cells (sometimes called erythrocytes) come from stem cells that reside in the bone marrow of your body’s long bones.  This is a complicated process (called erythropoiesis), and since RBC’s only last about 4 months, it needs to happen all of the time.  As a matter of fact, the body produces red blood cells at the amazing rate of about 2 million per second!  Of course, to remain in balance, the body is losing about the same number each and every second.  Maintaining that balance takes a great deal of biochemical coordination on the part of several body systems.

For one example, the speed at which new blood cells are produced is, in part, regulated by a hormone called erythropoietin (EPO), which itself is produced by the kidneys.  So, producing enough RBC’s depends upon having healthy stem cells, healthy bone marrow and healthy kidneys.

In order to fulfill their job of carrying as much oxygen as possible, red blood cells use an amazing protein called hemoglobin.  Hemoglobin requires iron to hang on to oxyegen, and it is the iron in hemoglobin that gives oxygenated blood its red color.  Since each adult has about 30 trillion RBC’s in their blood at any given moment, and each RBC holds at least 250 million hemoglobin molecules … that requires a lot of iron!  A deficiency of iron is a common cause of anemia, and that is why it has been commonly referred to as “iron poor blood.”

Before going further, it is also important to realize that a person with lupus, like anyone else, can become anemic for reasons that are not specifically associated with lupus itself.   However, lupus presents added risks that can make the anemia even worse.  Also, those with SLE should be concerned about anemia, not only because of the symptoms that it causes (see below), but also because it may indicate a serious underlying issue, such as lupus nephritis or other kinds of kidney disease or failure.  For this reason, it is common for a hematologist, along with a rheumatologist and others, to be a member of a lupus patient’s medical team.

Symptoms

Depending upon the person’s level of anemia, symptoms can range from being basically unnoticeable (asymptomatic) to very serious or life threatening.  In general the most common symptoms include:

• Fatigue or exhaustion
• Feeling weak (there is a difference)
• Pale skin color
• Chest pain
• Poor appetite
• Rapid or irregular heartbeat
• Feeling dizzy or lightheaded
• Shortness of breath, especially with exertion
• Headaches
• Trouble sleeping or thinking clearly

 

Types of Anemia and Causes

As mentioned, there are many types of anemia.  Some are temporary conditions, while others are chronic or life-long.  Here are some of the most important for those living with lupus to consider:

Iron Deficiency Anemia (IDA):  This is the most common form of anemia in all populations and can occur at the same time as other forms of anemia.  As the name indicates, it results from insufficient iron, which can occur for several reasons. Pregnancy, blood loss due to heavy menstruation or bleeding ulcers can produce temporary iron deficiency anemia.  Also, the chronic use of NSAID’s such as ibuprofen or aspirin can create a small but continuous loss of blood (microbleeding) into the digestive tract.

Low iron can also be due to having a low iron diet or difficulty in absorbing iron from food that is eaten. Celiac disease, vasculitis or other inflammatory conditions of the gut (perhaps caused by lupus) can prevent sufficient iron from being absorbed.  This is an example where multiple autoimmune issues can compound their effects on each other.

Anemia of Chronic Disease (ACD): This is the second most common form of anemia worldwide, and the most common form of anemia for those living with lupus.  It can be caused by many types of chronic inflammatory disorders, such as cancer, chronic infections, kidney and autoimmune disease, especially rheumatoid arthritis and SLE.  The chronic inflammation associated with ACD slows down red blood cell production by keeping iron from being recycled into new red blood cells. It also shortens the lifecycle of the RBC’s that are produced.  The best way to treat ACD is to treat the underlying causes of inflammation.

Autoimmune Hemolytic Anemia (AIHA):  This refers to the direct autoimmune attack on red blood cells by anti-erythrocyte antibodies – destroying them prematurely.  In severe cases, the RBC’s may only last for a few days, rather than the normal 120 days.  It is a rare form of anemia, but some have estimated that up to 10% of anemia’s associated with lupus may be this variety.  There are several kinds of AIHA.  Some are triggered by viral infections (like measles and Epstein-Barr) other, in very rare cases, by some drugs like penicillin.  Usually AIHA is easily controlled with prednisone and immunosuppressive drugs.

Chronic Renal Insufficiency:  Chronic kidney disease can affect the amount of erythropoietin that those organs produce.  It is possible that this condition develops for reasons other than lupus, but since lupus nephritis (LN) is such a serious and not uncommon form of lupus kidney involvement, it is something to watch.

Drug Induced Myelotoxity:  This is the form of anemia caused by the use of drugs, some which are often prescribed for lupus, such as azathioprine and cyclophosphamide.  These drugs can reduce the bone marrow’s ability to produce RBC’s, and in turn, induce anemia.

Other forms of anemia that are less related to lupus include:

Aplastic Anemia:  This is a rare, but life-threatening anemia where the bone marrow, for many various reasons, loses its ability to produce enough red blood cells.  Beyond medications and blood transfusions, this form of anemia may require bone marrow transplants.

Sickle Cell Anemia:  This is a genetic mutation in the hemoglobin molecule that creates problems for the red blood cells so that they are removed from the blood stream relatively quickly.  It is more prevalent in people from African descent, and so it can occur with populations where lupus is more prevalent as well.

Vitamin Deficiency Anemia:  This type occurs if for some reason a person’s diet is lacking vitamin B-12 and folate (vitamin B-9), both of which are important for producing red blood cells.  There are also some digestive issues (due to autoimmunity or the surgical removal of key parts of the digestive tract) that prevent the body from absorbing B-12 in enough quantity. This leads to what is called pernicious anemia (PA), and is often treated with regular B-12 injections.

Tests and Diagnoses

Complete Blood Count (CBC):  Anemia is often first diagnosed through a blood test called the CBC, which stands for “complete blood count.”  This is a standard test that may be ordered during a routine checkup, and is used for a wide range of conditions other than anemia, including chronic infections, leukemia, and such things as blood clotting problems.  The results from the CBC include:

• The number and types of white blood cells (WBC’s), which are the most important cells in the blood for immunity and fighting infections.
• The number of platelets, which are critical for blood clotting.
• The number and size of red blood cells, for characterizing and diagnosing various anemia’s.
• Hematocrit level, which measures the percentage of your blood that is composed of red blood cells by volume. This is one way of describing how dense your blood is with RBC’s.  According to the Mayo Clinic:
  • Normal range for women is 35.5% – 44.9% (40% average).
  • Normal range for men is 38.3% – 548.6% (45% average).

• Hemoglobin levels, the amount of hemoglobin in every 100 ml. of blood. Since carrying hemoglobin is the main job of RBC’s, hemoglobin levels are another way of defining and measuring anemia.  According to the Mayo Clinic:
  • Normal levels for women are 12.0 -15.5 grams/100ml.
  • Normal levels for men are 13.5 -17.5 grams/100ml.

Ferritin Test:  This test measures ferritin levels in the blood, which is an indirect way to also measuring how much iron is stored in the body in general for making RBC’s.  Lower than normal ferritin levels may indicate iron deficiency anemia.  Higher than normal can indicate many things, including taking too many iron supplements.  According to the Mayo Clinic:

• Normal ferritin levels for women are 11 – 307 micrograms/ml.
• Normal ferritin levels for men are 24 – 336 micrograms/ml.

Erythrocyte Sedimentation Rate (ESR):  This blood test measures how quickly red blood cells settle to the bottom of a test tube at intervals of 15 minutes, 1 hour or 2 hours. A faster than normal rate may indicate any number of inflammatory conditions. This test is not specific to anemia, but it is useful in diagnosing related autoimmune conditions.

Coombs’ Test:  This blood test detects the presence of antibodies specifically against red blood cells, so it is used in the diagnosis of autoimmune hemolytic anemia.

Stool Test:  In order to determine whether intestinal bleeding may be the cause of iron deficiency, a stool sample may be ordered to look for the presence of blood.

Reticulocyte Test:  This blood test measures the levels of immature red blood cells (reticulocytes) and this helps gauge the rate of RBC production in bone marrow.

Once these tests have helped diagnose the type of anemia involved, treatment options can be selected.

Treatments

As mentioned several times, the treatment of anemia depends upon which type a person has.  If the lack of iron is the underlying problem, then increasing iron levels through diet or medications is a first step.  If there are complex autoimmunity issues involved, then other treatments may be used.  Here is a partial list:

Iron Rich Diet or Supplements:  Eating a diet rich in iron is always a good idea.  This includes green leafy vegetables, like spinach, and red meat, poultry or fish and eggs. Dried fruits (such as raisins), legumes (like peas and beans) and iron-fortified cereals and pasta can help. Of course, it is common for those with anemia to take iron supplements as well if necessary.  Iron in pill form can be difficult for some people to take, but there are various formulations from which to choose.  Also, it has been found that iron is more easily absorbed if vitamin C is taken at the same time.

Iron Infusion or Blood Transfusion:  If iron levels are not helped through diet, then direct injections or infusions of iron (IV) may be necessary. Red blood cell transfusions can quickly add RBC’s and iron to a patient with severe iron deficient anemia.  However, depending upon the anemia, the supplemental RBC’s may not last long.  Iron infusions provide a longer-term dose of iron that can last for several months or more.  Neither of these cure the anemia, but they can significantly help boost red blood cell counts and lesson the symptoms of anemia.

Recombinant Erythropoietin (EPO):  In cases where renal disease has reduced the ability of the kidneys to produce normal levels of EPO, injections of artificial erythropoietin-stimulating agents, like Procrit, Epogen or Aranesp, may be prescribed. These are powerful medications and require great care and medical supervision.

Steroids and Immunosuppressive Medications:  For inflammatory causes of anemia, and in the case of autoimmune hemolytic anemia, high doses of prednisone and immunosuppressive medications, like Imuran, may be prescribed.  For someone living with lupus, these medications may already be familiar and align with their treatment plan for lupus.

Surgery:  If, after a colonoscopy or upper endoscopy, the cause of the anemia is found to be significant bleeding in the gastro-intestinal tract, surgery may be needed to stop the bleeding.  Also, though used as a last resort, the spleen might be surgically removed in cases where the red blood cells are so affected that the spleen removes them from the blood too quickly for other treatments to compensate.

Prevention

There are several things you can do if you have lupus and potentially anemia is an issue:

• Avoid smoking
• Eat a well-balanced diet, high in iron.
• Reduce the amount of caffeine you take, because caffeine actually reduces your ability to absorb iron.
• Take vitamin supplements, especially folic acid, vitamin B-12, and vitamin C, but only do so after asking your healthcare provider.

In Conclusion

Anemia is a significant condition for many living with SLE.  The causes and type of anemia are numerous – with some being directly related to or perhaps even caused by lupus. Other types arise from completely unrelated sources.  It is important to note, that one of the most common complaints for both conditions is fatigue.  In this way, it is common for symptoms of lupus and anemia to overlap and exacerbate each other..  So, keep on the look out for any signs of anemia, and contact your healthcare provider if you have any questions about your symptoms or treatment options.  Anemia is just one more thing to have to consider when living with lupus, but the resources and treatments are available to not let it seriously affect your quality of life!

 

References

Ardalan, M. (2013). Anemia in lupus nephritis; etiological profile. Journal of Renal Injury Prevention, 2(3), 103-104. DOI: 10.12861/jrip.2013.32

Giannouli, S., Voulgarelis, M., & Tzioufas, A. G. (2006). Anaemia in systemic lupus erythematosus: From pathophysiology to clinical assessment. Annals of the Rheumatic Diseases, 65(2), 144-148.  Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1798007/

Lipowsky, R., & Sackmann, E. (Ed.). (1995). Biological membranes architecture and function. Handbook of biological physics (Vol. 1a) Amsterdam, Netherlands: North Holland Publishing.

Samohvalov, E., & Samohvalov, S. (2018). The pattern of anemia in lupus. In J. Khan (Ed.), Current topics in anemia (pp. 165-187).  London, England: IntechOpen.  Retrieved from https://www.intechopen.com/books/current-topics-in-anemia/the-pattern-of-anemia-in-lupus

Velo-García, A., Guerreiro Castro, S., Isenberg, D. A. (2016). The diagnosis and management of the haemotologic manifestations of lupus. Journal of Autoimmunity, 74, 139-160. https://doi.org/10.1016/j.jaut.2016.07.001

Voulgarelis, M., Kokori, S.I.G., Ioannidis, J., Tzioufas, A.G., Kyriaki, D., & Moutsopoulos, H.M. (2000). Anaemia in systemic lupus erythematosus: Aetiological profile and the role of erythropoietin. Annals of the Rheumatic Diseases, 59(3), 217-222. http://dx.doi.org/10.1136/ard.59.3.217

Wallace, D.J. (2019). The lupus book: A guide for patients and their families. New York, NY: Oxford University Press.

 

 

Author: Liz Heintz

Liz Heintz is a technical and creative writer who received her BA in Communications, Advocacy, and Relational Communications from Marylhurst University in Lake Oswego, Oregon. She most recently worked for several years in the healthcare industry. A native of San Francisco, California, Liz now calls the beautiful Pacific Northwest home.

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