Systemic lupus erythematosus, often referred to as lupus or in short SLE, is a chronic autoimmune disease characterized by a potential multisystem involvement and the production of various autoantibodies. Lupus patients produce autoantibodies, which attack healthy proteins, tissue, and organs, leading to inflammation and damage. In contrast, normal antibodies are not directed against our healthy cells, but they are a part of the immune system that protects us from foreign invaders and infections.
The clinical manifestations of lupus vary greatly from relatively mild symptoms to an organ- and life-threatening disease. The most commonly affected organs by lupus are skin, joints, and kidneys. Other organs that can be involved are muscles, lung, heart, brain, blood vessels, and blood cells.
Blood disorders affect the ability of blood cells to perform adequately. Some blood disorders called "cytopenias," cause a decrease in blood cells leading to low numbers. Other disorders relate to an increase in blood cells.
The blood is made up of liquid and cellular components, and comprises of four main parts:
Commonly used terms to describe blood cell disorders are:
Other types of blood disorders rapidly increase the numbers of blood cells, such as leukemia or lymphoma, or blood clotting disorders, such as antiphospholipid syndrome. In this article, we will focus only on lupus-related blood cell disorders.
Hematologic (related to blood) manifestations in lupus are relatively frequent and range from mild to severe. All three blood cell lines (red blood cells, white, blood cells and platelets) can be affected. These abnormalities can be caused by the autoimmune disease itself or by to medications taken to treat the disease.
Anemia is seen in 50% of lupus patients over the course of the disease. There may be different underlying causes of anemia in lupus patients, which may sometimes overlap:
Half of patients with SLE may develop leukopenia (decrease in white blood cells), especially one type of the white blood cells called lymphocytes, which are part of the special task force of the immune system. There are two main possibilities for the drop in white blood cells:
Among patients with SLE, up to 25% may develop thrombocytopenia (low platelet count). Severe thrombocytopenia (< 50,000 mm3) is rare, approximately 10%. Lupus-related causes of thrombocytopenia include:
It should be mentioned that lupus patients can develop anemia, leukopenia, or thrombocytopenia due to reasons other than lupus, for example infection.
The drugs causing anemia, leukopenia, and thrombocytopenia are often part of the lupus treatment.
A common side effect of immunosuppressive drugs like azathioprine, cyclophosphamide, or methotrexate is bone marrow suppression. The bone marrow is the production site of the blood cells, and reduced activity therefore leads to an abnormally low blood cell count.
A variety of medications can interfere with blood cells. These include:
Depending on the severity of anemia that results, patients might have either no symptoms or multiple symptoms, which may include:
Leukopenia can lead to a higher risk of infections, especially bacterial, as the immune system is weakened. However, infections mostly occur when the white blood cell count is very low. Common general symptoms of an infection are fever, chills and sweats, and joint and muscle soreness.
Since platelets play an important role regarding blood clotting, a significant decrease in platelet count results in abnormal bleeding. Your skin can show "petechiae," which are small red spots, due to blood leaking from blood vessels, or larger red spots called "purpura," Furthermore, you can experience nosebleeds or bleeding from your gums, blood in urine or stool or heavy menstrual bleeding.
The first step to diagnose lupus-related blood cell disorders is a complete blood cell count (CBC) to measure cellular components of your blood. This test should be done regularly not only to assess the disease activity but also to monitor medication side effects. Furthermore, a peripheral blood smear should be prepared to examine red blood cell size, pallor, and shape.
The analysis of red blood cells can also help to distinguish the type of anemia. When all three blood cell lines are affected, a bone marrow biopsy could be considered to evaluate the possibility of bone marrow failure. As discussed above, infections can result in abnormalities in blood cell counts. If suspected, appropriate screening should be performed to rule out an infection. (Find a doctor at HSS who treats lupus.)
Depending on the type of anemia, the treatment strategy may vary. Independent of the cause, severe anemia could require blood transfusions to increase the blood cell count.
Mild leukopenia in lupus usually does not require any treatment. If there is moderate-to-severe leukopenia, the first step is decreasing the dose or even discontinuing medications that could be responsible for the decreased blood cell counts.
Steroids remain the mainstay of treatment in case of severe leukopenia. Other immunosuppressants or immunomodulators (see above Question 8) can be used with caution (because they can also suppress blood cell counts) for their steroid-sparing effect. Granulocyte colony stimulating factor (G-CSF) is a controversial but effective medication to treat leukopenia, which induces a rapid increase of white blood cells. In patients with severe leukopenia, in order to decrease the risk of infections, preventive measures should be taken such as updating all the vaccinations, for example, COVID-19, flu, pneumonia, and shingles.
The strategy in patients with low platelet counts is similar to the management of lupus-related leukopenia. Mild thrombocytopenia (100,000 mm3 to 140,000 mm3) does not require any treatment. If there is moderate-to-severe thrombocytopenia (20,000 mm3) to 100,000 mm3), the first step is decreasing the dose or even discontinuing medications that could be responsible for the decreased blood cell counts.
For moderate-to-severe thrombocytopenia unrelated to medications, corticosteroids are the first treatment. However, some patients might need an alternative steroid sparing immunosuppressive agents (those down regulate the overshooting immune system) such as hydroxychloroquine, azathioprine, mycophenolate mofetil, belimumab, or rituximab. The use of intravenous immunoglobulins (IVIG) is also well established in the treatment of severe steroid-resistant thrombocytopenia. There are certain medications that can stimulate the production of platelets; romiplostim and eltrombopag may be considered in patients with chronic and severe thrombocytopenia.
As a last resort, the spleen could be removed to treat refractory thrombocytopenia, as the spleen eliminates platelets. Appropriate prophylactic measures against infection, including vaccinations, should be considered in these patients, since the spleen is critical for the immune system.
The authors want to thank Dr. Ray Pastore (Division of Hematology, Weill Cornell Medicine) for his critical review of this article.