Lupus and Blood Cell Disorders – Top 10 Series

1. What is systemic lupus erythematosus?
2. What are the most common symptoms in lupus patients?
3. How do you define blood disorders?
4. What are different types of blood cell disorders that can develop because of lupus?
5. What is the mechanism of medication-related blood cell disorders?
6. What are the symptoms that patients can experience when lupus attacks the blood cells?
7. Which tests are performed to diagnose lupus-related blood cell disorders?
8. How do you treat lupus-related anemia?
9. How do you treat lupus-related leukopenia?
10. How do you treat lupus-related thrombocytopenia?

1. What is systemic lupus erythematosus?

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.

2. What are the most common symptoms in lupus patients?

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.

3. How do you define blood disorders?

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:

• the fluid plasma
• red blood cells (responsible for oxygen transportation)
• white blood cells (responsible for immune activities)
• platelets (responsible for clotting)

Commonly used terms to describe blood cell disorders are:

• anemia – a decrease of red blood cells
• erythrocytosis – an increase of red blood cells
• leukopenia – a decrease of white blood cells to less than 4,000 per cubic millimeter (< 4,000/mm3)
• leukocytosis – an increase of white blood cells to > 10,000 mm3
• thrombocytopenia – a decrease of platelets to < 150,000 mm3
• thrombocythemia – an increase of platelets to > 450,000 mm3

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.

4. What are different types of blood cell disorders that can develop because of lupus?

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:

• Iron deficiency anemia due to reduced iron stores.
• "Anemia of chronic disease" (anemia as a secondary condition caused by a chronic disease) due to chronic lupus disease activity – that is, ongoing inflammation and its interference with the production of red blood cells and utilization.
• Lupus nephritis (lupus-caused kidney disease) and chronic kidney insufficiency that results in a decrease of red blood cells. This is because the potentially damaged kidneys do not produce a certain hormone, which normally stimulates the production of red blood cells.
• Autoimmune hemolytic anemia, which is characterized by autoantibodies destroying red blood cells.
• Medications that suppress red blood cell production.

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:

• Autoantibodies directed against white blood cells, causing their destruction. This immune-mediated decline in white bloods cells is generally associated with lupus activity.
• Drug-induced suppression of white blood cell production.

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:

• The presence of anti-platelet-antibodies.
• Increased peripheral destruction, therefore causing an abnormally low platelet count.
• A complication of medications used in lupus treatment.
• Antiphospholipid antibodies.

It should be mentioned that lupus patients can develop anemia, leukopenia, or thrombocytopenia due to reasons other than lupus, for example infection.

5. What is the mechanism of medication-related blood cell disorders?

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:

• Nonsteroidal anti-inflammatory drugs like ibuprofen or diclofenac.
• Angiotensin-converting enzyme inhibitors, medication to control blood pressure, which reduce the amount of white blood cells and platelets.
• Proton-pump inhibitors, which are used to reduce stomach acid.
• Statins, cholesterol-lowering drugs, which can cause thrombocytopenia.

6. What are the symptoms that patients can experience when lupus attacks the blood cells?

Depending on the severity of anemia that results, patients might have either no symptoms or multiple symptoms, which may include:

• fatigue
• weakness
• pale or yellowish skin and pale mucous membranes
• shortness of breath
• irregular heartbeats
• a heart murmur caused by a change in the blood consistency
• dizziness or lightheadedness
• cold hands and feet

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.

7. Which tests are performed to diagnose lupus-related blood cell disorders?

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.)

8. How do you treat lupus-related anemia?

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.

• Since the reason for iron deficiency anemia could be chronic bleeding, patients should be evaluated for possible sources of bleeding. Iron supplementation is the first line of treatment for iron deficiency.
• Patients with symptomatic anemia of chronic disease may benefit from a erythropoiesis-promoting (blood building) agents, such as epoetin alfa or darbepoetin alfa. These drugs can also be effective in patients with anemia of chronic kidney disease.
• Autoimmune hemolytic anemia is usually responsive to steroids, as they suppress the immune system and reduce the disease activity. Steroid-sparing agents can be used as well, especially in long-term treatment of lupus related anemia. These immunosuppressive drugs help taper the steroid dose and thereby reduce the risk of steroid-related side-effects. Azathioprine or hydroxychloroquine are commonly used. Mycophenolate or cyclophosphamide have been also successfully for persistent forms of anemia. These agents reduce the number of certain immune cells, which produce the auto-reactive antibodies attacking the blood cells.
• When medication-induced anemia is suspected, it is essential to adjust the dose or even stop the medication depending on the severity of the anemia.

9. How do you treat lupus-related leukopenia?

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.

10. How do you treat lupus-related thrombocytopenia?

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.

Posted: 2/15/2023

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References

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