The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 75

I get asked a lot about how mast cell disease can affect common blood test results. I have broken this question up into several more manageable pieces so I can thoroughly discuss the reasons for this. The next few 107 series posts will cover how mast cell disease can affect red blood cell count; white blood cell count, including the counts of specific types of white blood cells; platelet counts; liver function tests; kidney function tests; electrolytes; clotting tests; and a few miscellaneous tests.

 

88. How does mast cell disease affect white blood cell counts?

Firstly, remember that while mast cells are technically considered white blood cells, they don’t actually live in the blood. That means that except in very severe malignant cases of aggressive systemic mastocytosis and mast cell leukemia, mast cells won’t directly contribute to white blood cell count in a blood test at all. This means that in a regular white blood cell level blood test, none of those cells are mast cells.

There are a couple of ways in which mast cell disease can cause low white blood cell counts. It can also cause low counts of certain types of white blood cells even if it doesn’t cause low white blood cell count overall.

  • Swelling of the spleen. This can happen in some forms of systemic mastocytosis, and may also happen in some patients with mast cell activation syndrome, although the reason why it happens in MCAS is not as clear. Swelling of the spleen can damage blood cells, including white blood cells, causing lower white blood cell counts. If the spleen is very stressed and working much too hard, a condition called hypersplenism, the damage to blood cells is much more pronounced. This may further lower the white blood cell count. Hypersplenism occurs in aggressive systemic mastocytosis or mast cell leukemia. It is not a feature of other forms of systemic mastocytosis and I am not aware of any cases as a result of mast cell activation syndrome.
  • Medications. Some medications for mast cell disease can cause low white blood cell count. These are not common medications, but are sometimes used, especially in patients with long term symptoms that have not responded to other medications, or where organs could potentially be damaged, like in smoldering or aggressive systemic mastocytosis, or severe mast cell activation syndrome. These include medications like cyclosporine and interferon.
  • Chemotherapy. These medications can also decrease white blood cell count. Chemotherapy is used in smoldering systemic mastocytosis, aggressive systemic mastocytosis, and mast cell leukemia. It is sometimes also used in very aggressive presentations of mast cell activation syndrome. Newer chemotherapies are more targeted and can cause fewer side effects. However, all of the chemotherapies used for mast cell disease can cause the side effect of low blood cell counts, including white blood cell count.
  • Myelofibrosis. Myelofibrosis is a myeloproliferative neoplasm that is related to systemic mastocytosis. In myelofibrosis, the bone marrow becomes filled with deposits of scar tissue so that the body cannot make blood cells correctly or in normal numbers. This can decrease white blood cell counts.
  • Excess fluid in the bloodstream (hypervolemia). In this situation, the body doesn’t actually have too few red blood cells, it just looks like it. If your body loses a lot of fluid to swelling (third spacing) and that fluid is mostly reabsorbed at once, the extra fluid in the bloodstream can make it look like there are too few red cells if they do a blood test. This can also happen if a patient receives a lot of IV fluids.

Even if the overall white blood cell count is normal, mast cell patients sometimes have low levels of certain types of white blood cells.

  • Anaphylaxis. Anaphylaxis can cause basophils to be low.
  • Allergic reactions. These can also cause basophils to be low.
  • Chronic urticaria. Chronic hives and rashes can cause basophils to be low.
  • Use of corticosteroids like prednisone elevates certain types of white blood cells while suppressing others. Lymphocytes, monocytes, eosinophils and basophils can also be low from using corticosteroids like prednisone.
  • Prolonged physical stress. Mast cell disease can cause a lot of damage to the body over time, triggering a chronic stress response. This can selectively lower the amount of lymphocytes and the eosinophils in the body.
  • Autoimmune disease. Autoimmune disease often causes one type of white blood cell to be high and another to be low. Many mast cell patients have autoimmune diseases, so while this is not directly caused by mast cell disease, it often occurs in mast cell patients. For example, rheumatoid arthritis can cause low neutrophils.

There are many more ways that mast cell disease can trigger high white blood cell counts, or high amounts of certain types of white blood cells.

  • Inflammation. Any type of chronic inflammation can cause high white blood cell counts and mast cell disease causes a lot of inflammation.
  • Medications. Use of corticosteroids especially can cause high white blood cell counts. Epinephrine and beta-2 agonists like salbutamol/albuterol, used to open the airway, can also cause high white blood cell counts.
  • Autoimmune disease. Many mast cell patients have autoimmune diseases, so while this is not directly caused by mast cell disease, it often occurs in mast cell patients.

There are several instances where mast cell disease can trigger elevated levels of certain subsets of white blood cells.

  • Swelling of the spleen. I mentioned above that spleen swelling can damage blood cells, causing their levels to be low. Paradoxically, sometimes having a swollen spleen can cause lymphocytes to be high. There are several theories about why this may occur but there is no definitive answer currently.
  • GI inflammation. Chronic inflammation in the GI tract can cause the body to overproduce monocytes. Certain types of inflammatory bowel disease, like ulcerative colitis, can cause high basophils.
  • Allergies. Allergic reactions of any kind will elevate both basophils and eosinophils.
  • Mast cell activation of eosinophils. Mast cells activate eosinophils, which activate mast cells. It is a nasty cycle that causes a lot of symptoms and can be very damaging to organs affected. It is not unusual for mast cell patients to have high numbers of circulating eosinophils. It is also not unusual for mast cell patients to have higher than expected numbers of eosinophils in biopsies, especially GI biopsies. Eosinophilic GI disease also has some overlap with mast cell disease so some patients have both.
  • Mast cell activation of basophils. Basophils are closely related to mast cells and also degranulate in response to allergic triggers and during anaphylaxis.
  • Autoimmune disease. Autoimmune disease often causes one type of white blood cell to be high and another to be low. Many mast cell patients have autoimmune diseases, so while this is not directly caused by mast cell disease, it often occurs in mast cell patients. For example, lupus can cause eosinophilia.
  • Anemia. Iron deficiency is common in mast cell disease. Iron deficiency anemia can increase basophil levels.
  • Vascular inflammation. Mast cell activation has been repeatedly linked to inflammation of blood vessels. This can elevate blood monocyte level.
  • Medication. Use of corticosteroids like prednisone directly increase neutrophil levels.
  • Proliferation of myeloid cells. Overproduction of certain types of blood cells by the bone marrow, including mast cells, can elevate basophils.
  • Obesity. Obesity has been linked many times to chronic inflammation. Mast cell disease can directly cause weight gain by causing high levels of the hormone leptin. Obesity may cause high levels of monocytes.
  • Third spacing. If a lot of fluid from the bloodstream becomes trapped in tissues (third spacing), there is less fluid in the bloodstream so it makes it look like there are too many cells. As I mentioned above, this is not really a scenario where you are making too many white blood cells, it just looks like that on a blood test.

For additional reading, please visit the following posts:

Allergic effector unit: The interactions between mast cells and eosinophils

Anemia of chronic inflammation

Effect of anemia on mast cells

Explain the tests: Complete blood cell count (CBC) – White blood cell count

Explain the tests: Complete blood cell count (CBC) – High white blood cell count

Explain the tests: Complete blood cell count (CBC) – Low white blood cell count

Mast cell disease and the spleen

MCAS: Anemia and deficiencies

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 72

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 73

Third spacing