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The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 76

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.

89. How does mast cell disease affect platelet counts?

Before I continue, I want to explain one basic fact. Even though they are often included in the term “blood cells”, platelets are not actually cells. They are actually pieces of an original large cell called a megakaryocyte that lives in the bone marrow. Even though platelets are not really cells, they more or less act like they are.

An unusual thing about platelets is that sometimes a specific trigger can cause platelets to become lower or higher.

There are several ways in which mast cell disease can make platelet counts lower.

  • 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 and platelets, causing lower platelet counts. If the spleen is very stressed and working much too hard, a condition called hypersplenism, the damage to blood cells and platelets is much more pronounced. This may further lower platelet counts. 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 that are used to manage mast cell disease can cause low red blood cell count. Chemotherapies, including targeted chemotherapies like tyrosine kinase inhibitors, can cause low platelet counts. Non steroidal anti-inflammatory drugs (NSAIDs) are used by some mast cell patients to decrease production of prostaglandins. They can interfere with platelet production in the bone marrow. Proton pump inhibitors, often used by mast cell patients to help with GI symptoms like heart burn, can decrease platelet coun Some H2 antihistamines can also lower platelet production. However, none of these H2 antihistamines are currently used in medicine.
  • Heparin induced thrombocytopenia. Mast cells make and release large amounts of heparin, a powerful blood thinner. When there is an excessive amount of heparin circulating, it can cause your body to incorrectly produce antibodies that cause an immune response to heparin. A side effect of this situation is that platelets are activated incorrectly, which can lead to the formation of blood clots and low platelet counts. Heparin induced thrombocytopenia has only been definitively described in patients who receive medicinal heparin as a blood thinner. However, it is reasonable to assume that this situation can also affect mast cell patients who have higher than normal levels of platelets circulating in the blood.
  • Liver damage. Liver damage is associated with malignant forms of systemic mastocytosis such as aggressive systemic mastocytosis and mast cell leukemia. Liver damage can also occur as the result of IV nutrition, which is sometimes needed by patients with mastocytosis or mast cell activation syndrome. When the liver is damaged enough, it may not make enough of the molecules that tell the bone marrow to make platelets.
  • Excessive production of blood cells. In very aggressive forms of systemic mastocytosis, aggressive systemic mastocytosis or mast cell leukemia, the bone marrow is making huge amounts of mast cells. As a result, the bone marrow makes fewer platelets and cells of other types.
  • Vitamin and mineral deficiencies. Chronic inflammation can affect the way your body absorbs vitamins and minerals through the GI tract, and the way it uses vitamins and minerals that it does absorb. Deficiency of vitamin B12 or folate can decrease platelet production.
  • Excess fluid in the bloodstream (hypervolemia). In this situation, the body doesn’t actually have too few platelets, 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 platelets if they do a blood test. This can also happen if a patient receives a lot of IV fluids.

There are also reasons why mast cell disease can cause the body to make too many platelets.

  • Anemia of chronic inflammation. This is when chronic inflammation in the body affects the way the body absorbs and uses iron. It can result in iron deficiency. Iron deficiency can increase platelet counts.
  • Hemolytic anemia. In hemolytic anemia, the body destroys red blood cells. This can happen for several reasons that may be present in mast cell patients. Hemolytic anemia can increase platelet counts.
  • Iron deficiency. Iron deficiency for any reason can elevate platelet counts.
  • Excessive bleeding. Mast cell disease can cause excessive bleeding in several ways. Mast cells release lots of heparin, a very potent blood thinner that decreases clotting. This makes it easier for the body to bleed. It is not unusual for mast cell patients to have unusual bruising. Bleeding in the GI tract can also occur. Mast cell disease can cause ulceration, fissures, and hemorrhoids, among other things. Mast cell disease can contribute to dysregulation of the menstrual cycle, causing excessive bleeding in this way. It is not unusual for mast cell patients to have GI bleeding, as well as ulceration, fissures, and hemorrhoids.
  • Sustained GI inflammation. Sustained GI inflammatory disease can cause elevated levels of platelets. Given what we know about mast cell driven GI inflammation, it is reasonable to infer that mast cell GI effects and damage may also elevate platelet levels.
  • Clot formation. If a large clot forms, it can affect the amount of platelets circulating in the blood. Some mast cell patients require central lines for regular use of IV therapies or to preserve IV access in the event of an emergency. Blood clots can form on the outside surface of the line, inside the line, or between the line and the wall of the blood vessel it is in.
  • General inflammation. Platelets are activated by a variety of molecules released when the body is inflamed for any reason. This can translate to increased levels of platelet production.
  • Allergic reactions. Platelets can be directly activated by mast cell degranulation through molecules like platelet activating factor (PAF).
  • Heparin. Heparin can cause platelet levels to increase. As I mentioned above, it can also cause platelet levels to decrease.
  • Removal of the spleen. The spleen can become very stressed and work too hard, a condition called This situation is remedied by removing the spleen. 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.
  • Glucocorticoids. In particular, prednisone is known to increase platelet counts. Prednisone and other glucocorticoids can be used for several reasons in mast cell patients.
  • 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 red blood cells, it just looks like that on a blood test.

For additional reading, please visit the following posts:

Anemia of chronic inflammation

Effect of anemia on mast cells

Mast cell disease and the spleen

MCAS: Anemia and deficiencies

Mast cells, heparin and bradykinin: The effects of mast cells on the kinin-kallikrein system

MCAS: Blood, bone marrow and clotting

Third spacing

Gastrointestinal manifestations of SM: Part 1

Gastrointestinal manifestations of SM: Part 2

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