The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 74

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.

  1. How does mast cell disease affect red blood cell counts?

There are several ways in which mast cell disease can make red blood cell count lower.

  • 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 is used to make hemoglobin, the molecule used by red blood cells to carry around oxygen to all the places in the body that need it. If there’s not enough iron to make hemoglobin, the body will not make a normal amount of red blood cells.
  • Vitamin and mineral deficiencies. Like I mentioned above, 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. While iron deficiency is the most obvious example of this, deficiency of vitamin B12 or folate can also slow red cell production.
  • 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 red blood cells, causing lower red 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 red 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 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 red blood cell count. Medications that specifically interfere with the immune system can do the same thing, including medications for autoimmune diseases like mycophenolate. Non steroidal anti-inflammatory drugs (NSAIDs) are used by some mast cell patients to decrease production of prostaglandins. They can interfere with red blood cell production in the bone marrow and also cause hemolytic anemia, when the immune system attacks red blood cells after they are made and damages them.
  • 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.
  • Excessive production of other types 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 cells of other types, including red blood cells. Some medications can also increase production of other blood types, causing less production of red cells. Corticosteroids can do this.
  • 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.

There are also a couple of scenarios where mast cell disease can make the red blood cell count higher. This is much less common.

  • Chronically low oxygen. If a person is not getting enough oxygen for a long period of time, the body will make more red blood cells in an effort to compensate for the low oxygen. This could happen in mast cell patients with poor oxygenation.
  • 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

Effects of estrogen and progesterone and the role of mast cells in pregnancy

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

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

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

Gastrointestinal manifestations of SM: Part 1

Gastrointestinal manifestations of SM: Part 2

Mast cell disease and the spleen

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

MCAS: Anemia and deficiencies

MCAS: Blood, bone marrow and clotting

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 3

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 12

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 19

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 20

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 45

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

Mast cell disease and the spleen

Spleen is known mostly for having a stupid name, but it actually does a lot of really important things.  It is located in the upper left quadrant of the abdomen.  It is essentially a filter.  It removes old or damaged red blood cells.  It retains a supply of blood that can be used to regulate blood pressure in case of hemorrhage.  It also recycles and conserves iron by metabolizing hemoglobin removed from red blood cells filtered out.  The spleen also produces antibodies and filters out bacteria and blood cells that have been attacked by antibodies and marked for removal.  In this way, it is effectively a very large lymph node. 

Another very important function of the spleen is creation of blood cells.  In cases where the bone marrow is producing fewer blood cells than normal (like myelofibrosis), the spleen can actually compensate to produce red and white blood cells.  About ¼ of the body’s white cells are stored in the spleen at any time. 
Swelling of the spleen is called splenomegaly.  If a swollen spleen can be felt manually, it is at least twice its normal size.  The spleen usually swells when it is working harder than normal.  This can happen for several reasons. 
Swelling of the spleen often has no symptoms.  It can cause abdominal, chest or back pain and the feeling of having a “small stomach,” being able to eat less than normal in one sitting.  Anemia may also be present.  The most common reason is developed countries is mononucleosis, followed by infiltration by benign or neoplastic cells, or portal hypertension.  Bacterial infections like syphilis can also cause a swollen spleen.  In people whose bone marrow is not producing enough cells, the spleen can become swollen by the effort of producing extra cells. 
It is should be stated that swelling of the spleen is pretty common in blood disorders.  It is sometimes found in systemic mastocytosis.  As the spleen gets bigger, it grows beyond the borders of the protective rib cage and can be more easily damaged.  Swollen spleens present an increased risk of rupture. 
In SM, splenomegaly (swollen spleen) is NOT a C finding indicating aggressive disease.  It is a B finding.  This is because mast cells often infiltrate the spleen, causing swelling, but not necessarily impairing function.  Hypersplenism with splenomegaly is a C finding.  Hypersplenism is when the spleen is working too hard. 
Hypersplenism is indicated by swelling of the spleen, reduction in circulating red blood cells, platelets or granulocytes (neutrophils, eosinophils, basophils or mast cells), increased proliferation by the bone marrow to compensate for the decrease in circulating cells, and probable resolution of these symptoms by removal of the spleen.    Hypersplenism can cause additional complications, including portal hypertension and ascites.
Portal hypertension is increased pressure in the vein that connects the GI tract and spleen to the liver.  Ascites is free fluid in the abdomen.  Both portal hypertension and ascites are also mastocytosis C findings.  Removal of the spleen can decrease the patient’s risk of portal hypertension and ascites, thus improving prognosis.  Additionally, in the context of mast cell disease, an infiltrated organ is inflamed, which is in turn activating to mast cells.  Removal of a source of inflammation can cause relief of systemic activation.
People living without a spleen are more susceptible to certain types of infections, including H. influenzae, S. pneumoniae, and Meningococcus spp.  They should receive vaccinations for these organisms and also regular flu vaccinations.  In some cases, long term prophylactic antibiotics are needed.  Often, patients without a spleen develop a stable high white blood cell or platelet count as their numbers are not regulated by the spleen.