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

Third spacing

The human body essentially keeps fluids in two spaces called compartments.  The first compartment is inside of cells.  This is called intracellular fluid.  It holds about 60% of the body’s fluids.  The second compartment is outside of the cells in the extracellular fluid, which holds about 40% of the body’s fluids.  This second compartment includes spaces like the interstitial compartment and the intravascular compartment.  The interstitial compartment is the fluid that surrounds the cells in tissues.  The intravascular component is mostly blood. 

Third spacing is when body fluids collect somewhere that is not in one of the two compartments where your body can use it.  When fluids are inside cells, your body can use it for chemical reactions.  When fluids are in the interstitial and intravascular compartments, your body can use it for lubrication, chemical reactions and moving chemicals from one place to another.  Fluid in third spaces is outside of the circulatory system and cannot be used by the body.
A common third space is in the abdominal cavity.  When fluid becomes trapped between the tissues and organs of the abdomen, it is called “ascites.”  When fluid accumulates in the interstitial area around the lungs, it is called “pulmonary edema.”  When fluid is found between the layers of the skin or mucous membranes, it is called “angioedema.”
Third spacing is a problem for multiple reasons.  The first is that it compresses the structures around the fluid, like when angioedema puts pressure on the throat and makes it difficult to breathe.  The fluid sometimes affects organ function.  Another reason third spacing is problematic is because it can cause the fluid level in the circulatory system to drop.  This means the amount of blood moving through the body is less than it should be, which decreases blood pressure and increases heart rate.  This can be very dangerous.  If there is not enough blood for the heart to pump, it will stop pumping.
People with a lot of third spacing often have symptoms of dehydration.  This includes things like excessive thirst, fatigue, and reduced urine output. 
Third spacing occurs as a result of anaphylaxis.  It is also a common problem for people with mast cell disease in the absence of anaphylaxis due to “leaking” of chemicals like histamine that push fluid out of the blood vessels and into the tissues.  Fluid replacement is very important to staying stable.
There is a lot of anecdotal information that suggests that IV fluids are helpful to counteracting third spacing in people with mast cell disease.  I get 2L of fluids overnight three times a week, and it has helped immensely.  For me, the IV fluids have stabilized my blood pressure, decreased my heart rate and keep my GI tract moving.  My abdominal pain has improved significantly since starting the IV fluids. My energy is better.  I don’t think that it has been formally written up in article form, but this is a treatment that is quickly gaining momentum in the mast cell community.