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

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

I have answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

6. What symptoms does mast cell disease cause?

  • Mast cell disease can cause just about any symptom. Seriously.
  • Mast cell disease can cause symptoms in every system of the body. This is because mast cells are found in tissues throughout the body. They are intimately involved in lots of normal functions of the human body. When mast cells are not working correctly, lots of normal functions are not carried out correctly. When this happens, it causes symptoms. In short, mast cells can cause symptoms anywhere in the body because they were there already to help your body work right.
  • Skin symptoms can include flushing, rashes, hives (urticaria), itching, blistering, and swelling under the skin (angioedema).
  • GI symptoms include nausea, vomiting, diarrhea, constipation, problems with the GI not moving correctly in general (GI dysmotility), swelling of the GI tract, chest and abdominal pain, belching, bloating, discolored stool, excessive salivation, dry mouth, and trouble swallowing.
  • Cardiovascular symptoms include high or low blood pressure, fast or slow heart rate, irregular heartbeat, and poor circulation.
  • Neuropsychiatric symptoms include brain fog, difficulty concentrating, difficulty sleeping at night, excessive tiredness during the day, grogginess, anxiety, depression, tremors, numbness, weakness, burning and tingling (pins and needles), hearing loss, and auditory processing (difficulty understanding what was said to you).
  • Genitourinary symptoms include bladder pain, painful urination, painful intercourse/sexual activities, painful or irregular menstrual cycle (periods), and excessive or inadequate urination (too much or too little urine produced).
  • Respiratory symptoms include cough, excessive phlegm, wheezing, runny nose, sinus congestion, sneezing, and swelling of the airway.
  • General symptoms include fatigue, lack of stamina, difficulty exercising, itchy or watery eyes, and bruising easily.
  • There are some additional symptoms that I have observed in a large number of people that are not classically considered mast cell symptoms, but I now firmly believe them to be. One is fever. I think discoloration of the skin may be mast cell related for some people. Another is dystonia, involuntary muscle contraction, which can mimic appearance of a seizure. There are also different seizure-type episodes that may occur due to the nervous system being overactive. I am reluctant to call them pseudoseizures because that term specifically means they are caused as a result of mental illness. I have no evidence that these seizure-type episodes in mast cell patients occur due to mental illness. I personally refer to them as “mast cell derived seizures.” (For people who are wondering, I have been heavily researching this phenomenon and have some theories about why this happens. It’s not fleshed out enough yet to post but it’s on my think list.)
  • Having mast cell disease can make you more likely to have other conditions that cause symptoms.
  • I’m sure there are other symptoms I have forgotten to mention.

7. Why are skin and GI symptoms so common?

  • The skin has a lot of mast cells relative to other tissues. Your skin also comes into contact with lots of things in the environment. Think about the things your skin touches on a daily basis! It makes sense that it would get the exposure so skin symptoms can be common. Additionally, some of the chemicals mast cells release can cause fluid to become trapped in the skin. For these reasons, symptoms affecting the skin are pretty common.
  • The GI tract also has a lot of mast cells relative to other tissues. Your GI tract also comes in contact with lots of things in the environment. Let’s think about this for a minute. Your GI tract is essentially one long tube through your body. You put things from the environment in your GI tract at the top and they come back out the bottom of the tract. In a way, your GI tract is kind of like the outside of the inside of your body.
  • This is the analogy I learned in anatomy and physiology class to visualizing the GI tract as the outside of the inside of the body. Think of the body as a donut. (A low histamine, fully allergy friendly, requires no GI motility, wonderful donut.) Now think of the GI tract as the donut hole. You can put your finger through the hole in the middle of the donut. Only that center part of the donut will touch your finger. This is kind of like putting food throughout the GI tract. That food only touches a very small part of the body as it passes through.
  • Since what we put into our mouths (or other GI openings) is from the outside, your body has many mast cells in the GI tract to protect the body. Some of the chemicals mast cells release can cause fluid to become trapped in the layers of GI tissue. Some of the medications we take for mast cell disease can affect the GI tract. Some of them change how much acid we make in our stomachs. Some of them slow down the GI tract. A few of them speed it up or make the GI tract more fragile. For these reasons, symptoms affecting the GI tract are very common.

For more detailed reading, please visit these posts:

The Provider Primer Series: Management of mast cell mediator symptoms and release

The Provider Primer Series: Mast cell activation syndrome (MCAS)

The Provider Primer Series: Cutaneous Mastocytosis/ Mastocytosis in the Skin

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (ISM, SSM, ASM)

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (SM-AHD, MCL, MCS)

Take home points: July 2015

Mast cell interactions with B and T cells
• Mast cells communicate with other cells by:
o Releasing chemicals to tell another cell to do something
o Other cells releasing chemicals to tell mast cells to do something
o Moving right up against other cells, which allows the cells to “talk”
• B cells are white blood cells that make antibodies and protect against infections.
o Mast cells can tell B cells to make IgE, an allergy antibody.
o When mast cells touch B cells, the mast cells can release IL-6 which tells B cells to live longer.
o Mast cells can tell B cells to make IgA, an antibody.
• T cells are white blood cells that have many functions.
o T cells and mast cells are found close together in many inflammatory conditions, like ulcerative colitis.
o Activated T cells can activate mast cells.
o Mast cells can tell T cells to proliferate and produce inflammatory molecules.
o A kind of T cell called Treg (T reg, like in regulatory) cells can make mast cells harder to activate and interfere with degranulation.

Mast cells in kidney disease
• Kidney disease is often not identified until 60-70% of functional kidney cells have been damaged beyond repair.
• Mast cells are rare in healthy kidneys.
o Damaged kidneys can have up to 60x the normal amount of mast cells.
o Mast cell count is not related to disease severity.
• Atopic disease, like atopic dermatitis and allergic asthma, is linked to idiopathic nephrotic disease, kidney disease of unknown origin.
o The nephrotic disease and atopic disease could be manifestations of the same overarching condition.
o In patients with both, IgE levels are high.
• Tryptase is elevated in some patients with kidney damage.
• Mast cells are responsible for bringing other inflammatory cells to the damaged kidney.
• Mast cells can cause fibrosis in kidneys.
• In some roles, mast cells can protect kidneys from damage.

Regulation of mast cells by IgE and stem cell factor (SCF)
• Mast cells are mostly regulated in two ways
• IgE binds to the IgE receptor (FceRI) on mast cells and activates them
o Activation by IgE results in degranulation and secretion of mediators
o IgE induces mediator release by affecting the amount of calcium inside mast cells
• Stem cell factor (SCF) binds to the CKIT receptor on mast cells and tells them to stay alive
o SCF also increases degranulation and production of cytokines
o SCF helps mast cells to adhere to other cells

Mast cells in vascular disease: Part 3
• Mast cells are involved in the formation and growth of aneurysms
• Activated mast cell populations are increased in vessels that rupture
• Chymase, a mast cell mediator, can degrade vessels and increase risk of rupture
• Leukotrienes contribute to aneurysm formation