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

 

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 Mast Cell Diseases, Part 12

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

20. Why do a lot of mast cell patients get intravenous (IV) fluids?
• Use of IV fluids is becoming increasingly common for mast cell patients as word spreads that it helps with fatigue, overall energy, and general reactivity.
There have not been any studies showing that IV fluids work directly for mast cell disease. However, there have been papers demonstrating that it helps with deconditioning (when your body is out of shape from being sick), POTS (which a lot of mast cell patients have), and other chronic illnesses.
• A lot of chemicals that mast cells release can cause some of the liquid in your bloodstream to fall out through the walls of the bloodstream and become trapped in the tissues there. This phenomenon is called third spacing.
• The term “third spacing” is derived from the idea that fluids like blood or other fluids can be in one of three “spaces” in the body. One space is inside the cells, where cells can use it. Another space is right outside the cells, where cells can still use it. When fluids are stuck in a place that can’t be used by cells, and therefore is not useful to the body, it is said to be in a third space. So third spacing is when the fluids your body needs is stuck in the wrong place.
Third spacing is the cause of most types of swelling and edema.
• When you have fluid that should be in your bloodstream stuck in a third space, you are functionally dehydrated. This is important because bloodwork may not always show that you are truly dehydrated when you have a lower amount of third spacing but you will still have a lot of the symptoms of it.
IV fluids puts more fluids back into the blood to compensate for the fluids that get sucked out of the bloodstream and aren’t useful to the body. When this fluid is replaced, it helps stabilize blood pressure and heart rate. It also takes stress off many other cells so they calm down too, calming down mast cells.

For more detailed reading, please visit this post:

Third spacing

I also wrote a seven part series on third spacing and IV fluids. The first post is here.

 

Do all mast cell patients need central lines? No. But some do.

A newer patient asked a couple of days if everyone with mast cell disease needs a PICC line, Broviac/Hickman or port for IV access. The answer is no, but I think we should talk about this a bit.

Central lines are usually given for people who need chemo or long term IV treatmet. These lines are not really designed to be left in your body forever, even ports. They generally are pulled once treatment is done, although ports can be left in for years as long as they are flushed monthly.

In my experience, mast cell patients get central lines for a few reasons:

  1. They have very poor IV access, so poor that it could delay treatment in an emergency (anaphylaxis).
  2. They get regular IV medications (this is not very common, although it’s hard to tell in this group).
  3. They regularly take IV medication that can damage veins if given frequently in peripheral veins (like Benadryl).
  4. They get them for IV hydration (it is not recommended to get a central line just for IV hydration, however some people do get them).

In the groups, it seems like there are so many patients who have these lines. Please keep in mind that those with more disabling disease are the most likely to be present in those forums. This group often also has other diagnoses for which central lines may be beneficial. On the other hand, the other group that is quite visible is the rookies. So the new patients see this very severe face on a disease which is quite manageable for many. You are seeing a subset of the population. Central lines in the mast cell community are not as common as it seems.

Regarding IV hydration, there are a few reasons why people receive this. Some of us vomit frequently and so fluids are difficult to get into us orally. Some of us have POTS or dysautonomia and have low blood volume, so the IV hydration stabilizes our blood pressure and heart rate. Some of us third space badly, and oral fluids end up in the wrong place.

This patient asked if they could just drink fluids. The answer is absolutely yes. If you can keep oral fluids down and are functioning, then I would do that. Receiving regular IV fluids can help with some symptoms, but there is no reason they need to be delivered through a central line. I used to get IV fluids at the infusion center with a new IV everytime. It is a pain but it’s not awful.

In an acute situation, IV fluids can be very helpful to mast cell patients. Long term, you need to be monitored properly as it can affect your electrolytes and for some this may raise kidney concerns. I would not get IV fluids based simply upon “feeling dehydrated”. If you “feel dehydrated” and also your blood pressure is wacky and you can’t keep down oral fluids, I think that then regular IV hydration might be useful.

I know it is frustrating to feel that you are not doing as well as you used to, but if you have mast cell disease, it is very possible you never will again, even with IV fluids. I am sorry, but that is the reality. You need to adapt to the level of ability you can manage currently.  Get some stability and things will improve.

If you and your doctor feel that IV hydration is appropriate, I would try it outpatient for a few weeks. If they then feel you need to do it at home, placing a PICC line is a good place to start. If you have a problem with the PICC line, it can be pulled without much trouble. The other lines are implanted and require surgery to remove them. The risk of bloodstream infections from central lines is real and these are very serious situations with long term effects.

Mast cell patients also run the risk of reacting to the materials used to make the line. They can also react to the maintenance of the line, such as flushing, use of heparin and alcohol swabs. This is a real problem for some people. So any time you can avoid an indwelling line long term, that is the better option.

Lastly, central lines require maintenance so you need to be sure that if your doctor wants to order one, they will also order the solutions and nursing care needed to keep you safe.

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.