Skip to content

white blood cells

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


Explain the tests: Complete blood cell count (CBC) – White blood cell count (Part five)

White blood cells, also called leukocytes, are key functionaries of the immune system.  There are several types of white blood cells and each is specialized for certain types of immune response.

White blood cell levels are useful for pointing to many conditions.  They can be high or low for many reasons.  They are commonly used to determine whether or not a patient has an infection.  A “left shift” in the white count indicates presence of high numbers of immature white cells, often called bands.  A left shift can occur for a number of reasons.  It is a natural response to infection as the body tries to make enough white cells to fight the infection.  A “right shift” refers to the absence or low level of bands, new white cells.  This indicates suppression of bone marrow.

Normal range for white blood cell count:

  • 0-11.0 x 109 cells/L

Types of white blood cells can be quantified as either a percentage of total white cells or as an absolute count.  Normal white cell count varies with age, especially neutrophils, lymphocytes and monocytes.

Normal range for neutrophil count:

  • 8-7.7 x 109 cells/L
  • 35-80% of total white cells

Normal range for eosinophil count:

  • 0-0.8 x 109 cells/L
  • 0-4% of total white cells

Normal range for lymphocyte count:

  • 8-4.8 x 109 cells/L
  • 18-44% of total white cells

Normal range for monocyte count:

  • 2-0.9 x 109 cells/L
  • 7-12.5% of total white cells

Normal range for basophil count:

  • 0-0.1 x 109 cells/L
  • 0-1.2% of total white cells

Explain the tests: Complete blood cell count (CBC) – High white blood cell count (Part seven)

High white blood cell count is called leukocytosis. High white blood cell count is often due to a healthy process, such as immune defense or inflammatory response after an injury.

Reasons for leukocytosis:

  • Infection response, especially bacterial infection
  • Inflammation
  • Physical stress and tissue death
  • Allergic disease
  • Proliferative diseases of white blood cells, such as leukemias

Conditions that cause tissue death and elevate white blood cells:

  • Physical trauma
  • Surgery
  • Ischemia
  • Heart attack
  • Burns

Allergic conditions that elevate white blood cells:

  • Allergic reaction, acute or chronic
  • Anaphylaxis
  • Asthma
  • Atopic disease

Inflammatory conditions that cause elevation of white blood cells:

  • Autoimmune diseases such as rheumatoid arthritis
  • Inflammatory bowel diseases

Medications that trigger excessive production of white blood cells:

  • Corticosteroids
  • Beta agonists


Explain the tests: Complete blood cell count (CBC) – Low white blood cell count (Part six)

Low white blood cell count is called leukopenia. Due to mast cell involvement in many bodily processes, leukopenia can occur for many reasons.

Reasons for leukopenia:

  • Bone marrow suppression
  • Disorder of white cell production or white cell precursors
  • Proliferative disease of other cell types in the bone marrow
  • Mechanical destruction of white blood cells, as in splenomegaly (swollen spleen)

Some conditions that interfere with making enough white blood cells:

  • Certain infections, such as tuberculosis, malaria, dengue fever, Lyme disease and viral infections
  • Sepsis
  • Nutritional deficiency, such as low copper or zinc
  • Nutritional toxicity of certain minerals, such as arsenic

Some proliferative diseases that interfere with making white blood cells:

  • Hodgkin’s lymphoma
  • Myelofibrosis

Conditions that affect white cell precursors:

  • Aplastic anemia
  • Myelodysplastic syndrome
  • Damage to precursors by radiation exposure or chemotherapy

Conditions that cause damage to white cells:

  • Splenomegaly, swollen spleen
  • Lupus


Medications that interfere with making enough white blood cells:

  • Immunosuppressants, like mycophenolate, cyclosporine and TNF blockers
  • Interferon preparations, like Betaseron
  • Other medications like clozapine, bupropion, minocycline, lamotrigine and valproic acid
  • Chemotherapy
  • Radiation

Mast cell interactions with B and T cells

Mast cells communicate with many other cells of various types in the body. The type of communication we have discussed here most often is via mediator release – mast cells release mediators and they trigger an action in another cell by binding to a receptor, or the other cells release mediators that act on mast cell receptors. Another method of interaction is for cells to physically contact with each other. Mast cells use these techniques to impact the behavior of other cells.

B cells are lymphocytes, a kind of white blood cell. They form part of the adaptive immune system, the arm of immunity that is learned over the course of your life. They make antibodies when exposed to allergens or antigens from infectious agents. They help amplify the immune response during infection, can release cytokines and some become memory B cells, which allow for rapid response to a previously encountered organism.

Mast cells produce and release IL-4, IL-5, IL-6 and IL-13, all of which regulate the development of B cells and which role they develop toward. Mast cells can induce IgE production by B cells via binding of OX40 on the B cell to the OX40 receptor on the mast cell. In the absence of an activating signal, mast cells are able to cause unactivated B cells to proliferate and become IgM producing cells.

Resting and activated mast cells inhibit B cell death and promote proliferation of undifferentiated B cells. When the B cells are activated, this effect is exaggerated. These changes occur when mast cells and B cells are in contact and mast cells have released IL-6. Activated mast cells can drive B cells toward becoming CD138+ plasma cells or producing IgA.

T cells are also lymphocytes. There are several types of T cells and all perform very specialized functions. Mast cells and T cells are often found in close physical proximity in inflamed spaces. Conditions in which this commonly occurs include sarcoidosis, irritable bowel disease, rheumatoid arthritis and prolonged allergic processes.

Contact between mast cells and T cells initiates gene expression in mast cells. When the T cells are activated, it also induces mast degranulation, production/release of TNFa, release of MMP-9, inhibition of MMP-1, and release of IL-4 and IL-6. This occurs due to binding between the surface molecules LFA-1 and ICAM-1. Another receptor on mast cell surfaces, LTβR, can be bound by T cells. This initiates release of IL-4, IL-6, TNFa, CXCL2 and CCL5 by mast cells. In the presence of TNFa, binding to OX40 on activated CD4+ T cells by mast cells causes T cell proliferation and cytokine production.

Mast cells can express proteins on their surfaces called major histocompatibility complex I and II. These proteins literally show pieces of a phagocytosed, or “eaten”, pathogen. Showing these pieces to other cells allows them to fight infection in a specialized way. When mast cells express MHC II, they can steer T cells toward developing into specific types, including Treg cells. When mast cells express MHC I, they increase CD8+ T cell populations and ability to kill infectious agents. CD8+ T cells can cause MHC I expression by mast cells.

Mast cells and Treg cells are found in close proximity in secondary lymphoid and mucosal tissues. Activated Treg cells reduce the amount of IgE receptors on mast cells when they come into contact. They also cause release of TGF-b and IL-10. Treg cells interfere with degranulation via the OX40 receptor on mast cells.


Gri, Giorgia, et al. Mast cell: an emerging partner in immune interaction. Front. Immunol., 25 May 2012.

Brill, A., Baram, D., Sela, U., Salamon, P., Mekori, Y. A., and Hershkoviz, R. Induction of mast cell interactions with blood vessel wall components by direct contact with intact T cells or T cell membranes in vitro. Clin. Exp. Allergy 2004; 34, 1725–1731.


Mast cells, eosinophils and the perfect storm of inflammation

Mast cells and eosinophils have a lot of common functions.  In allergic and inflammatory states, these cells come into physical contact with each other, as well as communicate using chemical signals called cytokines and chemokines.  Mast cells and eosinophils are often found together in affected tissues in disorders like allergic rhinitis, atopic dermatitis, and asthma.  Mast cells initiate the allergic inflammatory response once activated.  This signals for eosinophils to come to the tissue.  Increased numbers of mast cells and eosinophils are found in diseases like eosinophilic esophagitis, chronic gastritis, GI neoplasms, parasitic infections and IBD.  Both mast cells and eosinophils respond to eotaxins, molecules that draw eosinophils to the inflamed area.  So one signal causes both cell types to go to the affected tissue. 

Mast cells and eosinophils interact a lot by using chemicals.  Mast cell released heparin stabilizes eotaxins.  Mast cells produce IL-3 and IL-5, which lengthen the lives of eosinophils in tissue.  Mast cell mediator chymase suppresses eosinophil death and causes eosinophils to release several chemicals.   Tryptase can limit eosinophil activation.  In turn, eosinophils produce stem cell factor (SCF), which attract mast cells and protects them from cell death.  Both cell types express some common receptors, like Siglec-8, which induces eosinophil death and inhibits IgE-mediated mast cell activation.  Interactions between these cells increase activation and proliferation. 
Patients with SM may have another blood disorder, including CEL or hypereosinophilic syndrome (HES.)  SM-HES and SM-CEL with the D816V CKIT mutation has been found, and the mutation is present in both the mast cells and the eosinophils.  However, it is likely that the FIP1L1-PDGFRA fusion gene (an aberrant tyrosine kinase) is the cause of the coexistent eosinophilic and abnormal mast cell proliferations.  The FIP1L1-PDGFRA fusion has been found in several cell types, including neutrophils, monocytes and mast cells.  This finding is consistent with a mutational origin in a blood stem cell that makes mutated mast cells and overproduces eosinophils.  When these cells are not neoplastic, they are derived from separate stem cell lineages.
Shortly after the discovery of this fusion gene, there was significant debate over whether FIP1L1-PDGFRA+ disease was an eosinophilic neoplasm with increased mast cells or systemic mastocytosis with eosinophilia.  Patients with FIP1L1-PDGFRA+ eosinophilia have a lot of symptoms in common with SM: swollen spleen, hypercellular bone marrow, high numbers of abnormally shaped bone marrow cells, marrow fibrosis and elevated serum tryptase.  However, these bone marrows show less dense clusters of mast cells.  In some cases, mast cells were spindled and expressed CD2 or CD25.  Still, the WHO considers it a distinct entity and not a subset of SM.
In CKIT+ patients, GI symptoms, UP, thrombocytosis, serum tryptase value, and dense mast cell clusters aggregates in bone marrow are significantly increased.  Cardiac and pulmonary symptoms, eosinophilia, eosinophil to tryptase ratio, elevated serum B12 and male sex were higher in FIP1L1-PDGFRA+ group.
Eosinophilia in SM patients has no effect on prognosis.  Eosinophilia in MDS patients predicted significantly reduced survival.  In T lymphoblastic leukemia, eosinophilia was unfavorable for survival.  Density and activation of tissue eosinophils is related to disease progression in several neoplasms.  Mast cells and eosinophils are found in increased numbers in neoplastic disorders like Hodgkin lymphoma. 
Presence of FIP1L1-PGDFRA indicates treatment with imatinib (Gleevec), regardless of organ dysfunction.  It can show remission within 4 weeks, even at low doses.  Some patients with CKIT+ SM with HES or CEL have rapid and complete normalization of severe eosinophilia with midostaurin treatment. 

Gotlib, Jason, Akin, Cem.  2012.  Mast cells and eosinophils in mastocytosis, chronic eosinophilic leukemia, and non-clonal disorders.  Semin Hematol 49:128-137.