MCAS: Blood, bone marrow and clotting

One of the reasons MCAS is so difficult to diagnose is because it often has no effect on routine blood work.  Mast cells leave the bone marrow early in their lives, circulate in the blood stream very briefly, and then live in peripheral tissues for life spans of several months to about three years.  The reason many MCAS patients have no obvious hematologic abnormalities is that mediator release in these peripheral tissues usually doesn’t affect generation of blood cells or the blood cells already circulating. 

Hematologic issues are more commonly found in proliferative disease, like SM.  Still, one study found that in SM patients, random bone marrow biopsies missed the diagnosis 1/6 of the time.  For patients in whom SM is suspected, a second BMB can be helpful and bilateral biopsies are being ordered more frequently. 

MCAS patients very rarely have increased numbers of mast cells, spindled cells, CD2/25 receptor expression or the CKIT D816V mutation.  On examination of marrow, when irregularities are found, they are off a mild “myeloproliferative/myelodysplastic” nature, which sometimes leads to a diagnosis of MDS.  These patients do not respond to MDS treatments.

When serum tryptase is less than twice the upper limit of normal, BMB is not recommended due to how infrequently abnormalities are found.  Even during reactions, MCAS patients usually have normal tryptase values.  In recent years, a tryptase of 20% + 2 ng/ml above baseline has become regarded as evidence of activation, but this is not universally accepted.

MCAS patients often have normal blood counts, white blood cell differentials and bone marrow findings.  But there is now a growing population of MCAS patients with evident abnormalities.  Elevation of monocytes is the most common irregularity, followed by elevation of eosinophils, and then elevation of basophils.  High reactive lymphocytes are often identified in these patients on manual differential.  White blood counts can be high or low, often for no clear reason, and usually mild, but sometimes severe.  Likewise, platelets can be high or low, which sometimes garners patients a diagnosis of essential thrombocytosis or immune thrombocytopenia. 

Overproduction of red blood cells can occur to excessive release by mast cells or other cells of mediators stimulating production.  Sometimes patients are originally diagnosed with and treated for polycythemia vera, but do not improve. 

Poor clotting and easy bruising is found in a lot of MCAS patients due to activation that releases heparin.  By itself, it does not typically require treatment.  The bleeding is often localized, such as excessive bleeding from a surgical site but clotting correctly elsewhere.  Antihistamines typically help, with protamine being reserved for severe cases and transexamic acid and aminocaproic acid being reserved for the most severe.

Thromboembolism, formation of a clot in one vessel that breaks away and impedes blood flow in another vessel, is not rare in MCAS patients, even those with normal coagulation labs.  Some patients have low or high PT or PTT values.  Antiphospholipid syndrome should be excluded. 

Heparin released by mast cells activates anti-thrombin III and factor XII, which activate the rest of the intrinsic clotting cascade.  Heparin also stimulates the formation of bradykinin, which in turn causes vascular dilation and loss of fluid volume from the vessels into the tissues.  This is notable as a non-histamine route that can cause angioedema, low blood pressure and fainting in MCAS patients.

References:

Afrin, Lawrence B. Presentation, diagnosis and management of mast cell activation syndrome.  2013.  Mast cells.

Sur R. Cavender D. Malaviya R. Different approaches to study mast cell functions. Int. Immunopharmacol. 2007 May; 7(5):555-567.

Butterfield JH, Li C-Y. Bone marrow biopsies for the diagnosis of systemic mastocytosis: is one biopsy sufficient? Am. J. Clin. Pathol. 2004; 121:264-267.