Determination of Plasma Heparin Level Improves Identification of Systemic Mast Cell Activation Disease

Abstract

Diagnosis of mast cell activation disease (MCAD), i.e. systemic mastocytosis (SM) and idiopathic systemic mast cell activation syndrome (MCAS), usually requires demonstration of increased mast cell (MC) mediator release. Since only a few MC mediators are currently established as biomarkers of MCAD, the sensitivity of plasma heparin level (pHL) as an indicator of increased MC activation was compared with that of serum tryptase, chromogranin A and urinary N-methylhistamine levels in 257 MCAD patients. Basal pHL had a sensitivity of 41% in MCAS patients and 27% in SM patients. Non-pharmacologic stimulation of MC degranulation by obstruction of venous flow for 10 minutes increased the sensitivity of pHL in MCAS patients to 59% and in SM patients to 47%. In MCAS patients tryptase, chromogranin A, and N-methylhistamine levels exhibited low sensitivities (10%, 12%, and 22%, respectively), whereas sensitivities for SM were higher (73%, 63%, and 43%, respectively). Taken together, these data suggest pHL appears more sensitive than the other mediators for detecting systemic MC activity in patients with MCAS. The simple, brief venous occlusion test appears to be a useful indicator of the presence of pathologically irritable MCs, at least in the obstructed compartment of the body.

Characterization of Mast Cell Activation Syndrome

“…Work was funded by a grant from The Mastocytosis Society and by the University of Minnesota Clinical and Translational Science Institute. All diagnoses met published criteria [history consistent with chronic/recurrent aberrant MC mediator release affecting two or more organ systems, absence of any other evident disease (including mastocytosis) better accounting for all symptoms/findings in the case, and at least two elevated levels of mediators relatively specific to MCs (serum tryptase [12], serum chromogranin A (absent confounders of heart or renal failure or recent proton pump inhibitor use or neuroendocrine cancer) [13,14], plasma prostaglandin D 2 [15,16], plasma histamine [12,16], plasma heparin [16,17,18], urinary prostaglandin D 2 [15,16], urinary N-methylhistamine [19,20], urinary leukotriene E4 [21,22], urinary 11-β-prostaglandin-F 2α [15,16]) and/or increased MCs identified in extracutaneous tissue] [23] and were made at age 16 or older. For purposes of follow-up, data cut-off was June 30, 2014.…”

Characterization of Mast Cell Activation Syndrome

“…Work was funded by a grant from The Mastocytosis Society and by the University of Minnesota Clinical and Translational Science Institute. All diagnoses met published criteria [history consistent with chronic/ recurrent aberrant MC mediator release affecting two or more organ systems, absence of any other evident disease (including mastocytosis) better accounting for all symptoms/findings in the case, and at least two elevated levels of mediators relatively specific to MCs (serum tryptase [12], serum chromogranin A (absent confounders of heart or renal failure or recent proton pump inhibitor use or neuroendocrine cancer) [13,14], plasma prostaglandin D 2 [15,16], plasma histamine [12,16], plasma heparin [16,17,18], urinary prostaglandin D 2 [15,16], urinary N-methylhistamine [19,20], urinary leukotriene E4 [21,22], urinary 11-βprostaglandin-F 2α [15,16]) and/or increased MCs identified in extracutaneous tissue] [23] and were made at age 16 or older. For purposes of follow-up, data cut-off was June 30, 2014.…”

Mast cell disorders in Ehlers–Danlos syndrome

“…Heparin may be the single best performing diagnostic marker for MC activation [Vysniauskaite et al, ]. However, the level of endogenous plasma heparin found normally and even in most cases of MCAS is below the lower limits of detection of most clinical assays for this metabolite (typically 0.10–0.30 anti‐Factor Xa units/ml).…”