Systemic mast cell activation disease during adolescence and heparin levels in blood plasma

M. Vysniauskaite*, A. Selbitz, S. Unkrig, F.-J. Dumoulin, J. Homann, J. Oldenburg, G. J. Molderings*, H.-J. Hertfelder*, *equally contributing authors (Bonn, Germany)

Pediatric and neonatal thrombosis and hemostasis
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: Introduction Systemic mast cell activation disease (MCAD) presents with a multisystemic spectrum of clinical symptoms induced by the release of mast cell-derived mediators including irritations in the CNS (such as headache, paraesthesia, chronic fatigue syndrome/CFS), irritable bowel syndrome/IBS, musculature, skin reactions, and of other tissues. Aims In our previous studies in adult MCAD patients endogenous heparin levels (heparin) was increased in the majority of the patients. In the present study we correlated the medical history, clinical signs and heparin in the adolescent MCAD patients subset of all MCAD patients of our outpatient clinic from 01-2011 until 06-2016.

Methods: 22 MCAD patients (age 10.3 to 20.8 years [y], N=12 female, N=10 male) diagnosed according to the current international criteria were included. CTAD blood (Monovette tubes Sarstedt) was sampled at baseline (BL) and after venous occlusion (VO) as previously described (Seidel, Thromb Haemost 2011). Heparin was determined by anti-factor Xa (AXa) assay (COAMATIC Heparin, Chromogenix/IL).

Results: Increased BL heparin, i.e. > 0.05 AXa IU/ml was detected in 59% of the patients. After VO heparin was increased in 86%. All 6 patients <15 y showed elevated VO heparin. 12/13 patients with CNS signs (92%), 10/12 patients with CFS (83%), 17/19 patients with IBS (89%) and 6/8 patients with skin reactions (75%) had increased VO heparin.

Conclusion: Basal heparin levels, and after VO were increased in >75% of adolescent MCAD patients. Similar to our previous data obtained in adult MCAD patients with CNS signs, CFS, IBS and/or combinations thereof, heparin appeared to be a highly sensitive biomarker with a sensitivity >89%; in patients with skin reactions the sensitivity was >75%. Thus, careful evaluation of clinical signs and medical history in combination with our diagnostic procedure allows to identify adolescent MCAD patients via their heparin levels with a high sensitivity.