title: A French National Survey on Clotting Disorders in Mastocytosis.
abstract: Mastocytosis is characterized by a clonal mast cell proliferation with organ infiltration and uncontrolled degranulation. Although not characteristic and poorly explained, some patients develop clotting abnormalities. We retrospectively identified patients with established diagnosis of mastocytosis and related clotting abnormalities (clinical and/or biological) using the national French Reference Centre for Mastocytosis database. From our cohort of 14 adult patients with clotting abnormalities (median age 46 years [range 26-75]), 4 had a presentation suggestive of a primary hemostasis disorder alone (by their symptoms and/or abnormal clotting tests [PFA, von Willebrand's disease [vWD] screening]) and 10 had a laboratory impairment of secondary hemostasis. Among these, 7 had bleeds characteristic of a coagulation cascade disorder (severe/life-threatening in 5 and mild in 2 patients). Clotting abnormalities were of variable severity, typically related to intense crisis of degranulation, such as anaphylactic reactions, and/or to severe organ infiltration by mast cells. Importantly, classical hemostatic management with platelet transfusion, fresh frozen plasma, or vitamin K infusions was unsuccessful, as opposed to the use of agents inhibiting mast cell activity, particularly steroids. This illustrates the crucial role of mast cell mediators such as tryptase and heparin, which interfere both with primary (mainly via inhibition of von Willebrand factor) and secondary hemostasis. There was interestingly an unusually high number of aggressive mastocytosis (particularly mast cell leukemia) and increased mortality in the group with secondary hemostasis disorders (n = 5, 36% of the whole cohort). Mast cell degranulation and/or high tumoral burden induce both specific biologic antiaggregant and anticoagulant states with a wide clinical spectrum ranging from asymptomatic to life-threatening bleeds. Hemostatic control is achieved by mast cell inhibitors such as steroids.
authors.affiliation: From the French Reference Centre for Mastocytosis (CEREMAST), Necker Children's Hospital, Assistance Publique - Hôpitaux de Paris (APHP), France (ABC, GD, DC, CB, SB, LF, OL, OH, M-OC); Haemostasis and Thrombosis Unit, Haemophilia Clinic, Division of Haematology, St-Luc University Hospital, Brussels, Belgium (ABC, CH); Department of Internal Medicine, Caen University Hospital, France (AA); Department of Haematology, Caen University Hospital, France (GD); Department of Pathology, Necker Children's Hospital, APHP, France (DC); Department of Biological Haematology, Necker Children's Hospital, APHP, France (CB); Department of Haematology and Cell Therapy, Tours University Hospital, France (EG); Department of Internal and Vascular Medicine, Lyon Sud University Hospital, France (SD, ID); Department of Internal Medicine, Saint-Etienne University Hospital, France (PC); Department of Internal Medicine, Cochin Hospital, APHP, France (NC-C); Department of Internal Medicine, Lille University Hospital, France (DL); Infectious Diseases Department, Necker Children's Hospital, APHP, France (BP, OL); Department of Dermatology, Tenon University Hospital, APHP, France (SB); Department of Haematology, Necker Children's Hospital, APHP, France (LF, OH, M-OC); and Sorbonne Paris Cité, Paris Descartes University, Imagine Institute, Paris, France (LF, OL, OH, M-OC).
authors.forename: Ana B
authors.initials: AB
authors.lastname: Carvalhosa
authors.forename: Achille
authors.initials: A
authors.lastname: Aouba
authors.forename: Gandhi
authors.initials: G
authors.lastname: Damaj
authors.forename: Danielle
authors.initials: D
authors.lastname: Canioni
authors.forename: Chantal
authors.initials: C
authors.lastname: Brouzes
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gyan
authors.forename: Stéphane
authors.initials: S
authors.lastname: Durupt
authors.forename: Isabelle
authors.initials: I
authors.lastname: Durieu
authors.forename: Pascal
authors.initials: P
authors.lastname: Cathebras
authors.forename: Nathalie
authors.initials: N
authors.lastname: Costédoat-Chalumeau
authors.forename: David
authors.initials: D
authors.lastname: Launay
authors.forename: Benoit
authors.initials: B
authors.lastname: Pilmis
authors.forename: Stephane
authors.initials: S
authors.lastname: Barete
authors.forename: Laurent
authors.initials: L
authors.lastname: Frenzel
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Cedric
authors.initials: C
authors.lastname: Hermans
authors.forename: Marie-Olivia
authors.initials: MO
authors.lastname: Chandesris
mesh_terms: D000328:Adult; D000368:Aged; D001778:Blood Coagulation Disorders / Q000453:epidemiology / Q000209:etiology* / Q000628:therapy; D005602:France / Q000453:epidemiology; D006801:Humans; D008415:Mastocytosis / Q000150:complications* / Q000453:epidemiology; D008875:Middle Aged; D012189:Retrospective Studies; D011795:Surveys and Questionnaires