The influence of genetic variations on activation of blood coagulation: a possible explanations for the increased thrombotic risk in bullous pemphigoid
Poster
Data di Pubblicazione:
2010
Citazione:
The influence of genetic variations on activation of blood coagulation: a possible explanations for the increased thrombotic risk in bullous pemphigoid / M. Cugno, A. Tedeschi, D. Fanoni, L. Venegoni, S. Griffini, E. Berti, C. Crosti, A.V. Marzano. - In: PATHOPHYSIOLOGY OF HAEMOSTASIS AND THROMBOSIS. - ISSN 1424-8832. - 37:Suppl. 1(2010), pp. A84-A85. ((Intervento presentato al 21. convegno International Congress on Thrombosis :
the start of a new era for antithrombotic agents tenutosi a Milan nel 2010 [10.1159/000318097].
Abstract:
Background: Bullous pemphigoid (BP) is an inflammatory blistering skin disease
mainly affecting elderly subjects and associated with an elevated thrombotic risk.
It is caused by autoantibodies to hemidesmosomal proteins, with eosinophils
participating in blister formation.
Aims: Since eosinophils are a source of tissue factor (TF), the main initiator of blood
coagulation, we evaluated the local and systemic activation of coagulation in BP.
Methods: We studied 60 patients with active BP (sixteen re-evaluated during
remission) and 60 sex- and age-matched healthy controls. The coagulation
markers prothrombin fragment F1+2 and D-dimer were measured in plasma
of all subjects and in both plasma and blister fluid of patients with BP. TF was
evaluated immunohistochemically in skin specimens from 40 patients and in 20
normal samples. In lesional skin specimens from 5 BP patients, we evaluated TF
mRNA expression by in situ hybridization as well as the colocalization of TF and
eosinophil cationic protein (a classic eosinophil marker) by confocal microscopy
using immunofluorescence techniques.
Results: F1+2 and D-dimer levels were higher in plasma of patients with BP than
in plasma of controls (p=0.0001 for both), and were very high in blister fluid
(p=0.0001 vs plasma). Plasma and blister fluid F1+2 and D-dimer levels paralleled
blood and tissue eosinophilia and disease severity. In the sixteen patients reevaluated
during remission, there was a marked reduction in F1+2 (from 600±377
to 193±151 pmol/L; p=0.0001) and D-dimer (from 3225±3010 to 561±476 ng/
ml; p=0.0001). Immunohistochemistry revealed strong TF reactivity in BP skin
(p=0.0001) confirmed by in situ hybridization. Colocalization studies by confocal
microscopy identified eosinophils as a source of TF.
Conclusions: The coagulation cascade is activated in BP most likely via TF
expressed by eosinophils. The hypercoagulability correlates with the severity of the
disease and possibly contributes to inflammation, tissue damage, blister formation
and thrombotic risk in BP.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Bullous pemphigoid ; blood coagulation ; thrombosis ; tissue factor,
Elenco autori:
M. Cugno, A. Tedeschi, D. Fanoni, L. Venegoni, S. Griffini, E. Berti, C. Crosti, A.V. Marzano
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