title: Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk.
abstract: Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.
authors.affiliation: Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cugno
authors.affiliation: Unità Operativa di Allergologia e Immunologia Clinica, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Tedeschi
authors.affiliation: Department of Medical Sciences, Section of Dermatology, University of Ferrara, Ferrara, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Borghi
authors.affiliation: A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bucciarelli
authors.affiliation: Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano (MI), Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Asero
authors.affiliation: Unità Operativa di Dermatologia, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Luigia
authors.initials: L
authors.lastname: Venegoni
authors.affiliation: Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Samantha
authors.initials: S
authors.lastname: Griffini
authors.affiliation: Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Grovetti
authors.affiliation: Unità Operativa di Dermatologia, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Berti
authors.affiliation: Unità Operativa di Dermatologia, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Angelo Valerio
authors.initials: AV
authors.lastname: Marzano
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000378:metabolism / Q000473:pathology*; D001777:Blood Coagulation / Q000502:physiology*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010391:Pemphigoid, Bullous / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000378:metabolism / Q000473:pathology*; D012882:Skin Tests / Q000379:methods; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology*; D014581:Urticaria / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C036309:fibrin fragment D; C044183:prothrombin fragment 2; D011516:Prothrombin; D013925:Thromboplastin