Antiphospholipid Antibody Syndrome: From Bench to Bedside

273 Pages·2015·6.018 MB·English

by  Pier Luigi Meroni (eds.)

Rare Diseases of the Immune System
Series Editors: Lorenzo Emmi · Domenico Prisco
Pier Luigi Meroni Editor
Antiphospholipid
Antibody
Syndrome
From Bench to Bedside
R are Diseases of the Immune System
Series Editors Autoinfl ammatory Syndromes
Lorenzo Emmi M. Gattorno
Domenico Prisco F. De Benedetti
R. Cimaz
Editorial Board:
Systemic Vasculitis Primary Immunodefi ciency
L. Emmi A. Plebani
C. Salvarani C.T. Baldari
R.A. Sinico M.M. D’Elios
Autoimmune Disease Systemic Fibroinfl ammatory Disorders
P.L. Meroni A. Vaglio
D. Roccatello
M. Matucci Cerinic
L. Emmi
For further volumes
http://www.springer.com/series/11643
Sentiero Rosa
Laura Maddii Emmi
(private collection)
Pier Luigi M eroni
Editor
Antiphospholipid
Antibody Syndrome
From Bench to Bedside
Editor
Pier Luigi Meroni
Department of Rheumatology
Gaetano Pini Institute
Milan
Italy
ISBN 978-3-319-11043-1 ISBN 978-3-319-11044-8 (eBook)
DOI 10.1007/978-3-319-11044-8
Springer Cham Heidelberg New York Dordrecht London
Library of Congress Control Number: 2014956675
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In spite of the great achievements in APS
knowledge, the story is not over and we have
to look at the future. So, as the Editor of this
book, I would like to dedicate the text and the
contents to who is now the future of my
family: my grandson Leonardo
born on April 28, 2014.

Pref ace
I t is commonly thought that the antiphospholipid syndrome (APS) is a new disorder,
but this actually is not correct. The paradox of the association of thrombotic events
with the prolongation of blood clotting – the so-called lupus anticoagulant (LAC)
phenomenon – has been known since the beginning of the 1950s. Such an associa-
tion was originally described in a few patients suffering from systemic lupus erythe-
matosus but was then found also in subjects without any other autoimmune
condition.
W hat was thought to represent just an “esoteric” phenomenon was later struc-
tured as a condition characterized by the association between LAC and recurrent
thrombotic vascular events and/or miscarriages by several groups between 1954 and
1963. However, the milestone in the APS story is represented by the publication in
Lancet at the end of 1983 by Graham Hughes’s group which clearly identifi ed
patients with APS for the fi rst time.
I n spite of the initial skepticism, APS has grown in the last years as an indepen-
dent autoimmune disease and generated a large interest in both clinicians and
researchers. So, the knowledge on the disease improved in an exponential manner,
and it justifi es the idea to collect new information in a book dedicated to the clinical
and the basic aspects of APS – Antiphospholipid Antibody Syndrome: From Bench
to Bedside .
The book covers the origin of the so-called antiphospholipid antibodies (aPL)
which actually are directed against PL-binding proteins that have been recently
characterized. The disease fulfi lls the usual aspects of every autoimmune condition
requiring a genetic background and additional environmental triggers to develop.
aPL are not only diagnostic markers but also pathogenic autoantibodies. These
aspects are discussed in separate chapters in the book, spanning from the descrip-
tion of the laboratory classifi cation criteria, the pathogenic mechanisms responsible
for the vascular and the obstetric manifestations of the syndrome, to the LAC
paradox.
T hanks to the new diagnostic tools (in particular, the discovery of the beta-2
glycoprotein I (β2GPI)-dependent aPL), it has been possible to better describe the
clinical manifestations of the syndrome and to recognize well-defi ned clinical clas-
sifi cation criteria. However, the larger number of the epidemiological studies sug-
gested new clinical variants such as the catastrophic APS or APS nephropathy. At
the same time, additional clinical manifestations have been suggested to represent
vii
viii Preface
non-classifi cation criteria still a matter of research. All these aspects are covered by
dedicated chapters in the book.
APS can be primary or associated to other systemic autoimmune diseases; in
such a case, the presence of aPL may affect the course and the prognosis of the
underlying disease in a signifi cant way. This is the reason for a special chapter on
the issue. The same is also true for asymptomatic aPL-positive carriers that repre-
sent a not-so-rare challenging condition for the physicians in real life.
The treatment of APS is another hot issue. Two different chapters cover the ther-
apy for the vascular and the obstetric manifestations of the syndrome, addressing all
the aspects, including the conditions in which there are no well-defi ned therapeutic
approaches. Besides old and new anticoagulant and/or antiplatelet drugs, new thera-
peutic tools are under active investigation and likely to become available soon. This
is covered by a specifi c chapter.
I do hope that the book may offer a real overview of the APS – from bench to
bedside – and represent a useful tool for all the people interested in the syndrome.
Milan, Italy Pier Luigi Meroni
Contents
1 Genetics and Origin of Antiphospholipid Syndrome. . . . . . . . . . . . . 1
Alessandra Soriano, Miri Blank, and Yehuda Shoenfeld
2 The Paradox of Lupus Anticoagulant . . . . . . . . . . . . . . . . . . . . . . . . . 13
Alessandra Banzato and Vittorio Pengo
3 Antiphospholipid Antibody Mechanisms of Thrombosis. . . . . . . . . . 25
Pier Luigi Meroni, Chiara Crotti, and Cecilia Chighizola
4 The Pathogenic Mechanisms for Antiphospholipid Antibodies
(aPL)-Mediated Pregnancy Loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Nicoletta Di Simone and Silvia D’Ippolito
5 Classifi cation Criteria for the Antiphospholipid Syndrome . . . . . . . 47
Ronald H.W.M. Derksen and Ruth Fritsch-Stork
6 Non-classifi cation Criteria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Maria Gerosa and Francesca Rovelli
7 Obstetric APS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Micaela Fredi and Angela Tincani
8 APS and the Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
Cecilia Beatrice Chighizola, Davide Sangalli, Barbara Corrà,
Vincenzo Silani, and Laura Adobbati
9 Antiphospholipid Syndrome (APS) and the Renal Involvement. . . . 103
Nicoletta Mezzina and Renato Alberto Sinico
10 Non-Thrombotic Hematologic Manifestations in APS. . . . . . . . . . . . 113
Wilma Barcellini and Carolina Artusi
11 Heart and APS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Gentian Denas and Vittorio Pengo
12 Skin Involvement in Antiphospholipid Syndrome . . . . . . . . . . . . . . . 151
Angelo Valerio Marzano, Silvia Alberti Violetti,
Riccardo Lazzari, and Emilio Berti
ix