Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients.
OBJECTIVE
To assess the prevalence of the main causes of morbi-mortality in the antiphospholipid syndrome (APS) during a 10-year-follow-up period and to compare the frequency of early manifestations with those that appeared later.


METHODS
In 1999, we started an observational study of 1000 APS patients from 13 European countries. All had medical histories documented when entered into the study and were followed prospectively during the ensuing 10 years.


RESULTS
53.1% of the patients had primary APS, 36.2% had APS associated with systemic lupus erythematosus and 10.7% APS associated with other diseases. Thrombotic events appeared in 166 (16.6%) patients during the first 5-year period and in 115 (14.4%) during the second 5-year period. The most common events were strokes, transient ischaemic attacks, deep vein thromboses and pulmonary embolism. 127 (15.5%) women became pregnant (188 pregnancies) and 72.9% of pregnancies succeeded in having one or more live births. The most common obstetric complication was early pregnancy loss (16.5% of the pregnancies). Intrauterine growth restriction (26.3% of the total live births) and prematurity (48.2%) were the most frequent fetal morbidities. 93 (9.3%) patients died and the most frequent causes of death were severe thrombosis (36.5%) and infections (26.9%). Nine (0.9%) cases of catastrophic APS occurred and 5 (55.6%) of them died. The survival probability at 10 years was 90.7%.


CONCLUSIONS
Patients with APS still develop significant morbidity and mortality despite current treatment. It is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.
Departament of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
R
R
Cervera
Departament of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
R
R
Serrano
Departament of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
G J
GJ
Pons-Estel
Lupus Unit, Rayne Institute, St Thomas' Hospital, London, UK.
L
L
Ceberio-Hualde
Zabludowicz Centre for Autoimmune Diseases, Chaim-Sheba Medical Centre, Sackler Faculty of Medicine Tel Aviv University, Tel-Hashomer, Israel.
Y
Y
Shoenfeld
Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital Carlos Haya, Málaga, Spain.
E
E
de Ramón
Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital Carlos Haya, Málaga, Spain.
V
V
Buonaiuto
Departament of Infectious Diseases and Rheumatology, Copenhagen University Hospital at Rigshospitalet, Copenhagen, Denmark.
S
S
Jacobsen
3rd Departament of Medicine, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary.
M M
MM
Zeher
3rd Departament of Medicine, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary.
T
T
Tarr
Servizio di Inmunologia Clinica e Allergologia, Spedali Civili, Azienda Ospidaliera, Brescia, Italy.
A
A
Tincani
Servizio di Inmunologia Clinica e Allergologia, Spedali Civili, Azienda Ospidaliera, Brescia, Italy.
M
M
Taglietti
Transfusion and Haemophilia Centre, Hippocration Hospital, Athens, Greece.
G
G
Theodossiades
Transfusion and Haemophilia Centre, Hippocration Hospital, Athens, Greece.
E
E
Nomikou
Unità Operativa Complessa di Reumatologia, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
M
M
Galeazzi
Unità Operativa Complessa di Reumatologia, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
F
F
Bellisai
Allergy and Clinical Immunology Unit, Dipartimento di Medicina Interna, IRCCS Istituto Auxologico, Università di Milano, Milan, Italy.
P L
PL
Meroni
Department of Rheumatology and Clinical Immunology, University Medical Centre, Utrecht, The Netherlands.
R H W M
RH
Derksen
Department of Haematology, Laboratory of Thrombosis and Haemostasis, University Medical Centre, Utrecht, The Netherlands.
P G D
PG
de Groot
Laboratory of Clinical Immunology, Clinical Centre of Allergology, Medical University, Sofia, Bulgaria.
M
M
Baleva
Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
M
M
Mosca
Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
S
S
Bombardieri
Service de Rhumatologie, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
F
F
Houssiau
Laboratoire dHématologie, CHU, Nîmes, France.
J-C
JC
Gris
Laboratoire dHématologie, CHU, Nîmes, France.
I
I
Quéré
Service de Médecine Interne, Hôpital Claude Huriez, Université Lille Nord-de-France, Lille, France.
E
E
Hachulla
Unidade de Imunologia Clínica, Hospital Santo António, Centro Hospitalar do Porto and UMIB, ICBAS, Universidade do Porto, Portugal.
C
C
Vasconcelos
Department of Rheumatology, Hospital Regional Universitario de Málaga, University of Málaga, IBIMA, Málaga, Spain.
A
A
Fernández-Nebro
Department of Rheumatology, Hospital Regional Universitario de Málaga, University of Málaga, IBIMA, Málaga, Spain.
M
M
Haro
Department of Internal Medicine, French National Reference Center for Lupus and Antiphospholipid Syndrome, Hôpital Pitié-Salpetrière, Paris, France.
Z
Z
Amoura
Department of Internal Medicine, French National Reference Center for Lupus and Antiphospholipid Syndrome, Hôpital Pitié-Salpetrière, Paris, France.
M
M
Miyara
First Department of Internal Medicine, University of Athens School of Medicine, Athens, Greece.
M
M
Tektonidou
Departament of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
G
G
Espinosa
Lupus Unit, Rayne Institute, St Thomas' Hospital, London, UK.
M L
ML
Bertolaccini
Lupus Unit, Rayne Institute, St Thomas' Hospital, London, UK.
M A
MA
Khamashta
D000022:Abortion, Spontaneous / Q000453:epidemiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000453:epidemiology / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004827:Epilepsy / Q000209:etiology; D005260:Female; D005317:Fetal Growth Retardation / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007239:Infections / Q000209:etiology / Q000401:mortality; D002546:Ischemic Attack, Transient / Q000209:etiology; D054068:Livedo Reticularis / Q000209:etiology; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology; D047928:Premature Birth / Q000453:epidemiology; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000209:etiology / Q000401:mortality; D020521:Stroke / Q000209:etiology / Q000401:mortality; D013921:Thrombocytopenia / Q000209:etiology; D013927:Thrombosis / Q000209:etiology / Q000401:mortality*; D020246:Venous Thrombosis / Q000209:etiology / Q000401:mortality; D055815:Young Adult
Anticardiolipin Antibodies; Antiphospholipid Antibodies; Antiphospholipid Syndrome; Autoimmune Diseases; Systemic Lupus Erythematosus