Silvia Bucciarelli

Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients

Objectives 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.

Catastrophic antiphospholipid syndrome during pregnancy and puerperium: maternal and fetal characteristics of 15 cases

Background: The catastrophic variant of the antiphospholipid syndrome (APS) is a life-threatening form of presentation of this syndrome that can be triggered by several factors. Aim: To describe the characteristics of patients who developed catastrophic APS triggered during pregnancy and puerperium. Methods: A review of the first 255 cases collected in the website-based “CAPS Registry” was undertaken. Three new and unpublished cases of catastrophic APS developed during pregnancy and puerperium were added. Results: Fifteen cases were identified. The mean (range) age was 27 (17–38) years. Most patients had a previous unsuccessful obstetric history. In 7 of 14 (50%) cases with available medical history, the catastrophic APS appeared during pregnancy, in 6 (43%) during the puerperium and in 1 (7%) after curettage for a fetal death. The main clinical and serological characteristics were similar to those patients with catastrophic APS triggered by other factors, except for a history of a higher prevalence of previous abortions (p<0.01). Several specific features were found, including the HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome in 8 (53%) patients, placental infarctions in 4 (27%) patients, and pelvic vein thrombosis and myometrium thrombotic microangiopathy in 1 (7%) patient each. Mortality rate was high for the mothers (46%), and for the babies (54%). Conclusions: It is important to consider the possibility of the development of catastrophic APS in those patients with signs of HELLP syndrome and multiorgan failure during pregnancy or puerperium, especially in those patients with previous history of abortions and/or thrombosis.

The acute respiratory distress syndrome in catastrophic antiphospholipid syndrome: analysis of a series of 47 patients

Background: The acute respiratory distress syndrome (ARDS) is a non-cardiogenic form of pulmonary oedema characterised by severe hypoxaemia refractory to oxygen therapy, with diffuse pulmonary infiltrates on chest radiographs. It can be precipitated by various serious medical and surgical conditions, including systemic autoimmune diseases. The “catastrophic” variant of the antiphospholipid syndrome (APS) is an accelerated form of this systemic autoimmune condition which results in multiorgan failure because of multiple small vessel occlusions. Objective: To analyse the clinical and laboratory characteristics of patients with catastrophic APS who develop ARDS. Methods: Cases with ARDS were selected from the web site based international registry of patients with catastrophic APS (CAPS registry) (http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM) and their characteristics examined. Results: Pulmonary involvement was reported in 150 of 220 patients with catastrophic APS (68%) and 47 patients (21%) were diagnosed as having ARDS. Nineteen (40%) of these patients died. Pathological studies were undertaken in 10 patients and thrombotic microangiopathy was present in seven. There were no differences in age, sex, precipitating factors, clinical manifestations, or mortality between catastrophic APS patients with and without ARDS. Conclusions: ARDS is the dominant pulmonary manifestation of catastrophic APS. Thus the existence of ARDS in the context of an APS makes it necessary to rule out the presence of the catastrophic variant of this syndrome.

Morbidity and mortality in the catastrophic antiphospholipid syndrome: pathophysiology, causes of death, and prognostic factors.

The catastrophic variant of the antiphospholipid syndrome (APS) is a condition characterized by multiple vascular occlusive events, usually affecting small vessels and evolving over a short period of time, together with laboratory confirmation of the presence of antiphospholipid antibodies. The pathogenesis of catastrophic APS is not completely understood. The mortality rate was ~50% in the earliest published series, but recently it has clearly fallen by some 20% due to the use, as first-line therapies, of full anticoagulation, corticosteroids, plasma exchanges, and intravenous immunoglobulins. Cerebral involvement has been identified as the main cause of death, being present in one third of patients, and consisting mainly of stroke, cerebral hemorrhage and encephalopathy, followed by cardiac involvement and infection. The only identified prognostic factor for a higher mortality rate is the presence of systemic lupus erythematosus.

Catastrophic antiphospholipid syndrome: treatment, prognosis, and the risk of relapse.

The “catastrophic” variant of the antiphospholipid syndrome (APS) is characterized by multiple vascular occlusive events, usually affecting small vessels and developing over a short period of time. Although patients with catastrophic APS represent less than 1% of all patients with APS, they are usually in a life-threatening situation with a 50% mortality rate. The purpose of this paper is to review the treatment strategies and prognostic factors in patients with catastrophic APS. A detailed description of the clinical and laboratory features of the syndrome can be found in the other articles of this issue.

Amputation of Digits or Limbs in Patients with Antiphospholipid Syndrome

OBJECTIVE To describe the characteristics of patients with peripheral vascular disease leading to amputation of digits or limbs encountered in patients with the antiphospholipid syndrome (APS). METHODS Twenty-one cases derived from several geographical centers (Brazil, Serbia, Italy, Israel, United Kingdom, and South Africa) are presented. The major clinical, serological, and histopathological data (where available) of this cohort are described, documented, and analyzed. RESULTS Patients were suffering mainly from systemic lupus erythematosus (9 patients) or primary APS (8 patients). Peripheral vascular occlusions occurred during the course of the catastrophic APS in 5 patients. The vascular occlusions occurred both early and very late in the course of the disease (time after APS diagnosis, 0-38 years). Vasculitis was present in 7 patients and 5 demonstrated the typical antiphospholipid antibody (aPL)--vasculopathy with complicating bland thrombosis. Myocardial infarctions had occurred in 4 patients but it was not possible to determine whether they suffered from premature atherosclerotic disease or whether the infarctions were aPL-related. The appearance of livedo reticularis preceding the arterial thrombosis was noted in 9 patients. Cryoglobulinemia was detected in only 1 patient. CONCLUSIONS Peripheral vascular disease leading to amputation of digits or limbs is a severe complication encountered in patients with APS. In the absence of histopathology, it may be difficult to distinguish whether concomitant atherosclerotic occlusions, vasculitis, or aPL-related thrombosis of peripheral vessels is the main cause of the vascular ischemia. Treatment should, therefore, include full anticoagulation as well as corticosteroids and immunosuppression in these patients.

Catastrophic antiphospholipid syndrome : Lessons from the CAPS registry -A tribute to the late josep font

Abstract:  Although less than 1% of patients with the antiphospholipid syndrome (APS) develop the catastrophic variant, its potentially lethal outcome emphasizes its importance in clinical medicine today. However, the rarity of this variant makes it extraordinarily difficult to study in any systematic way. In order to put together all the published case reports as well as the new diagnosed cases from all over the world, an international registry of patients with catastrophic APS (“CAPS Registry”) was created in 2000 by the European Forum on Antiphospholipid Antibodies. Currently, it documents the entire clinical, laboratory, and therapeutic data of more than 300 patients whose data have been fully registered. This registry can be freely consulted at the Internet (http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM) and it is expected that the periodical analysis of these data will allow us to increase our knowledge of this condition.

Chapter 1 History, Classification, and Subsets of the Antiphospholipid Syndrome

Abstract The antiphospholipid syndrome (APS) is defined by the occurrence of venous and arterial thromboses, often multiple, and pregnancy morbidity, in the presence of antiphospholipid antibodies, namely lupus anticoagulant, anticardiolipin antibodies, or anti-β2glycoprotein I antibodies. The APS can be found in patients having neither clinical nor laboratory evidence of another definable condition (primary APS) or it may be associated with other diseases, mainly systemic lupus erythematosus, but occasionally with other autoimmune conditions, infections, drugs and malignancies. Rapid chronological occlusive events, occurring over days to weeks, have been termed the catastrophic APS. Other postulated APS subsets include the microangiopathic and the seronegative APS. In this chapter, we will review the main historical events related with the discovery and characterization of this syndrome as well as the efforts to classify and subdivide its wide spectrum of presentations.