Catastrophic antiphospholipid syndrome (CAPS): Descriptive analysis of a series of 280 patients from the “CAPS Registry”

doi:10.1016/j.jaut.2009.02.008

Journal of Autoimmunity

Volume 32, Issues 3–4, May–June 2009, Pages 240-245

This article is dedicated to the memory of Ronald A. Asherson and Josep Font who coordinated this registry since its creation and passed away recently.

https://doi.org/10.1016/j.jaut.2009.02.008 Get rights and content

Abstract

Objective

To describe the clinical and laboratory features, as well as the precipitating factors, treatment and outcome of patients with catastrophic antiphospholipid syndrome (APS).

Methods

We analyzed the 280 patients included until September 2008 in the website based international registry of patients with catastrophic APS (“CAPS Registry”) (http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM).

Results

The entire series includes 201 (72%) female and 79 (28%) male patients with a mean age of 37 ± 14 years (range, 11–60 years). A total of 129 (46%) patients suffered from primary APS, 112 (40%) from systemic lupus erythematosus, 14 (5%) from lupus-like disease, and 25 (9%) from other autoimmune diseases. The catastrophic episode was the first manifestation of the APS in 129 (46%) patients. A precipitating factor was reported in 53% of the patients. The first clinical manifestation at the time of the catastrophic episode was a pulmonary complication in 24% of the cases, a neurologic feature in 18% and a renal feature in 18%. During the catastrophic episode, intraabdominal involvement was identified in the majority of patients, mainly consisting of renal (71%), hepatic (33%), gastrointestinal (25%), splenic (19%), adrenal (13%), and pancreatic (8%) manifestations. 123 (44%) patients died at the time of the catastrophic APS event but the higher recovery rate was achieved by the combination of anticoagulants plus corticosteroids plus plasma exchange (PE) and/or intravenous immunoglobulins (IVIG) (69% versus 54%).

Conclusions

The catastrophic APS is an uncommon but potentially life-threatening condition that needs high clinical awareness. The therapeutical connotation is that this may be corrected with the combination of anticoagulation plus steroids plus attempts at achieving a prompt reduction of antiphospholipid antibody titer (i.e. PE and/or IVIG).

Introduction

The descriptive adjective “catastrophic” was added to the term antiphospholipid syndrome (APS) by Asherson [1] in order to highlight an accelerated form of this syndrome resulting in multi-organ failure. Patients with catastrophic APS (currently also known as Asherson's syndrome) [2] have in common: a) clinical evidence of multiple organ involvement developing over a very short period of time; b) histopathological evidence of multiple small vessel occlusions, and c) laboratory confirmation of the presence of antiphospholipid antibodies (aPL), usually in high titer. Furthermore, the majority of the catastrophic episodes are preceded by a precipitating event, mainly infections [3], [4].

Although less than 1% of patients with the APS develop this complication [5], its potentially lethal outcome emphasizes its importance in clinical medicine today. The majority of patients with catastrophic APS end up in Intensive Care Units (ICU) with multi-organ failure and, unless the condition is considered in the differential diagnosis by attending physicians, it may be completely missed, resulting in a disastrous outcome for these patients [6].

The rarity of this syndrome makes it extraordinarily difficult to study in any systematic way. In order to compile all the published case reports as well as newly 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, a study group devoted to the development of multicenter projects with large populations of APS patients [7]. This registry can be freely consulted through Internet at www.med.ub.es/MIMMUN/FORUM/CAPS.HTM. The initial analysis of this registry allowed the first characterization of the clinical and laboratory features of the catastrophic APS [8], [9], [10], [11], [12], [13] as well as the establishment of preliminary criteria for its classification and guidelines for its management [14], [15].

Currently, the CAPS Registry documents the entire clinical, laboratory and therapeutic data of 280 patients whose data have been fully registered. In the present study, we describe the clinical and laboratory features, as well as the precipitating factors, treatment and outcome of these 280 patients with catastrophic APS.

Section snippets

Methods

We analyzed the case reports included in the website based international registry of patients with catastrophic APS (CAPS Registry) until September 2008. It contains clinical, laboratory, and therapeutic data on all reported cases of catastrophic APS. The sources of information are the personal communications of the physicians who treated these patients and the periodically computer-search assisted (Medline) of published reports to locate all cases of patients with catastrophic APS. We

General characteristics

Precipitating factors and clinical presentation

The main precipitating factors and clinical features of the 280 patients with catastrophic APS from the

Discussion

In 1992, an attempt to single out a seemingly different and important group of patients was adopted by introducing the term catastrophic APS to describe their potentially life-threatening clinical course [1]. From the current review of the 280 patients from the CAPS Registry, certain differences which appear to distinguish this minority group of patients suffering from catastrophic APS from the overwhelming majority of APS patients have been confirmed. The major differences are that large

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Cited by (283)

French National Diagnostic and Care Protocol for antiphospholipid syndrome in adults and children
2023, Revue de Medecine Interne
Antiphospholipid syndrome (APS) is a chronic autoimmune disease involving vascular thrombosis and/or obstetric morbidity and persistent antibodies to phospholipids or certain phospholipid-associated proteins. It is a rare condition in adults and even rarer in children. The diagnosis of APS can be facilitated by the use of classification criteria based on a combination of clinical and biological features. APS may be rapidly progressive with multiple, often synchronous thromboses, resulting in life-threatening multiple organ failure. This form is known as “catastrophic antiphospholipid syndrome” (CAPS). It may be primary or associated with systemic lupus erythematosus (associated APS) and in very rare cases with other systemic autoimmune diseases. General practitioners and paediatricians may encounter APS in patients with one or more vascular thromboses. Because APS is so rare and difficult to diagnosis (risk of overdiagnosis) any suspected case should be confirmed rapidly and sometimes urgently by an APS specialist. First-line treatment of thrombotic events in APS includes heparin followed by long-term anticoagulation with a VKA, usually warfarin. Except in the specific case of stroke, anticoagulants should be started as early as possible. Any temporary discontinuation of anticoagulants is associated with a high risk of thrombosis in APS. A reference/competence centre specialised in autoimmune diseases must be urgently consulted for the therapeutic management of CAPS.
Le syndrome des antiphospholipides (SAPL) est une maladie auto-immune chronique qui associe des thromboses vasculaires et/ou une morbidité obstétricale, et la présence, confirmée dans le temps, d’anticorps dirigés contre des phospholipides ou certaines protéines associées aux phospholipides. Il s’agit d’une affection rare chez les adultes et exceptionnelle chez les enfants. Le diagnostic du SAPL peut être facilité par l’utilisation de critères de classification qui reposent sur la combinaison de critères cliniques et biologiques. Exceptionnellement, le SAPL peut donner des thromboses multiples, souvent synchrones, parfois responsables de défaillance multiviscérale engageant le pronostic vital (syndrome catastrophique des antiphospholipides ou CAPS). Le SAPL peut être primaire ou associé au lupus systémique (SAPL associé) et plus rarement à d’autres maladies auto-immunes systémiques. Tout médecin généraliste ou pédiatre peut être confronté au SAPL en présence d’une ou plusieurs thromboses vasculaires. Du fait de la rareté et la difficulté du diagnostic (risque de surdiagnostic) de la maladie, il est nécessaire de faire confirmer le diagnostic rapidement et parfois de manière urgente par un médecin ayant une expertise en matière de SAPL. Le traitement des événements thrombotiques dans le SAPL repose sur l’utilisation initiale d’héparine suivie d’une anticoagulation à long terme avec un AVK, généralement la warfarine. En dehors de la situation spécifique de l’accident vasculaire cérébral, l’anticoagulation doit être débutée le plus tôt possible. L’arrêt temporaire du traitement anticoagulant comporte un risque élevé de thrombose. En cas de CAPS, l’avis d’un centre de référence/compétence dédié aux maladies auto-immunes est nécessaire en urgence pour la prise en charge thérapeutique.
Precipitating factors of catastrophic antiphospholipid syndrome: the role of anticoagulant treatment in a series of 112 patients
2023, Journal of Thrombosis and Haemostasis
The prevention of catastrophic antiphospholipid syndrome (CAPS), a rare complication of antiphospholipid syndrome (APS), is a major goal.
We analyzed its precipitating factors, focusing on anticoagulation immediately before CAPS episodes.
We retrospectively analyzed patients in the French multicenter APS/systemic lupus erythematosus database with at least 1 CAPS episode. Then we compared each patient with known APS before CAPS with 2 patients with non-CAPS APS matched for age, sex, center, and APS phenotype.
We included 112 patients with CAPS (70% women; mean age, 43 ± 15 years). At least 1 standard precipitating factor of CAPS was observed for 67 patients (64%), which were mainly infections (n = 28, 27%), pregnancy (n = 23, 22%), and surgery (n = 16, 15%). Before the CAPS episode, 67 (60%) patients already had a diagnosis of APS. Of the 61 treated with anticoagulants, 32 (48%) received vitamin K antagonists (VKAs), 23 (34%) heparin, and 2 (3%) a direct oral anticoagulant. They were less likely than their matched patients with APS without CAPS to receive VKA (48% vs 66%, p = .001). Among those treated with VKA, 72% had a subtherapeutic international normalized ratio (ie, <2) versus 28% in patients with APS without CAPS (p < .001). Finally, excluding pregnant patients (n = 14) for whom we could not differentiate the effect of treatment from that of pregnancy, we were left with 47 cases, 32 (68%) of whom had recently begun a direct oral anticoagulant, planned bridging therapy, or had VKA treatment with international normalized ratio <2.
These results strongly suggest that suboptimal anticoagulation management can trigger CAPS in patients with thrombotic APS.
Bilateral adrenal hemorrhage: A rare presentation of catastrophic anti-phospholipid syndrome: Rare presentation of catastrophic anti-phospholipid syndrome
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Catastrophic anti-phospholipid syndrome (CAPS) is characterized by microvascular thrombosis in multiple sites leading to multi-organ damage. It is a rare and fatal complication of antiphospholipid syndrome (APS). We present a rare case of CAPS that presented with bilateral (b/l) adrenal hemorrhage making the diagnosis challenging in this otherwise rare disease. A 51-year-old female was initially admitted with abdominal pain and found to have bilateral adrenal hemorrhage. Patient had a fulminant disease course in which she had thrombotic manifestations involving multiple organ systems. This case was especially challenging as the patient's bilateral adrenal hemorrhage was the first manifestation of CAPS; the diagnosis of APS had to be made while treatment for presumed CAPS was emergently commenced for this life-threatening disease. Key to managing this condition is having a high index of suspicion for the diagnosis in patients presenting with multi-organ failure and multiple thromboses and hemorrhage.
The presentation, etiologies, pathophysiology, and treatment of pulmonary renal syndrome: A review of the literature
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Pulmonary renal syndrome (PRS) is a constellation of different disorders that cause both rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage. While antineutrophil cytoplasmic antibody associated vasculitis and anti-glomerular basement membrane disease are the predominant causes of PRS, numerous other mechanisms have been shown to cause this syndrome, including thrombotic microangiopathies, drug exposures, and infections, among others. This syndrome has high morbidity and mortality, and early diagnosis and treatment is imperative to improve outcomes. Treatment generally involves glucocorticoids and immunosuppressive agents, but treatment targeted to the underlying disorder can improve outcomes and mitigate side effects. Familiarity with the wide range of possible causes of PRS can aid the clinician in workup, diagnosis and early initiation of treatment. This review provides a summary of the clinical presentation, etiologies, pathophysiology, and treatment of PRS.
Kidney disease in antiphospholipid antibody syndrome: Risk factors, pathophysiology and management
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Antiphospholipid antibody syndrome (APLS) is a rare autoimmune disease characterized by recurrent arterial and venous thromboembolic events, pregnancy related complications as well as the persistent detection of antiphospholipid antibodies at a 12 week interval. Renal complications tend to occur in 3% of APLS patients, with renal artery stenosis being the most common kidney related complication. Renal pathology may be subdivided into macro as well as microvascular thrombotic complications with stenosis, thrombosis and infarction representing the principle macrovascular events and APLS nephropathy representing the predominant microvascular complication. APLS related kidney disease may present with an array of heterogenous manifestations ranging from hematuria and non-nephrotic range proteinuria to hypertension or as part of a severe, life threatening and fulminant multiorgan failure disorder known as catastrophic antiphospholipid antibody syndrome (CAPS). Management of APLS related renal complications depends on the site of vascular injury, the thromboembolic risk profile based on the subtype, isotype and titer of the autoantibodies as well as the severity of the injury. Primary prophylaxis in these patients primarily revolves around the use of low dose aspirin, with prophylactic anticoagulation during events that increase thromboembolic like surgery and hospitalization. Anticoagulation is the cornerstone of treatment of APLS related kidney disease with INR targets varying depending on the associated venous or arterial thrombosis. Immunosuppression with the likes of rituximab, mTOR inhibitors, eculizumab and belimumab have been used with some success, but lack randomized control trial validation for their use. Pulsed corticosteroids with Plasmapheresis and intravenous immunoglobulins is the recommended treatment for CAPS.
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In 2007 and 2009, the regulatory approval of the first-in-class complement inhibitor eculizumab revolutionized the clinical management of 2 rare, life-threatening clinical conditions: paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Although being completely distinct diseases affecting blood cells and the glomerulus, PNH and aHUS remarkably share several features in their etiology and clinical presentation. An imbalance between complement activation and regulation at host surfaces underlies both diseases precipitating in severe thrombotic events that are largely resistant to anticoagulant and/or antiplatelet therapies. Inhibition of the common terminal complement pathway by eculizumab prevents the frequently occurring thrombotic events responsible for the high mortality and morbidity observed in patients not treated with anticomplement therapy. Although many in vitro and ex vivo studies elaborate numerous different molecular interactions between complement activation products and hemostasis, this review focuses on the clinical evidence that links these 2 fields in humans. Several noninfectious conditions with known complement involvement are scrutinized for common patterns concerning a prothrombotic statues and the occurrence of certain complement activation levels. Next to PNH and aHUS, germline-encoded CD59 or CD55 deficiency (the latter causing the disease complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy), autoimmune hemolytic anemia, (catastrophic) antiphospholipid syndrome, and C3 glomerulopathy are considered. Parallels and distinct features among these conditions are discussed against the background of thrombosis, complement activation, and potential complement diagnostic and therapeutic avenues.

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: See complete list of members of the CAPS Registry at the end of the article

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Catastrophic antiphospholipid syndrome (CAPS): Descriptive analysis of a series of 280 patients from the “CAPS Registry”

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Methods

General characteristics

Precipitating factors and clinical presentation

Discussion

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