Catastrophic Antiphospholipid Syndrome Registry Research Articles

Catastrophic Antiphospholipid Syndrome: A Review of Current Evidence and Future Management Practices.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by blood clots and pregnancy complications due to antiphospholipid antibodies. Catastrophic APS (CAPS), a severe variant, leads to multiorgan failure and is often fatal. Pathogenesis involves antiphospholipid antibodies, particularly anti-beta-2-glycoprotein I (aβ2GPI), which trigger endothelial cell (EC) activation, cytokine release, and a prothrombotic state. Infections, surgeries, and other triggers can precipitate CAPS, leading to widespread microthromboses and systemic inflammatory responses. CAPS predominantly affects younger patients and those with systemic lupus erythematosus (SLE), with a high mortality rate, though recent treatment advances have improved survival. Diagnosing CAPS involves identifying clinical manifestations, including rapid organ involvement and small vessel occlusions, confirmed by histopathology and high antiphospholipid antibody levels. The CAPS registry data indicate that commonly affected organs include kidneys, lungs, central nervous system, and the heart, with a high prevalence of lupus anticoagulant and anticardiolipin antibodies (aCL). Current management strategies focus on therapeutic anticoagulation, immunosuppressive therapies like corticosteroids, and adjunct treatments such as plasmapheresis and intravenous immunoglobulin (IVIG). Early use of glucocorticoids and combination therapy has significantly improved outcomes. In life-threatening cases, especially with microangiopathy, experts recommend performing plasma exchange (PE). Patients with associated autoimmune conditions or refractory cases may receive cyclophosphamide (CY) and rituximab while considering PE for treatment. Maintenance of anticoagulation with an appropriate international normalized ratio (INR) is crucial to prevent recurrence.This article reviews the pathogenesis and epidemiology of CAPS. It also examines the current management strategies, and discusses the challenges and controversies associated with these strategies. It hereafter offers recommendations for future management and outlines directions for further research.

Cardiac involvement in the catastrophic antiphospholipid syndrome (CAPS): Lessons from the “CAPS registry”

ObjectiveTo analyze the demographic, clinical, and laboratory characteristics of catastrophic antiphospholipid syndrome (CAPS) patients with cardiac involvement, and to identify the factors associated with this cardiac involvement. Material and methodsBased on the analysis of the “CAPS Registry”, the demographic, clinical, and serological characteristics of patients with cardiac involvement were analyzed. Cardiac involvement was defined as heart failure, valvular disease, acute myocardial infarction, pericardial effusion, pulmonary arterial hypertension, systolic dysfunction, intracardiac thrombosis, and microvascular disease. Univariate and multivariate analysis was used for multiple comparisons. Results749 patients (293 [39 %] women and mean age 38.1 ± 16.2 years) accounting for 778 CAPS events were included, of them 404 (52 %) had cardiac involvement. The main cardiac manifestations were heart failure in 185/377 (55 %), valve disease in 116/377 (31 %), and acute myocardial infarction in 104/378 (28 %). Of 58 patients with autopsy/biopsy, 48 (83 %) had cardiac thrombotic microangiopathy, Stroke (29% vs. 21 %, p = 0.012), transient cerebral vascular accident (2% vs. 1 %, p = 0.005), pulmonary infarction (26% vs. 3 %, p = 0.017), renal infarction (46% vs. 35 %, p = 0.006), acute kidney injury (70% vs. 53 %, p < 0.001), and livedo reticularis (24% vs. 17 %, p = 0.016) were significantly more frequent during CAPS events with versus without heart involvement. Multivariate analysis identified acute kidney injury (OR 1.068, IC 95 % 1.8–4.8, p < 0.001) as the only clinical characteristics that were, independently, associated with cardiac involvement in CAPS events. Cardiac involvement was not related to higher mortality. ConclusionsCardiac involvement is frequent in CAPS, with association with kidney involvement, and it is not related to higher mortality. The presence of cardiac microthrombosis was demonstrated in most biopsies/autopsies performed.

Pulmonary involvement in catastrophic antiphospholipid syndrome: A descriptive analysis from the “CAPS Registry”

ObjectivesTo describe the pulmonary involvement in patients with catastrophic antiphospholipid syndrome (CAPS), focusing on its relationship with extrapulmonary involvement, laboratory, radiological, and pathological findings. MethodsThis retrospective cross-sectional study includes all patients grouped in the “CAPS Registry”. All cases were reviewed, and those with pulmonary thromboembolism (PE) and/or diffuse alveolar hemorrhage (DAH) were selected. Data on pulmonary and extrapulmonary clinical presentation, radiologic patterns, laboratory findings, associated autoimmune diseases, treatments, and outcomes were analyzed. Frequency distribution and measures of central tendency were used to describe the cohort. Comparison between groups regarding qualitative variables was undertaken by chi-square or Fisher exact test, while T-test for independent variables was used to compare groups regarding continuous variables. IBM-SPSS v.22 was used for data analysis. ResultsPE was reported in 129 (48.6 %) episodes, DAH in 75 (28.3 %) episodes, and overlap (DAH plus PE) in 7 (2.6 %) episodes. Bronchoalveolar lavage (BAL) was performed in 35 (4.9 %) CAPS episodes, and lung pathology samples were obtained in 84 (10.5 %) episodes (including autopsies). A significant relationship was observed between DAH and laboratory features of thrombotic microangiopathy (TMA). A meaningful relationship was also found between triple antiphospholipid antibody positivity and pathological TMA (26.5 %) as well as hypocomplementemia and DAH (24 %). ConclusionsPulmonary involvement may include both TMA and non-thrombotic inflammation, which can be differentiated into three patterns: PE, DAH with systemic TMA with hypocomplementemia or DAH without systemic TMA with/without hypocomplementemia.

The clinical significance of low complement levels in patients with catastrophic antiphospholipid syndrome: A descriptive analysis of 73 patients from the "Catastrophic antiphospholipid syndrome registry".

To explore the prevalence and clinical significance of low complement levels in patients with catastrophic antiphospholipid syndrome (CAPS). We reviewed data from the "CAPS Registry" on C3 and/or C4 complement plasma protein levels during acute CAPS episodes. Patients were classified into those with low and normal complement levels. Data on clinical presentation, with special focus on thrombotic microangiopathy (TMA) features, diagnosis of systemic lupus erythematosus (SLE), and antiphospholipid antibody (aPL) profile were reviewed. The chi-square exact test was performed to evaluate differences between categorical data. The "CAPS Registry" includes 566 patients with a total of 578 episodes of CAPS. Data on complement plasma protein levels was available in 73 episodes from the same number of patients. Low levels of C3 and/or C4 complement plasma proteins were detected in 42 (58%) CAPS episodes. Low complement levels were more common in SLE patients (55% SLE vs. 19% No SLE; p<0.001). The frequencies of clinical TMA (72% vs. 80%; p=0.4) or TMA syndrome (86% vs. 84%, p=0.9), frequency of triple aPL triple positivity (67% vs 33%; p=0.3), or the mortality (35% vs. 31%; p=0.7) were similar between low and normal complement groups. In our study, low levels of C3 and C4 plasma proteins are detected in 58% episodes of CAPS, which were not associated with clinical presentation including TMA features, aPL triple positivity, or mortality.

Catastrophic antiphospholipid syndrome: an update.

Catastrophic antiphospholipid syndrome (CAPS) is a rare variant that accounts for 1% of patients with APS. Despite its low frequency, the mortality-related is very high ranging from 50% of patients in the first series to 37% in the most recent data. The current knowledge of this potential devastating entity comes from the International Registry of patients with CAPS, named CAPS Registry. Small vessel thrombosis, laboratory features of microangiopathic haemolytic anemia, and development of multisystem involvement in a very short period of time are the main characteristics of this syndrome. Clinical manifestations are due to thrombosis but also, although the evidences are indirect, to excess of proinflammatory cytokines. Therefore, treatment strategy is based on the combination of anticoagulation, glucocorticoids, plasma exchange and/or intravenous immunoglobulins, the so-called triple therapy. In refractory cases or in those with initial life-threatening situation, rituximab may be an effective option. Recently, some cases of CAPS have been effectively treated with the addition of eculizumab to the triple therapy.

Catastrophic antiphospholipid syndrome (CAPS): Descriptive analysis of 500 patients from the International CAPS Registry

To analyze the clinical and immunologic manifestations of patients with catastrophic antiphospholipid syndrome (CAPS) from the "CAPS Registry". The demographic, clinical and serological features of 500 patients included in the website-based "CAPS Registry" were analyzed. Frequency distribution and measures of central tendency were used to describe the cohort. Comparison between groups regarding qualitative variables was undertaken by chi-square or Fisher exact test while T-test for independent variables was used to compare groups regarding continuous variables. 500 patients (female: 343 [69%]; mean age 38±17) accounting for 522 episodes of CAPS were included in the analysis. Forty percent of patients had an associated autoimmune disease, mainly systemic lupus erythematosus (SLE) (75%). The majority of CAPS episodes were triggered by a precipitating factor (65%), mostly infections (49%). Clinically, CAPS was characterized by several organ involvement affecting kidneys (73%), lungs (60%), brain (56%), heart (50%), and skin (47%). Lupus anticoagulant, IgG anticardiolipin and IgG anti-β2-glycprotein antibodies were the most often implicated antiphospholipid antibodies (83%, 81% and 78% respectively). Mortality accounted for 37% of episodes of CAPS. Several clinical differences could be observed based on the age of presentation and its association to SLE. Those cases triggered by a malignancy tended to occur in older patients, while CAPS episodes in young patients were associated with an infectious trigger and peripheral vessels involvement. Additionally, CAPS associated with SLE were more likely to have severe cardiac and brain involvement leading to a higher mortality (48%). Although the presentation of CAPS is characterized by multiorgan thrombosis and failure, clinical differences among patients exist based on age and underlying chronic diseases, e.g. malignancy and SLE.

Treatment of catastrophic antiphospholipid syndrome.

Catastrophic antiphospholipid syndrome (CAPS) is a severe manifestation of antiphospholipid syndrome (APS). Although affecting only 1% of patients with APS, the condition is frequently fatal if not recognized and treated early. Here, we will review the current approach to diagnosis and treatment of CAPS. Data from the international 'CAPS registry', spearheaded by the European Forum on Antiphospholipid Antibodies, have improved our understanding of at-risk patients, typical clinical features, and precipitating diagnoses. Current guidelines also continue to support the role of anticoagulants and glucocorticoids as foundation therapy in all patients. Finally, new basic science and case series suggest that novel therapies, such as rituximab and eculizumab, warrant further study. Attention to associated diagnoses, such as infection and systemic lupus erythematosus (SLE), is critical at the time of diagnosis. All patients should be treated with anticoagulants, corticosteroids, and possibly plasma exchange. In patients with SLE, cyclophosphamide should be considered. In refractory or relapsing cases, new therapies, such as rituximab and possibly eculizumab, may be options, but need further study.

Update on the Catastrophic Antiphospholipid Syndrome and the “CAPS Registry”

Although less than 1% of patients with the antiphospholipid syndrome (APS) develop the catastrophic variant known as catastrophic antiphospholipid syndrome (CAPS), 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. To collate all the published case reports as well as the newly diagnosed cases from all over the world, an international registry of patients with CAPS ("CAPS Registry") was created in 2000 by the European Forum on Antiphospholipid Antibodies (www.med.ub.es/MIMMUN/FORUM/CAPS.HTM). Currently, this database documents the entire clinical, laboratory, and therapeutic data of more than 350 fully registered patients.

Recurrent Thrombotic Events after Catastrophic Antiphopholipid Syndrome

To the Editor, A 40-year-old man was transferred to our hospital in March 1994 for gross hematuria and decreased urine output. The patient exhibited chest pain and shortness of breath 2 weeks prior to the initial visit. These symptoms were relieved without particular management. Fever and chills developed thereafter followed by abdominal pain. The patient visited a local clinic and was managed for acute pancreatitis and gastritis for 1 week. However, his symptoms did not subside and urine output decreased progressively. On admission, he complained of severe headache, nausea, and both flank and back pain. Initial hemoglobin levels and platelet counts were 16.9 g/dL and 478 × 109/L, respectively. In the course of 3 days, anemia and thrombocytopenia rapidly developed, with a hemoglobin level of 12.0 g/dL and a platelet count of 29 × 109/L. Peripheral blood smear showed schistocytes suggesting hemolytic anemia. Initial blood urea nitrogen and creatinine levels were 69 and 6.0 mg/dL, respectively. Magnetic resonance imaging of the kidney revealed acute cortical necrosis. He also had blood tinged sputum, and the lung perfusion scan revealed perfusion defects in the right lower lobe, suggesting pulmonary embolism. Despite fluid therapy and the administration of diuretics, azotemia progressed rapidly over a 3-day period and he consequently underwent hemodialysis. Azotemia improved with increased urine output only after hemodialysis (Fig. 1). Figure 1 Azotemia progressed rapidly with fluid and diuretics therapy. Urine output increased only after hemodialysis. HD, hemodialysis; Cr, creatinine. The serologic results showed the presence of lupus anticoagulant and IgM anticardiolipin antibody, and the patient was diagnosed with antiphospholipid syndrome (APS) with multiorgan failure. Retrospectively, his clinical presentation fits into the category of probable catastrophic APS (CAPS). However, neither intravenous heparin nor warfarin was used due to hemoptysis. Thereafter, he was admitted several times for coronary events and pulmonary infarction. Two months after the first attack, he was readmitted due to chest pain. The echocardiogram showed inferior and septal myocardial infarction and he was discharged with aspirin and clopidogrel. Three months later, he was readmitted due to chest pain, and a coronary angiogram showed right coronary artery focal stenosis (Fig. 2). He was lost to follow-up for 3 years and was readmitted to the hospital in 1997 for pleuritic chest pain. Chest computed tomography scans revealed both lower lobe pulmonary infarctions. He was lost again to follow-up without antithrombotic agents. Figure 2 Coronary angiogram showed right coronary artery 50% focal stenosis, suggesting embolic infarct rather than atherosclerosis. Recently, he was admitted for facial cellulitis associated with a burn, and the involved skin showed multiple ulcerations and necrosis (Fig. 3). His facial lesions improved with antibiotics. We started antithrombotic treatment for long-term prevention of recurrent thrombotic events. Figure 3 The patient developed facial cellulitis with multiple necrotic ulcerations after burn, suggesting possible microangiopathic thrombosis. CAPS is a life-threatening medical situation with a high mortality rate, although it represents in less than 1% of patients with APS [1]. Therefore, clinical suspicion and early diagnosis are important for improving survival from CAPS. Asherson et al. [1] and Erkan [2] noted that the recurrence of CAPS was not common, although patients had been on continuous anticoagulation therapy. Among 73 CAPS survivors, 14 patients (19%) had further APS-related manifestations but no patient developed recurrent CAPS episodes during a follow-up of median 67.2 months [3]. Our case presents recurrent APS-related events after an initial CAPS episode. No standardized treatment guideline for CAPS has been established due to the rarity of the disease and the lack of controlled studies [2]. Current treatment recommendations are based on case series. Previous studies emphasized the importance of early anticoagulation, steroid, and plasma exchange during CAPS episodes [1,4,5]. Bucciarelli et al. [4] demonstrated that the mortality rate decreased from 53% to 33% with a combination therapy of anticoagulation, steroids, and plasma exchange and/or intravenous immunoglobulins in 250 patients in the CAPS registry. The reported patient could not maintain anticoagulation therapy because he had a bleeding episode at the initial admission and did not regularly visit clinics. The recurrent thrombotic events may have been due to the lack of anticoagulation therapy. This case suggests that continuous anticoagulation is important for the prevention of recurrent thrombotic events after CAPS.

Catastrophic antiphospholipid syndrome (CAPS): update from the ‘CAPS Registry’

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 of 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 (see http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM). Currently, it documents the entire clinical, laboratory and therapeutic data of more than 300 patients whose data has been fully registered.

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

ObjectiveTo describe the clinical and laboratory features, as well as the precipitating factors, treatment and outcome of patients with catastrophic antiphospholipid syndrome (APS). MethodsWe 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). ResultsThe 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%). ConclusionsThe 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).

The role of malignancies in patients with catastrophic anti-phospholipid (Asherson’s) syndrome

The catastrophic anti-phospholipid syndrome (CAPS) differs from the anti-phospholipid syndrome in its accelerated systemic involvement leading to multi-organic failure. In this study, the occurrence of malignancies in patients with CAPS was evaluated and the clinical findings of CAPS patients with and without malignancies were compared. We investigated the web site-based international registry of patients with CAPS for all cases in which both CAPS and underlying malignancies were present. The clinical characteristics of these cases were subsequently evaluated to establish common characteristics. The CAPS registry included information on a total of 262 cases. Twenty-three (9%) patients suffered from malignancies. In 78% of these patients, the malignancy itself or the treatment modalities instituted for the carcinoma was the precipitating factor of CAPS. Only 39% of CAPS patients with malignancies recovered in comparison to 58% of patients without malignancies (p = 0.07). Treatment modalities, however, did not differ significantly between these patients. Infections were not evident as precipitating factors for any of the malignancy patients. The mean age of patients with malignancies was 9 years older than the average age of other patients with CAPS and the prevalence of SLE was significantly less common than in patients without malignancy. Malignancy may play a pathogenic role in patients with CAPS, whereas infections are more important as triggering factors in patients without malignancies. CAPS patients with malignancies are generally older than CAPS patients without malignancies; they generally have the worst prognosis of the entire CAPS cohort.

Mortality in the catastrophic antiphospholipid syndrome: Causes of death and prognostic factors in a series of 250 patients

To assess the main causes of death and the prognostic factors that influence mortality in patients with the catastrophic antiphospholipid syndrome (CAPS). We analyzed the case reports of 250 patients included in the CAPS Registry up to February 2005. To identify prognostic factors for CAPS, we compared the main clinical and immunologic features and the types of treatment in the patients who died with those features in the patients who survived. Recovery occurred in 56% of the episodes of CAPS and death occurred in 44%. Cerebral involvement, consisting mainly of stroke, cerebral hemorrhage, and encephalopathy, was considered the main cause of death, being present in 27.2% of patients, followed by cardiac involvement (19.8%) and infection (19.8%). The only factor we identified that was prognostic of a higher mortality rate was the presence of systemic lupus erythematosus (SLE). A higher recovery rate was associated with combined treatment with anticoagulants (ACs) plus corticosteroids (CS) plus plasma exchange (PE) (77.8%), followed by ACs plus CS plus PE and/or intravenous immunoglobulins (69%). In contrast, concomitant treatment with cyclophosphamide did not demonstrate additional benefit. Cerebral involvement (mainly consisting of stroke), cardiac involvement, and infections were considered the main causes of death in patients with CAPS. The presence of SLE was related to a higher mortality rate. According to the results of the present study, ACs plus CS plus PE should be the first line of therapy in patients with CAPS.