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Objectives: To explore the prevalence and clinical significance of low complement levels in patients with catastrophic antiphospholipid syndrome (CAPS). Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

To 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. Based 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. 749 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. Cardiac 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. [ABSTRACT FROM AUTHOR]

Background: Treatments for catastrophic antiphospholipid syndrome (CAPS) rose from recommendations and consensus of international experts based on case series or case reports. We aimed to evaluate the treatment scheme with the best cost-effectiveness ratio associated with lower mortality as a high-impact clinical benefit. Methods: The CAPS Registry was used as our source of structured data on the different therapeutic strategies, their frequency, and their effectiveness (survival). Starting from around 50 different schemes, we identified those with a mortality of less than 33% within the 18 most frequently utilized. After applying the efficiency frontier method, we included two schemes to conduct a cost-effectiveness analysis from the Colombian healthcare sector perspective. Scheme 1 (Glucocorticoids + Anticoagulation + Anti-aggregation + Intravenous IgG immunoglobulin) and scheme 2 (Glucocorticoids + Anticoagulation + Anti-aggregation + Plasma exchange) were compared in terms of costs and survival. Deterministic and probabilistic sensitivity analyses (Monte Carlo simulation) were conducted to evaluate model robustness and uncertainty. Results: Our analysis uses the information corresponding to 427 cases from the CAPS registry, the majority being women (68.8%), with a mean age of 45.7 years and bearing general mortality of 38.17% (female: 38.4%, male: 37.5%). Scheme 2 was the cost-effective strategy over scheme 1. The results were robust on discrete sensitivity analysis and probability sensitivity analysis (Monte Carlo simulation). Conclusion: To our knowledge, this is the first economic evaluation focused on the treatment of CAPS. For the Colombian health system, schemes 1 and 2 have similar behavior; nevertheless, scheme 2 represents the best cost-effectiveness ratio. This treatment approach is highly susceptible to the allocation of resources by the system and beneficial in terms of health outcomes. [ABSTRACT FROM AUTHOR]

The Task Force on Catastrophic Antiphospholipid Syndrome (CAPS) met again on occasion of the 16th International Congress on Antiphospholipid Antibodies (aPL) that was held in Manchester, England, in September 2019. Its aims were to assess the up-to-date knowledge on pathogenesis, clinical and laboratory features, diagnosis and classification, precipitating factors, and treatment of CAPS. This article summarizes the main aspects that were presented during the Task Force meeting at that Congress. [ABSTRACT FROM AUTHOR]

• Pulmonary thromboembolism was the most common pulmonary involvement. • Hypocomplementemia associated with DAH is explained by the complement synthesis in CAPS-related cytokines storm. • Pulmonary capillaritis findings might point to a possible non-thrombotic pathogenesis. To describe the pulmonary involvement in patients with catastrophic antiphospholipid syndrome (CAPS), focusing on its relationship with extrapulmonary involvement, laboratory, radiological, and pathological findings. This 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. PE 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 %). Pulmonary 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. [Display omitted] [ABSTRACT FROM AUTHOR]

The catastrophic antiphospholipid syndrome (CAPS) is a life-threating variant of the antiphospholipid syndrome characterized by the development of multiple thrombosis in a short period of time, usually ending up in the failure of function of several vital organs. Most CAPS episodes are related to a prothrombotic situation or precipitating factor such as infections, surgical procedures or malignant diseases. In patients with CAPS, the development of multiple thrombosis leads to an important cytokine release that worsens the already critical patient's situation. The disease usually involves the kidneys, the lungs and the heart, although any organ system can be affected. Although occasionally the disease affects large vessels, in the majority of cases it affects small vessels, leading to a disseminated microangiopathic syndrome resembling thrombotic thrombocytopenic purpura. Treatment is based on the administration of anticoagulants, corticosteroids, plasma exchange and/or intravenous immunoglobulins. Cyclophosphamide is recommended in those CAPS cases associated to systemic lupus erythematosus. Additionally, rituximab and eculizumab have been used in refractory cases. Mortality is still around 30% despite current treatment. [ABSTRACT FROM AUTHOR]

Objectives. The objective of this study was to assess the effect that triple therapy (anticoagulation plus CS plus plasma exchange and/or IVIGs) has on the mortality risk of patients with catastrophic APS (CAPS) included in the CAPS Registry. Methods. Patients from the CAPS Registry were grouped based on their treatments: triple therapy; drugs included in the triple therapy but in different combinations; and none of the treatments included in the triple therapy. The primary endpoint was all-cause mortality. Multivariate logistic regression models were used to compare mortality risk between groups. Results. The CAPS Registry cohort included 525 episodes of CAPS accounting for 502 patients. After excluding 54 episodes (10.3%), a total of 471 patients with CAPS were included [mean (S.D.) age 38.5 years (17); 68.2% female; primary APS patients 62%]. Overall, 174 (36.9%) patients died. Triple therapy was prescribed in 189 episodes (40.1%), other combinations in 270 (57.3%) and none of those treatments in 12 episodes (2.5%); the mortality rate in the three groups was 28.6, 41.1 and 75%, respectively. Triple therapy was positively associated with a higher chance of survival when compared with non-treatment [adjusted odds ratio (OR) = 9.7, 95% CI: 2.3, 40.6] or treatment with other combinations of drugs included in the triple therapy (adjusted OR = 1.7, 95% CI: 1.2, 2.6). No statistical differences were found between patients that received triple therapy with plasma exchange or IVIGs (P = 0.92). Conclusion. Triple therapy is independently associated with a higher survival rate among patients with CAPS. [ABSTRACT FROM AUTHOR]

Objective To analyze the clinical and immunologic manifestations of patients with catastrophic antiphospholipid syndrome (CAPS) from the “CAPS Registry”. Methods 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. Results 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%). Conclusion 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. [ABSTRACT FROM AUTHOR]

The catastrophic antiphospholipid syndrome (CAPS) is characterized by thrombosis in more than three organs or systems developing over a short period of time. Despite conventional treatment with a combination of anticoagulation plus corticosteroids plus plasma exchange, and/or intravenous immunoglobulin, mortality remains high and some patients suffer from recurrent CAPS episodes. In selected patients, new therapies such as rituximab may be a treatment option. In this review, the rationale for using rituximab in CAPS is discussed. [ABSTRACT FROM PUBLISHER]

Abstract: Given the lack of information about catastrophic antiphospholipid syndrome (APS) in pediatric patients, the objective of the current study was to describe the clinical characteristics, laboratory features, treatment, and outcome of pediatric patients with catastrophic APS and compare them with the adult patients with catastrophic APS. We identified patients who were under 18years of age at time of catastrophic APS diagnosis included in the international registry of patients with catastrophic APS (CAPS Registry). Their main demographic and clinical characteristics, laboratory features, treatment, and outcome were described and compared with those of adult patients with catastrophic APS. From the 446 patients included in the CAPS Registry as of May 2013, 45 (10.3%) patients developed 46 catastrophic events before 18years of age (one patient presented two episodes). Overall, 32 (71.1%) patients were female and the mean age was 11.5±4.6years (range, 3months–18years). A total of 31 (68.9%) patients suffered from primary APS and 13 (28.9%) from systemic lupus erythematosus (SLE). The main differences between the two groups of patients were the higher prevalence of infections as precipitating factor for catastrophic event in the pediatric population (60.9% versus 26.8% in the adult population, p<0.001) and of peripheral vessel thrombosis (52.2% versus 34.3%, p=0.017). In addition, catastrophic APS was the first manifestation of APS more frequently in pediatric patients (86.6% versus 45.2%, p<0.001). Interestingly, pediatric patients showed a trend of lower mortality, although the difference was not statistically significant (26.1% versus 40.2%; odds ratio, 1.9; 95% confidence interval, 0.96–3.79; p=0.063). No differences were found neither in the laboratory features nor in the isolated or combination treatments between groups. Catastrophic APS in pediatric patients is a rare disease. There are minimal differences in the clinical and laboratory features, treatment, and outcome of pediatric and adult catastrophic APS patients. [Copyright &y& Elsevier]

To describe the real-world experience of eculizumab use in patients with catastrophic antiphospholipid syndrome (CAPS) according to the information provided by the "CAPS Registry". We analyzed the demographic, clinical and immunological data from all the patients included in the "CAPS Registry" treated with eculizumab and described the indications for eculizumab administration, dose, outcome, use of prophylactic vaccines and adverse effects. The "CAPS Registry" currently includes 584 patients from whom 39 (6.7%) were treated with eculizumab (it was used as a rescue therapy in 30 cases while in 6 cases it was used as first line therapy). Mean age of eculizumab treated patients was 39 years (SD = 14.6), 72% were female, 77% had a primary APS and 79% had a precipitating factor before the CAPS event. Thrombocytopenia was present in 28 (72%) cases and features of microangiopathic hemolytic anemia were present in 15 (38.5%). Twenty-nine (74.4%) patients recovered from the episode of CAPS (four showed only partial remission). Symptoms worsened in 9 patients, from whom 5 finally died despite the treatment. There was only one relapse after a median follow up of 10.7 months. The most common treatment regimen was 900 mg weekly for four weeks and 1200 mg fortnightly. According to the real-world experience provided by the "CAPS Registry", eculizumab can be considered in some patients with CAPS refractory to previous therapies, especially if they present with features of complement-mediated thrombotic microangiopathy. • Complement pathway has been identified as a critical mechanism in the development of CAPS. • Eculizumab is a humanized monoclonal antibody that binds to the C5 complementprotein. • 74.4% of CAPS patients treated with eculizumab recovered without recurrence of thrombosis. • We suggest considering eculizumab in CAPS patients who present with complement mediated thrombotic microangiopathy. [ABSTRACT FROM AUTHOR]

Abstract: The catastrophic variant of the antiphospholipid syndrome (APS) is characterized by thrombosis in multiple organs developing over a short period of time. First-line treatment for the catastrophic APS is the combination of anticoagulation plus corticosteroids plus plasma exchange and/or intravenous immunoglobulin. Despite this regimen, the mortality remains high and new treatment options are needed. By a systematic review of the Catastrophic APS Registry (CAPS Registry), we identified 20 patients treated with rituximab. The purpose of this study is to describe the clinical manifestations, laboratory features, and outcomes of rituximab-treated CAPS patients. In addition, the rationale for using rituximab in catastrophic APS is discussed. [Copyright &y& Elsevier]

Objective: To analyze the clinical and laboratory characteristics of patients with catastrophic antiphospholipid syndrome (APS) who suffer relapses. Methods: We analyzed the Web site--based international registry of patients with catastrophic APS (“CAPS Registry”) http://infmed.fcrb.es/es/web/caps and selected those cases that relapsed. Results: Relapses were reported in 9 of 282 (3.2%) patients with catastrophic APS. A total of 35 episodes of catastrophic APS were found: 6 patients presented 2 relapses, 2 patients suffered 3 relapses, and 1 patient developed 17 relapses. However, the last patient was not included in the statistical analysis because his clinical and immunologic characteristics were not fully described. Therefore, a total of 18 episodes were analyzed. In 9 (50%) episodes, a precipitating factor was identified. The most frequent precipitating factor, found in 5 (28%) episodes, was infection. Brain, kidney, heart, and lung were the most common organs involved. Laboratory features of microangiopathic hemolytic anemia (MHA) were present in 13 of 18 (72%) episodes (definitive in 9, corresponding to 4 patients, and probable in 4, corresponding to 2 patients). Three relapses did not present with features of MHA and in the remaining 2 these data were not reported. The mortality rate was 38%. Conclusions: Although relapses are rare in patients with catastrophic APS, these results support the hypothesis that an association between MHA and relapsing of catastrophic APS could be present. [Copyright &y& Elsevier]