Cardiac involvement in the catastrophic antiphospholipid syndrome (CAPS): Lessons from the "CAPS registry".

OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Heart Valve Involvement in Patients with Antiphospholipid Syndrome: A Long-Term Follow-Up Study of a Single Centre.

BACKGROUND: Valve involvement is the most common cardiac manifestation in antiphospholipid syndrome (APS). The objective of the study was to describe the prevalence, clinical and laboratory features, and evolution of APS patients with heart valve involvement. METHODS: A retrospective longitudinal and observational study of all APS patients followed by a single centre with at least one transthoracic echocardiographic study. RESULTS: 144 APS patients, 72 (50%) of them with valvular involvement. Forty-eight (67%) had primary APS, and 22 (30%) were associated with systemic lupus erythematosus (SLE). Mitral valve thickening was the most frequent valve involvement present in 52 (72%) patients, followed by mitral regurgitation in 49 (68%), and tricuspid regurgitation in 29 (40%) patients. Female sex (83% vs. 64%; p = 0.013), arterial hypertension (47% vs. 29%; p = 0.025), arterial thrombosis at APS diagnosis (53% vs. 33%; p = 0.028), stroke (38% vs. 21%; p = 0.043), livedo reticularis (15% vs. 3%; p = 0.017), and lupus anticoagulant (83% vs. 65%; p = 0.021) were more prevalent in those with valvular involvement. Venous thrombosis was less frequent (32% vs. 50%; p = 0.042). The valve involvement group suffered from higher mortality (12% vs. 1%; p = 0.017). Most of these differences were maintained when we compared patients with moderate-to-severe valve involvement (n = 36) and those with no or mild involvement (n = 108). CONCLUSIONS: Heart valve disease is a frequent manifestation in our cohort of APS patients and is associated with demographic, clinical and laboratory features, and increased mortality. More studies are needed, but our results suggest that there may be a subgroup of APS patients with moderate-to-severe valve involvement with its own characteristics that differs from the rest of the patients with mild valve involvement or without valve involvement.

Outcomes beyond the Third Month of Anticoagulation in Patients Aged >75 Years with a First Episode of Unprovoked Venous Thromboembolism.

Background The ideal duration of anticoagulant therapy in elderly patients with unprovoked venous thromboembolism (VTE) has not been consistently evaluated. Methods We used the RIETE ( R egistro I nformatizado E nfermedad T rombo E mbólica) registry to compare the rate and severity of pulmonary embolism (PE) recurrences versus major bleeding beyond the third month of anticoagulation in patients >75 years with a first episode of unprovoked VTE. Results As of September 2017, 7,830 patients were recruited: 5,058 (65%) presented with PE and 2,772 with proximal deep vein thrombosis (DVT). During anticoagulant therapy beyond the third month (median, 113 days), 44 patients developed PE recurrences, 36 developed DVT recurrences, 101 had major bleeding, and 241 died (3 died of recurrent PE and 19 of bleeding). The rate of major bleeding was twofold higher than the rate of PE recurrences (2.05 [95% confidence interval, CI: 1.68-2.48] vs. 0.90 [95% CI: 0.66-1.19] events per 100 patient-years) and the rate of fatal bleeding exceeded the rate of fatal PE events (0.38 [95% CI: 0.24-0.58] vs. 0.06 [95% CI: 0.02-0.16] deaths per 100 patient-years). On multivariable analysis, patients who had bled during the first 3 months (hazard ratio [HR]: 4.32; 95% CI: 1.58-11.8) or with anemia at baseline (HR: 1.87; 95% CI: 1.24-2.81) were at increased risk for bleeding beyond the third month. Patients initially presenting with PE were at increased risk for PE recurrences (HR: 3.60; 95% CI: 1.28-10.1). Conclusion Prolonging anticoagulation beyond the third month was associated with more bleeds than PE recurrences. Prior bleeding, anemia, and initial VTE presentation may help decide when to stop therapy.

Eficacia y seguridad de rituximab en el tratamiento del síndrome antifosfolipídico primario: análisis de 24 casos a partir de la revisión de la bibliografía / Efficacy and safety of rituximab in the treatment of primary antiphospholipid syndrome: Analysis of 24 cases from the bibliography review

Fundamento y objetivo: El síndrome antifosfolipídico (SAF) se caracteriza por la presencia de anticuerpos antifosfolipídicos (AAF) y complicaciones trombóticas y/o obstétricas. Cuando no se asocia a ninguna otra enfermedad autoinmunitaria recibe el nombre de SAF primario. En algunas ocasiones, el tratamiento antitrombótico no es suficiente para evitar la recurrencia trombótica, y algunas manifestaciones clínicas no responden al tratamiento estándar. Rituximab puede ser una alternativa en estos casos. Nuestro objetivo fue revisar la evidencia científica publicada del uso de rituximab en el tratamiento del SAF primario. Pacientes y métodos: Descripción de un caso propio y revisión de la literatura médica con análisis descriptivo de las características demográficas, clínicas, analíticas, terapéuticas y evolutivas de los pacientes incluidos. Resultados: Se han identificado 24 pacientes (15 mujeres [62,5%]), con una edad media (DE) de 37,0 (13,4) años. Las indicaciones de uso de rituximab fueron trombocitopenia (41,7%), afectación cutánea (33,3%), afectación neurológica y valvular cardíaca (12,5%), anemia hemolítica (8,3%) y afectación pulmonar y renal (4,2%). El anticoagulante lúpico fue positivo en el 72,7% de los casos, los isotipos IgG e IgM de los anticuerpos anticardiolipina en el 75 y 50%, respectivamente, y los anticuerpos anti-β2GPI (IgG e IgM) en el 80%. Trece (54,1%) pacientes recibieron 2 dosis quincenales de 1.000 mg de rituximab, 10 (41,7%) 4 dosis semanales de 375 mg/m2, y uno (4,2%) 8 dosis semanales de 375 mg/m2. Once (45,8%) pacientes presentaron una respuesta clínica completa, 7 (29,2%) una respuesta parcial y 6 (25%) no experimentaron ningún cambio sustancial. Cuatro pacientes con mejoría clínica presentaron una reducción en el título de los AAF, y en uno, los valores no cambiaron. Un paciente sin respuesta clínica los mantuvo positivos. Existió una disociación clínico-analítica en un par de casos. Conclusiones: Los datos obtenidos evidencian un posible beneficio potencial de rituximab en el tratamiento de alguna de las manifestaciones clínicas del SAF primario, como la trombocitopenia, la afectación cutánea y la afectación valvular cardíaca (AU)

Background and objective: Antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) and thrombotic and/or obstetric manifestations. Patients without another associated autoimmune disease are considered to have primary APS. Some patients develop thrombosis recurrence despite anticoagulant treatment and some clinical features do not respond to standard therapy. Rituximab may be an alternative in these cases. We review the published scientific evidence on the use of rituximab in the treatment of primary APS. Patients and methods: Description of a case and review of the literature with descriptive analysis of the demographic, clinical, and immunologic features, treatment and outcome of patients. Results: We identified 24 patients (15 women [62.5%]), with a mean age of 37.0 ± 13.4 years. The reasons for the use of rituximab were thrombocytopenia (41.7%), skin involvement (33.3%), neurologic and heart valve involvement (12.5%), hemolytic anemia (8.3%) and pulmonary and renal involvement (4.2%). Lupus anticoagulant was present in 72.7% of the cases, the IgG and IgM isotypes of anticardiolipin antibodies in 75 and 50%, respectively, and the anti-β2GPI (IgG e IgM) antibodies in 80% of patients. Thirteen (54.1%) patients received 2 doses of 1,000 mg of rituximab fortnightly, 10 (41.7%) 4 doses of 375 mg/m2 weekly and one (4.2%) 8 doses of 375 mg/m2 weekly. Eleven (45.8%) patients presented a complete clinical response, 7 (29.2%) a partial response and 6 (25%) did not respond to rituximab. Four patients with clinical improvement presented with aPL titer decrease and in one patient, aPL levels did not change. In one patient without clinical response, aPL remained positive. A clinical-immunologic dissociation existed in 2 additional cases. Conclusions: The results obtained suggest a possible potential benefit of rituximab in the treatment of some clinical manifestations of primary APS such as thrombocytopenia, skin and heart valve involvement (AU)

[Efficacy and safety of rituximab in the treatment of primary antiphospholipid syndrome: analysis of 24 cases from the bibliography review]. / Eficacia y seguridad de rituximab en el tratamiento del síndrome antifosfolipídico primario: análisis de 24 casos a partir de la revisión de la bibliografía.

BACKGROUND AND OBJECTIVE: Antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) and thrombotic and/or obstetric manifestations. Patients without another associated autoimmune disease are considered to have primary APS. Some patients develop thrombosis recurrence despite anticoagulant treatment and some clinical features do not respond to standard therapy. Rituximab may be an alternative in these cases. We review the published scientific evidence on the use of rituximab in the treatment of primary APS. PATIENTS AND METHODS: Description of a case and review of the literature with descriptive analysis of the demographic, clinical, and immunologic features, treatment and outcome of patients. RESULTS: We identified 24 patients (15 women [62.5%]), with a mean age of 37.0 ± 13.4 years. The reasons for the use of rituximab were thrombocytopenia (41.7%), skin involvement (33.3%), neurologic and heart valve involvement (12.5%), hemolytic anemia (8.3%) and pulmonary and renal involvement (4.2%). Lupus anticoagulant was present in 72.7% of the cases, the IgG and IgM isotypes of anticardiolipin antibodies in 75 and 50%, respectively, and the anti-ß2GPI (IgG e IgM) antibodies in 80% of patients. Thirteen (54.1%) patients received 2 doses of 1,000 mg of rituximab fortnightly, 10 (41.7%) 4 doses of 375 mg/m(2) weekly and one (4.2%) 8 doses of 375 mg/m(2) weekly. Eleven (45.8%) patients presented a complete clinical response, 7 (29.2%) a partial response and 6 (25%) did not respond to rituximab. Four patients with clinical improvement presented with aPL titer decrease and in one patient, aPL levels did not change. In one patient without clinical response, aPL remained positive. A clinical-immunologic dissociation existed in 2 additional cases. CONCLUSIONS: The results obtained suggest a possible potential benefit of rituximab in the treatment of some clinical manifestations of primary APS such as thrombocytopenia, skin and heart valve involvement.