Cáncer de mama triple negativo, abortos a repetición e isquemia digital grave / Triple negative breast cancer, repeated abortions and severe digital ischemia

Resumen El presente caso corresponde a una mujer con antecedentes de tres abortos de menos de 10 semanas y cáncer de mama, que desarrolló isquemia digital grave luego del segundo ciclo de capecitabina. Se determinó la presencia de anticuerpos antifosfolipídicos positivos. Dado que las pacientes con síndrome antifosfolipídico obstétrico tienen incremento del riesgo de desarrollar neoplasia y que la isquemia digital grave puede ser la forma de presentación del síndrome antifosfolipídico en los pacientes con cáncer, se presenta el caso para remarcar el beneficio de pesquisar y realizar un diagnóstico temprano de estas características de la enfermedad.

Abstract The present case corresponds to a woman with history of three miscarrieges less than10 weeks and breast cancer, who develops severe digital ischemia after the second cycle of capecitabine. Positive antiphospholipid antibodies were determined. Patients with obstetric antiphospholipid syndrome have an increased risk of developing cancer, and severe digital ischemia could be an unusual form of presentation of the antiphospholipid syndrome in patients with cancer. This case is presented to highlight the benefit of researching and making an early diagnosis of these characteristics of the disease.

[Triple negative breast cancer, repeated abortions and severe digital ischemia]. / Cáncer de mama triple negativo, abortos a repetición e isquemia digital grave.

The present case corresponds to a woman with history of three miscarrieges less than10 weeks and breast cancer, who develops severe digital ischemia after the second cycle of capecitabine. Positive antiphospholipid antibodies were determined. Patients with obstetric antiphospholipid syndrome have an increased risk of developing cancer, and severe digital ischemia could be an unusual form of presentation of the antiphospholipid syndrome in patients with cancer. This case is presented to highlight the benefit of researching and making an early diagnosis of these characteristics of the disease.

El presente caso corresponde a una mujer con antecedentes de tres abortos de menos de 10 semanas y cáncer de mama, que desarrolló isquemia digital grave luego del segundo ciclo de capecitabina. Se determinó la presencia de anticuerpos antifosfolipídicos positivos. Dado que las pacientes con síndrome antifosfolipídico obstétrico tienen incremento del riesgo de desarrollar neoplasia y que la isquemia digital grave puede ser la forma de presentación del síndrome antifosfolipídico en los pacientes con cáncer, se presenta el caso para remarcar el beneficio de pesquisar y realizar un diagnóstico temprano de estas características de la enfermedad.

Niveles de anticuerpos anti-anexina A5 y manifestaciones de síndrome antifosfolípido primario obstétrico / Levels of anti-anexinal antibodies A5 and manifestations of obstetric primary antiphospholipid syndrome

El Síndrome Antifosfolípidos (SAF) describe un trastorno trombofílico autoinmune caracterizado por complicaciones obstétricas. La Anexina A5 (Anx A5) es una proteína que se estudia como un nuevo autoantígeno presente en el SAF, la presencia de autoanticuerpos frente a Anx A5 podría causar trombosis placentaria y pérdida del embarazo. El objetivo de este estudio fue analizar los niveles de IgG e IgM anti-Anx A5 en mujeres con SAF primario obstétrico y su asociación con diferentes complicaciones en una población de la ciudad de Córdoba. Se trabajó con muestras de pacientes puérperas que asistieron al Hospital Córdoba y al Hospital Materno Neonatal durante los años 2013-2017 con diagnóstico de SAF obstétrico y un grupo control formado por pacientes con embarazos normales. En la mayoría de las pacientes estudiadas, los niveles de IgG e IgM anti-Anx A5 se encontraron por debajo del rango de referencia, se mostró un aumento estadísticamente significativo de los niveles de IgG en pacientes con SAF respecto al grupo control. Pero no existieron asociaciones específicas entre los niveles de anticuerpo y los tres tipos de manifestaciones clínicas presentes en los criterios de clasificación. Estos hallazgos podrían sugerir una relación entre los anticuerpos anti-Anx A5 con el SAF obstétrico.

Antiphospholipid Syndrome (APS) describes an autoimmune thrombophilic disorder characterized by obstetric complications. Annexin A5 (Anx A5) is a protein that is studied as a new autoantigen present in APS, the presence of autoantibodies against Anx A5 could cause placental thrombosis and possibly pregnancy loss. The aim of this study was to analyze levels of IgG and IgM anti-Anx A5 in women with primary obstetric APS and its association with different complications in a population of the city of Córdoba. We worked with samples of puerperal patients who attended the Córdoba Hospital and the Maternal Neonatal Hospital during the years 2013-2017 with a diagnosis of obstetric APS and a control group formed by patients with normal pregnancies. In most of the patients studied, levels of IgG and IgM anti-Anx A5 were below the reference range, is demonstrate an increase statistically significant in the levels of the IgG in patients with APS compared with control group. But there were no specific associations between antibody levels and the three types of obstetric clinical manifestations present in the classification criteria. These findings could suggest a relationship between anti-Anx A5 antibodies and obstetric APS.

What is the best time to assess the antiphospholipid antibodies (aPL) profile to better predict the obstetric outcome in antiphospholipid syndrome (APS) patients?

Serological risk factors are the most important determinant in predicting unsuccessful pregnancy in obstetric antiphospholipid antibodies syndrome (OAPS) despite conventional treatment. It is not clear if changes in the profile of antiphospholipid antibodies (aPL) during pregnancy modify the risk associated with a poor response to conventional treatment. The aim of our study was to compare the value of a serological tag for aPL obtained before and during the first trimester of pregnancy to predict the response to conventional treatment. We carefully selected 97 pregnancies in women who were included in our study only if they were diagnosed with OAPS prior to a new pregnancy (basal serological risk), retested for aPL during the first trimester of pregnancy (serological risk during pregnancy), and treated with conventional therapy. High baseline serological risk was associated with pregnancy failure in 62.1% of cases (18/29) and predicted 82.5% of pregnancy outcomes with conventional treatment: OR = 16.9, CI = 5.5-52.1, p < 0.001. High serological risk during pregnancy was associated with pregnancy failure in 86.3% of cases (19/22) and predicted 91.8% of pregnancy outcomes with conventional treatment: OR = 88.7, CI = 19.4-404.8, p < 0.001. According to these results, we found that risk categorization performed during pregnancy was better in predicting pregnancy outcome (82.5 vs. 91.8%). Moreover, risk categorization during pregnancy had an increased specificity regarding the prediction: 84.9% at baseline and 95.9% during pregnancy (p = 0.024). Our findings suggest that it is important to perform aPL during the first trimester of pregnancy since that is the best time to establish the serological risk factors.

Aspirin: The Mechanism of Action Revisited in the Context of Pregnancy Complications.

Aspirin is one of the most frequently used and cheapest drugs in medicine. It belongs to the non-steroidal anti-inflammatory drugs with a wide range of pharmacological activities, including analgesic, antipyretic, and antiplatelet properties. Currently, it is accepted to prescribe a low dose of aspirin to pregnant women who are at high risk of preeclampsia (PE) because it reduces the onset of this complication. Another pregnancy alteration in which a low dose of aspirin is recommended is the obstetric antiphospholipid syndrome (APS). The most recognized mechanism of action of aspirin is to inhibit the synthesis of prostaglandins but this by itself does not explain the repertoire of anti-inflammatory effects of aspirin. Later, another mechanism was described: the induction of the production of aspirin-triggered lipoxins (ATLs) from arachidonic acid by acetylation of the enzyme cyclooxygenase-2. The availability of a stable analog of ATL has stimulated investigations on the use of this analog and it has been found that, similar to endogenously produced lipoxins, ATL resolves inflammation and acts as antioxidant and immunomodulator. If we consider that in PE and in the obstetric APS, there is an underlying inflammatory process, aspirin might be used based on the induction of ATL. The objective of this review is to revisit the old and new mechanisms of action of aspirin. In particular, it intends to show other potential uses of this drug to prevent certain pregnancy complications in the light of its ability to induce anti-inflammatory and pro-resolving lipid-derived mediators.