Recomendaciones para el abordaje clínico de pacientes con púrpura trombocitopénica trombótica / Recommendations for the diagnosis and treatment of patients with thrombotic thrombocytopenic purpura

La púrpura trombocitopénica trombótica (PTT) es una microangiopatía trombótica (MAT) caracterizada por el desarrollo de anemia hemolítica microangiopática, trombocitopenia y disfunción orgánica isquémica asociada a niveles de ADAMTS13 inferiores al 10% en la mayoría de los casos.Recientemente se han producido numerosos avances en el campo de la PTT. Se han desarrollado nuevas técnicas rápidas y accesibles capaces de cuantificar los niveles de ADAMTS13 y los posibles inhibidores. Los sistemas de secuenciación masiva del gen ADAMTS13 facilitan la identificación de polimorfismos en este gen. Además, han aparecido nuevos fármacos como caplacizumab y se plantean estrategias de prevención de recaídas con el uso de rituximab.Los registros de pacientes con PTT permiten ahondar en el conocimiento de esta enfermedad, pero la gran variabilidad en el diagnóstico y tratamiento hace necesaria la elaboración de un documento que homogenice la terminología y la práctica clínica.Las recomendaciones recogidas en el presente documento se han elaborado siguiendo la metodología AGREE. Las preguntas de investigación se formularon de acuerdo con el formato PICO. Se realizó una búsqueda bibliográfica de la literatura publicada durante los últimos 10 años. Las recomendaciones se establecieron por consenso entre todo el grupo puntualizando las fortalezas y limitaciones existentes de acuerdo al nivel de evidencia obtenido.En conclusión, en el presente documento se recogen recomendaciones sobre el tratamiento, diagnóstico y tratamiento de la PTT con el objetivo final de elaborar pautas basadas en la evidencia publicada hasta la fecha que permitan a los profesionales sanitarios optimizar el tratamiento de la PTT. (AU)

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) characterized by the development of microangiopathic haemolytic anaemia, thrombocytopenia, and ischaemic organ dysfunction associated with ADAMTS13 levels lower than 10% in most cases.Recently there have been numerous advances in the field of PTT, new, rapid and accessible techniques capable of quantifying ADAMTS13 activity and inhibitors. The massive sequencing systems facilitate the identification of polymorphisms in the ADAMTS13 gene. In addition, new drugs such as caplacizumab have appeared and relapse prevention strategies are being proposed with the use of rituximab.The existence of TTP patient registries allow a deeper understanding of this disease but the great variability in the diagnosis and treatment makes it necessary to elaborate guidelines that homogenize terminology and clinical practice.The recommendations set out in this document were prepared following the AGREE methodology. The research questions were formulated according to the PICO format. A search of the literature published during the last 10 years was carried out. The recommendations were established by consensus among the entire group, specifying the existing strengths and limitations according to the level of evidence obtained.In conclusion, this document contains recommendations on the management, diagnosis, and treatment of TTP with the ultimate objective of developing guidelines based on the evidence published to date that allow healthcare professionals to optimize TTP treatment. (AU)

Recommendations for the diagnosis and treatment of patients with thrombotic thrombocytopenic purpura. / Recomendaciones para el abordaje clínico de pacientes con púrpura trombocitopénica trombótica.

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) characterized by the development of microangiopathic haemolytic anaemia, thrombocytopenia, and ischaemic organ dysfunction associated with ADAMTS13 levels lower than 10% in most cases. Recently there have been numerous advances in the field of PTT, new, rapid and accessible techniques capable of quantifying ADAMTS13 activity and inhibitors. The massive sequencing systems facilitate the identification of polymorphisms in the ADAMTS13 gene. In addition, new drugs such as caplacizumab have appeared and relapse prevention strategies are being proposed with the use of rituximab. The existence of TTP patient registries allow a deeper understanding of this disease but the great variability in the diagnosis and treatment makes it necessary to elaborate guidelines that homogenize terminology and clinical practice. The recommendations set out in this document were prepared following the AGREE methodology. The research questions were formulated according to the PICO format. A search of the literature published during the last 10 years was carried out. The recommendations were established by consensus among the entire group, specifying the existing strengths and limitations according to the level of evidence obtained. In conclusion, this document contains recommendations on the management, diagnosis, and treatment of TTP with the ultimate objective of developing guidelines based on the evidence published to date that allow healthcare professionals to optimize TTP treatment.

Medication related osteonecrosis of the jaws (MRONJ): Factors related to recurrence after treatment with surgery and platelet rich plasma (PRP) placement / Osteonecrosis de los maxilares relacionada con medicamentos (MRONJ): Factores relacionados con la recurrencia después del tratamiento con cirugía y colocación de plasma rico en plaquetas (PRP)

Background: Medication-related osteonecrosis of the jaws (MRONJ) is a well-known complication associatedwith antiresorptive and antiangiogenic therapies. The purpose of this study was to analyse if there is any predic-tive factor of recurrence after local debridement plus platelet rich plasma (PRP) placement in MRONJ patients.Material and Methods: Seventy MRONJ patients treated at the department of Oral and Maxillofacial Surgery inLa Paz Hospital (Madrid, Spain) were included in this retrospective study. All of them were treated surgicallyby local debridement and PRP placement. The observation period was between January 2012 and January 2019.Information regarding use, type, administration, and duration of therapy with BP/denosumab was recorded. Thefollow-up period ranged from 2-52 months. A descriptive analysis, a bivariate and a multivariate study were per-formed.Results: Most of the patients were women (82.9%) between 50-70 years old (64.3%), with a stage II disease(74.3%). The therapy lasted more than 12 months in 54.8% of them. Zoledronic acid was the main antiresorptiveused (44.3%), followed by oral administered BPs (29 patients, 41.4%) and denosumab (10 patients, 14.3%). Oste-oporosis (48.6%), breast cancer (30%) and multiple myeloma (11.4%) were the main diseases because the patientswere taking antirresorptives. 13 patients (18.6%) experienced recurrence. We found that breast cancer patients(p>0.0001), smokers (p>0.016), and administration of zoledronic acid (p>0.0001) were related to recurrence.After performing the multivariate model, we found that the only factor related to recurrence was smoking habit(Wald 3.837, p=0.05, OR 6.12). Conclusions: recurrence after local debridement plus PRP placement in our MRONJ series affected to 18.6% ofpatients. It seems to be more frequent in breast cancer patients, smokers, and after zoledronic acid administration.Smoking habit was the only independent factor related to recurrence in our series.(AU)

In vitro thromboelastometric evaluation of the efficacy of frozen platelet transfusion.

BACKGROUND: Although frozen platelets are extensively used in remote locations and military environments, scientific evidence of their efficacy is scarce. The objective of this study was to evaluate the in vitro hemostatic efficacy of frozen versus fresh platelet transfusions by rotational thromboelastometry (ROTEM) to ascertain whether the freezing and thawing process impaired platelet contribution to clot strength. METHODS: An experimental study was performed using platelet in vitro transfusions. Blood samples were collected from 12 patients with non-autoimmune thrombocytopenia. The samples were each transfused with one of 6 pairs of fresh platelet concentrates and platelet concentrates frozen with dimethylsulfoxyde. Optical platelet counts, coagulation studies and ROTEM (EXTEM and FIBTEM) were performed for the baseline and the post-transfusion samples. RESULTS: Only fresh platelet transfusions significantly increased the EXTEM maximum clot firmness (MCF) and maximum clot elasticity (MCE) over baseline (p<0.001), achieving values within the normal range. The frozen platelet contribution to MCE was negligible. However, the EXTEM clotting time (CT) was significantly (p<0.001) shorter after the frozen platelet transfusion compared with the fresh platelet transfusion. The EXTEM clot formation time (CFT) was significantly shortened after the transfusion of fresh platelets (p=0.002). CONCLUSION: The ROTEM analysis assessment indicates a dual effect in frozen platelet transfusion: it produces a hypercoagulable state (shortening of CT), and a second, more predominant effect of frozen platelets' functionality impairment compared with fresh platelets (shorter MCF/MCE and longer CFT).

Hemocromatosis neonatal: tratamiento con inmunoglobulinas en la gestación / Neonatal haemochromatosis: treatment with immunoglobulins in pregnancy

La hemocromatosis neonatal (HN) es una enfermedad hepática grave neonatal con alta tasa demortalidad y recurrencia. Se postulaun origen a lo inmunitario, resultado de la presencia de un anticuerpo materno aún por determinar que interfiera con el metabolismo férrico fetal. En esta teoría se basa el tratamiento materno con inmunoglobulinas por vía intravenosa en gestaciones sucesivas. Describimos el caso de una paciente con un hijo anterior diagnosticado y fallecido por HN, que tratamos en la siguiente gestación con inmunoglobulinas por vía intravenosa. Es el primer caso descrito en España y demuestra el éxito de la terapia, tal como describe la literatura científica (AU)

Neonatal hemochromatosis is a severe neonatal liver disease with a high mortality and recurrence rate. In theory, it is a gestational alloimmune disease due to there being maternal antibodies against fetal hepatic metabolism. On the basis of this hypothesis, the administration of intravenous immunoglobulin has been reported as a succesful treatment during subsequent pregnancies. Here, we describe the first case of this treatment in Spain which confirms the data available in the literature (AU)

Nueva terapia con inmunoglobulinas en un caso de hemocromatosis neonatal / Immunoglobulin therapy for natal hemochromatosis

La hemocromatosis neonatal es una enfermedad hepática muy severa del recién nacido y se asocia a una alta mortalidad. Se cree que su etiología es de tipo aloinmune, debido a la presencia de un anticuerpo materno hasta ahora desconocido que interfiere con el metabolismo férrico del feto, llegando a producir gran morb i mortal ¡dad. Basándonos en esta teoría, el tratamiento materno con inmunoglobulinas intravenosas en gestaciones sucesivas podría prevenir el desarrollo de un nuevo cuadro de hemocromatosis neonatal. Se describe el caso de una gestante con un hijo anterior diagnosticado y fallecido neonatalmente por hemocromatosis, a la que en el embarazo actual se le trató con inmunoglobulinas intravenosas consiguiendo un hijo sano y vivo. Es el primer caso descrito en España y demuestra el éxito de esta terapia, tal como describe la literatura.

Neonatal hemochromatosis is a severe neonatal liver disease with a high mortality and recurrence rate. It is supposed to be a gestational alloimmune disease because of the existence of maternal antibodies against fetal hepatic metabolism. On the basis of this hypothesis, the administration of intravenous immunoglobulin has been reported as a successful treatment during the following pregnancy. We describe the first case of this treatment in Spain which confirms the data available in the literature.

Oral surgery in patients undergoing oral anticoagulant therapy.

UNLABELLED: There is an evident need for procedural protocol for oral surgery patients who undergo oral anticoagulant treatment (OAT) because of: 1) the possible severity of complications and 2) the growing demand for OAT, which in some cases may be as much as 8% of the oral surgery patients that are referred to the hospital from primary care centers. In this study, the authors define the parameters for creating a proto- col applicable to this group of patients. The conclusion is that it is not necessary to suspend OAT before surgery; rather, these procedures should be performed under multidisciplinary medical control. OBJECTIVE: The authors demonstrate that it is possible to perform oral surgery on OAT patients, without having to sus- pend treatment beforehand. STUDY DESIGN: A longitudinal study was performed in OAT patients that required some type of oral surgical procedures. After an INR control, the patient underwent surgery and afterwards the patient was given tranexamic acid as a mouth rinse. Postoperative hemorrhage was classified as slight when it lasted less than 5 minutes, moderate when it lasted longer than five minutes, and severe when it required blood transfusion. RESULTS: The study was performed over a 5-year period (1996-2000), by the maxillofacial surgery department. In that time period, 125 patients with OAT were treated; 90 of them were males and 35 were females. Tooth extraction was per- formed in 229 sessions and a total of 367 teeth were extracted, with an average of 1.6% per session. With regards to postoperative hemorrahage, it was slight in 210 cases (91.7%), moderate in 18 (7.9%) and severe only in one case (0.4%). All the variables were compared and no statistically significant differences were found. CONCLUSIONS: We believe that OAT should not be suspended before oral surgery, but it surgery should be performed under multidisciplinary control-especially in the case of the elderly (over 65) or with those patients that have other concomitant illnesses such as renal insufficiency or anemia or other medical treatments.

Cirugía oral en pacientes en tratamiento con anticoagulantes orales. Pauta de actuación / Oral surgery in the patients undergoing oral anticoagulant therapy

Hay una necesidad evidente de protocolizar los procedimientos de cirugía oral en pacientes sometidos a tratamiento anticoagulante por vía oral (TAO), tanto por la gravedad de las complicaciones como por la frecuencia creciente de la demanda, que puede cuantificarse en algunos casos en el 8 por ciento de los pacientes referidos desde atención primaria al hospital para tratamiento quirúrgico oral. En este estudio se definen los parámetros para crear un protocolo aplicable a este grupo de pacientes. Se concluye que los pacientes en TAO no deben suspenderlo previamente a la cirugía oral si bien debería realizarse con control multidisciplinario. especialmente si se trata de mayores de 65 años o con patología concomitante como insuficiencia renal o anemia o con otros tratamientos médicos, Objetivo: Pretendemos demostrar que es posible la realización de cirugía oral en pacientes anticoagulados, sin necesidad de retirar el tratamiento previamente. Diseño del estudio: Se realizó un estudio longitudinal en aquellos pacientes que precisaron algún procedimiento quirúrgico a nivel oral de los que estaban en TAO. Tras un con trol de INR se procedía a la intervención quirúrgica y posteriormente se suministraba al paciente ácido tranexámico para enjuagues bucales. La hemorragia postoperatoria se catalogó leve cuando el sangrado fue inferior a 5 minutos, moderado mavor de 5 minutos e intenso cuando se precisó transfusión. Resultados: Durante 5 años (1996-2000) se atendieron en nuestro Servicio 125 pacientes con TAO, 90 hombres y 35 mujeres, a los que se les exodonciaron 367 piezas dentarias, en 229 sesiones, con una media de 1,6 exodoncias por sesión. Con respecto a la hemorragia postoperatoria, fue leve en 210 casos (91,7 por ciento), moderada en 18 (7,9 por ciento) y grave en un solo caso (0,4 por ciento).Se compararon todas las variables observándose que no existieron diferencias estadísticamente significativas. Conclusiones: Consideramos que el TAO no debe suspenderse previamente' a la cirugía oral si bien debería realizarse bajo control multidisciplinario, especialmente si se trata de mayores de 65 años o con patología concomitante como insuficiencia renal o anemia o con otros tratamientos médicos (AU)