Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total neoadjuvant therapy of locally advanced rectal cancer: the preliminary single-center findings of a prospective, multicentre, randomized phase II trial (TORCH) / 中华胃肠外科杂志

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.

Relatório de recomendação para adoção de um protocolo estadual para atendimento de casos suspeitos ou confirmados de síndrome de trombose com trombocitopenia (STT) associada à vacinação com as vacinas de vetor de adenovírus não replicante contra a covid-19 em Santa Catarina / Recommendation report for the adoption of a state protocol for the care of suspected or confirmed cases of thrombosis syndrome with thrombocytopenia (STT) associated with vaccination with non-replicating adenovirus vector vaccines against covid-19 in Santa Catarina

Este relatório refere-se à análise crítica dos documentos apresentados pelo CRIE/DIVE/SES/SC para a elaboração de um Protocolo Estadual de atendimento para casos de Síndrome de Trombose com Trombocitopenia (STT) associada à vacinação com vacinas de vetor de adenovírus não replicante contra a COVID-19, baseados na Nota Técnica CGPNI/DEIDT/SVS/MS nº 933/2021. Na Nota Técnica emitida pelo Ministério da Saúde consta uma breve contextualização, a investigação da STT, protocolo de investigação laboratorial, manejo clínico de casos e definição de casos para investigação de STT. O documento enviado pelo CRIE/DIVE/SES/SC intitulado "Fluxograma de Atendimento TTS" apresentou os dados da nota supracitada resumidos com a adição de um fluxograma de atendimento hospitalar. Este relatório visa avaliar e emitir um parecer técnico embasado em evidências científicas sobre a disponibilização dos medicamentos Imunoglobulina Humana intravenosa (IGHIV) e Rivaroxabana para o tratamento de STT, fluxo de aces o aos medicamentos e avaliação do impacto orçamentário, para posterior elaboração de um Protocolo Estadual para esta síndrome, destinado aos profissionais da saúde, pacientes e gestores do estado de Santa Catarina.

Síndrome do anticorpo antifosfolípide e trombocitopenia induzida por heparina: relato de caso / Antiphospholipid antibody syndrome and heparin-induced thrombocytopenia: a case report

RESUMO A Síndrome do Anticorpo Antifosfolípide (SAAF) é uma trombofilia mediada por autoanticorpos protrombóticos responsáveis por aumentar o risco de complicações cardiovasculares e obstétricas. O diagnóstico de SAAF requer elevação de pelo menos um dos autoanticorpos antifosfolipídeos acompanhado de pelo menos um evento de trombose vascular e/ou morbidade gestacional. A Trombocitopenia Induzida por Heparina (HIT) é uma reação medicamentosa adversa protrombótica na qual a heparina forma complexos com fator plaquetário 4, formando neoantígenos que são reconhecidos pelos autoanticorpos. Apresentamos um caso raro de HIT associado à SAAF com tromboembolismo venoso recorrente apesar de anticoagulação. PALAVRAS-CHAVE: Síndrome do anticorpo antifosfolípide, trombose, trombocitopenia induzida por heparina

ABSTRACT Antiphospholipid Antibody Syndrome (APS) is a thrombophilia mediated by prothrombotic autoantibodies responsible for increasing the risk of cardiovascular and obstetric complications. The diagnosis of APS requires elevation of at least one of the antiphospholipid autoantibodies accompanied by at least one event of vascular thrombosis and/or gestational morbidity. Heparin-Induced Thrombocytopenia (HIT) is a prothrombotic adverse drug reaction in which heparin forms complexes with platelet factor 4, forming neoantigens that are recognized by autoantibodies. We present a rare case of HIT associated with APS with recurrent venous thromboembolism despite anticoagulation. KEYWORDS: Antiphospholipid syndrome, thrombosis, heparin-induced thrombocytopenia

Efectividad de Rituximab en el tratamiento de citopenias autoinmunes refractarias en adultos / Effectiveness of Rituximab in the treatment of cytopenias refractory autoimmune in adults

The term autoimmune cytopenias is referred to a heterogeneous group of diseases characterized by a reduced peripheral blood cell counts in one or more cellular series, because an immunological disorder. The first line therapy is steroids, followed by splenectomy or immunesupressant therapy in non-responders. Rituximab is an anti CD20 monoclonal antibody used as a third line in refractory patients or as an alternative to splenectomy. We present a retrospective study of nine patients with autoimmune cytopenias treated in a public hospital setting with rituximab. Five patients with the diagnosis of inmune thrombocytopenic purpura received it, all of them achieved hematological response (4 complete and one partial). The median time to the best response was 6 weeks, staying in this category after 6 months of follow up. Four patients with autoimmune hemolytic anemia received rituximab, three of them achieving partial response and one was lost from follow up. No severe adverse effects related to rituximab were registered.

Miocardiopatia não compactada em gestante com linfoma não Hodgkin. Relato de caso / Non-compaction cardiomyopathy in pregnant women with non-Hodgkin lymphoma: a case report

A miocardiopatia não compactada é uma doença congênita rara, que pode ocorrer isoladamente ou associada a outros defeitos, por falha no processo de compactação das fibras miocárdicas, resultando na persistência de trabeculações e recessos profundos. A associação entre a miocardiopatia não compactada e gestação é incomum na literatura, assim como a relação com macroglobulinemia de Waldenstrom, um tipo de linfoma não Hodgkin. Descrevemos aqui a rara associação destas três patologias. Trata-se de paciente do sexo feminino, sem antecedentes hematológicos, neoplasias ou cardiopatias, que procurou o serviço com queixa de astenia progressiva, dores no corpo, perda ponderal importante e anemia. Na investigação diagnóstica, a imunoeletroforese de proteína constatou pico monoclonal em IgM Kappa, com inventário medular por imunofenotipagem e biópsia de medula óssea com Kappa+, CD19+, CD20+, CD38 e CD79b, confirmando diagnóstico de neoplasia de linfócitos B maduros. Na terapêutica, optou-se pelo esquema de primeira linha com dexametasona, rituximabe e ciclofosfamida (DRC) − este último considerado agente alquilante cardiotóxico. Em triagem pré-quimioterápica, o eletrocardiograma mostrou alteração da repolarização ventricular anterosseptal. O ecocardiograma transtorácico evidenciou trabeculações excessivas no ápice do ventrículo esquerdo, sugerindo não compactação do miocárdio. A ressonância magnética confirmou o diagnóstico. Foi iniciada terapia com metoprolol e ácido acetilsalisílico. Todavia, após o último ciclo de terapia quimioterápica, paciente descobriu gravidez (G1P1A0). O período gestacional e o puerpério evoluíram sem manifestações clínicas de insuficiência cardíaca, em classe funcional I (New York Heart Association), mesmo com redução da fração de ejeção do ventrículo esquerdo ao ecocardiograma transtorácico. (AU)

Non-compaction cardiomyopathy is a rare congenital disease that can occur in isolation or associated with other defects, due to failure in compaction of myocardial fiber, resulting in persistence of myocardial trabeculations and deep recesses. The association between non-compaction cardiomyopathy and gestation, as well as the relationship with Waldenstrom's macrobulinemia, a type of Non-Hodgkin's Lymphoma (NHL), are not common in the literature. This study describes the rare association of these three pathologies. This is the case of a female patient with no history of hematological, neoplastic, or heart diseases, who sought the service with complaints of progressive weakness, body aches, important weight loss, and anemia. During the diagnostic investigation, protein immunoelectrophoresis showed a monoclonal peak in IgM Kappa monoclonal gammopathy, with a medullary inventory by immunophenotyping and bone marrow biopsy with Kappa+, CD19+, CD20+, CD38 and CD79b, confirming the diagnosis of mature B-cell lymphocyte neoplasm. The first line therapy chosen was dexamethasone, rituximab, and cyclophosphamide (CKD), with the latter being considered a cardiotoxic alkylating agent. At pre-chemotherapy screening, the electrocardiogram showed an alteration of the anteroseptal ventricular repolarization. Transthoracic echocardiography (ETT) showed excessive trabeculations at the apex of the left ventricle (LV), suggesting no compaction of the myocardium. The magnetic resonance imaging confirmed the diagnosis.Therapy with metoprolol and acetylsalicylic acid was started. However, after the last cycle of chemotherapy, the patient found she was pregnant (G1P1A0). The gestational and puerperium period progressed with no clinical manifestations of heart failure, in functional class I (New York Heart Association), albeit the reduction of the ejection fraction of the left ventricular shown in the transthoracic echocardiography. (AU)

Rivaroxaban para el tratamiento de la trombocitopenia inducida por heparina: caso clínico / Treatment of heparin-induced thrombocytopenia with rivaroxaban: case report

Heparin-induced thrombocytopenia (HIT) is immune-mediated. It occurs more frequently with unfractionated heparin (UFH) than with low molecular weight heparins (LMWH). It is associated with thromboembolic rather than hemorrhagic events, as opposed to thrombocytopenia of other etiologies. The key in therapy is the cessation of heparin and the start of another anticoagulant. We report a 58 years old female with HIT secondary to the use of Enoxaparin who was successfully managed with Rivaroxaban. Our goal is to report a novel therapy and provide the evidence that supports its use.

Trombocitopenia inducida por heparina: Nuevas opciones terapéuticas / Heparin-induced thrombocytopenia. New therapeutical options

La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica mediada por la formación de anticuerpos contra el complejo heparina-factor plaquetario 4 (FP4), caracterizada por la presencia de trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es una complicación poco frecuente pero grave del uso de cualquier tipo de heparina. En tratados con procedimientos cardiovasculares como intervención coronaria percutánea y cirugía de revascularización cardiaca, la prevalencia de anticuerpos es significativamente mayor que en otros escenarios clínicos. El reconocimiento de las características clínicas y de laboratorio permite la suspensión inmediata de la heparina y la instauración de tratamiento anticoagulante alternativo, para evitar la progresión y formación de nuevos trombos y sus complicaciones. En la presente revisión se resumen las diferentes alternativas terapéuticas para la TIH, en particular los anticoagulantes orales directos (DOACS) como el dabigatran, rivaroxaban y apixaban que pueden proporcionar una nueva opción para el tratamiento de TIH.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.

Seguridad y eficacia de rituximab en el tratamiento detrombocitopenia inmune refractaria al tratamiento estándar en pacientes con diagnóstico de lúpus eritematoso sistémico / Safety and efficacy of rituximab in the treatment of immune defrombocytopenia refractory to standard treatment in patients with systemic lupus erythematosus

INTRODUCCIÓN: Antecedentes: El presente dictamen expone la evaluación del medicamento rituximab con relación a su uso en pacientes con trombocitopenia inmune secundaria a lupus eritematoso sistémico refractario a tratamiento con glucocorticoides, inmunosupresores e inmunoglobulinas. Aspectos Generales: El lupus es una enfermedad autoinmune crónica, en la cual el cuerpo ataca a las células sanas, mediante la producción de anticuerpos específicos para componentes del núcleo de la célula(1). Esta enfermedad afecta las células de distintos tejidos y órganos tales como la piel, riñones, corazón, pulmones, cerebro, vasos sanguíneos y articulaciones, ocasionando diversas manifestaciones clínicas tales como rash, artritis, serositis, nefritis, convulsiones, psicosis, anemia hemolítica y citopenia (e.g., trombocitopenia). Tecnología Sanitaria de Interés: Rituximab: Rituximab es un anticuerpo monoclonal quimérico que tiene como blanco el antígeno de transmembrana (CD20) expresado en los estadios intermedios de maduración de los linfocititos. Una vez que este anticuerpo se une a CD20 bloquea su activación y diferenciación, lo que resulta en la eliminación de los linfocitos b, las células B de memoria y las células plasmáticas de vida corta; disminuyendo especialmente su función como célula presentadora de antígenos (APC por sus siglas en inglés). Asimismo, la disminución de linfocitos B modifica los niveles de linfocitos T reguladores, los cuales se encargan de modular la respuesta inmune, lo cual podría suponer un beneficio clínico. Por último, la disminución de las citoquinas producida por los linfocitos B también podría estar involucrada en el mecanismo de acción de rituximab. METODOLOGÍA: Estrategia de Búsqueda: El paciente que inspiró la presente pregunta PICO tiene un diagnóstico de LES con complicaciones hematológicas, específicamente trombocitopenia, que ha progresado a tratamiento con glucocorticoides, inmunoglobulina e inmunosupresores. Debido a las diferentes formas de abordar la condición de interés y con la finalidad de lograr ser lo más sensibles posibles a la hora de incluir evidencia que permita responder a la pregunta PICO original del presente dictamen, se consideraron tres preguntas PICO finales, las cuales incluyen 1) pacientes con LES, 2) pacientes con ITP (i.e., trombocitopenia inmune por cualquier causa) y 3) pacientes con trombocitopenia secundaria a LES. Si bien la pregunta PICO original parecería encajar mejor con la tercera opción de pregunta PICO final (i.e., pacientes con trombocitopenia secundaria a LES), se consideró una pregunta que incluyera pacientes con ITP de forma general, contemplando la posibilidad de que la trombocitopenia fuese concomitante y no secundaria a LES. Asimismo, se consideró otra pregunta PICO considerando toda la población con LES, para así lograr tener más sensibilidad al momento de seleccionar los estudios a incluir en la presente evaluación, sin riesgo de perder especificidad, ya que de igual modo se incluyeron a pacientes con ITP y con trombocitopenia secundaria a LES. Es por ello que se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de rituximab para el tratamiento de lupus eritematoso sistémico (LES), trombocitopenia inmune (ITP) y trombocitopenia inmune secundaria a lupus eritematosos sistémico (ITP asociada a LES). Estas búsquedas se realizaron en las bases de datos de MEDLINE y TRIPDATABASE. Una vez identificado los artículos que respondían a las tres preguntas PICO, se pasó a revisar la bibliografía incluida en dichos artículos seleccionados, con la finalidad de identificar algún artículo no identificado previamente en la búsqueda inicial. Adicionalmente, se hizo una búsqueda complementaria en www.clinicaltrials.gov, para poder identificar ensayos aún en elaboración o que no hayan sido publicados. Asimismo, se realizó una búsqueda dentro de bases de datos pertenecientes a grupos que realizan revisiones sistemáticas, evaluación de tecnologías sanitarias y guías de práctica clínica. RESULTADOS: La búsqueda bibliográfica y de evidencia científica para el sustento del uso de rituximab se expandió para considerar de forma amplia la población de las tres preguntas consideradas en la presente evaluación, considerando a pacientes que fueran refractarios a tratamiento que incluyen glucocorticoides, inmunoglobulinas e inmunosupresores. Primero, se realizó una búsqueda bibliográfica y de evidencia científica para el sustento del uso de rituximab como tratamiento de LES en pacientes refractarios a tratamiento estándar (los cuales incluyen glucocorticoides e inmunosupresores). Luego se realizó una búsqueda en pacientes con trombocitopenia inmune idiopática refractarios a tratamiento estándar (incluyendo también glucocorticoides e inmunoglobulina humana intravenosa). Por último, se realizó una búsqueda en pacientes con trombocitopenia inmune secundaria a LES. Con respecto a esta última búsqueda (i.e., pacientes con trombocitopenia inmune secundaria a LES) no se encontraron guías, evaluaciones de tecnología sanitaria, revisiones sistemáticas, ni ensayos clínicos específicos para esta población en particular. Sin embargo, sí se encontró una GPC de LES que menciona el tratamiento para pacientes con manifestaciones hematológicas. Asimismo, cierta información de la evidencia encontrada para LES e ITP podría también ser aplicable a pacientes con LES que manifiestan trombocitopenia. Así, se presenta la evidencia disponible, de dos de las tres preguntas PICO consideradas en el presente dictamen (i.e., para población con LES y para población con ITP), en guías de práctica clínica, evaluación de tecnologías sanitarias, revisiones sistemáticas/meta-análisis y ensayos clínicos. CONCLUSIONES: A la fecha, la evidencia encontrada sugiere que rituximab no supone un beneficio adicional al ya adquirido frente a la terapia estándar para LES e ITP. Así, no es posible justificar el uso de rituximab como una alternativa eficaz para el tratamiento de LES ni de ITP en pacientes refractarios a terapia convencional (e.g., glucocorticoides, inmunosupresores e inmunoglobulina). Adicionalmente, en la búsqueda realizada no se ha encontrado evidencia del uso de rituximab en pacientes con ITP secundaria a LES. Sin embargo, se considera que existe plausibilidad biológica para extrapolar la evidencia encontrada en pacientes con LES y con ITP, como evidencia indirecta para pacientes con ITP secundaria a LES refractarios a tratamiento convencional. Por lo tanto, tampoco se puede sustentar el uso de rituximab como alternativa eficaz para dichos pacientes. El Instituto de Evaluación de Tecnologías en Salud e Investigación- IETSI, no aprueba el uso de rituximab para el tratamiento de LES, ITP ni de ITP secundaria a LES en pacientes refractarios a terapia estándar.

Tratamiento exitoso con fondaparinux en trombocitopenia inducida por heparina y trombosis / Successful treatment with fondaparinux in heparin-induced thrombocytopenia and thrombosis

La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica caracterizada por trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es causada por la formación de anticuerpos IgG contra el complejo multimolecular de heparina-factor plaquetario 4 (FP4). Fondaparinux es un inhibidor selectivo del factor Xa que tiene escasa afinidad por el FP4 y posee un menor potencial para inducir una respuesta inmunológica, haciendo del mismo un agente potencialmente útil en el tratamiento de la TIH. Se presenta el caso de una mujer de 73 años con TIH asociada a fenómenos trombóticos arteriales y venosos, que recibió exitosamente fondaparinux, con normalización del recuento plaquetario y sin progresión trombótica.

Heparin induced thrombocytopenia (HIT) is an immune-mediated adverse reaction characterized by thrombocytopenia and paradoxical arterial or venous thrombosis, due to the formation IgG antibodies directed to a multimolecular complex of heparin-platelet factor 4 (PF4). Fondaparinux is a selective factor Xa inhibitor with little affinity for PF4 and thus less likely to induce an immune response, making fondaparinux a potentially useful drug for the treatment of HIT. Herein we report the case of a 73 years old woman with HIT associated with arterial and venous thrombosis that was successfully treated with fondaparinux, with normalization of the platelet countand without progression of thrombosis.

A Pilot Study to Evaluate the Effectiveness of Carica Papaya Leaf Extract in Increasing the Platelet Count in Cases of Dengue with Thrombocytopenia.

The pilot study was conducted to investigate the platelet increasing property of Carica papaya leaf extract (CPLE) in patients with dengue fever (DF). An open labeled randomized controlled trial was carried out at two centres of Bangalore metropolis on 30 subjects in patients with thrombocytopenia associated with dengue. The subjects were randomized into two groups, as control and intervention group. Both the groups were managed by the standard management guidelines for dengue except steroid administration. In addition to this, the intervention group received CPLE tablet three times daily for five days. All of them were followed daily with platelet monitoring. The results showed that CPLE had significant increase in the platelet count (p<0.003) over the therapy duration, in dengue fever patients, reiterating that it accelerates the increase in platelet count compared to the control group. There were few adverse events related to GI disturbance like nausea and vomiting which were similar in both groups. Thus this study concluded that Carica papaya leaf extract (CPLE) does significantly increase the platelet count in patients with thrombocytopenia associated with dengue with fewer side effects and good tolerability.

Randomized clinical trial of human interleukin-11 in dengue fever-associated thrombocytopenia

To assess the effectiveness of recombinant human [rh] IL-11 to increase platelets count in patients suffering from Dengue fever [DF]. Randomized double blind placebo control study. Farooq Hospital, Lahore, from July to October 2011. Forty hospitalized patients suffering from Dengue fever having platelets count A[2] 30000 per micro liter were randomly categorized into two groups, rhIL-11 [test] and distilled water [placebo] groups. The efficacy outcomes [as indicated by step up in platelets count at 48 hours] for the treatment group were compared with the outcomes for the placebo group. The data revealed that the increase in platelet response with recombinant human interleukin 11, 1.5 mg subcutaneously is significantly more brisk than the placebo group. The platelets response in patients with severe thrombocytopenia was greater in the treatment group [50%] at 48 hours as compared to the placebo group [20%] [p=0.047]. Response rate was slightly greater among males [6/10, 60%] than females [8/16, 50%]; moreover, three-fourth [75%] female responders were in the placebo group, compared to half [50%] male responders in the treatment group. Results of the study suggest that treatment of severe thrombocytopenia accompanying DF with recombinant human interleukin11 may be a useful therapeutic option

Trombocitopenia inmune primaria refractaria: opciones terapéuticas / Refractory primary immune thrombocytopenia: treatment options

La trombocitopenia inmune primaria (PTI) es un trastorno autoinmune adquirido caracterizado por una disminución transitoria o persistente del recuento de plaquetas con riesgo incrementado de sangramiento. La forma crónica de la enfermedad afecta fundamentalmente a los adultos. Puesto que las remisiones espontáneas son muy poco frecuentes, los pacientes son tratados desde el inicio, usualmente con esteroides. Aproximadamente un tercio de los casos no responden a los regímenes esteroideos y el tratamiento de segunda línea es la esplenectomía, tratamiento con el que se logran las mayores tasas de curación. Sin embargo, entre el 10 y el 30 por ciento de los pacientes no responden a la exéresis quirúrgica del bazo, que constituyen el grupo de pacientes con PTI crónica refractarios al tratamiento. No existen evidencias sobre cuál esquema terapéutico es el más efectivo en estos casos, por lo que el tratamiento continúa siendo empírico. En este trabajo se revisan las diferentes opciones terapéuticas que pueden ser utilizadas en la PTI crónica refractaria, el mecanismo de acción de las drogas, las dosis y los efectos adversos más frecuentes

The primary immune thrombocytopenia (PIT) is an acquired autoimmune disorder characterized by transient or persistent decreased platelet count with increased risk of bleeding. The chronic form of this disease primarily affects adults. Since spontaneous remissions are rare, patients usually are treated with steroids from the start. Approximately one third of the cases does not respond to steroid regimens; the second-line treatment is splenectomy, achieving the highest cure rates. However, between 10 to 30 percent of patients do not respond to spleen surgical removal, which is the group of patients with refractory chronic PIT. There is no evidence on whether this therapeutic regimen is most effective in these cases, so the treatment remains empirical. In this paper, various treatment options that can be used in refractory chronic PIT, the action mechanism of drugs, doses and more frequent adverse effects were reviewed

Successful rituximab therapy in refractory autoimmune hepatitis and Evans syndrome / Tratamiento exitoso de hepatitis autoinmune y síndrome de Evans con rituximab

A 44-year-old woman was found to have elevated aminotransferases, twice the upper limit of normal. Liver biopsy demonstrated a mixed inflammatory process suggestive of both primary biliary cirrhosis and autoimmune hepatitis (AIH). Prednisone and azathioprine were started, with normalization of aminotransferases. Six months later, she returned with worsening pruritus and re-evaluation demonstrated probable reactivation of AIH with acute elevation of liver injury tests. Repeat liver biopsy was suggestive of a flare of AIH which did not respond to prednisone, azathioprine, or mycophenolate mofetil. One month later the patient was hospitalized for sudden onset of anemia and thrombocytopenia, suggestive of autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura consistent with Evans syndrome. Rituximab was initiated and mycophenolate mofetil discontinued. After one infusion of rituximab, liver injury tests significantly improved. Within four weeks of rituximab infusion (4 doses) the patient's Evans syndrome completely resolved with normal hemoglobin and platelet levels; aminotransferases also significantly improved to less than twice the upper limit of normal.

Management of acquired thrombophilic disorders in 2011: focus on heparin-induced thrombocytopenia, antiphospholipid syndrome, myeloproliferative neoplasms and paroxysmal nocturnal hemoglobinuria

Arterial and venous thrombosis are interrelated disorders at the interplay of platelets and fibrin. Arterial thrombi are platelet-rich and occur at sites vulnerable to atherosclerotic plaque rupture where blood shear rates are high; on the contrary, venous thrombi occur in association with slow blood flow and shear rates. These differences may underlie why anti-platelet agents are more effective in prevention of arterial thrombosis, while anticoagulants are preferred for venous thrombosis. Although some common thrombophilic disorders [e.g., Factor V Leiden, prothrombin gene mutation, etc.] are almost exclusively associated with venous thromboembolism, there are several disorders that are important to consider when caring for patients with both arterial and venous thromboembolism. This article will review the evidence-based management of heparin induced thrombocytopenia with thrombosis, anti-phospholipid antibody syndrome and catastrophic anti-phospho-lipid antibody syndrome, thrombohemorrhagic manifestations of Philadelphia chromosome-negative chronic myeloproliferative neoplasms including polycythemia vera, essential thrombocythemia and primary myelofibrosis, as well as paroxysmal nocturnal hemoglobinuria

Considerations in the management of hepatitis c virus-related thrombocytopenia with eltrombopag

Thrombocytopenia is a common clinical problem in HCV-infected cases. Multiple studies have consistently shown a rise in platelet count following a successful HCV treatment thus proving a cause-effect relationship between the two. Although, many therapeutic strategies have been tried in the past to treat HCV-related thrombocytopenia [e.g. interferon dose reductions, oral steroids, intravenous immunoglobulins, splenectomy etc], the success rates have been variable and not always reproducible. After the cessation of clinical trials of PEG-rHuMGDF due to immunogenecity issues, the introduction of non-immunogenic second-generation thrombopoietin-mimetics [eltrombopag and Romiplostim] has opened up a novel way to treat HCV-related thrombocytopenia. Although the data is still sparse, eltrombopag therapy has shown to successfully achieve the primary endpoint platelet counts of >/= 50, 000/micro L in phase II and III, randomized, double-blind, placebo-controlled trials. Likewise, though it is premature to claim safety of this drug especially in high-risk patient groups, reported side effects in the published literature were of insufficient severity to require discontinuation of the drug. Based on the current and emerging evidence, a review of the pharmacologic basis, pharmacokinetics, therapeutic efficacy, safety profile and future considerations of eltrombopag in the context of HCV-related thrombocytopenia is given in this articfie. A MEDLINE search was conducted [1990 to August 2009] using the search terms eltrombopag, HCV, thrombocytopenia

Successful Treatment of Refractory Thrombocytopenia with Mycophenolate Mofetil in a Patient with Systemic Lupus Erythematosus

While mild thrombocytopenia in systemic lupus erythematosus (SLE) is frequently seen in the context of active disease, severe thrombocytopenia causing significant bleeding is not that common. Corticosteroids are considered the first line therapy for severe thrombocytopenia in SLE. Second-line therapeutic agents or splenectomy have been reported to be effective for patients who fail to respond to steroids or those who require moderate doses of steroids to maintain the platelet counts. Recent randomized controlled studies have shown that mycophenolate mofetil (MMF) is an efficacious and safe therapeutic agent in patients with proliferative forms of lupus nephritis. However, little information has been available regarding the role of MMF in the treatment of immune thrombocytopenia complicated with SLE. Hereby I describe a patient with SLE in whom thrombocytopenia was refractory to corticosteroids, intermittent intravenous cyclophosphamide, azathioprine, cyclosporine, intravenous gamma globulin, danazol, and splenectomy, and whose platelet counts eventually normalized during therapy with MMF. In this patient, thrombocytopenia is initially thought to be associated with active SLE involving major organ. However, after immunosuppressive agents were given, the refractory nature of thrombocytopenia seems to be an isolated phenomenon, independently of SLE activity.

Eptifibatide-induced profound thrombocytopenia.

We report a case of profound thrombocytopenia, 2 hours following eptifibatide therapy which got reversed within 12 hours of discontinuation of eptifibatide.