Recent Advances in SARS-CoV-2-Induced Immune Thrombocytopenia --Review / 中国实验血液学杂志

SARS-CoV-2-induced immune thrombocytopenia (SARS-CoV-2-induced ITP) is an autoimmune disease secondary to virus infections. Its diagnosis is often based on exclusion of other possible causes of thrombocytopenia in COVID-19 patients. Common laboratory examinations include coagulation function, thrombopoietin and drug-dependent antibodies. Since both bleeding and thrombosis risks are seen in SARS-CoV-2-induced ITP patients, individual remedy is essential for the treatment of this disease. Because thrombopoietin receptor agonist(TPO-RA) has the side effect of accelerating thrombosis and may aggravate the pulmonary embolism symptoms of patients, it should be used for refractory SARS-CoV-2-induced ITP patients only. This review briefly summarizes the recent research progress in the pathogenesis, diagnosis and treatment of SARS-CoV-2-induced ITP.

The Treatment of Newly Diagnosed Primary Immune Thrombocytopenia by Recombinant Human Thrombopoietin Combined with Glucocorticoid / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with glucocorticoid in treatment of newly diagnosed adult primary immune thrombocytopenia (ITP).@*METHODS@#Eleven male and 23 female patients with the diagnosis of primary ITP in our hospital from November 2018 to October 2019 were enrolled and randomly divided into test group (17 cases) and control group (17 cases), the median age was 52 years old (range: 20-76 years old). The patients in test group were treated with rhTPO 300 IU/(kg·d) combined with glucocorticoid , while the patients in control group were treated with rhTPO (15 000 IU/d) combined with glucocorticoid. Platelet count, platelet increase, as well as the overall response rate were compared. At the same time, the drug tolerance and any adverse drug reactions were observed.@*RESULTS@#The platelet counts and platelet increase of the patients in the test group were significantly higher than those in control group (P<0.05). There was no significant difference in platelet counts and platelet increase between the patients in the test group and control group at day 3, 7 after treatment. There was no significant difference in overall response rates and complete response rates at day 7, 14 between the two groups either. In test group, there were 13 cases received platelet transfusion, while 12 cases in control group. The muscle aches occurred in one patient, and mild aminotransferase increased in another patient in test group which was self-recovery without treatment.@*CONCLUSION@#RhTPO 300 U/(kg·d) combined with glucocorticoid could rapidly increase the platelet count with a low incidence of tolerable adverse events compared with conventional dose rhTPO with glucocorticoid.

Effect of rhTPO and rhIL-11 on Thrombocytopenia after Chemotherapy in Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze and compare the efficacy of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-11 (rhIL-11) in the treatment of thrombocytopenia after chemotherapy in acute leukemia patients.@*METHODS@#180 patients with acute leukemia complicated with thrombocytopenia after chemotherapy in the First Affiliated Hospital of Anhui Medical University were analyzed retrospectively. Among them, 50 patients who treated with rhTPO and did not receive platelet transfusion were set as group A, 50 patients treated with rhTPO and receive platelet transfusion were set as group B, Forty patients treated with rhIL-11 without platelet transfusion were set as group C, Forty patients who treated with rhIL-11 and received platelet transfusion were set as group D. The duration of PLT below 20×109/L, the days it takes for PLT to recover to more than 100×109/L, and the incidence of different bleeding degrees were compared among several groups.@*RESULTS@#The duration of PLT<20×109/L in group A(3.72±1.14 d) was significantly shorter than that in group C(4.93±1.33 d) (P<0.001), and there was no significant difference from group B (P>0.05). The duration of PLT<20×109/L in group B(3.06±0.91 d) was significantly shorter than that in group D(4.65±0.98 d) (P<0.001), while the difference in duration of days between group C and D was not statistically significant (P>0.05). The times for PLT to recover to 100×109/L in group A(13.46±1.67 d) were significantly shorter than that in group C(16.85±2.13 d) (P<0.05), but there was no significant difference from group B (P>0.05). The time required for PLT to recover to 100×109/L in group B(13.36±1.49 d) were significantly shorter than that in group D(16.18±1.78 d) (P<0.05), while the difference in the days required for group C and group D was not statistically significant (P>0.05). The incidence of high bleeding risk in group B was significantly lower than that in group A (22% vs 44%, P<0.05), the incidence of high bleeding risk in group D was significantly lower than that in group C (32% vs 65%, P<0.05), and the incidence of high bleeding risk in group A was significantly lower than that in group C (44% vs 65%, P<0.05). The incidence of high bleeding risk in group B(22%) was lower than that in group D(32.5%), and the difference was not statistically significant (P>0.05).@*CONCLUSION@#In the treatment of acute leukemia patients with thrombocytopenia after chemotherapy, compared with rhIL-11, rhTPO can significantly shorten the duration for patients in a status with extremely low levels of PLT and the recovery time of PLT to normal range. In addition, PLT transfusion cannot speed up the time for patients to raise platelets to a safe range, nor can it shorten the duration of low PLT levels, but it can reduce the incidence of high bleeding risk events.

Trombocitopenia imune associada à COVID-19: relato de caso e revisão de literatura / Immune thrombocytopenia associated to Covid-19: case report and literature review

Pacientes com COVID-19 podem apresentar trombocitopenia grave. Esse achado tem importante impacto no aumento de desfechos negativos e mortalidade, representando um importante fator prognóstico da doença. Vários mecanismos etiopatogênicos foram descritos, sendo a trombocitopenia imune um dos fatores mais frequentes. A abordagem terapêutica inclui como opções: corticoterapia, imunoglobulina, transfusão de plaquetas e análogos da trombopoietina. Este estudo tem como objetivo apresentar o relato de caso de uma paciente com PCR positivo para SARS-CoV-2, que desenvolveu queda acentuada e abrupta das plaquetas no 20º dia de internação. Além disso, casos semelhantes na literatura foram analisados e as possibilidades terapêuticas elencadas. Por fim, conclui-se que há a necessidade de estudos mais amplos para auxiliar a criação de protocolos sistematizados para o diagnóstico e abordagem dessa condição.

COVID-19 patients may experience severe thrombocytopenia. Such finding has an important impact on the increase in negative outcomes and mortality, representing an important prognostic factor of the disease. Several etiopathogenetic mechanisms have been described, in which immune thrombocytopenia is one of the most frequent. The therapeutic approach includes as options: corticosteroid therapy, immunoglobulin, platelet transfusion and thrombopoietin analogs. The following study aims to present a case report of a patient with positive PCR for SARSCoV-2 who developed a severe and abrupt drop in platelets on the 20th day of hospitalization. In addition, similar cases reports in the literature were analyzed and the therapeutic possibilities were listed. Finally, it is concluded that there is a need for broader studies to help create systematic protocols for the diagnosis and approach of this condition.

Seguridad y eficacia del uso de eltrombopag en púrpura trombocitopénica inmune primaria que ha fracasado a la primera línea de tratamiento / Safety and efficacy of the use of eltrombopag in primary immune thrombocytopenic purpura that has failed to the first line of treatment

INTRODUCCIÓN: Antecedentes: El presente informe expone la evaluación de Eltrombopag en pacientes con diagnóstico de púrpura trombocitopénica inmune primaria que han fracasado a la primera línea de tratamiento. Aspectos Generales: La púrpura trombocitopénica inmune primaria o púrpura trombocitopénica idiopática (PTI) es una condición autoinmune usualmente benigna y de curso autolimitado caracterizada por el aumento de la destrucción plaquetaria y la sub-optima producción plaquetaria. Está definida como la presencia de plaquetas disminuidas, médula ósea normal y ausencia de otras causas de trombocitopenia. Tecnología Sanitaria de Interés: Eltrombopag: Eltrombopag (ETP), Revolade o Promacta (GlaxoSmithKline Inc), es un agente hematopoyético que actúa como agonista no peptídico del receptor de la trombopoyetina. Interacciona con el dominio transmembrana e induce a la proliferación y diferenciación de los megacariocitos produciendo, a consecuencia de ello, un incremento en el recuento plaquetario. Este medicamento se indica para el tratamiento de PTI. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de ETP para el tratamiento de pacientes con PTI con fracaso a tratamiento de primera línea en las bases de datos de MEDLINE, EMBASE, CENTRAL, DARE y TRIPDATABASE. Se hizo una búsqueda adicional en www.clinicaltrials.gov, para poder identificar ensayos clínicos aún en elaboración o que no hayan sido publicados. Adicionalmente, se hizo una búsqueda dentro de la información generada por las principales instituciones internacionales hematológicas y agencias de tecnologías sanitarias que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC). RESULTADOS: Se realizó la búsqueda bibliográfica y de evidencia científica que sustente el uso ETP para el tratamiento de pacientes con PTI con fracaso a tratamiento de primera línea según la pregunta PICO establecida. Para el presente documento se seleccionó el siguiente cuerpo de evidencia que es resumido a continuación: Guías Clínicas: Se identificaron dos GPC (una de Estados Unidos, una de España). Evaluaciones de tecnología sanitaria: Dos ETS (Reino Unido y Canadá). Revisiones sistemáticas: \r\nNo se identificaron RS de ECAs específicamente para ETP que responder nuestra pregunta PICO. Sin embargo se seleccionó una RS indirecta de ECAs que compara ETP con otro agonista del receptor de la trombopoyetina (romiplostim). Ensayos clínicos: Se identificador tres ECAs. Ensayos Clínicos registrados: \r\nSe encontró un ECA registrados uno contando con resultados preliminares. CONCLUSIONES: La púrpura trombocitopénica inmune primaria o púrpura trombocitopénica idiopática (PTI) es una condición autoinmune usualmente benigna y de curso auto-limitado caracterizada por el aumento de la destrucción plaquetaria y la sub-optima producción plaquetaria. Eltrombopag una droga que actúa como agonista no peptídico del receptor de la trombopoyetina por lo que se le considera de la familia de los agonistas de receptores de la trombopoyetina. Interacciona con el dominio transmembrana e induce a la proliferación y diferenciación de los megacariocitos produciendo un incremento en el recuento plaquetario. Las guías de práctica clínica recomiendan eltrombopag en indicaciones seleccionadas incluido el tratamiento después de un fracaso terapéutico de primera línea. Sin embargo no especifican una recomendación por sobre otra de las alternativas de tratamiento. En general, las recomendaciones sitúan a eltrombopag como una alternativa de tratamiento de segunda línea en pacientes con PTI, sin presentar una evidencia comparativa robusta con otras alternativas. Otras opciones de tratamiento generalmente mencionadas son esplenectomía, danazol (el cual se encuentra incluido en el Petitorio Farmacológico de Essalud) y rituximab. Las evaluaciones de tecnologías sanitarias son discordantes con respecto a su recomendación. La ETS que lo recomienda lo hace basado en un estudio de costo-efectividad y preferencias de pacientes con un descuento acordado con el fabricante. Mientras que la otra no la recomienda en ninguna indicación. Los ensayos clínicos que demuestran la seguridad y eficacia de eltrombopag en PTI en comparación al placebo son de buena calidad metodológica aunque con una muestra pequeña para ciertos subgrupos y evidentes conflictos de intereses \r\nde los autores. No existen estudios comparativos de eltrombopag con otros medicamentos o procedimiento para el manejo de pacientes con diagnóstico de PTI y falla de tratamiento de primera línea. Así, al momento, la evidencia clínica que apoya el uso de eltrombopag en púrpura trombocitopénica inmune primaria que ha fracasado a la primera línea de tratamiento es limitada, lo que se traduce en recomendaciones no consistentes en las guías de práctica clínica y evaluaciones de tecnología existentes. El Instituto de Evaluación de Tecnologías en Salud e Investigación- 'ETS' no autoriza el uso de eltrombopag en pacientes con púrpura trombocitopénica inmune primaria que ha fracasado a la primera línea de tratamiento.