The immune thrombocytopenia paradox: Should we be concerned about thrombosis in ITP?

Despite the predisposition to bleeding, patients with immune thrombocytopenia (ITP) may also have an increased risk of arterial and venous thrombosis, which can contribute to significant morbidity. The risk of thrombosis increases with age and the presence of cardiovascular risk factors. This narrative review explores the multifactorial nature of thrombosis in ITP, focusing on new pathological mechanisms, emerging evidence on the association between established treatments and thrombotic risk, the role of novel treatment approaches, and the challenges in assessing the balance between bleeding and thrombosis in ITP. The review also explores the challenges in managing acute thrombotic events in ITP, since the platelet count does not always reliably predict either the risk of bleeding or thrombosis and antithrombotic strategies lack specific guidelines for ITP. Notably, second-line therapeutic options, such as splenectomy and thrombopoietin receptor agonists (TPO-RAs), exhibit an increased risk of thrombosis especially in older individuals or those with multiple thrombotic risk factors or previous thrombosis, emphasizing the importance of careful risk assessment before treatment selection. In this context, it is important to consider second-line therapies such as rituximab and other immunosuppressive agents, dapsone and fostamatinib, which are not associated with increased thrombotic risk. In particular, fostamatinib, an oral spleen tyrosine kinase inhibitor, has promisingly low thrombotic risk. During the current era of the emergence of several novel ITP therapies that do not pose additional risks for thrombosis, it is critical to outline evidence-based strategies for the prevention and treatment of thrombosis in ITP patients.

Efecto de las vacunas inactivada y de ARNm contra la COVID-19 sobre la trombocitopenia en pacientes con trombocitopenia inmunitaria / Effect of inactivated and mRNA COVID-19 vaccines on thrombocytopenia in immune thrombocytopenia patients

Este estudio observacional retrospectivo tuvo como objetivo abordar los posibles efectos de las vacunas inactivada y de ARNm en pacientes con trombocitopenia inmunitaria relacionados con la exacerbación. Para definir exacerbación, se consideró una disminución de más del 30 por ciento en el recuento de plaquetas con respecto al valor basal o un recuento de plaquetas disminuido a menos de 30×109/L o el desarrollo de una nueva hemorragia. Cincuenta y nueve (hombres 30,5 por ciento, mujeres 69,5 por ciento) de 208 pacientes con trombocitopenia inmunitaria, se inscribieron en el estudio. La mediana de edad fue de 47 años (rango 18-86). Se realizó un total de 171 vacunaciones en 59 pacientes. El 38 por ciento y el 62 por ciento de los pacientes fueron vacunados con Sinovac® y BioNTech®, respectivamente. En total, 10 (16,9 por ciento) pacientes experimentaron una disminución del recuento de plaquetas por debajo de 30×109/L tras la vacunación. Durante el último año antes de la pandemia, 19 de la misma cohorte (32,2 por ciento) experimentaron dicha disminución. Después de la primera, segunda y la dosis de refuerzo de la vacunación, el 12,7 por ciento, 13,8 por ciento y 15 por ciento de los pacientes experimentaron exacerbaciones, respectivamente; las exacerbaciones con hemorragias leves fueron del 2,3 por ciento y todos los episodios hemorrágicos se trataron con éxito comenzando con esteroides o aumentando la dosis de esteroides. No se registró ninguna hemorragia grave o potencialmente mortal. Se documentó una diferencia estadística en la exacerbación en los pacientes vacunados con la vacuna de ARNm (p =0,041) sólo después de la primera dosis y los pacientes más jóvenes experimentaron una mayor tasa de exacerbación sin significación estadística (p=0,06) después de la primera dosis. En conclusión, tanto la vacuna de ARNm como la inactivada parecen ser seguras para los pacientes con trombocitopenia inmunitaria con complicaciones hemorrágicas poco frecuentes. Especialmente los pacientes más jóvenes y los vacunados con vacunas de ARNm deben ser objeto de un seguimiento estrecho durante 1-2 meses después de la vacunación para detectar trombocitopenia(AU)

This retrospective observational study was aimed to address the possible effects of inactivated and mRNA vaccines in immune thrombocytopenia patients related to exacerbation. To define exacerbation, more than 30percent decrease in platelet counts from baseline or platelet counts decreased to less than 30×109/L and/or development of new bleeding were considered. Fifty-nine (male 30.5percent, female 69.5percent) out of 208 immune thrombocytopenia patients, were enrolled in the study. The median age was 47 (range18-86). A total of 171 vaccinations were performed in 59 patients. Thirty-eight and 62percent of patients were vaccinated with Sinovac® and BioNTech®, respectively. Overall, 10 (16.9percent) patients experienced decrease in platelet count below 30×109/L after vaccination. During the last year before pandemic, 19 of the same cohort (32.2percent) experienced such decrease. After first, second and booster dose vaccinations, 12.7percent, 13.8percent and 15percent of patients experienced exacerbation respectively; exacerbation with minor bleeding was 2.3percent and all bleeding episodes were successfully treated by starting with steroid or increasing the steroid dose. We did not report any severe and life-threatening bleeding. A statistical difference in exacerbation was documented in patients vaccinated with mRNA vaccine (p =0.041) only after the first dose and younger patients experienced a higher rate of exacerbation without statistical significance (p=0.06) after the first dose. In conclusion, both mRNA and inactivated vaccines seem to be safe for immune thrombocytopenia patients with rare bleeding complications. Especially younger patients and those vaccinated with mRNA vaccines should be followed up closely for 1-2 months post vaccination for thrombocytopenia(AU)

Evaluation of the Effects of Atorvastatin and N-Acetyl Cysteine on Platelet Counts in Patients with Primary Immune Thrombocytopenia: An Exploratory Clinical Trial.

Objective: We aimed to evaluate the efficacy of the combination of atorvastatin and N-acetyl cysteine in increasing platelet counts in patients with immune thrombocytopenia who were resistant to steroid therapy or had a relapse after treatment. Material and Methods: The patients included in this study received oral treatment of atorvastatin at a dose of 40 mg daily and N-acetyl cysteine at a dose of 400 mg every 8 h. The desired treatment duration was 12 months, but we included patients who completed at least 1 month of treatment in the analysis. The platelet counts were measured prior to the administration of the study treatment and in the first, third, sixth, and twelfth months of treatment (if available). A p value < 0.05 was considered statistically significant. Results: We included 15 patients who met our inclusion criteria. For the total treatment duration, the global response was 60% (nine patients); eight patients (53.3%) had a complete response and one patient (6.7%) had a partial response. Six patients (40%) were considered as having undergone treatment failure. Of the responder group, five patients maintained a complete response after treatment (55.5%), three patients maintained a partial response (33.3%), and one patient (11.1%) lost their response to the treatment. All of the patients in the responder group had significant increases in their platelet counts after treatment (p < 0.05). Conclusion: This study provides evidence of a possible treatment option for patients with primary immune thrombocytopenia. However, further studies are needed.

FcγRIIa and Fcγ RIIIa genes polymorphism in Egyptian children with primary immune thrombocytopenia

Abstract Introduction Phagocytosis of autoantibody-sensitized coated platelets through Fc gamma receptors on phagocytic cells is an important mechanism of thrombocytopenia in primary immune thrombocytopenia (ITP). Objective We aimed to investigate the contribution of the FcγRIIa and FcγRIIIa genes polymorphism to the risk of ITP and their association with disease characteristics in Egyptian children. Methods A case control study was conducted on eighty children with primary ITP and eighty age and sex healthy matched subjects as a control group. The FcγRIIa and FcγRIIIa genes polymorphism was detected using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results We found that the FcγRIIa‐131H and ‐131R allele frequencies were 51.3 % and 48.7%, respectively, in children with ITP, versus 75% and 25%, respectively, in controls (p= 0.002). The compound heterozygous HR genotype was significantly higher in ITP patients (p < 0.05). The FcγRIIIa-158F and ‐158V allele frequencies were 46.3% and 53.7%, respectively, in children with ITP, versus 70% and 30%, respectively, in controls (p= 0.002). The compound heterozygous VF genotype was significantly higher in ITP patients (p < 0.05). The combined HR/FV genotype was 47.5% in ITP patients, versus 10% in controls (p < 0.001). No significant difference was found between children with newly diagnosed ITP and those who developed chronic ITP, regarding the frequency distribution of the FcγRIIa and FcγRIIIa alleles and genotypes (p > 0.05). Conclusion There is a possible association of the FcγRIIa and FcγRIIIa genes polymorphism with the risk for, and genetic susceptibility to ITP in Egyptian children, but large-scale studies are still needed to support our findings.

Cytomegalovirus Infection-related Immune Thrombocytopenia: A Case Report / Púrpura Trombocitopênica Imune Associada à Infecção por Citomegalovírus: Relato de Caso

Immune thrombocytopenia (ITP) is an acquired cause of thrombocytopenia characterized by the presence of autoantibodies against platelets. It may be primary or secondary to several conditions. We present the case of a 63-year-old woman with a diagnosis of immune thrombocytopenia refractory to conventional therapy. After she was tested for secondary causes of ITP, a diagnosis of acute cytomegalovirus (CMV) infection was made. She was treated with ganciclovir and presented normalization of platelet count. CMV-related Immune Thrombocytopenia should always be considered in certain cases of refractory ITP. If the diagnosis of ITP secondary to acute CMV infection is made, specific antiviral therapy with ganciclovir should be considered. In these cases, immunosuppressive agents, such as steroids, may worsen the ITP and should be tapered or withdrawn as rapidly as feasible.

A Púrpura Trombocitopênica Imune (PTI) é uma causa de trombocitopenia adquirida caracterizada pela presença de autoanticorpos contra plaquetas. A doença pode ser primária ou secundária a diversas condições. Apresentamos o caso de uma mulher de 63 anos com diagnóstico de PTI refratária à terapêutica convencional. A investigação de causas secundárias evidenciou infecção aguda por citomegalovírus (CMV). A paciente foi tratada com ganciclovir e evoluiu com normalização no nível de plaquetas. A PTI relacionada ao CMV deve sempre ser investigada em pacientes com PTI refratária, sendo a terapia antiviral específica com ganciclovir o tratamento de escolha. Nestes casos, os agentes imunossupressores, como os corticosteroides, podem piorar a PTI e devem ser reduzidos gradualmente ou retirados o mais rapidamente possível.

[Clinical evolution of 31 adult patients with immune thrombocytopenia treated with rituximab]. / Evolución clínica de 31 pacientes adultos con trombocitopenia inmune tratados con rituximab.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune disease that could cause different grades of bleeding, which could even threat the patients' life or make them experience poor quality of life. ITP can be treated with rituximab either as a first or second-line therapy option, resulting in an overall response of 60%. The best results have been observed on young women with a short time of disease evolution. Objective: To report the response and clinical evolution by providing therapy with rituximab, which was used as a rescue in adult patients with either persistent or chronical ITP. Material and methods: 4 weekly doses of rituximab were administered to 31 adult patients and it was made a follow-up with them for a year. Results: Out of the 31 patients, a complete response was observed (CR, platelets ≥ 100 x 109 /L) in 22 patients (71%), and a partial response (PR, platelets ≥ 30 and ≤ 99 x 109 /L) in 5 patients (16%); the global response was of 87%. 3 patients relapsed during follow-up and sustained response after rituximab (≥ 12 months) was held in 24 patients, 21 (67%) with CR and 3 (10%) with PR. Side effects were from low to moderate in 13% of patients. Conclusions: Rituximab showed its effectiveness in patients with ITP as a rescue therapy in both chronical and persistent phases. Sustained response ≥ 12 months was of 77%, with good tolerance and acceptable toxicity.

Introducción: la trombocitopenia inmune primaria (TIP) es una enfermedad autoinmune que puede causar hemorragias de diferente intensidad, las cuales llegan a poner en peligro la vida y alteran la calidad de vida de los pacientes. Puede ser tratada con rituximab como primera o segunda línea y la respuesta global es de 60%. Los mejores resultados se han observado en mujeres jóvenes con tiempo breve de evolución. Objetivo: reportar la respuesta y la evolución clínica con el tratamiento de rituximab usado como un rescate en pacientes adultos con TIP en fase crónica o persistente de la enfermedad. Material y métodos: se le administró rituximab de forma semanal por cuatro dosis a 31 pacientes adultos y se les hizo seguimiento durante un año. Resultados: de los 31 pacientes adultos, se observó respuesta completa (RC, plaquetas ≥ 100 x 109 /L) en 22 pacientes (71%) y respuesta parcial (RP, plaquetas ≥ 30 y ≤ 99x 109 /L) en 5 pacientes (16%); la respuesta global fue de 87%. Tres pacientes recayeron durante el seguimiento y la respuesta sostenida (≥ 12 meses) se mantuvo en 24 pacientes, 21 (67%) con RC y 3 (10%) con RP. Los efectos secundarios fueron de leves a moderados en 13% de los pacientes. Conclusiones: el rituximab demostró su utilidad en pacientes con TIP como tratamiento de rescate en las fases crónica y persistente. La respuesta sostenida ≥ 12 meses fue de 77%, con buena tolerancia y toxicidad aceptable.

FcγRIIa and FcγRIIIa genes polymorphism in Egyptian children with primary immune thrombocytopenia.

INTRODUCTION: Phagocytosis of autoantibody-sensitized coated platelets through Fc gamma receptors on phagocytic cells is an important mechanism of thrombocytopenia in primary immune thrombocytopenia (ITP). OBJECTIVE: We aimed to investigate the contribution of the FcγRIIa and FcγRIIIa genes polymorphism to the risk of ITP and their association with disease characteristics in Egyptian children. METHODS: A case control study was conducted on eighty children with primary ITP and eighty age and sex healthy matched subjects as a control group. The FcγRIIa and FcγRIIIa genes polymorphism was detected using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: We found that the FcγRIIa-131H and -131R allele frequencies were 51.3 % and 48.7%, respectively, in children with ITP, versus 75% and 25%, respectively, in controls (p = 0.002). The compound heterozygous HR genotype was significantly higher in ITP patients (p < 0.05). The FcγRIIIa-158F and -158V allele frequencies were 46.3% and 53.7%, respectively, in children with ITP, versus 70% and 30%, respectively, in controls (p = 0.002). The compound heterozygous VF genotype was significantly higher in ITP patients (p < 0.05). The combined HR/FV genotype was 47.5% in ITP patients, versus 10% in controls (p < 0.001). No significant difference was found between children with newly diagnosed ITP and those who developed chronic ITP, regarding the frequency distribution of the FcγRIIa and FcγRIIIa alleles and genotypes (p > 0.05). CONCLUSION: There is a possible association of the FcγRIIa and FcγRIIIa genes polymorphism with the risk for, and genetic susceptibility to ITP in Egyptian children, but large-scale studies are still needed to support our findings.

Epidemiology of immune thrombocytopenia: study of adult patients at a referral hematology service in Northeastern Brazil.

Immune thrombocytopenia (ITP) is an acquired bleeding disorder observed in the clinical practice. Little is known about its epidemiology in Brazil. The present study was conducted at a hematology referral center which covers a population of over 8 million in 184 municipalities in the state of Ceará. The purpose of this study was to draw a demographic profile of adult ITP patients with regard to sex, age, geographical origin and distribution across the state, and the proportion of secondary ITP. Following ethics committee approval, information was collected with an ad hoc instrument. The sample consisted of 187 adult ITP patients attending the Walter Cantídio University Hospital in 2015. The median follow-up time was 67 months (range: 1 month to 29 years). Female sex (n = 154; 82.35 %) was strongly prevalent in all age brackets, with an overall female/male ratio of 4.7:1. The median age was 41 ± 16.1 with an interquartile range of 29-55.5 years; there was no difference between the genders. Secondary ITP (18/187; 9.6 %) displayed a bimodal distribution and a linear increase between 38 and >68 years of age. The results of this survey on the epidemiology of ITP in Brazil suggest that ethnic and geographical factors may have a great impact on age and sex distribution and on the distribution of secondary ITP.

Immune thrombocytopenia associated with lymph node tuberculosis: a case report

ABSTRACT Extrapulmonary tuberculosis associated with immune thrombocytopenia (ITP) is extremely rare. A likely association between ITP and pulmonary and lymph node tuberculosis was reported in a 29-year-old male patient. His platelet count decreased to 4,000/µL. Chest tomography revealed mediastinal adenomegaly, lymph node clusters in the aorta, and consolidation in the left upper lung lobe. Immunoglobulin and methylprednisolone were administered intravenously. The histopathology of the left upper lung lobe confirmed tuberculosis. The rifampicin/isoniazid/pyrazinamide/ethambutol regimen was initiated, and the corticosteroids were tapered off. This case suggests an association of tuberculosis with ITP, since the platelet count effectively normalized after tuberculosis treatment.

Splenectomy outcomes in patients with autoimmune cytopenias and persistent antiphospholipid antibodies.

BACKGROUND: Splenectomy is a therapy for patients with treatment-refractory autoimmune cytopenias. Antiphospholipid antibodies (aPL) can be identified in 25%-85% of these patients. In this study, we sought to identify whether the presence of aPL was associated with worse outcomes in autoimmune cytopenia's patients who had undergone splenectomy. METHODS: We conducted a retrospective cohort study of patients who underwent splenectomy from 2000 to 2018. We describe clinical characteristics and outcomes in patients with autoimmune cytopenia's diagnosis with positive determinations of aPL. Additionally, we performed a case-control sub-analysis 1:1 of the cases with autoimmune cytopenia's matched control patients with negative aPL determination. RESULTS: A splenectomy was performed in 707 patients, of which we included 34 for the analysis. The median age at the time of splenectomy was 37 years (range 19-61), 53% corresponded to immune thrombocytopenia (ITP) and 47% to autoimmune hemolytic anemia (AIHA). Compared with controls (n = 34), patients had more treatment lines in addition to steroids (p = .02). There were no differences in complete response rate, 65% in cases and 80% in controls (p = .17). However, there was numerically a higher incidence of early infections (21% of cases vs. 3% controls, p = .05). During the entire follow-up, 15% of aPL patients compared with 9% of control patients had a thrombotic event (p = .70). DISCUSSION: Splenectomy for treatment-refractory autoimmune cytopenia's patients with persistent aPL is an effective treatment despite some safety concerns related to early infections. These results suggest that the presence of aPL should not impact the decision to undergo splenectomy.

Oseltamivir as rescue therapy for persistent, chronic, or refractory immune thrombocytopenia: a case series and review of the literature.

Immune thrombocytopenia (ITP) is an autoimmune disease that results from antibody-mediated platelet destruction and impaired platelet production. Novel therapies have emerged in the last decade, but 15-20% of patients will relapse or fail and require further therapy. We performed a prospective, single-arm intervention study on seven patients with chronic, persistent, or refractory ITP from the Hospital Universitario "Dr. José E González", in Monterrey, Mexico between 2015 and 2019. Eligible patients received oral oseltamivir 75 mg twice daily for 5 days and were followed up for six months. Most patients received a median of three distinct therapies (range 2-6). Four patients (57.1%) received combined therapy. The median time for any response was 55.5 days (range = 14-150). All patients responded at some point in time (ORR = 100%, six had a proportion of loss of response [PR], and one achieved [CR]). Six months after oseltamivir administration, three patients (42.9%) maintained a response, and one patient had a CR (14.3%). Oseltamivir was well tolerated with a good overall response rate and was useful for treating chronic ITP. We observed an initial increase in the number of platelets; however, this response was not maintained.

Distribution of peripheral blood cells after splenectomy in immune thrombocytopenia patients.

BACKGROUND: There are some difficulties regarding the evaluation of the post-splenectomy state. OBJECTIVE: The objective of the study is to compare the post-splenectomy blood changes of immune thrombocytopenia (ITP) patients with those of trauma patients, 1 month and ≥ 6 months after surgery. METHODS: Medical records of patients, who had undergone total splenectomy for ITP and trauma at a tertiary center between January 2009 and December 2019, were retrospectively reviewed. RESULTS: The current study included 52 patients, who had undergone splenectomy for ITP (57.7%), and trauma (42.3%). Splenectomy, irrespective of the indications, resulted in an increase in hemoglobin concentration, hematocrit, and platelet levels. Neutrophils were responsible for the preoperative leukocytosis in ITP patients, and neutrophilia was ameliorated by splenectomy and also withdrawal of the steroid therapy in some patients. Decreased neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio supported the finding that splenectomy ameliorated inflammation in ITP patients. Splenectomy resulted in a change in percentages of leukocytes in favor of basophils in ITP patients. CONCLUSIONS: Splenectomy, irrespective of the indications, resulted in an increase in hemoglobin concentration, hematocrit and platelet levels, lymphocyte, monocyte, and eosinophil counts. Splenectomy ameliorated inflammation in ITP patients and resulted in a change in percentages of leukocytes in favor of basophils.

ANTECEDENTES: Existen algunas dificultades con respecto a la evaluación del estado post-esplenectomía. OBJETIVO: Comparar los cambios sanguíneos post-esplenectomía de pacientes con PTI con los de pacientes traumatizados, 1 mes y ≥ 6 meses después de la cirugía. MÉTODOS: Se revisaron retrospectivamente las historias clínicas de los pacientes que habían sido sometidos a esplenectomía total por PTI y trauma en un centro terciario entre enero de 2009 y diciembre de 2019. RESULTADOS: El presente estudio incluyó a 52 pacientes, que habían sido sometidos a esplenectomía por PTI (57.7%) y traumatismo (42.3%). La esplenectomía, independientemente de las indicaciones, resultó en un aumento de la concentración de hemoglobina, hematocrito y niveles de plaquetas. Los neutrófilos fueron responsables de la leucocitosis preoperatoria en pacientes con PTI, y la neutrofilia mejoró mediante esplenectomía y también la suspensión de la terapia con esteroides en algunos pacientes. La disminución de NLR y PLR apoyó el hallazgo de una disminución de la inflamación en la esplenectomía en pacientes con PTI. La esplenectomía resultó en un cambio en los porcentajes de leucocitos a favor de los basófilos en pacientes con PTI. CONCLUSIONES: La esplenectomía, independientemente de las indicaciones, resultó en un aumento de la concentración de hemoglobina, niveles de hematocrito y plaquetas, recuentos de linfocitos, monocitos y eosinófilos. Una disminución de la inflamación en la esplenectomía en pacientes con PTI resultó en un cambio en los porcentajes de leucocitos a favor de los basófilos.

Trombocitopenia neonatal: Revisión. I. Definiciones, diagnóstico diferencial, causas, trombocitopenias inmunes / Neonatal thrombocytopenia: A review. I. Definitions, differential diagnosis, causes, immune thrombocytopenia

La trombocitopenia, definida como recuento plaquetario inferior a 100 x 109/l, es un hallazgo muy frecuente en el período neonatal, que ocurre, en especial, en niños críticamente enfermos y en prematuros. Sus causas son múltiples: puede deberse tanto a enfermedades del niño como a otros factores involucrados en la interrelación niño-placenta-madre. En este primer artículo, se enumeran las causas de trombocitopenia; se plantea el enfoque diagnóstico frente a un neonato trombocitopénico y se describen detalladamente las distintas entidades correspondientes a trombocitopenias de etiología inmune. Se presentan los diferentes mecanismos causales y se revisan las distintas características de la trombocitopenia secundaria a trombocitopenia inmune materna y de la trombocitopenia neonatal aloinmune. Se describen las diversas estrategias terapéuticas disponibles para cada una de ellas, tanto para su manejo posnatal como para el prenatal. Se enfatiza sobre la gravedad de la enfermedad y las serias complicaciones y secuelas asociadas a la trombocitopenia neonatal aloinmune

Thrombocytopenia, defined as a platelet count below 100 x 109/L, is a very common finding in the neonatal period, especially in critically ill infants and preterm newborns. Its causes are multiple: it may be due both to pediatric conditions and to other factors involved in the fetal-placental-maternal interface. This initial article describes the causes of thrombocytopenia, proposes a diagnostic approach to manage a thrombocytopenic newborn infant, and provides a detailed description of the different conditions corresponding to thrombocytopenia of immune etiology. It also describes the different causative mechanisms and reviews the varying characteristics of thrombocytopenia secondary to maternal immune thrombocytopenia and neonatal alloimmune thrombocytopenia. The different treatment approaches to each of the different conditions are described both for their pre- as well as their postnatal management. The severity of thrombocytopenia and the serious complications and sequelae associated with the neonatal alloimmune thrombocytopenia are highlighted.

A retrospective analysis of 122 immune thrombocytopenia patients treated with dapsone: Efficacy, safety and factors associated with treatment response.

BACKGROUND: The optimum second-line treatment or best sequence of treatments for immune thrombocytopenia (ITP) are yet to be determined. Our institution has accumulated extensive experience regarding the use of dapsone as second-line therapy for ITP. OBJECTIVES: We aimed to assess the efficacy rate and safety of dapsone treatment in ITP patients. PATIENTS/METHODS: Here we report our experience in a retrospective study, including 122 patients, with a median treatment duration with dapsone of 6 months and a median follow-up period of 3.4 years. RESULTS: The overall response rate in this cohort was 66%, including 24% of complete responses. Among responders, in 24% a relapse occurred while on treatment. Therefore, a sustained response was observed in 51% of patients. Interestingly, 81% of the responders maintained the response after the interruption of treatment, for a median time of 26 months. Side effects were reported in 16% of the patients in this cohort and treatment was interrupted due to side effects in 11% of patients. The main cause in these cases was hemolytic anemia and methemoglobinemia. Reductions in hemoglobin levels during the use of dapsone were seen in 94% of the patients. Responders presented significantly greater reductions in their hemoglobin levels than nonresponders did: median hemoglobin drop of 1.9 g/dl vs. 1.2 g/dl (p = .004). CONCLUSIONS: Our findings suggest that dapsone has adequate efficacy and is well tolerated. Although the mechanism of action is still unclear, our observation that the degree in the drop of hemoglobin is greater in responders suggest a possible role of the blockage of the reticuloendothelial system in the therapeutic effect of the drug.

Neonatal thrombocytopenia: A review. I. Definitions, differential diagnosis, causes, immune thrombocytopenia. / Trombocitopenia neonatal: Revisión. I. Definiciones, diagnóstico diferencial, causas, trombocitopenias inmunes.

Thrombocytopenia, defined as a platelet count below 100 x 109/L, is a very common finding in the neonatal period, especially in critically ill infants and preterm newborns. Its causes are multiple: it may be due both to pediatric conditions and to other factors involved in the fetal-placental-maternal interface. This initial article describes the causes of thrombocytopenia, proposes a diagnostic approach to manage a thrombocytopenic newborn infant, and provides a detailed description of the different conditions corresponding to thrombocytopenia of immune etiology. It also describes the different causative mechanisms and reviews the varying characteristics of thrombocytopenia secondary to maternal immune thrombocytopenia and neonatal alloimmune thrombocytopenia. The different treatment approaches to each of the different conditions are described both for their pre- as well as their postnatal management. The severity of thrombocytopenia and the serious complications and sequelae associated with the neonatal alloimmune thrombocytopenia are highlighted.

La trombocitopenia, definida como recuento plaquetario inferior a 100 x 109/l, es un hallazgo muy frecuente en el período neonatal, que ocurre, en especial, en niños críticamente enfermos y en prematuros. Sus causas son múltiples: puede deberse tanto a enfermedades del niño como a otros factores involucrados en la interrelación niño-placenta-madre. En este primer artículo, se enumeran las causas de trombocitopenia; se plantea el enfoque diagnóstico frente a un neonato trombocitopénico y se describen detalladamente las distintas entidades correspondientes a trombocitopenias de etiología inmune. Se presentan los diferentes mecanismos causales y se revisan las distintas características de la trombocitopenia secundaria a trombocitopenia inmune materna y de la trombocitopenia neonatal aloinmune. Se describen las diversas estrategias terapéuticas disponibles para cada una de ellas, tanto para su manejo posnatal como para el prenatal. Se enfatiza sobre la gravedad de la enfermedad y las serias complicaciones y secuelas asociadas a la trombocitopenia neonatal aloinmune.

Diagnostic characteristics of immature platelet fraction for the assessment of immune thrombocytopenia.

The diagnosis of immune thrombocytopenia (ITP) remains an exclusion, as a specific biomarker is missing. We aimed to investigate the diagnostic characteristics, establish a cut-off point for reticulated platelets, and compare it with the clinical exclusion diagnosis used in the assessment of ITP. Forty-one patients with ITP and 187 healthy individuals were enrolled in Santa Maria, Brazil. Sysmex XE-5000 was used to measure IPF. We obtained an IPF cut-off point of 6.3% with a sensitivity of 92.7% (95% CI: 80.1-98.5) and a specificity of 92.5% (95% CI: 87.8-95.8). The area under the curve was 0.97. The kappa coefficient was 0.85 (95% CI: 0.75-0.95), which shows high agreement between methods. The positive (PPV) and negative predictive values (NPV) were 81.25% and 96.42%, respectively. From the cut-off point, kappa index, PPV, and NPV obtained, it is possible to conclude that IPF can be an efficient laboratory marker for diagnosing ITP.

Trombocitopenia inmune primaria. Tratamiento y recomendaciones ante la pandemia por COVID-19 / Primary immune thrombocytopenia. Treatment and recommendations for the COVID-19 pandemic

Resumen La trombocitopenia inmune primaria (TIP) es una trastorno autoinmune adquirido caracterizado por el recuento bajo de plaquetas como resultado de la destrucción de plaquetas y la producción de plaquetas deteriorada. La falta de ensayos aleatorizados sobre el manejo de la TIP ha dado como resultado controversias significativas y gran variación en la práctica clínica para su diagnóstico y tratamiento. Aunado a esto, la pandemia actual de enfermedad por coronavirus 2019 (COVID-19), causada por el nuevo coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2), plantea una serie de dilemas para el estudio y tratamiento de los pacientes con trombocitopenia inmune, incluyendo las ventajas y desventajas de las opciones terapéuticas estándar para la TIP de reciente diagnóstico o en recaída y cronicidad, en cada uno de los enfoques de manejo: observación, corticosteroides, inmunoglobulina intravenosa, inmunoglobulina anti-D (anti-DIg), rituximab, esplenectomía y agonistas de los receptores de trombopoyetina, así como el reconocimiento de los desafíos planteados al manejo de pacientes con TIP con manifestaciones hemorrágicas y riesgo trombótico observado en pacientes hospitalizados con infección por SARS-CoV-2. Por tal motivo, el presente trabajo tiene como objetivo plasmar y ofrecer recomendaciones y pautas a seguir tanto en niños como en adultos con y sin COVID-19, ante el riesgo y beneficio en cada escenario, basado en consenso de expertos y guías ya establecidas (sobre todo para pacientes adultos) para el manejo, tratamiento y seguimiento de la TIP en el contexto de la actual pandemia.

Abstract Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by low platelet count as a result of platelet destruction and impaired platelet production. The lack of randomized trials on the management of IPT has resulted in significant controversy and great variation in clinical practice for its diagnosis and treatment. In addition to this, the current coronavirus disease 2019 (COVID-19) pandemic, caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a series of dilemmas for the study and treatment of patients with immune thrombocytopenia, including the advantages and disadvantages of therapeutic options standard for newly diagnosed or relapsed and chronic IPT, in each of the management approaches: observation, corticosteroids, IV immunoglobulin, anti-D immunoglobulin, rituximab, splenectomy and thrombopoietin receptor agonists, as well as recognition of the challenges posed to the management of patients with IPT with hemorrhagic manifestations and thrombotic risk observed in hospitalized patients with SARS-CoV-2 infection. For this reason, the present work aims to capture and offer recommendations and guidelines to follow in both children and adults with and without COVID-19, given the risk and benefit in each scenario, based on consensus of experts and already established guidelines (on all for adult patients) for the management, treatment and follow-up of IPT in the context of the current pandemic.

Diagnosis and management of coronavirus disease-associated immune thrombocytopenia: a case series

Abstract Data on health problems and fatal complications associated with coronavirus disease (COVID-19) have consistently been reported. Although immune thrombocytopenia has been associated with multiple viral infections, only few studies have shown its association with COVID-19. Here, we have reported a case series of two cases pertaining to patients diagnosed with COVID-19-associated immune thrombocytopenia, elaborating on the clinical course, management, and response to treatment.

Síndrome de Evans Fisher / Evans fisher syndrome

Paciente femenina de 35 años de edad con color de la piel blanca, con antecedentes de cefalea migrañosa. Comenzó con manifestaciones purpúreas en forma de petequias y equimosis diseminadas por todo el cuerpo; palidez cutánea mucosa e íctero en piel y esclera, además de coluria. Se realizaron estudios hematológicos, humorales e inmunológicos. Es atendida en la sala de Medicina Interna del Hospital General Docente Comandante Pinares. Con evolución satisfactoria al tratamiento con esteroides y la inmunoglobulina intravenosa. Se realizó la discusión diagnóstica del caso confirmándose el Síndrome de Evans-Fisher, se revisa la bibliografía actualizada sobre la enfermedad(AU)

We report a case of a 35-year-old female patient, white skin color, with a history of migraine headache. She began with purple manifestations in the form of petechiae and ecchymoses spread throughout the body; mucous skin pallor and icterus in skin and sclera, as well as coluria. Hematological, humoral and immunological studies were carried out. She was treated in the Internal Medicine ward at Comandante Pinares General Teaching Hospital. She evolved satisfactorily to treatment with steroids and intravenous immunoglobulin. The diagnostic discussion of this case was carried out, confirming the Evans-Fisher Syndrome, the updated bibliography on the disease was reviewed(AU)