Trasplante de médula ósea haploidéntico en un paciente pediátrico con síndrome de Wiskott-Aldrich. A propósito de un caso / Haploidentical bone marrow transplantation in a pediatric patient with Wiskott-Aldrich syndrome. A case report

El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.

Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.

Myelotoxicity and kidney dysfunction related to the use of trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia: a case report of severe adverse events with a common drug

ABSTRACT Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary therapeutic option for Pneumocystis jirovecii pneumonia (PCP). Gastrointestinal symptoms and cutaneous rash are common side effects, with hyperkalemia being uncommon in patients without kidney dysfunction, and myelotoxicity being even rarer. We present the case of a male patient with hypertension and a recent diagnosis of non-Hodgkin lymphoma, undergoing rituximab treatment for two months. He was admitted to the intensive care unit due to dyspnea, tachypnea, and pleuritic pain, requiring mechanical ventilation. Chest computed tomography showed bilateral and multilobed ground-glass opacities, compromising more than 80% of the lung parenchyma. Pulmonary tuberculosis and COVID-19 were ruled out. An angiotomography and Doppler ultrasound revealed an extensive pulmonary thrombus and deep venous thrombosis. Empiric treatment with TMP-SMX for PCP was initiated, but within four days, the patient experienced metabolic acidosis and severe hyperkalemia, necessitating hemodialysis. He also presented with progressive pancytopenia and critical levels of leukopenia and thrombocytopenia. The hypothesis of TMP-SMX-induced myelotoxicity was suspected. Considering the unavailability of an alternative treatment, it was opted to continue TMP-SMX and initiate a granulocyte-colony-stimulating factor. However, the patient maintained medullary deterioration, becoming refractory to the transfusion of blood derivates. On the 17th day of treatment, a clinical decision was made to suspend TMP-SMX, leading to improvements within 48 hours in marrow and kidney functions, metabolic acidosis, and hyperkalemia. Despite all efforts, the patient died after 35 days of hospitalization due to hospital-acquired infections. This case highlights the importance of clinicians recognizing potential myelotoxicity with TMP-SMX and promptly discontinuing the drug if necessary.

To study the effect of 'Covishield' vaccination on pre-donation platelet counts of plateletpheresis donors

ABSTRACT Introduction: Approximately 55.52% of the Indian population had been fully vaccinated by Jan. 2022, since its first roll out on January 16, 2021. A few concerns were raised concerning the Covishield vaccination related to thrombotic thrombocytopenia. Apheresis-derived platelet concentrates are frequently required in a plethora of clinical situations and post-vaccination decrement of platelet counts might lead to increased deferral of the plateletpheresis donors. Objectives. The aim of the study was to discover the effect of the Covishield vaccination on deferral rates of plateletpheresis donors. Methods: Blood samples were collected from the potential platelet donors for the completion of the standard questionnaire for the complete blood count. The data collected were tabulated in the MS Excel spreadsheet and the biostatistical analysis was performed with the SPSS v23. A p-value of < 0.05 was taken as significant. We compared this data with age-and sex-matched controls. Results: The mean age of cases and controls was 29.69 ± 8.57 and 30.15 ± 7.11, respectively. There was a significant difference in platelet counts of cases (188496.35 ± 72065.66/cumm) and controls (269524.50 ± 53981.60/cumm). Furthermore, donors who received one dose had higher platelet counts of 248676.47 ± 80075.24/cumm than those who received both doses of vaccine (179970.83 ± 66773.73/cumm). The difference in deferral rates between the two groups was remarkable (34.7% vs. 0.9%, with the p-value < 0.001). Conclusion: Vaccination certainly increased the deferral rates of plateletpheresis donors due to low platelet counts. Average platelet counts were low in fully vaccinated individuals, however, the platelets returned to normal counts as the post-vaccination days progressed.

Síndrome hemolítico urémico secundario a Streptococcus pneumoniae. Reporte de un caso clínico

El síndrome hemolítico urémico secundario a Streptococcus pneumoniae (SHU-Sp) es una complicación poco frecuente de las enfermedades invasoras por S. pneumoniae. Presenta una alta morbimortalidad, con requerimiento de transfusiones de glóbulos rojos y plaquetas, terapia de sustitución de la función renal de inicio precoz y más prolongada, así como mayores complicaciones a largo plazo, comparado con las formas secundarias a infección entérica por Escherichia coli productora de toxina Shiga. Presentamos el caso clínico de una preescolar de dos años, previamente sana, vacunada con tres dosis de PCV13, que desarrolló una insuficiencia renal aguda, anemia hemolítica y plaquetopenia, en el contexto de una neumonía con empiema y bacteriemia por S. pneumoniae.

Streptococcus pneumoniae associated hemolytic uremic syndrome (Sp-HUS) is an uncommon complication of invasive pneumococcal infections. Patients with Sp-HUS have a higher mortality and long term morbidity than those due to HUS from Shiga toxin-producing Escherichia coli infections (STEC-HUS). They often require more red blood cells and platelet transfusions, and early initiation of renal substitution therapy, presenting a higher rate of arterial hypertension and chronic renal disease in the long term, compared to STEC-HUS. We report a healthy 2 year-old infant, vaccinated with three doses PCV13, that developed acute renal failure, hemolytic anemia and thrombocytopenia in the course of a complicated pneumococcal pneumonia with empyema and bacteremia.

Treatment of grade four hemorrhoids in a patient with acute myeloid leukemia with severe thrombocytopenia by laser hemorrhoidopexy: A case report

Here, we present the case of a 66-year-old female patient with acute myeloid leukemia and severe thrombocytopenia who came with the complaints of painful per anal mass and bleeding per rectum for 1 year. The patient is a known case of hypertension, and diabetes mellitus and has received three cycles of chemotherapy with decitabine. On examination, she was found to have fourth-degree hemorrhoids at 3, 7, and 11 oclock positions with acute edematous changes. We successfully treated this patient with laser hemorrhoidopexy, whereby laser energy was delivered to each hemorrhoidal cushion. While lasers for the successful treatment of grade 2 and 3 hemorrhoids are well documented in the literature, we successfully treated this patient with prolapsing fourth-degree hemorrhoids with just laser energy delivery. With these results, we would also like to consider laser hemorrhoidopexy as an effective treatment option for four-degree hemorrhoids for which open Milligan–Morgan hemorrhoidectomy and stapler hemorrhoidectomy are currently considered treatment options

Correlation between parasitemia and different complications of malaria – The clinical outlook

Background: Malaria is one of the most severe public health problems worldwide. India contributes a substantial burden of malaria. It can cause several complications. Aims and Objectives: This study was conducted to determine the association of parasitemia of current malaria with age of patients, hemoglobin level, liver function test (LFT), platelet count, previous history of malaria, and relapse/recrudescence of malaria up to 1 year. Materials and Methods: An observational study conducted in hospital settings included thin and thick smear preparation with Leishman’s staining to determine the parasitemia as per the WHO guidelines from the blood samples of 280 malaria parasite dual antigen (MPDA) kit positive patients and their details were taken during study period of 2 years. Hemoglobin, LFT, and platelet count were tested and they were correlated with parasitemia. The previous history of malaria was taken and follow-up was done up to 1 year for relapse/recrudescence and their association with parasitemia in current disease was evaluated. Statistical tool R was used for data analysis. Results: Age group 20–40 years was most commonly affected with maximum mean percentage parasitemia. Higher parasitemia was associated with higher grade of anemia, LFT derangement, and thrombocytopenia. Disease severity was maximum for mixed infection followed by falciparum and vivax malaria. About 9.28% of patients with the previous history of malaria developed lower parasitemia in current infection. Relapse rate in vivax malaria –2.325% and recrudescence rate in falciparum malaria–12.5%. Conclusion: Malaria parasitemia should be reported routinely as it carries prognostic importance.

Síndrome inflamatorio multisistémico en pediatría: importancia de la evaluación inicial de los parámetros de laboratorio / Multisystem Inflammatory Syndrome in children: the importance of evaluation of early laboratory parameters

RESUMEN Introducción : El síndrome inflamatorio multisistémico en pediatría (SIM-C) es una infrecuente entidad asociada a COVID-19 con un amplio espectro de presentación: desde un cuadro similar a la enfermedad de Kawasaki a una afectación multisistémica con shock. Se han descripto asociaciones entre valores de laboratorio y mala evolución, pero no existen puntos de corte que predigan la misma. Objetivo : El objetivo de este estudio fue describir y analizar las características de los pacientes con SIM-C y las relaciones de estas con los hallazgos de laboratorio. Material y métodos : Se realizó un estudio analítico y retrospectivo de niños internados con diagnóstico de SIM-C entre mayo 2020 y junio 2021 en el HNRG. Se estudiaron 32 pacientes, 17 femeninas (53,13%) y 15 masculinos (46,87%), edad promedio de 7,67 años (rango 0,5-14,91). Diez de los pacientes (31,25%) presentaron shock. Se obtuvieron datos clínicos, ecocardiográficos y valores de troponina I ultrasensible, NT-proBNP, plaquetas y linfocitos al momento del diagnóstico; y se analizaron comparativamente entre quienes presentaron shock durante la evolución (Grupo 1) y quienes no (Grupo 2). Resultados : La diferencia en un valor inicial de NT-proBNP elevado fue estadísticamente significativa entre ambos grupos (p=0,008), en tanto que la troponina y el recuento de linfocitos y plaquetas, no. De los 13 pacientes que requirieron inotrópicos, el 58% presentó linfopenia inicialmente (p=0,006 vs aquellos que no los necesitaron). Conclusiones : Si bien la mortalidad debido al SIM-C es baja, la afectación cardiovascular y el compromiso hemodinámico en los paci entes que presentaron este síndrome puede ser frecuente. Poder contar con una herramienta de laboratorio ampliamente difundida para la categorización de pacientes podría ayudar a mitigar riesgos y obtener una derivación temprana a centros especializados.

ABSTRACT Background : Multisystem inflammatory syndrome in children (MIS-C) is an uncommon condition associated with COVID-19 with a wide spectrum of presentations, ranging from Kawasaki-like disease to multisystem involvement with shock. The as sociation between the laboratory characteristics and unfavorable outcome has been described, but the cut-off points associated with higher risk have not yet been defined. Objective : The aim of this study was to describe and analyze the characteristics of patients with MIS-C and their associations with the laboratory findings. Methods : We conducted an analytical and retrospective study of pediatric patients hospitalized between May 2020 and June 2021 with diagnosis of MIS-C in Hospital General de Niños Dr. Ricardo Gutiérrez (HNRG). The cohort was made up of 23 patients, 17 female (53.13%) and 15 male (46.87%); mean age was 7.67 years (range 0.5-14.91). Ten patients (31.25%) presented shock. Clinical and echocardiographic data and values of high-sensitive troponin I, N-terminal pro-B-type natriuretic peptide (NT-proBNP), platelets and lymphocytes at the time of diagnosis were obtained and compared between those with shock during evolution (group 1) and those without shock (group 2). Results : There was a significant difference in baseline elevated NT-proBNP values between both groups (p = 0.008), but not in troponin levels and lymphocyte and platelet counts. Of the 13 patients who required inotropic agents, 58% had baseline lymphopenia (p = 0.006 vs those who did not require inotropic drugs). Conclusions : Although mortality due to MIS-C is low, cardiac involvement and hemodynamic impairment may be common. The availability of a commonly used laboratory tool for patient categorization could help to mitigate risks and obtain early referral to specialized centers.

Efficacy and safety of biosimilar romiplostim in Indian patients with chronic immune thrombocytopenia: A multicentric retrospective study

Context and Aims: To evaluate the efficacy and safety of biosimilar romiplostim in Indian patients with immune thrombocytopenic purpura (ITP). Settings and Design: Multicentre, retrospective observational study. Methods and Material: Patients with chronic ITP who received biosimilar romiplostim from July 2019 to March 2020 across 3 major hospitals in Guwahati, India, were included. The study outcomes were the platelet response (platelet count > 50 × 109/L), time to first response, number of dose-limiting events, and the median effective dose. Statistical Analysis Used: Descriptive. Results: Of 32 patients included in this analysis, majority (59.4%) were females. The mean (SD) age was 40.37 (15.79) years, and mean age at ITP diagnosis was 38.53 years. The median number of romiplostim doses were 27.5 (range: 10-42) over a period of 10 months; median romiplostim dose used was 4.2 ?g/kg (range: 2.8-5 ?g/kg). Platelet response was achieved as early as after one week in 9 (28.12%) patients, which continued to increase to 24 (75%) patients after the second, 30 (93.75%) patients after the third and all 32 (100%) patients after four weeks of romiplostim administration. The median platelet count was 161 × 109/L. Dose reduction was done in a total of 21 patients. Thrombocytosis (46.88%), elevated liver enzymes (15.63%) and myalgia (15.63%) were the most common adverse events. Conclusions: Biosimilar romiplostim was effective in achieving and maintaining platelet response without any new safety concerns in Indian adult patients with chronic ITP. The median effective dose of romiplostim required in our patients was lower as compared with the standard prescribed dose.

Acute Acquired Immune Thrombocytopenia After Cardiac Surgery: A Challenging Case

Thrombocytopenia is a common condition that recognizes an infinite number of possible causes, especially in specific settings like the one covered in this case report: the postoperative period of cardiac surgery. We report a case of an old male with multiple comorbidities who underwent a coronary angioplasty procedure and aortic valve replacement. He showed severe thrombocytopenia in the postoperative days. Differential diagnosis required a big effort, also for the experts in the field. Our goal was to aggressively treat the patient with prednisolone, platelets, and intravenous immunoglobulins to maximize the prognosis. Our patient developed no complications and was discharged successfully

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.

Progressive kaposiform hemangioendothelioma and sirolimus-related severe thrombocytopenia

Kaposiform hemangioendothelioma is a locally invasive tumor and we were unable to find any previous reports of multifocal progression. Sirolimus, a mammalian target of rapamycin inhibitor, has been widely used to treat kaposiform hemangioendothelioma. Herein, we report a case of multifocal progressive kaposiform hemangioendothelioma, wherein sirolimus treatment caused severe thrombocytopenia. A 12-year-old East Asian girl presented with indurated dark-purple masses on her back. The patient had received three surgical interventions following the first appearance of the masses in 2012 and subsequent reappearances in 2014 and 2016. Kaposiform hemangioendothelioma was diagnosed based on radiological and pathological findings. Two more masses appeared in the following year. The patient was treated with oral sirolimus (2.5 mg/ m2/day) and developed grade 3 thrombocytopenia 8 days later. The patient was uneventfully relieved 5 days later after the withdrawal of sirolimus and the administration of appropriate medications. This rare case indicated that kaposiform hemangioendothelioma could be progressive with local metastatic characteristics in children. Besides, the severe sirolimus-induced complication highlights the importance of serum drug level monitoring during treatment. Physicians should be extremely cautious while treating kaposiform hemangioendothelioma patients with sirolimus.

Trombocitopenia severa inducida por un oclusor para DAP: reporte de caso en tecnovigilancia

Introducción: El ductus arterioso persistente (DAP) es una cardiopatía congénita de especial interés. La oclusión intervencionista es el tratamiento de elección, no obstante, el dispositivo médico "oclusor para DAP", usado en este procedimiento, puede dar lugar a la aparición de eventos adversos de rara frecuencia como hemorragia, trombocitopenia, entre otros. Reporte de caso: Se presenta un caso de una paciente pediátrica con trombocitopenia severa posterior a la intervención. Durante su hospitalización, la paciente mantuvo niveles bajos de plaquetas hasta que logra su recuperación y sale de alta sin una nueva manifestación hematológica. El caso fue reportado como sospecha de incidente adverso asociada al oclusor para DAP. Conclusión: Al realizarse el análisis causa-raíz, se concluye que el tamaño del oclusor para DAP podría ser la principal causa de la trombocitopenia. El presente caso es una muestra que los dispositivos médicos pueden causar eventos adversos severos, por lo que, es necesaria la implementación de tecnovigilancia, principalmente a los dispositivos médicos de alto riesgo.

Introduction: Patent ductus arteriosus (PDA) is a congenital heart condition of special interest. Interventional occlusion is the treatment of choice; however, a PDA occlude, used in this procedure, is a medical device that rarely could lead to adverse events such as hemorrhage, thrombocytopenia, etc. Case report: We present a case of a pediatric patient with severe thrombocytopenia after surgery. During her hospitalization, platelet levels remained lower and, finally, she was fully recovered without any hematological manifestation. The case was reported as a suspected adverse incident related to PDA occlude. Conclusion: After performing a cause-root analysis, we concluded that the size of the PDA occlude may be the main cause of thrombocytopenia. This case demonstrates that medical devices could lead to adverse events. Thus, it is important for clinicians to implement medical device surveillance, mainly for high-risk medical devices.

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.

Radiocirugía estereotáxica por gamma knife en un paciente con cavernoma cerebral y síndrome de Evans

El cavernoma cerebral es una malformación vascular de diagnóstico infrecuente. Se define como una malformación a nivel de la vasculatura microcerebral que, dependiendo a la ubicación y si existe la posibilidad de ruptura, conlleva a una emergencia que puede terminar en la muerte del paciente. En esta oportunidad se reporta el caso de un paciente con cavernoma cerebral asociado al síndrome de Evans. Se decide manejo quirúrgico de la lesión por aumento de intensidad de cefalea e intolerancia oral. Dada la coexistencia del Síndrome de Evans y la alta tasa de morbimortalidad es que se decide manejo quirúrgico mediante radiocirugía estereotáxica con gamma knife. El uso de dosis de margen bajo para tratamiento con gamma knife para uso en cavernomas cerebrales produce un manejo controlado para sintomatología de convulsiones y mejor expectativa de calidad de vida.

Cerebral cavernoma is an infrequently diagnosed vascular malformation. It is defined as a malformation at the level of the microcerebral vasculature that, depending on the location and if there is a possibility of rupture, leads to an emergency that can end in the death of the patient. On this occasion, we report a case of a patient with cerebral cavernoma associated with Evans syndrome. Surgical management of the lesion was decided due to increased intensity of headache and oral intolerance. Given the coexistence of Evans Syndrome and the high rate of morbidity and mortality, surgical management was decided by stereotaxic radiosurgery with a gamma knife. The use of low-margin doses for treatment with gamma knife for use in brain cavernomas produces controlled management for seizure symptoms and better quality of life expectancy.

Sepsis and septic shock: epidemiology, clinical parameters, and prognostic factors in a brazilian intensive care unit / Sepse e choque séptico: epidemiologia, parâmetros clínicos e fatores prognósticos em uma unidade de terapia intensiva brasileira / Sepsis y shock séptico: epidemiología, parámetros clínicos y factores pronósticos en una unidad de cuidados intensivos brasileña

Sepsis is an organ dysfunction caused by a dysregulated host response to infection and is associated with high morbidity and mortality. The identification of prognostic markers in this syndrome has been a strategy to increase treatment efficacy. The objectives of this study were: 1) to describe the epidemiological and microbiological profile of septic patients and 2) to investigate the association between laboratory/clinical parameters and mortality rate, identifying prognostic markers. Using a prospective observational protocol, epidemiological, clinical and laboratory data were collected from adult patients with sepsis or septic shock admitted to a Brazilian Intensive Care Unit. During the study period, 120 patients were diagnosed with sepsis and 71.67% (n = 86) were included in the protocol. The overall mortality was 69.76% and chronic diseases were identified in 79.07% of cases. The mortality rates for sepsis and septic shock were 51.06% and 92.31%, respectively. SOFA scores on the first, third, and seventh days of hospitalization gradually increased for patients who had clinical worsening. Hyperlactatemia and hyperglycemia were identified in 45.9% and 27% of patients, respectively, and were associated with mortality. INR values greater than 1.5 or thrombocytopenia were related to 92.9% and 88.6% mortality, respectively. In the study, gender, age, ICU stay, site of infection and microbiological agent were not associated with the risk of death. However, the presence of comorbidities, high SOFA scores, three or more organ dysfunctions, and sepsis severity correlated directly with mortality rate.

A sepse é uma disfunção orgânica causada por uma resposta desregulada do hospedeiro à infecção e está associada a alta morbidade e mortalidade. A identificação de marcadores prognósticos nessa síndrome tem sido uma estratégia para aumentar a eficácia do tratamento. Os objetivos deste estudo foram: 1) descrever o perfil epidemiológico e microbiológico de pacientes sépticos e 2) investigar a associação entre parâmetros laboratoriais/clínicos e a taxa de mortalidade, identificando marcadores prognósticos. Por meio de um protocolo observacional prospectivo foram coletados dados epidemiológicos, clínicos e laboratoriais de pacientes adultos com sepse ou choque séptico internados em uma Unidade de Terapia Intensiva brasileira. No período do estudo, 120 pacientes foram diagnosticados com sepse e 71,67% (n = 86) foram incluídos no protocolo. A mortalidade geral foi de 69,76% e doenças crônicas foram identificadas em 79,07% dos casos. As taxas de mortalidade por sepse e choque séptico foram de 51,06% e 92,31%, respectivamente. Os escores SOFA no primeiro, terceiro e sétimo dias de internação aumentaram gradativamente para os pacientes que apresentaram piora clínica. Hiperlactatemia e hiperglicemia foram identificadas em 45,9% e 27% dos pacientes, respectivamente, tendo sido associadas à mortalidade. Valores de INR maiores que 1,5 ou trombocitopenia foram relacionados a 92,9% e 88,6% de mortalidade, respectivamente. No estudo, sexo, idade, permanência na UTI, local da infecção e agente microbiológico não se associaram ao risco de óbito. No entanto, a presença de comorbidades, altos escores SOFA, três ou mais disfunções orgânicas e a gravidade da sepse correlacionaram-se diretamente com a taxa de mortalidade.

La sepsis es una disfunción orgánica causada por una respuesta desregulada del huésped a la infección y se asocia a una elevada morbilidad y mortalidad. La identificación de marcadores pronósticos en este síndrome ha sido una estrategia para aumentar la eficacia del tratamiento. Los objetivos de este estudio fueron: 1) describir el perfil epidemiológico y microbiológico de los pacientes sépticos y 2) investigar la asociación entre los parámetros de laboratorio/clínicos y la tasa de mortalidad, identificando marcadores pronósticos. Mediante un protocolo observacional prospectivo, se recogieron datos epidemiológicos, clínicos y de laboratorio de pacientes adultos con sepsis o shock séptico ingresados en una Unidad de Cuidados Intensivos brasileña. Durante el período de estudio, 120 pacientes fueron diagnosticados de sepsis y el 71,67% (n = 86) fueron incluidos en el protocolo. La mortalidad global fue del 69,76% y se identificaron enfermedades crónicas en el 79,07% de los casos. Las tasas de mortalidad por sepsis y shock séptico fueron del 51,06% y el 92,31%, respectivamente. Las puntuaciones SOFA en el primer, tercer y séptimo día de hospitalización aumentaron gradualmente en los pacientes que presentaron empeoramiento clínico. La hiperlactatemia y la hiperglucemia se identificaron en el 45,9% y el 27% de los pacientes, respectivamente, y se asociaron a mortalidad. Los valores de INR superiores a 1,5 o la trombocitopenia se relacionaron con un 92,9% y un 88,6% de mortalidad, respectivamente. En el estudio, el sexo, la edad, la estancia en la UCI, el lugar de la infección y el agente microbiológico no se asociaron con el riesgo de muerte. Sin embargo, la presencia de comorbilidades, las puntuaciones SOFA elevadas, tres o más disfunciones orgánicas y la gravedad de la sepsis se correlacionaron directamente con la tasa de mortalidad.

Pediatric Evans Syndrome: A 20-year experience from a tertiary center in Brazil

Abstract Introduction The Evans syndrome (ES) is a rare, often chronic, relapsing and treatment-refractory hematological disorder. We described the clinical features, diagnostic workup, treatment and outcome in patients with ES. Method We performed a retrospective chart review of patients aged < 18 years with ES admitted to a tertiary center in Brazil from 2001 to 2021. The analysis of the data was primarily descriptive, using median, interquartile range and categorical variables presented in absolute frequencies. Main results Twenty patients (12 female, 8 male) were evaluated in this study. The median age at the initial cytopenia was 4.98 years (1.30-12.57). The ES was secondary in nine cases (45%), of which six patients (30%) showed autoimmune disease (AID) or primary immunodeficiencies (PID) and one presented a spontaneous recovery. Steroids and intravenous immunoglobulin were first-line therapy in 19 cases. Twelve patients (63%) required second-line treatments (rituximab, cyclosporine, splenectomy, sirolimus, cyclophosphamide, mycophenolate mofetil, azathioprine and eltrombopag). The median follow-up period was 2.41 years (1.4 -7.52). One patient (5%) died of underlying neuroblastoma, one case (5%) was lost to follow-up and four patients (20%) received a medical discharge. The median age for the 14 remaining cases was 12.6 years. Twelve patients (85.7%) were in complete response (CR) with no therapies. Two patients (14.3%) were in CR with chronic therapy. Conclusion As ES may be a symptom of AID and PID, a thorough rheumatological, immunologic and genetic workup and a careful follow-up are essential. The second-line treatment remains a dilemma. Further prospective studies are needed to address the optimal therapeutic combinations, morbidity and mortality in this disorder.

Análisis molecular de un paciente boliviano con trombocitopenia sindrómica relacionada al gen myh9 / Análisis molecular de un paciente boliviano con trombocitopenia sindrómica relacionada al gen myh9

La trombocitopenia como motivo de consulta, requiere la búsqueda intencionada de orientar manifestaciones extrahematológicas. La megacariogénesis pasa por distintas etapas dependientes de la interacción de varios genes, entre ellos el MYH9, cuya expresión permite una adecuada formación y migración de las proplaquetas al ser liberadas al torrente sanguíneo, al mismo tiempo, existen estructuras con fisiología similar a nivel de citoesqueleto (podocitos, cilios cocleares, etc.) que podrían vincular a datos de pérdida de audición, enfermedad renal, cataratas y elevación de enzimas hepáticas conllevando a una enfermedad relacionada al gen MYH9. Se presenta el caso de un adolescente, de sexo masculino, con trombocitopenia recurrente, con el antecedente de padre con coagulopatía inespecífica, pérdida de audición, falla renal crónica, quien falleció a los 34 años por hemorragia intraparenquimatosa y edema cerebral severo, en quien se identifica una variante patogénica en heterocigosis en el gen MYH9, poniendo en relevancia la expresividad variable y efectos pleiotrópicos de este gen.

Thrombocytopenia as a reason for consultation requires an intense search to guide extrahematological manifestations. Megakaryogenesis goes through different stages depending on the interaction of several genes, including MYH9, whose expression allows proper formation and migration of proplatelets when released into the bloodstream, at the same time, there are structures with similar physiology at the cytoskeleton level (podocytes, cochlear cilia, etc.) that could be linked to data on hearing loss, kidney disease, cataracts and elevated liver enzymes leading to a disease related to the MYH9 gene. We present the case of an adolescent, male, with recurrent thrombocytopenia, with a history of a father with nonspecific coagulopathy, hearing loss, chronic kidney failure, who died at the age of 34 due to intraparenchymal hemorrhage and severe cerebral edema, in whom identifies a heterozygous pathogenic variant in the MYH9 gene, highlighting the variable expressivity and pleiotropic effects of this gene.

Risk Factors of Thrombocytopenia After Cardiac Surgery with Cardiopulmonary Bypass

ABSTRACT Introduction: Postoperative thrombocytopenia is common in cardiac surgery with cardiopulmonary bypass, and its risk factors are unclear. Methods: This retrospective study enrolled 3,175 adult patients undergoing valve surgeries with cardiopulmonary bypass from January 1, 2017 to December 30, 2018 in our institute. Postoperative thrombocytopenia was defined as the first postoperative platelet count below the 10th quantile in all the enrolled patients. Outcomes between patients with and without postoperative thrombocytopenia were compared. The primary outcome was in-hospital mortality. Risk factors of postoperative thrombocytopenia were assessed by logistic regression analysis. Results: The 10th quantile of all enrolled patients (75×109/L) was defined as the threshold for postoperative thrombocytopenia. In-hospital mortality was comparable between thrombocytopenia and non-thrombocytopenia groups (0.9% vs. 0.6%, P=0.434). Patients in the thrombocytopenia group had higher rate of postoperative blood transfusion (5.9% vs. 3.2%, P=0.014), more chest drainage volume (735 [550-1080] vs. 560 [430-730] ml, P<0.001), and higher incidence of acute kidney injury (12.3% vs. 4.2%, P<0.001). Age > 60 years (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.345-3.765, P=0.002], preoperative thrombocytopenia (OR 18.671, 95% CI 13.649-25.542, P<0.001), and cardiopulmonary bypass time (OR 1.088, 95% CI 1.059-1.117, P<0.001) were positively independently associated with postoperative thrombocytopenia. Body surface area (BSA) (OR 0.247, 95% CI 0.114-0.538, P<0.001) and isolated mitral valve surgery (OR 0.475, 95% CI 0.294-0.77) were negatively independently associated with postoperative thrombocytopenia. Conclusion: Positive predictors for thrombocytopenia after valve surgery included age > 60 years, small BSA, preoperative thrombocytopenia, and cardiopulmonary bypass time. BSA and isolated mitral valve surgery were negative predictors.

Serum B7 homologous protein 2, tumor necrosis factor-related apoptosis-inducing ligand, interleukin-37, interleukin-17A levels in patients with primary immune thrombocytopenia and their clinical significance / 中国医师进修杂志

Objective:To explore the changes of serum B7 homolog 2 (B7-H2), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interleukin(IL)-37 and IL-17A levels in patients with primary immune thrombocytopenia (ITP), and to analyze the clinical guiding significance of each index level in the diagnosis and treatment of ITP.Methods:A total of 90 patients with ITP treated in Jining Hospital of Traditional Chinese Medicine from September 2018 to September 2020 were retrospectively selected as the research group, and 90 healthy patients during the same period were selected as the normal control group. The levels of serum B7-H2, TRAIL, IL-37, IL-17A and platelet count (PLT) in the two groups were compared, and the clinical guidance significance of each index level in the diagnosis and treatment of ITP were analyzed by receiver operating characteristic(ROC) curve.Results:The serum levels of B7-H2, TRAIL, IL-37 and IL-17A in the research group were higher than those in the normal control group, and PLT was lower than that in the normal control group: (25.12 ± 4.29) μg/L vs. (12.26 ± 3.10) μg/L, (0.92 ± 0.20) μg/L vs.(0.46 ± 0.13) μg/L, (145.02 ± 43.18) ng/L vs. (50.23 ± 14.07) ng/L, (21.63 ± 5.06) ng/L vs. (7.71 ± 2.04) ng/L, (16.12 ± 4.61) × 10 9/L vs. (200.86 ± 61.4) × 10 9/L, there were statistical differences ( P<0.05). After treatment for 3 months, 73 patients obtained remission, and 13 patients were non-remission. The levels of B7-H2, TRAIL, IL-37, IL-17A in the non-remission group before and after treatment were higher than those in the remission group, and PLT was lower than that in the remission group, there were statistical differences ( P<0.05). Pearson correlation analysis showed that the levels of serum B7-H2, TRAIL, IL-37 and IL-17A were negatively correlated with PLT ( P<0.05). The ROC curve analysis showed that the area under the curve of serum B7-H2, TRAIL, IL-37 and IL-17A in prognostic prediction was 0.916, the sensitivity and the specificity were 94.12% and 86.30%. Conclusions:The serum levels of B7-H2, TRAIL, IL-37 and IL-17A in patients with ITP are significantly elevated, and are closely related to the level of PLT. Combined detection can help clinically predict the direction of disease outcome.

Diagnosis and treatment recommendations and case study of severe thrombocytopenia caused by tirofiban / 中国输血杂志

【Objective】 To investigate the clinical manifestations, diagnosis, differential diagnosis and management strategies of thrombocytopenia caused by tirofiban. 【Methods】 The basic clinical data, platelet count changes and treatment course of 7 patients with acute coronary syndrome who used tirofiban resulting in severe thrombocytopenia during their hospitalization in our hospital from December 2021 to March 2023 were collected, and their individual and common characteristics were analyzed. 【Results】 Platelet counts were in the normal range in all 7 patients on admission. Six of the patients had thrombocytopenia occurring from 3 to 16 hours after tirofiban use, and one patient was detected at 34 h of tirofiban use. Their minimum platelet count ranged from (1-11)×109/L. All 7 cases discontinued tirofiban and other antithrombotic drugs, and the platelet count increased to 50×109/L in 6 patients in 2 to 4 days after stopping the drug and gradually returned to the normal range. During this period, there were no bleeding or acute thrombotic events, and no platelet transfusion was conducted. Five patients resumed antithrombotic therapy when the platelet count returned to (20-50)×109/L, 1 patient underwent elective coronary artery bypass grafting (CABG) surgery when the count rose above 50×109/L. One patient had bleeding manifestations after thrombocytopenia and required limited-duration CABG surgery, so 3 U platelet transfusion and immunoglobulin treatment were performed consecutively. CABG surgery was performed when the platelet count increased to 76×109/L. The differential diagnosis of the cause of thrombocytopenia was performed in all seven patients, and other causes of thrombocytopenia, such as heparin, were excluded. 【Conclusion】 Tirofiban can cause acute severe or extremely severe thrombocytopenia. Routine platelet count testing at 6 hours after medication can prevent serious adverse events by discontinuing tirofiban promptly after thrombocytopenia occurs. At the same time, it is determined whether to perform platelet transfusion based on whether the patient has bleeding and the risk of bleeding, and the timing of resuming antithrombotic treatment is determined based on the recovery of platelet count and the risk of thrombosis.