Validez de herramientas diagnósticas en pacientes pediátricos hospitalizados con diagnóstico presuntivo de dengue en un Hospital de Referencia de Paraguay / Validity of diagnostic tools in pediatric patients hospitalized with a presumptive diagnosis of dengue in a Reference Hospital in Paraguay

Introducción: El dengue es la enfermedad arboviral más común en los seres humanos. Un diagnóstico temprano y preciso del dengue puede respaldar el manejo clínico, la vigilancia y el control de la enfermedad y es fundamental, por ello en el diagnóstico del dengue es importante contar con pautas clínicas y epidemiológicas que permitan la identificación oportuna y una conducta terapéutica adecuada. Objetivos: Evaluar la validez de herramientas diagnósticas en pacientes pediátricos hospitalizados con diagnóstico presuntivo de dengue en un Hospital de Referencia de Paraguay durante los años de 2012 a 2020. Materiales y métodos: Estudio analítico de tipo observacional, retrospectivo correspondientes a pacientes pediátricos (0 a 18 años) internados en el Hospital de Referencia de Paraguay el periodo enero 2012 a julio 2020 con diagnostico presuntivo de dengue al ingreso. Se realizó́ un análisis bivariado relacionando las frecuencias de 20 grupos de criterios diagnósticos combinados y 3 criterios diagnósticos aislados (OMS 2009, nexo epidemiológico y antigenemia NS1 para dengue) con el gold standard de diagnóstico que fue la conversión serológica. Resultados: Participaron del estudio 342 sujetos. EL 44% tenía edad escolar y 70% tenía 5 años o más. El 52,76% (191) fueron masculinos. Se encontraron desnutrición y sobrepeso en el 13% y 2%, respectivamente. La combinación de proteína C reactiva con plaquetopenia se encontró́ en 0.45% de los pacientes sin dengue y en el 6% de los pacientes con diagnóstico final de dengue (p=0.004). Conclusión: Este resultado aporta la alternativa de uso de una combinación sencilla de exámenes de laboratorio que puede replicarse en salas de urgencias como en salas de internación en un primer contacto con pacientes febriles con sospecha de fiebre dengue.

Introduction: Dengue is the most common arboviral disease in humans. An early and accurate diagnosis of dengue can support the clinical management, surveillance and control of the disease and is essential, therefore in the diagnosis of dengue it is important to have clinical and epidemiological guidelines that allow timely identification and appropriate therapeutic conduct. Objectives: To evaluate the validity of diagnostic tools in pediatric patients hospitalized with a presumptive diagnosis of dengue in a Reference Hospital in Paraguay during the years 2012 to 2020. Materials and methods: Analytical study of case and control type, observational, longitudinal, retrospective corresponding to pediatric patients (0 to 18 years) admitted to the Reference Hospital of Paraguay from January 2012 to July 2020 with a presumptive diagnosis of dengue at income. A bivariate analysis was performed relating the frequencies of 20 groups of combined diagnostic criteria and 3 isolated diagnostic criteria (WHO 2009, epidemiological link and NS1 antigenemia for dengue) with the gold standard of diagnosis, which was serological conversion. Results: 342 subjects participated in the study. 44% were school age and 70% were 5 years old or older. 52.76% (191) were male. Malnutrition and overweight were found in 13% and 2%, respectively. The combination of C-reactive protein with thrombocytopenia was found in 0.45% of patients without dengue and in 6% of patients with a final diagnosis of dengue (p=0.004). Conclusion: This result provides the alternative of using a simple combination of laboratory tests that can be replicated in emergency rooms and inpatient wards in a first contact with febrile patients with suspected dengue fever.

Estudio observacional de las características clínicas, epidemiológicas y de laboratorio en pacientes pediátricos con dengue de la ciudad de Córdoba / Observational study of clinical, epidemiological, and laboratory characteristics of pediatric patients with dengue in the city of Córdoba

Introducción. El dengue es la enfermedad transmitida por mosquitos con mayor propagación mundial en los últimos años. Presenta un amplio espectro de manifestaciones clínicas y, en ocasiones, evoluciona a un estado crítico llamado dengue grave. Su tratamiento es de sostén. La información disponible acerca de las características clínicas, epidemiológicas y de laboratorio de la enfermedad en la población pediátrica es limitada. Objetivo. Describir la epidemiología y las manifestaciones clínicas y de laboratorio de la enfermedad. Población y métodos. Estudio descriptivo, observacional y retrospectivo. Incluyó pacientes entre 1 y 180 meses asistidos por dengue probable o confirmado en un hospital de niños, desde el 01 de enero de 2020 hasta el 31 de mayo de 2020. Resultados. Se incluyeron 85 pacientes por criterios microbiológicos de positividad o clínicoepidemiológicos. Veinticinco (29 %) confirmados por RT-PCR, todos serotipos DENV-1. La mediana de  edad fue de 108 meses (rango intercuartílico: 84-144). Las principales manifestaciones clínicas fueron fiebre, cefalea y mialgias. Los hallazgos de laboratorio más importantes fueron leucopenia, trombocitopenia y elevación de transaminasas. Conclusión. El reconocimiento y la comprensión de las alteraciones clínicas y de laboratorio que se presentan durante la enfermedad pueden permitir un abordaje eficaz y contribuir a la reducción de cuadros clínicos más graves en los niños.

Introduction. Dengue has been the most widespread mosquito-borne disease worldwide in recent years. It develops with a broad spectrum of clinical manifestations and sometimes progresses to a critical condition known as severe dengue. It is managed with supportive treatment. Available information about its clinical, epidemiological, and laboratory characteristics in the pediatric population is limited. Objective. To describe the clinical, epidemiological, and laboratory characteristics of dengue. Population and methods. Descriptive, observational, and retrospective study. It included patients aged 1 to 180 months seen due to probable or confirmed dengue at a children's hospital between 1/1/2020 and 5/31/2020. Results. A total of 85 patients with positive microbiological or clinical-epidemiological criteria were included. Of these, 25 (29%) were confirmed by RT-PCR; all corresponded to DENV-1 serotype. Patients' median age was 108 months (interquartile range: 84­144). The main clinical manifestations were fever, headache, and myalgia. The most important laboratory findings were leukopenia, thrombocytopenia, and high transaminase levels. Conclusion. The recognition and understanding of clinical and laboratory alterations that occur during dengue disease may allow an effective approach and help to reduce the more severe clinical form in children.

Síndrome hemolítico urémico secundario a Streptococcus pneumoniae. Reporte de un caso clínico / Streptococcus pneumoniae associated hemolytic uremic syndrome. Case report

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.

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.

Non-muscle myosin heavy chain 9 gene-related disorders with thrombocytopenia: report of two pedigrees and literature review / 中华儿科杂志

Objective: To summarize the clinical characteristics and gene variants of 2 pedigrees of non-muscle myosin heavy chain 9 related diseases (MYH9-RD) in children. Methods: The basic information, clinical features, gene variants and laboratory tests of MYH9-RD patients from 2 pedigrees confirmed in the First Affiliated Hospital of Zhengzhou University in November 2021 and July 2022 were analyzed retrospectively. "Non-muscle myosin heavy chain 9 related disease" "MYH9" and "children" were used as key words to search at Pubmed database, CNKI and Wanfang database up to February 2023. The MYH9-RD gene variant spectrum and clinical data were analyzed and summarized. Results: Proband 1 (male, 11 years old) sought medical attention due to epistaxis, the eldest sister and second sister of proband 1 only showed excessive menstrual bleeding, the skin and mucous membrane of the their mother were prone to ecchymosis after bumping, the uncle of proband 1 had kidney damage, and the maternal grandmother and maternal great-grandmother of proband 1 had a history of cataracts. There were 7 cases of phenotypic abnormalities in this pedigree. High-throughput sequencing showed that the proband 1 MYH9 gene had c.279C>G (p.N93K) missense variant, and family verification analysis showed that the variant was inherited from the mother. A total of 4 patients including proband 1 and family members were diagnosed with MYH9-RD. The proband 2 (female, 1 year old) sought medical attention duo to fever and cough, and the father's physical examination revealed thrombocytopenia. There were 2 cases of phenotypic abnormalities in this pedigree. High-throughput sequencing showed that there was a c.4270G>A (p.D1424N) missense variant in the proband 2 MYH9 gene, and family verification analysis showed that the variant was inherited from the father. A total of 2 patients including proband 2 and his father were diagnosed with MYH9-RD. A total of 99 articles were retrieved, including 32 domestic literatures and 67 foreign literatures. The MYH9-RD cases totaled 149 pedigrees and 197 sporadic patients, including 2 pedigrees in our study. There were 101 cases with complete clinical data, including 62 sporadic cases and 39 pedigrees. There were 56 males and 45 females, with an average age of 6.9 years old. The main clinical manifestations were thrombocytopenia, skin ecchymosis, and epistaxis. Most patients didn't receive special treatment after diagnosis. Six English literatures related to MYH9-RD caused by c.279C>G mutation in MYH9 gene were retrieved. Italy reported the highest number of cases (3 cases). Twelve literatures related to MYH9-RD caused by c.4270G>A mutation in MYH9 gene were retrieved. China reported the highest number of cases (9 cases). Conclusions: The clinical manifestations of patients in the MYH9-RD pedigrees varied greatly. MYH9 gene c.279C>G and c.4270G>A mutations are the cause of MYH9-RD.

Connotation of distal bleeding based on modern pathophysiological mechanism and application of Huangtu Decoction for acute coronary syndrome complicated with acute upper gastrointestinal hemorrhage in critical care medicine / 中国中药杂志

Huangtu Decoction, first recorded in Essentials from the Golden Cabinet(Jin Kui Yao Lue) from ZHANG Zhong-jing in Han dynasty, is used to treat distal bleeding. It is mainly treated for the syndrome of failing to control blood with spleen-yang deficiency. The connotation of distal bleeding is more extensive, including not only upper gastrointestinal bleeding in the traditional sense such as peptic ulcer bleeding, gastrointestinal tumors, gastric mucosal lesions, vascular dysplasia, esophagogastric variceal bleeding, and pancreatic and biliary tract injury, but also other anorectal diseases such as part colon and rectal cancer swelling or polyps, hemorrhoids, and anal fissure and other parts of bleeding such as epistaxis, thrombocytopenia, functional uterine bleeding, threatened abortion, and unexplained hematuria. Distal bleeding also involves syndromes of failing to keep part deficient and cold fluids in interior, such as nocturia, enuresis, clear nose, sweating, cold tears, and leucorrhea, and excessive gastrointestinal bleeding caused by anti-plate and anticoagulant drugs, unexplained positive in the fecal occult blood test, and other modern clinical new problems. The indications of Huangtu Decoction include not only lower blood, defecation before blood, distant blood, hematemesis, epistaxis, and other diseases in traditional Chinese medicine, but also three types of clinical manifestations including bleeding, deficiency syndrome, and stagnant heat syndrome. In the clinic, Huangtu Decoction can be used to treat acute upper gastrointestinal bleeding, acute coronary syndrome complicated with acute upper gastrointestinal bleeding, bleeding events caused by excessive antiplatelet and anticoagulant drugs, unexplained positive in the fecal occult blood test, gastrointestinal tumor with bleeding, thrombocytopenia, and other acute and critical diseases. The dosage of Cooking Stove Earthkey, Rehmanniae Radix, and Asini Corii Colla in Huangtu Decoction is the key to hemostasis.

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

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

Immune Thrombocytopenia Induced by Sintilimab in Lung Cancer: A Case Report and Literature Review / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) show unique advantages in the treatment of lung cancer, making the treatment of lung cancer enter the era of immunotherapy, but ICIs will also have adverse reactions, and the incidence of immune-induced hematological toxicity is not very high. Immunotherapy-induced thrombocytopenia is a rare adverse event.We report one case of thrombocytopenia induced by ICIs and review the literature on thrombocytopenia associated with ICIs and discuss the clinical features, possible mechanisms, and optimal treatment. 
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Clinical Anslysis of TAFRO Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics, diagnosis, and treatment of one patient with TAFRO syndrome, and to strengthen the understanding of this rare type.@*METHODS@#The clinical manifestations, diagnosis and treatment process, and prognosis of the patient admitted in Gansu Provincial People's Hospital were retrospectively analyzed.@*RESULTS@#Combined with laboratory tests, bone marrow examination, imaging, pathology, etc, the patient was diagnosed with TAFRO syndrome. After three cycles of treatment with pomalidomide (2-3 mg/d, d1-21), cyclophosphamide (300 mg/m2, 0.54 g once a week) and dexamethasone (20 mg/d, two days a week), platelet count, serum creatinine and procalcitonin returned to normal, the systemic edema disappeared, and the patient's condition was alleviated. The therapeutic effect was good.@*CONCLUSION@#TAFRO syndrome is rare, involves multiple systems, progresses rapidly, and has a worse prognosis. The choice of the "Pomalidomide+cyclophosphamide+dexamethasone" regimen is help to improve the survival prognosis of patient with TAFRO syndrome.

Chinese expert consensus on the clinical management of liver disease-associated thrombocytopenia syndrome / 中华肝脏病杂志

Liver disease-associated thrombocytopenia syndrome refers to thrombocytopenia caused by liver disease or the treatment of liver disease, and its incidence rate is related to the duration and severity of liver disease. The direct effect of thrombocytopenia on clinical outcomes is an increased risk of bleeding in patients with liver disease, whereas the indirect effect involves delay or termination of treatment due to the potential risk of bleeding. Liver disease-associated thrombocytopenia pathophysiological mechanisms involve decreased platelet production, abnormal distribution, destruction, or increased consumption. Presently, treatment strategies targeting different mechanisms include platelet-stimulating drugs, surgery, immunosuppressive drugs, and platelet transfusion, but the clinical application needs to be standardized further. The National Clinical Research Center for Infectious Diseases organized experts to discuss and formulate consensus with reference to the latest evidence-based medical evidence in the field so as to improve the clinical management level of liver disease-associated thrombocytopenia syndrome in China in terms of diagnosis, typing, and reasonable selection of treatment schemes.

Genetic analysis of a child with atypical Hemolytic uremic syndrome and nephrotic-range proteinuria / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology for a child with atypical Hemolytic uremic syndrome (aHUS) in conjunct with nephrotic level proteinuria.@*METHODS@#A child patient who had visited the Affiliated Hospital of Qingdao University on June 25, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing of the child and his parents.@*RESULTS@#The child, an 8-month-old male, had presented mainly with edema, oliguria, hematuria, nephrotic level proteinuria, anemia, thrombocytopenia, increased creatinine and urea, hypercholesterolemia but normal complement levels. Genetic testing revealed that he has harbored compound heterozygous variants of the DGKE gene, namely c.12_18dupGAGGCGG (p.P7fs*37) and c.1042G>T (p.D348Y), which were respectively inherited from his father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as likely pathogenic and variant of uncertain significance, respectively. By combining his clinical manifestations and results of genetic testing, the child was diagnosed with aHUS with nephrotic level proteinuria.@*CONCLUSION@#For infants and young children with aHUS in conjunct with nephrotic level proteinuria, variants of the DGKE gene should be screened. Above finding has expanded the mutational spectrum of the DGKE gene.

Factors influencing severe cytopenia in chronic phase chronic myeloid leukemia patients receiving initial second generation tyrosine kinase inhibitors and its impact on treatment responses and outcomes / 中华血液学杂志

Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.

Role of coagulation dysfunction in thrombocytopenia-related death in patients with septic shock / 中华危重病急救医学

OBJECTIVE@#To explore the effect of thrombocytopenia on the prognosis of patients with septic shock and its mechanism in leading to death.@*METHODS@#A retrospective case-control study was conducted. Patients with septic shock admitted to emergency intensive care unit (EICU) and intensive care unit (ICU) in Peking University People's Hospital from April 1, 2015 to January 31, 2023 were enrolled. Patients were divided into the thrombocytopenia group and the non-thrombocytopenia group, according to whether the minimum platelet count was less than 100×109/L within 24 hours after admission to ICU. The outcome index was the mortality during ICU stay. The baseline data, hospitalization information and laboratory test results of the two groups were compared, and the risk factors of in-hospital death were analyzed by Logistic regression, and the mediation effect was performed by Bootstrap method.@*RESULTS@#A total of 301 patients with septic shock were enrolled, of which 172 (57.1%) had thrombocytopenia and 129 (42.9%) did not. There were significant differences between the two groups in age, mortality, disseminated intravascular coagulation (DIC), continuous renal replacement therapy, and level of creatinine, urea nitrogen, total bilirubin, white blood cell count, lymphocyte count, prothrombin time (PT) and activated partial thromboplastin time (APTT). Univariate Logistic regression analysis showed thrombocytopenia [odds ratio (OR) = 4.478], continuous renal replacement therapy (OR = 4.601), DIC (OR = 6.248), serum creatinine (OR = 1.005), urea nitrogen (OR = 1.126), total bilirubin (OR = 1.006) and PT (OR = 1.126) were risk factors of death during hospitalization in patients with septic shock (all P < 0.05). Multivariate Logistic regression analysis showed that thrombocytopenia [OR = 3.338, 95% confidence interval (95%CI) was 1.910-5.834, P = 0.000], continuous renal replacement therapy (OR = 3.175, 95%CI was 1.576-6.395, P = 0.001) and PT (OR = 1.077, 95%CI was 1.011-1.147, P = 0.021) were independent risk factors for in-hospital mortality in patients with septic shock. Mediation analysis showed that 51% of the deaths due to thrombocytopenia in patients with septic shock were due to coagulopathy.@*CONCLUSIONS@#Thrombocytopenia is a powerful predictor of death in septic shock patients, and half of all thrombocytopenia-related deaths may be due to abnormal coagulation function.

Research Progress on Risk Factors and Intervention Measures for Prolonged Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation --Review / 中国实验血液学杂志

Prolonged thrombocytopenia (PT) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with an incidence of about 5%-37%, which is closely related to the poor prognosis of patients. Previous studies have shown that transplantation type, CD34+ cell number, pretreatment regimen, acute graft-versus-host disease, virus infection, pre-transplantation serum ferritin level and donor specific antibodies can affect platelet implantation after transplantation. Identifying the risk factors of PT is helpful to early identify high-risk patients and take targeted preventive measures according to different risk factors to reduce the incidence of PT, reduce the risk of bleeding and improve the prognosis of patients. This article reviews the latest research progress of risk factors and intervention measures related to PT after allo-HSCT, in order to provide reference for the prevention and treatment of PT after transplantation.

Advances in the Treatment of Glucocorticoid Resistance and Relapsed Immune Thrombocytopenia --Review / 中国实验血液学杂志

Immune thrombocytopenia (ITP) is an immune-mediated acquired hemorrhagic autoimmune disease. At present, the first-line therapeutic drugs for ITP include glucocorticoids and intravenous immunoglobulins. However, about 1/3 of the patients had no response to the first-line treatment, or relapsed after dose reduction or withdrawal of glucocorticoids. In recent years, with the gradual deepening of the understanding on the pathogenesis of ITP, the drugs targeting different pathogenesis continually emerge, including immunomodulators, demethylating agents, spleen tyrosine kinase (SYK) inhibitors and neonatal Fc receptor (FcRn) antagonist. However, most of these drugs are in clinical trials. This review summarized briefly the recent advances in the treatment of glucocorticoids resistance and relapsed ITP, so as to provide reference for the clinical treatments.

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.

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.

Trombocitopenia no paciente crítico oncológico e sua relação com a ocorrência de sangramentos / Thrombocytopenia in critical cancer patients and its relationship with the occurrence of bleeding

INTRODUÇÃO: A trombocitopenia é uma complicação comum em pacientes com câncer e nos pacientes críticos. A trombocitopenia está associada a maior mortalidade e sangramento nestas populações, porém não está descrita a associação do nível de plaquetas com sangramentos nos pacientes críticos com câncer. Também é escassa a descrição dos desfechos da trombocitopenia e da transfusão profilática de plaquetas em pacientes críticos com câncer. Finalmente não foi avaliado se o tipo de câncer está associado a sangramento espontâneo em pacientes críticos com câncer. OBJETIVO: Descrever as características e desfechos dos pacientes críticos com câncer e trombocitopenia grave na internação na UTI. Avaliar a associação do nível da trombocitopenia e do tipo de câncer (tumor sólido ou câncer hematológico) com a ocorrência de sangramentos espontâneos nos pacientes críticos com câncer. MATERIAL E MÉTODOS: Estudo observacional com dados coletados prospectivamente que analisou pacientes críticos com câncer em atividade e trombocitopenia grave na internação na UTI. O desfecho primário do estudo foi a ocorrência de sangramentos espontâneos. Para estudar a associação entre nível plaquetário ou tipo de câncer com a ocorrência de sangramentos espontâneo foi usada uma regressão logística ajustada para confundidores reconhecidos por directed acyclic graph. RESULTADOS: As características dos pacientes críticos com câncer na internação e durante a estadia na UTI são majoritariamente similares entre pacientes com e sem sangramento, e entre pacientes com sangramento maior ou menor. Todos os pacientes que tiveram sangramento espontâneo não haviam recebido transfusão profilática de plaquetas nas 24 horas que precederam o sangramento. O tipo de câncer não foi associado ao sangramento espontâneo com razão de chance ajustada de com neoplasias hematológicas de 0,6 (0,4-1,2). Níveis baixos de plaquetas foram associados a maior frequência de sangramentos espontâneos. A razão de chance ajustada para nível de plaquetas entre 20 e 49 x 109 /l foi de 4,5 (1,1-19,1), enquanto a razão de chance ajustada para nível de plaquetas < 20 x 109 /L foi de 17,4 (3,9-77,8). CONCLUSÃO: Mostramos a associação entre menores níveis de contagens de plaquetas com maior incidência de sangramento vii espontâneo em pacientes críticos com câncer. No entanto, não houve associação do tipo de câncer com sangramento espontâneo.

INTRODUCTION: Thrombocytopenia is a common complication in cancer patients and critically ill patients. Thrombocytopenia is associated with higher mortality and bleeding in these populations, but the association of platelet levels with bleeding in critically ill patients with cancer has not been well described. There are also few descriptions of the outcomes of thrombocytopenia and prophylactic platelet transfusion in critically ill patients with cancer. Finally, whether the type of cancer is associated with spontaneous bleeding, in critically ill cancer patients it has not been evaluated. OBJECTIVE: Describe the characteristics and outcomes of critically ill patients with cancer and severe thrombocytopenia when admitted to the ICU and evaluate the association between the level of thrombocytopenia and the type of cancer (solid tumor or hematological cancer) with the occurrence of spontaneous bleeding in critically ill patients with cancer. MATERIAL AND METHODS: Observational study with prospectively collected data that analyzed critically ill patients with active cancer and severe thrombocytopenia during ICU admission. The primary outcome of the study was the occurrence of spontaneous bleeding. To study the association between platelet level or type of cancer with the occurrence of spontaneous bleeding, a logistic regression adjusted for confounders recognized by directed acyclic graph was used. RESULTS: The characteristics of critically ill patients with cancer at admission and during the ICU stay are mostly similar between patients with and without bleeding, and between patients with major or minor bleeding. All patients who had spontaneous bleeding had not received prophylactic platelet transfusions in 24 hours preceding the bleeding. The type of cancer was not associated with spontaneous bleeding with an adjusted odds ratio of with hematologic malignancies of 0.6 (0.4-1.2). Low platelet levels have been associated with a higher frequency of spontaneous bleeding. The adjusted odds ratio for a platelet level between 49 and 20 x 109 /L was 4.5 (1.1- 19.1), while the adjusted odds ratio for a platelet level < 20 x 109 /L was 17.4 (3.9-77.8). CONCLUSION: We showed the association between lower levels of platelet counts and a higher incidence of spontaneous bleeding in critically ill cancer patients. However, there was no association between the type of cancer and spontaneous bleeding.

Síndrome de Evans asociada a infección por citomegalovirus en una niña de 13 meses / Evans Syndrome Associated With Cytomegalovirus Infection In A 13-Month-Old Girl

Introducción: El síndrome de Evans es un desorden autoinmune poco frecuente, caracterizado por el descenso de al menos dos líneas celulares hemáticas. Las publicaciones del síndrome de Evans e infección por citomegalovirus resultan escasas. Objetivo: Examinar el caso de una niña con síndrome de Evans e infección activa por citomegalovirus que respondió favorablemente a la terapia antiviral. Presentación del caso: Niña de 13 meses con antecedentes de prematuridad y bajo peso al nacer, que acudió a consulta por presentar palidez y equimosis en tórax, abdomen y extremidades. En los exámenes de laboratorio se encontró trombocitopenia y anemia severa con prueba de Coombs directo positiva. Recibió pulsos de metilprednisolona con respuesta desfavorable. La carga viral resultó positiva para citomegalovirus (4019 copias de ADN) y recibió valganciclovir con evolución favorable en el seguimiento. Conclusiones: El síndrome de Evans asociado a infección por CMV es infrecuente. El tratamiento con valganciclovir podría ser beneficioso para cierto grupo de pacientes; sin embargo, hacen falta más estudios que demuestren la eficacia y seguridad de este tratamiento en este síndrome; más aún si está asociado a una elevada carga viral(AU)

Introduction: Evans syndrome is a rare autoimmune disorder, characterized by the descent of at least two blood cell lines. Publications of Evans syndrome and cytomegalovirus infection are scarce. Objective: To examine the case of a girl with Evans syndrome and active cytomegalovirus infection who responded favorably to antiviral therapy. Case presentation: A 13-month-old girl with a history of prematurity and low birth weight, who attended the consultation for presenting pallor and ecchymosis in the thorax, abdomen and extremities. Laboratory tests found thrombocytopenia and severe anemia after a positive direct Coombs test. She received pulses of methylprednisolone with unfavorable response. The viral load was positive for cytomegalovirus (4019 copies of DNA) and received valganciclovir with favorable evolution at follow-up. Conclusions: Evans syndrome associated with CMV infection is uncommon. Treatment with valganciclovir may be beneficial for a certain group of patients. However, more studies are needed to demonstrate the efficacy and safety of this treatment in this syndrome; even more so if it is associated with a high viral load(AU)