Bleeding Manifestations Research Articles

Risk factors for dengue mortality: a 7-year retrospective cohort in Honduras

BackgroundDengue is the viral disease with the highest morbidity and mortality rates worldwide. The aim of this study was to describe the epidemiological trends of dengue cases and dengue death cases and identify the demographic, clinical and laboratory risk factors for dengue mortality in Honduras.MethodsA retrospective cohort study of suspected cases of dengue between 2016 and 2022 was conducted. Patients of the 18 departments of the country were included. Patients were classified as deceased and alive. In the univariate analysis, normality test was assessed. In bivariate analysis, the chi-square and Mann Whitney U tests were used as appropriate. Crude odds ratios (cOR) with their respective 95% confidence intervals (CIs), were estimated to determine the risk of death due to dengue. In multivariate analysis, a logistic regression model was built.ResultsA total of 23,811 suspected cases of dengue were recorded, of which 14,927 tested positive, resulting in 242 deaths. The predominant sex among both deceased and surviving patients was female, 54.1% and 54.2%, respectively. Among the deceased, the largest age group was 5–9 years (32.6%), followed by 20–49 years (26.9%). Among surviving patients, the largest age groups were 20–49 years (28.9%) and 10–19 years (28.2%). Francisco Morazán reported the most dengue cases, while Cortés had the highest dengue deaths. Risk factors for dengue mortality included older age (> 60 years; adjusted OR 3.30, 95% CI 1.08–10.09), residence in the departments of Choluteca (aOR 19.40, 95% CI 4.75–79.30), Cortés (aOR 6.57, 95% CI 2.00–21.47), and Yoro (aOR 10.80, 95% CI 2.97–39.26), clinical manifestations of bleeding (aOR 1.81, 95% CI 1.09–3.00), clinical manifestations of plasma leakage (aOR 1.72, 95% CI 1.53–1.93), shock (aOR 10.70, 95% CI 7.90–14.50), lethargy (aOR 1.80, 95% CI 1.25–2.59), presence of comorbidities (aOR 1.89, 95% CI 1.08–3.29), and pregnancy (aOR 2.18, 95% CI 1.37–3.48).ConclusionOlder age; residence in the departments of Choluteca, Cortés, and Yoro; clinical manifestations of bleeding, plasma leakage, shock, lethargy; comorbidities and pregnancy were identified as risk factors for dengue mortality. Early identification of risk factors can help recognize patients who require close and timely clinical monitoring, which could improve outcomes in terms of reducing dengue mortality.

A Case of Fulminant Hepatic Failure with Neonatal Cholestasis Caused by Disseminated Herpes Simplex Virus (HSV) Infection

Background: Disseminated herpes simplex virus infection is an life threatening infection which may initially present as cholestasis, but eventually lead to multiple organ failure with a high mortality rate. But the good news is that the introduction of antiviral agent like acyclovir for the treatment of neonatal herpes has significantly improved the outcome of this potentially devastating infection. The early initiation of acyclovir highly depends on clinician’s suspicion, especially when overt signs of the infection are absent. So the objective of our case report was to raise awareness among the physicians to consider herpes virus infection in the differential when a patient present with features of cholestasis and hepatic failure. Case Presentation: Our case is aone month old male infant who got admitted in Chittagong Medical Hospital on 7th January, 2023 with the complaints of lethargy, blood mixed vomiting and black stool for 1 day with a history of jaundice and pale stool from 3rd week of life. His bleeding manifestations exacerbated and developed features of hepatic failure with coagulopathy. He was treated with plasma transfusion, viamin k, injectable antibiotics and other supportive care. A TORCH panel was sent. HSV Ig G came positive with 12 folds increased titre. Observing his deteriorating consciousness level intravenous acyclovir 60 mg/kg/day was initiated on 16th January, 2023. Within 3-4 days his overall general condition improved. The baby was discharged after getting 21 days of acyclovir therapy. Conclusion: Neonatal herpes virus infection can be a life threatening condition. An early diagnosis and effective treatment with antiviral agent can reduce morbidity and mortality. Chatt Maa Shi Hosp Med Coll J; Vol.23 (1); January 2024; Page 99-103

Dengue fever complicated with bilateral Psoas hematoma and superadded infection - A case report.

Dengue hemorrhagic fever (DHF) typically presents with various bleeding manifestations such as epistaxis, gum bleeding, and gastrointestinal bleeding. However, spontaneous large muscle hematoma formation is a rare complication. This case report discusses a patient with DHF who developed bilateral psoas muscle hematomas, a very uncommon presentation. The patient experienced acute abdominal pain and was diagnosed with psoas muscle hematomas complicated by bacterial infection. Conservative treatment, including fluid management, blood transfusions, and antibiotics, led to the patient's full recovery. This case highlights the importance of suspecting muscle hematomas in DHF patients who present with sudden abdominal or flank pain, especially in the context of dropping hemoglobin and platelet counts. Imaging techniques such as ultrasonography and CT scans are critical for diagnosis. Early diagnosis, close monitoring, and appropriate conservative management are essential for preventing serious outcomes. Prompt treatment of any secondary infections is also crucial to patient recovery. This case report is reminding clinicians to consider this rare complication similar to previous studies as reviewed.

Pathological and Molecular Characterization of Grass Carp Co-Infected with Two Aeromonas Species.

The grass carp (Ctenopharyngodon idella) is highly susceptible to infections caused by Aeromonas species, particularly A. hydrophila and A. veronii. However, the immunological mechanisms underlying co-infection by these pathogens remain largely uncharted. This study investigated the pathogenesis and host immune response in grass carp following concurrent infection with A. hydrophila and A. veronii. Mortality was observed as early as 24 h post-infection, with cumulative mortality reaching 68%. Quantitative analysis demonstrated significantly elevated bacterial loads in hepatic tissue at 3 days post-infection (dpi). Histopathological evaluation revealed severe hepatic lesions characterized by cellular necrosis, cytoplasmic vacuolization, and hemorrhagic manifestations. Comparative transcriptomic analysis of hepatic tissues between co-infected and control specimens identified 868 and 411 differentially expressed genes (DEGs) at 1 and 5 dpi, respectively. Gene ontology and KEGG pathway analyses revealed significant enrichment of immune-related genes primarily associated with Toll-like receptor signaling and TNF signaling cascades. Notably, metabolic pathways showed substantial suppression while immune responses were significantly activated after infected. These findings provide novel insights into the host-pathogen interactions during Aeromonas co-infection in grass carp, which may facilitate the development of effective prevention and control strategies.

An Atypical Case of Neonatal Alloimmune Thrombocytopenia.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from maternal antibodies targeting fetal platelets during pregnancy, often causing hemorrhagic manifestations detectable antenatally or shortly after birth. We report an atypical form of FNAIT with delayed onset in a healthy, breastfed male infant who developed diffuse petechiae 2 weeks after birth due to severe thrombocytopenia. The mother was shown to be negative for the human platelet antigen-1a (HPA-1a) allele but had anti-HPA-1a IgG antibodies, while the father and newborn were HPA-1a positive, confirming the diagnosis. Despite intravenous immunoglobulins and platelet transfusions, the recovery was slow. Analysis of breast milk demonstrated the presence of anti-HPA-1a IgG antibodies. The unusual clinical presentation 2 weeks after birth and the slow platelet recovery under appropriate treatment suggest postnatal transfer of maternal anti-HPA-1a antibodies or B lymphocytes producing these antibodies to the newborn, which may possibly have occurred through breastfeeding. Further research is needed to validate these findings and understand the role of breast milk in provoking the disease. Early detection and management remain essential to prevent serious complications associated with FNAIT.

Changes in the epidemiology of Crimean-Congo hemorrhagic fever: Impact of travel and a One Health approach in the European region.

The World Health Organization has identified Crimean-Congo hemorrhagic fever (CCHF) as a priority disease for research and development in emergency contexts. The epidemiology of CCHF is evolving and this review highlights travel-associated cases and focuses on the need for a One Health approach in Europe. For this narrative review, two searches were performed in PubMed and Google Scholar for the period 1980-October 2024. The first search identified travel-associated CCHF cases globally, additional cases were identified in the ProMED mail database and through healthmap.org. The second search, with a focus on the European region, aimed to analyse reports of CCHF virus (CCHFV) detected in ticks, CCHF seroprevalence studies in animals and/or humans, and autochthonous CCHF cases. Seventeen cases of imported CCHF, the majority acquired in Africa, were identified. Importation to European countries accounted for eight of the cases. Most patients presented with fever and hemorrhagic manifestations and the estimated case fatality rate was 35%. In the WHO European region, at least 13 countries have reported ticks infected with different genotypes of CCHFV; 17 countries were found to have animals/humans with positive CCHF serology. Finally, 16 countries in the WHO European region have notified human cases of CCHF. The Russian Federation, Turkey, and several former USSR countries are considered highly endemic, followed by the Balkanic region, with sporadic cases emerging in Bulgaria, Greece, Spain, and recently Portugal. Travel-associated CCHF is infrequent. However, given the recently reported increased geographical distribution in ticks and animals in the European region, additional human cases may be anticipated in the near future. Europe receives over half of all international tourist arrivals annually, so healthcare professionals should be aware of risk factors and current protocols for the management of suspected and confirmed cases.

Clinical management of bleeding manifestations in a family with the thrombomodulin C1611>A (p.Cys537Stop) mutation

Clinical management of bleeding manifestations in a family with the thrombomodulin C1611>A (p.Cys537Stop) mutation

Marburg Virus: A comprehensive examination of a critical pathogen

Marburg virus infection is a rare, severe zoonotic illness caused by the Marburg virus (MARV), with the primary reservoir being Egyptian fruit bats. Marburgviruses have reemerged on multiple occasions, resulting in a very high fatality ratio of up to 88% during the most significant outbreaks. MVD exhibits prominent clinical signs and symptoms such as haemorrhagic fever, coagulopathies, multi-organ failure in the affected individuals. This review provides insight into the MVD structure, genomic organisation, replication, clinical manifestations, and special emphasis on the available treatment strategies. Although no specific therapeutic interventions exist for management, supportive care like fluid administration and treatment of specific symptoms can improve survival rates and clinical outcomes. T-705 Favipiravir blocks the influenza virus's RNA-dependent RNA polymerase (RdRp) and suggests potential effectiveness in patients exhibiting lower viral loads. Remdesivir has shown efficacy in a study of MARV-infected Cynomolgus macaques; treatment improved clinical ratings, decreased plasma viral RNA, and boosted kidney and liver functions. BCX4430 Galidesivir showed 24-hour and 48-hour survival in animal groups after receiving the drug with no apparent toxicity and improved liver enzyme values.MARV can induce significantly more severe epidemics than previously thought. These widespread outbreaks had a remarkably high mortality rate throughout a large geographical region, presenting substantial challenges in the field of medicine. High fever, haemorrhagic manifestation, organ failure, and coma are the prominent clinical signs of MVD. Supportive care and volume resuscitation are fervently recommended. Monoclonal antibodies and antivirals like Remdesivir and Favipiravir are potential treatment options; however, Galidesivir and Favipiravir can also be used.

Use of ISTH bleeding assessment scale to evaluate therapy-associated bleeding risk in patients undergoing coronary revascularization

Background — Currently, there is a challenge in the dynamic prognostic assessment of haemorrhagic risks, particularly in recognising the development of bleeding in patients who have undergone cardiac surgery (CS). Bleeding frequently occurs in post-CS patients as they are receiving antithrombotic therapy (ATT), prescribed for continuous a period of 3, 6, or 12 months after surgery. This not only worsens prognosis and quality of life but also, if therapy is discontinued, increases the risk of thrombotic events. Objective — To investigate the diagnostic value of scales for assessing bleeding and predicting bleeding outcomes in individuals who have undergone myocardial revascularisation, and to assess the applicability of the ISTH scale for evaluating bleeding in this patient group. Methods — A total of 98 patients undergone myocardial revascularisation participated in the prospective study. An assessment of hemorrhagic risks according to the PRECISE-DAPT scale and hemorrhagic manifestations according to the ISTH scale was performed at visit 1 and 2 (0-1 month after revascularization). Results — It was found that the assessment of bleeding risk during antithrombotic therapy (ATT) in the first month after myocardial revascularisation, when performed using the PRECISE-DAPT scale, is not comparable to the assessment using the ISTH scale. However, the ISTH scale proved to be a useful tool for evaluating haemorrhagic complications of ATT in patients following cardiac surgery (CS). Conclusion — The use of the ISTH scale allows the assessment of early signs of bleeding during dual antiplatelet therapy (DAPT) following revascularisation, helping to foster a proactive attitude in patients towards monitoring complications of antithrombotic therapy. This approach can reduce risks of fatal haemorrhages and the development and progression of anaemia. However, the ISTH scale is not comparable to the PRECISE-DAPT scale for assessing hemorrhagic risks and cannot be recommended for dynamic prediction of hemorrhagic risks in post-CS patients.

Molecular cloning, sequencing, expression and purification of Alkhumra hemorrhagic fever virus capsid protein in Saudi Arabia.

Alkhumra hemorrhagic fever virus (AHFV) is a newly discovered virus in the Flaviviridae family. It was discovered in 1995 among animal handlers in Saudi Arabia. AHFV spreads through close contact with infected animals and tick bites. Symptoms range from fever and flu-like symptoms to hemorrhagic manifestations, and rarely, encephalitis. The Saudi Arabian Ministry of Health has reported 604 cases so far. There are no approved vaccines, antiviral therapies, or routine screening systems for AHFV. This lack of preventive measures makes it challenging to predict future outbreaks or re-emergence in endemic regions of Saudi Arabia. We cloned, sequenced, analyzed, expressed, and purified the recombinant AHFV capsid protein (CP) using the PET-28a (+) vector. The CP gene was amplified through reverse transcriptase polymerase chain reaction (RT-PCR) and cloned into a vector. The expression and purification processes were carried out in E. coli. The sequence of the CP gene was deposited in GenBank (Accession number OR785375) and designated as AHFV-SIAU-1-KSA. Sequence analysis revealed similarities with other AHFV isolates obtained from humans, animals, and ticks. Phylogenetic analysis showed that the AHFV CP gene formed distinct clusters with other AHFV genomes collected at different time intervals. The expressed protein was successfully purified and analyzed by SDS-PAGE. This study is the first to document the cloning, expression, and purification of the recombinant AHFV CP gene from Saudi Arabia. The purified protein will be used to develop a serological assay for routine screening of AHFV samples in humans, animals, and ticks in Saudi Arabia.

ANALYSIS OF ANAMNESTIC DATA AND CLINICAL AND LABORATORY CRITERIA FOR FOOD INTOLERANCE IN PRETERM INFANTS TAKING INTO ACCOUNT THE SEVERITY OF PERINATAL PATHOLOGY

Every year, up to 10% of the total number of children in the world are born before term. Preterm birth is considered to be one of the main factors in the increase of neonatal morbidity and mortality. The morphological and functional immaturity of the body at premature birth is one of the factors in the development of severe metabolic disorders. The negative effect of intrauterine hypoxia causes a violation of the functional state of organ systems, causes the development of multiple organ failure after birth For the timely detection of these disorders, justification of the necessary preventive and therapeutic measures, the issues of improving diagnostic measures in children in the neonatal period, in order to prevent the development of gastrointestinal pathology in the future are discussed. The aim of the study. To analyze the anamnestic data and clinical and laboratory criteria for disorders of the functional state of the gastrointestinal system in premature infants, considering the severity of the course of perinatal pathology. Materials and methods of the study. The main group of the study consisted of 149 premature infants of gestational age 32-33/6 weeks: subgroup A - newborns with severe forms of perinatal pathology (67 children), subgroup B - children with clinical signs of moderate perinatal pathology (82 children). The comparison group consisted of 50 conditionally healthy children with gestational age of 34-36/6 weeks. Inclusion criteria: gestational age at birth 32-33/6 weeks, manifestations of digestive system dysfunction with the consent of the child's parents. The complex of laboratory methods included the study of the level of albumin, α-1-antitrypsin, fecal elastase-1, PMN-elastase and calprotectin in coprofiltrate. The studies were conducted in accordance with the provisions of GCP (1996), the Convention of the Council of Europe on Human Rights and Biomedicine (1997), the Declaration of Helsinki of the World Medical Association for the Ethical Principles of Scientific Medical Research Involving Human Subjects (1964-2008), the Order of the Ministry of Health of Ukraine No.690 dated 23.09.2009 (as amended by the Order of the Ministry of Health of Ukraine No.523 dated 12.07.2012). Approval of the Bioethics Committee of the Bukovinian State Medical University (Protocol No. 2 dated 9.02.2015). Statistical processing of the study results was performed using the software "STATISTICA" (StatSoft Inc., USA, version 10). Comparison of quantitative indicators with normal distribution was performed using Student's t-test (p<0.05; p<0.001). Qualitative differences between the comparison groups were evaluated using MedCalc software (Statistical Software Package for Biomedical Research, 2023, Version 16.1). The study was performed as part of the research work of the Department of Pediatrics, Neonatology and Perinatal Medicine of the Bukovinian State Medical University (Chernivtsi, Ukraine). Results of the study. The risk of developing food tolerance disorders in IPV depends on a complex of factors, namely, a burdened maternal history of gastroenterological diseases and the implementation of adverse factors during pregnancy and childbirth. Assessment of the newborn's somatic status should be comprehensive, with special attention to clinical and paraclinical criteria for gastrointestinal dysfunction. The clinical signs of combined gastrointestinal disorders are: increase in liver size beyond the physiological norm (100.0%) or hepatolithiasis (52.24%), jaundice (86.57%), edema (80.6%), endotoxemia syndrome (71.64%), intestinal flatulence (73.13%) and hemorrhagic manifestations (56.27%), including bleeding from the gastrointestinal tract (43.68%). The laboratory criteria confirming the presence of severe forms of food intolerance are an increase in the level of calprotectin > 390.15 µg/g, albumin > 37.25 µg/g, α-1-antitrypsin > 452.67 µg/g with a decrease in the level of PMN elastase < 95.49 ng/g in the newborn coprofiltrate. Conclusions. The significant risk of disorders of the functional state of the digestive system in conditions of perinatal hypoxia in critical conditions of the newborn period in premature infants requires special attention of practitioners to clarify the characteristics of the somatic history, the course of pregnancy and childbirth of the mother, as well as the nature of postnatal adaptation of the newborn. Such an approach will allow to identify newborns with increased risk of developing gastrointestinal disorders in the acute period of neonatal diseases, as well as long-term consequences, with due regard to the peculiarities of the formation of long-term adaptation processes.

Indexes of systemic inflammation in hemorrhagic stroke with effective blood flow: a dynamic observation

Increasing evidence suggests that stroke is a systemic disease affecting multiple organs. Systemic inflammatory response and immune dysregulation associated with hemorrhagic stroke, may play an important role in brain injury, its recovery, and stroke outcomes. However, it is worth of note that, from our point of view, the classical concepts about inflammation in pathophysiology and general pathology do not entirely meet the needs of modern medical practice. The existence of this problem is also typical for assessing pathogenesis, as well as for optimizing pathogenetic therapy of severe strokes. Therefore, within the framework of this work, a dynamic observation and assessment of pathogenesis in severe intracerebral hemorrhage was carried out using the criteria of a systemic inflammation scale. The study included patients with intracerebral hemorrhage and effective cerebral blood flow. Blood sampling was carried out on days 1-3 and 5-7 after clinical manifestation of intracerebral hemorrhage. To determine markers of systemic inflammation in the blood plasma of patients, the levels of IL-6, IL-8, IL-10, TNFá, procalcitonin, cortisol, myoglobin, troponin I and D-dimers were examined using an enzyme-linked immunosorbent assay. The Kolmogorov–Smirnov test was used to confirm the normal data distribution. Further comparison of quantitative data was carried out using the nonparametric Wilcoxon test for paired comparisons. All results were considered statistically significant at p 0.05. In patients on days 1-3 and 5-7, statistically significant differences were not observed in almost all studied markers of systemic inflammation, except for IL-8 and tumor necrosis factor-á. Such increased contents of pro-inflammatory cytokines may indicate increased systemic inflammation over time in the patients with intracerebral hemorrhage and effective cerebral blood flow. Hence, the condition of such patients may worsen on days 5-7 after manifestations of intracerebral hemorrhage, thus requiring more careful monitoring of patients’ blood counts and therapy aimed at suppression of increasing inflammation.

Combined thrombus fragmentation and catheter-directed thrombolysis in the treatment of pulmonary thromboembolism in high- and moderate-risk patients

Introduction: In recent years with the increase in the incidence of pulmonary embolism (PE) worldwide and the rapid development of new devices in interventional cardiology, there has been a tendency to expand the indications for the endovascular treatment of acute PE. Systemic thrombolysis significantly reduces mortality in patients without contraindications for the procedure but at the cost of an increased risk of bleeding. High mortality with a conservative approach in patients with high-risk PE and contraindications for fibrinolysis, as well as moderate-risk patients with a lack of clinical response to optimal anticoagulant therapy, requires a more selective treatment approach to ensure an inevitable positive hemodynamic response. Catheter-based therapy (CBT), including mechanical thrombus fragmentation and selective thrombolysis, is a combined approach with potentially increased efficacy and safety over systemic thrombolysis. In the published literature there is a lack of sufficient data on the application of this therapeutic strategy as a first-line treatment for PE. Large, randomized trials are needed to confirm the value of CBT in these patient groups and to establish precise criteria and recommendations for the initial and follow-up monitoring during treatment. Aim: To evaluate the safety and efficacy of CBT in high- and moderate-risk patients with acute PE as an initial treatment strategy at one-year follow-up. Material and methods: For the period of May 2021- 2024, a total of 35 patients with acute PE were treated in our clinic. In this retrospective study, 23 patients were included, in which a decision was made to conduct CBT as a primary strategy, (in one case there is not a long enough follow-up at this stage). The remaining 8 patients were treated conservatively with low-molecular-weight heprain (LMWH), and the systemic thrombolysis in three of patients was administered. Demographic indicators, history of deep venous thrombosis (DVT), hemodynamic status on admission, non-invasive and invasive parameters of right ventricular burden, contraindications for fibrinolysis, fatal and non-fatal post-procedural complications were recorded. The clinical follow-up is in-hospital conditions, at 6 and 12 months in terms of mortality, manifestations of heart failure, bleeding and hospitalization for PE relapse. All patients in the study group underwent right heart catheterization according to a standardized protocol. CBT includes defragmentation of the thrombi using a Pigtail catheter and selective fibrinolysis with recombinant tissue plasminogen activator /r-TPA, alteplase/ with a dosage of 0.3 mg/kg. Results: The PESI score, which evaluates 30-day mortality in patients with acute pulmonary thromboembolism based on 11 clinical criteria, was used for risk assessment The studied cohort included patients with very high and moderately high risk and an estimated PESI score in the III-V range. CBT was technically successful in 100% (n = 23) of patients. The overall clinical success of the procedure, defined as haemodynamic stability, reversal of hypoxia, reduction of respiratory rate and improvement of peripheral perfusion was achieved in 90.4% of patients. During the hospital stay, 2 deaths were registered (8.69%), the fatal outcome being due to treatment-refractory cardiogenic shock in the first case (the patient died 24 hours after admission) (4.35%) and haemorrhagic stroke in the second (4.35%). In the remaining patients, not a single haemorrhagic incident as well as serious periprocedural complications, were detected.  The comparative analysis between echocardiography and invasively assessed pulmonary artery pressure (PAP) before and after the CBT shows that the decrease in the mean PAP (m-PAP) after the treatment is statistically significant - on average 10 mm Hg, which suggests a positive effect of the treatment. During the 6-month follow-up, two more deceased patients were registered – an 81-year-old woman with previous melena before treatment for PE, and with a new episode and a large drop in haemoglobin, sent for treatment to a gastroenterology department, and a second patient with an unclear cause of death - probable sudden cardiac death (SCD). (Mortality at 6 months is 8.6%). Up to 12 months, no other adverse cardiovascular events were observed in the remaining patients. Conclusion: Our experience in endovascular therapy of acute PE showed that the methodology is both therapeutically and prognostically effective, but also low-risk for the patient. A large, randomized trial is needed before the technique can be recommended as a first-line treatment. 

Petechial and Purpuric Rashes During a Parvovirus B19 Outbreak: Are Skin Symptoms Differentiated?

Human parvovirus B19 typically causes erythema infectiosum, but unusual exanthems and hemorrhagic manifestations, such as purpuric-petechial rashes, have also been reported. PVB19-associated purpuric-petechial eruption (PAPPE) should be recognized as a distinct clinical feature of primary parvovirus B19 infection and considered in the differential diagnosis of patients with febrile purpura. This report aims to highlight several scenarios of B19V-associated petechial and purpuric rashes, which may present to pediatric departments during outbreaks.

Optimizing the Treatment of Acute Promyelocytic Leukemia: A Maintenance-Free Strategy for Complete Remission

Background: Acute promyelocytic leukaemia (APL) is a distinct variant of acute myeloid leukaemia (AML), comprising 5-10% of all AML cases. Characterized by the t(15; 17) chromosomal translocation, APL presents a unique challenge due to its associated bleeding manifestations and coagulopathy, emphasizing the need for urgent and specialized management. Methods: This prospective open-label pilot study enrolled ten newly diagnosed APL patients, stratified based on the Sanz risk score. Low and intermediate-risk patients underwent ATRA+ATO induction therapy without chemo, followed by consolidation therapy. High-risk patients received additional single dose chemo Daunorubicin or Mitoxantrone alongside ATRA+ATO induction. The study evaluated patient characteristics, clinical findings, laboratory results, and treatment outcomes, focusing on complete remission (CR) after induction therapy and disease-free survival (DFS) at 3 years. Results: The study observed a 100% CR rate after induction therapy, with favourable 3-year DFS and event-free survival (EFS). No treatment failures, mortality, or relapses were reported. Laboratory findings and clinical outcomes were consistent with the characteristics of APL, including the hematological parameters. The absence of maintenance therapy minimized associated toxicities, supporting the safety and efficacy of the chemotherapy-free ATRA+ATO approach. Conclusion: This pilot study underscores the potential paradigm shift in APL management by demonstrating the safety and efficacy of a chemotherapy-free ATRA+ATO strategy. The results align with the 2023 National Comprehensive Cancer Network (NCCN) update, endorsing the ATRA+ATO regimen for APL. The on-going nature of the research emphasizes its contribution to evolving APL management practices, encouraging further comprehensive evaluations on a broader scale.

Viral interactions with host factors (TIM-1, TAM -receptors, Glut-1) are related to the disruption of glucose and ascorbate transport and homeostasis, causing the haemorrhagic manifestations of viral haemorrhagic fevers.

The haemorrhagic features of viral haemorrhagic fevers may be caused by common patterns of metabolic disturbances of the glucose and ascorbate homeostasis. Haemorrhages and vasculature disfunctions are a clinical feature not only of viral haemorrhagic fevers, but also in scurvy, diabetes and thrombotic microangiopathic haemolytic anaemia. Interestingly, the expression of glucose and ascorbate transporter Glut-1 on the erythrocyte membrane is associated with the inability to synthesize ascorbate and is restricted to that very species that are susceptible to filoviruses (primates, humans and fruit bats). Glut-1 may play a pivotal role in haemorrhagic fever pathogenesis. TIM-1 and TAM receptors have been recognized to enhance entry of Ebola, Lassa and Dengue viruses and viral interferences with TIM-1 could disturb its function, disturbing the expression of Glut-1. In those species not able to synthesize ascorbate and expressing Glut-1 on erythrocytes virus could interact with Glut-1 or other functionally related protein, and the influx of glucose into the cells would be severely impaired. As a consequence, transient hyperglycemia and a marked oxidative stress coupled with the high levels of glucose in plasma would be established, and then promote the activation of NF–κB transcription, exacerbating a pro-inflammatory response mediated by cytokines and chemokines: The inability to synthesize ascorbate is an Achilles Heel when trying to counteract the oxidative stress.

A study of platelet transfusion support to dengue patients in a hospital based blood transfusion centre

Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are life threatening clinical manifestations of infection due to dengue virus. Thrombocytopenia is found to be a common finding in dengue. The clinical features of Dengue fever are due to bleeding diathesis and increased capillary leak. The suggested features contributing to bleeding include thrombocytopenia, coagulopathy and vasculopathy. This study was undertaken to find out the number of platelet transfusion in dengue patients and to assess whether platelets have been transfused according to AABB guidelines. This was a descriptive study over a period of one year conducted in Father Muller Medical College Hospital Blood Centre. Details of the platelet component transfused during this period were collected, which included name, age, gender, unique identification number, ward number, blood group, clinical symptoms and signs, indications for transfusion, platelet count, haemoglobin level, and number of units of transfusion. The total number of dengue patients were 227 for whom 835 platelet components were transfused during the study period one year (January 2017 to December 2017). Patients between the age group of 31 to 40 comprised of 25.6% who received platelet transfusion. There was male preponderance (68.3%), females accounting to 31.7%. Platelet transfusion was most common in patients belonging to O Rh positive blood group (41.4%) and least (0.4%) was in B Rh negative. Patients with petechiae comprised of 7.5%, gum bleeding (4.4%) and epistaxis (4.0%). Out of 227 patients, 50.7% required 4 units of platelets. This study provides an information on platelet component usage in dengue patients. Twenty seven patients (11.9%) had a count of <10000 and the utilisation was as per AABB guidelines which improved their platelet count and overall health condition. Patients with bleeding manifestation accounted to 15.9% and hence received transfusion

Mucocutaneous Ulcerations and Pancytopenia Secondary to Methotrexate Toxicity in a Patient With Rheumatoid Arthritis: A Case Report.

Toxicity from methotrexate overdosing is life threatening condition that requires prompt recognition and early treatment. A 71-year-old man from rural Bhutan with diabetes mellitus had symmetrical small joint pain for 3 years associated with early morning stiffness. He was evaluated and diagnosed with seropositive rheumatoid arthritis in a hospital in neighbouring India. He was initiated on Methotrexate and Hydroxychloroquine. The patient had inadvertently taken Methotrexate 10 mg OD for 2 weeks. Following this, he developed painful ulcers on the lips preventing him from swallowing and ulcers around the corona on the penis. He also had intermittent fever with chills. On examination, he had fluid responsive hypotension and pancytopenia without bleeding manifestations. He was managed with intravenous folinic acid, subcutaneous granulocyte colony stimulating factor and intravenous cloxacillin. He had an uneventful recovery and methotrexate has been restarted following adequate patient education. Education of patient and family members is key in preventing medication errors. Early identification and timely management of methotrexate toxicity is key in preventing mortality.

Clinical Analysis of 25 Cases of Acquired Hemophilia A in a Single Center

To explore the diagnosis and treatment of acquired hemophilia A (AHA) based on the analysis of clinical data. A retrospective analysis was conducted on the clinical manifestations, laboratory characteristics, treatment, and outcomes of 25 patients diagnosed with AHA who were admitted to the Second Hospital of Hebei Medical University. Among all patients, 11 cases had secondary factors, including 5 cases of autoimmune diseases, 3 cases of pregnancy-related disease, 1 case of pemphigoid, 1 case of Graves' disease, and 1 case of monoclonal gammaglobulinemia of unknown significance (MGUS). The bleeding sites include the skin, mucous membrane, muscle, joint cavity and brain tissue. Twenty-three patients were treated with prednisone combined with cyclophosphamide (CP regimen), one patient with rituximab combined with cyclophosphamide because of femoral head necrosis, and one case with rituximab monotherapy because of gastrointestinal bleeding after prednisone treatment. Among them, 23 cases achieved complete remission (CR), 2 cases were partial remission (PR), and 8 cases relapsed after CR. All of 10 patients including 2 cases with PR and 8 relapsed cases after CR were treated with rituximab. At last, 8 patients achieved CR, and 2 patients (both were patients with recurrence after first CR) achieved PR. These two patients achieving PR were treated with low-dose rituximab combined with bortezomib (RB regimen). One patient reached CR after 4 cycles and the other reached CR after 6 cycles of RB regimen. After CR, 4 of the 10 patients treated with rituximab received maintenance therapy with rituximab monotherapy for 1.5 to 2 years, in which, none of them relapsed. Among the 6 patients who did not receive maintenance therapy, 4 patients relapsed after CR, and the median time to relapse was 15 months. Eight patients treated with CP regimen developed common infections, and two patients treated with rituximab developed severe pneumonia. All 25 patients survived until the end of follow-up. Skin ecchymosis, mucous hemorrhage and muscle hematoma are the most common hemorrhagic manifestations in AHA, and joint hemorrhage and cerebral hemorrhage can also occur. CP regimen is the preferred option of first-line therapy for AHA. Rituximab can be used for patients with steroid contraindication or who failed to respond to the above therapy or relapsed after effective treatment, and maintenance therapy is recommended to reduce the risk of recurrence. Meanwhile, close attention should be paid to the occurrence of infection events during rituximab treatment. Rituximab in combination with bortezomib can also be used in patients with refractory or relapsing AHA.

Dermatological manifestations during Dengue, Chikungunya, and Zika infections.

Arboviral infections caused by Dengue, Zika, and Chikungunya viruses continue to pose a significant global health threat, particularly in endemic regions. This review is timely because of the increasing prevalence of these infections, driven by factors such as urbanization and climate change. Dermatological manifestations of these viruses are crucial for early diagnosis, especially given the overlap in symptoms, which can complicate differential diagnosis. Recent studies emphasize the importance of mucocutaneous symptoms in diagnosing arboviral infections. In Dengue, distinctive rashes like the 'islands of white in a sea of red' and hemorrhagic skin manifestations have been key diagnostic features. Zika is marked by a pruritic maculopapular rash and nonpurulent conjunctivitis, whereas Chikungunya often results in persistent rashes, desquamation, and hyperpigmentation, particularly on the face. Emerging research highlights the skin's role as both a primary infection site and an immune mediator in these viral diseases, offering new insights into their pathophysiology and potential therapeutic targets. The unique dermatological profiles of Dengue, Zika, and Chikungunya are critical for guiding clinical diagnosis and treatment, especially in resource-limited settings. Understanding these cutaneous manifestations can improve early recognition, particularly in differentiating between these viruses in co-endemic areas. Future research may uncover novel therapeutic strategies by focusing on the interaction between these viruses and the skin's immune responses.