Capillary Leak Research Articles

Leukopenia and thrombocytopenia in dengue patients presenting in the emergency department of a tertiary center in Nepal: a cross-sectional study

IntroductionDengue viruses cause either symptomatic infections or asymptomatic seroconversion. Symptomatic dengue has a wide clinical spectrum ranging from self-limiting infection to severe manifestations, mostly characterized by plasma leakage with or without hemorrhage. World Health Organization classification in 2009 classified dengue into dengue without warning signs, dengue with warning signs, and severe dengue. This study aimed to determine patient characteristics and hematological parameters (leukopenia, and thrombocytopenia) in patients with dengue infection in the emergency department of a tertiary center.MethodsA cross-sectional study was conducted among 252 patients with dengue confirmed by serological testing against dengue-specific nonstructural protein 1 (NS1) antigen and immunoglobulin M (IgM) by enzyme-linked immunosorbent assay from September to November 2022 who presented in the emergency department of a tertiary hospital in Nepal after ethical approval was obtained. Dengue was categorized according to the World Health Organization 2009 classification. Hematological parameters were recorded by reviewing patients’ laboratory records. Data analysis was done using descriptive statistical parameters and a chi-square test.ResultsDengue without warning signs was present in 166 (65.87%) patients, while dengue with warning signs and severe dengue was present in 68 (26.89%) and 18 (7.14%) patients, respectively. Leukopenia (< 4000 cells/mm3) was present among 163 (64.68%) patients. The lowest recorded leukocyte count was 1440. Similarly, thrombocytopenia (< 150000 cells/mm3) was present among 102 patients (40.48%). The lowest recorded platelet count was 26,000 cells/mm3. A significant association was found between the severity of dengue infection and leukopenia (χ2 13.268, p-value 0.001) and thrombocytopenia (χ2 43.924, p value < 0.001).ConclusionsMonitoring of warning signs and clinical parameters is important for identifying the progression of dengue infection to the critical phase. Leukopenia and thrombocytopenia are present among many dengue-infected patients presenting in the emergency department. The severity of the disease will usually only be apparent around defervescence, which often coincides with the onset of the critical phase. Leukopenia and thrombocytopenia could indicate progression to severe disease during emergency department admission.

A Case Report of Systemic Capillary Leak Syndrome: When More Than One Inciting Factor Exists, the Question Is Who Pulls the Trigger?

A Case Report of Systemic Capillary Leak Syndrome: When More Than One Inciting Factor Exists, the Question Is Who Pulls the Trigger?

Acute respiratory distress syndrome : Pathophysiology, definition and treatment strategies

Acute respiratory distress syndrome (ARDS) is defined as an acute inflammatory syndrome leading to increased pulmonary capillary leakage and subsequent interstitial and alveolar pulmonary edema. Hypoxia is the predominant symptom. The definition of ARDS comprises acute onset, bilateral patchy infiltration on chest X‑ray and areduction of the ratio of arterial partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2), which also determines the classification into mild (≤ 300), moderate (≤ 200) and severe (≤ 100) ARDS. Treating the underlying cause is the only causal treatment measure. The aim of adjunctive therapy is the maintenance of life or organ functions by ensuring an adequate gas exchange without further damaging the lungs. Adjunctive therapy consists mainly of individually adapted "protective" ventilation treatment and the prone position. In severest ARDS, the use of venovenous extracorporeal membrane oxygenation (VV-ECMO) can improve survival if strict criteria for indications and contraindications are followed.

Capillary Filtration of Plasma is Accelerated During General Anesthesia: A Secondary Population Volume Kinetic Analysis.

How infusion fluids are distributed and eliminated is of importance to how much and how fast they should be administered. This manuscript applies population pharmacokinetic modeling to intravenous infusions of crystalloid fluid, which is a common therapy in hospital care and mandatory during surgery. The analysis was based on the hemodilution and urine output measured during and after 262 infusions of 1647 ± 461 mL (mean ± SD) of fluid over 30 min in adults. The result shows that distribution of fluid from the plasma to the interstitial fluid space occurred twice as fast during general anesthesia as compared to the conscious state. The increased rate ensures adequate nutritional flow to the cells despite decreased flow in the macrocirculation, which is a characteristic of general anesthesia. This increased capillary leakage of fluid was coupled with an even greater reduction of the urinary output and accumulation of fluid in both the fast-exchange interstitial fluid space and a remote "third fluid space," the latter of which apparently serves as an overflow reservoir. During the first hour of the experiments, 88% more fluid resided extravascularly in the presence of general anesthesia than in the awake state. General anesthesia increased the half-life from 1.8 to 16.6 h, showing marked impairment in the handling of infused crystalloid fluid.

Unusual cause of Capillary leak syndrome with shock in a child

Unusual cause of Capillary leak syndrome with shock in a child

Capillary Leak Syndrome Following Russell\'s Viper Envenomation: A Death Bell that Needs Urgent Addressal

Capillary Leak Syndrome Following Russell\'s Viper Envenomation: A Death Bell that Needs Urgent Addressal

D-dimer a Clue for Severe Dengue / Dengue Shock Syndrome, An Observational Study

Background: Dengue fever, a mosquito-borne viral infection, poses a significant public health threat, particularly in tropical and subtropical regions. Caused by five serotypes of the dengue virus (DENV-1 to DENV-5), it affects an estimated 400 million people annually, leading to severe illness in around 96 million [1]. Dengue's clinical spectrum ranges from asymptomatic infection to mild febrile illness with flu-like symptoms, to severe dengue (SD) and dengue shock syndrome (DSS), characterized by plasma leakage, thrombocytopenia, and organ dysfunction [2]. Objective: To evaluate the correlation and diagnostic accuracy of D-dimer in differentiating severe dengue and dengue shock syndrome (SD/DSS) from mild dengue. Method: This is an observational study carried in BKL Walawalkar medical college for a period of 6 months. 125 patients were enrolled in the study which were diagnosed as Dengue positive (NS1, IG-G, IG-M) after taking their informed consent. Dimer, platelet creatinine, SGOT SGPT levels were monitored. Conclusion: The present study provides strong evidence for a link between D-dimer levels and the severity of dengue infection and it also address the correlation of low platelet count and high D dimer levels. This suggests that D-dimer could be a valuable marker for assessing dengue severity.

Talin1 dysfunction is genetically linked to systemic capillary leak syndrome.

Systemic capillary leak syndrome (SCLS) is a rare life-threatening disorder due to profound vascular leak. The trigger and the cause of the disease are currently unknown and there is no specific treatment. Here, we identified a rare heterozygous splice-site variant in the TLN1 gene in a familial SCLS case, suggestive of autosomal dominant inheritance with incomplete penetrance. Talin1 has a key role in cell adhesion by activating and linking integrins to the actin cytoskeleton. This variant causes in-frame skipping of exon 54 and is predicted to affect talin's C-terminal actin-binding site (ABS3). Modeling the SCLS-TLN1 variant in TLN1-heterozygous endothelial cells (ECs) disturbed the endothelial barrier function. Similarly, mimicking the predicted actin-binding disruption in TLN1-heterozygous ECs resulted in disorganized endothelial adherens junctions. Mechanistically, we established that the SCLS-TLN1 variant, through the disruption of talin's ABS3, sequestrates talin's interacting partner, vinculin, at cell-extracellular matrix adhesions, leading to destabilization of the endothelial barrier. We propose that pathogenic variants in TLN1 underlie SCLS, providing insight into the molecular mechanism of the disease that can be explored for future therapeutic interventions.

Efficacy and Safety of Denileukin Diftitox-Cxdl, an Improved Purity Formulation of Denileukin Diftitox, in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma.

Denileukin diftitox (DD)-cxdl is a fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2. This phase III, multicenter, open-label, single-arm registrational trial evaluated the efficacy and safety of DD-cxdl in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL). In the main study, which followed a dose-finding lead-in, DD-cxdl was administered intravenously daily (5 days; 9 µg/kg/d once daily) every 21 days for up to eight cycles. Patients in the primary efficacy analysis set (PEAS) were required to have stage IA-IIIB CTCL (mycosis fungoides and/or Sézary syndrome) and at least ≥one previous systemic therapy. The primary efficacy end point was objective response rate (ORR) using the Global Response Score. Secondary end points were duration of response (DOR), time to response (TTR), skin tumor burden, and safety and tolerability. The PEAS included 69 patients (median age, 64.0 years). The ORR was 36.2% (95% CI, 25.0 to 48.7), including 8.7% with complete response. The median DOR was 8.9 months (95% CI, 5.0 to not estimable), and the median (Q1-Q3) TTR was 1.4 (0.7-2.1) months. A total of 84.4% of patients showed decreased skin tumor burden, with 48.4% showing a ≥50% decrease. Treatment-emergent adverse events (TEAEs) of special interest, most of which were grade 1 or 2, included infusion reaction (73.9%), hypersensitivity (68.1%), hepatotoxicity (36.2%), and capillary leak syndrome (20.3% [grade ≥3, 5.8%]). Other common TEAEs were nausea (43.5%) and fatigue (31.9%). Efficacy and safety results show that DD-cxdl would potentially fulfill a serious, unmet medical need for patients with R/R CTCL.

Post-transplant complications revealed by mycophenolate mofetil related transporters and metabolic enzymes gene polymorphisms in pediatric patients with hematological disorders

BackgroundHaploidentical hematopoietic stem cell transplantation (Haplo-HSCT) serves as an important option for patients without an HLA matched donor in treating hematological disorders, while patients may experience various complications after transplantation. Mycophenolate mofetil (MMF), a cornerstone drug for graft-versus-host disease (GvHD) prophylaxis, effectively reduces the incidence of acute GvHD, and the efficacy of MMF varies among individuals associated with MMF-related transporters and metabolic enzymes single nucleotide polymorphisms (SNPs). However, limited studies have systematically reported the correlations between the MMF-related SNPs and post-transplant complications.MethodsHere, we conducted a retrospective study involving 90 pediatric patients with hematological disorders who underwent haplo-HSCT at a single center. All patients were subjected to MMF-related SNP testing, combined with common clinical characteristics, to be correlated with post-transplant complications.ResultsWe observed that all 15 MMF-related SNPs were in Hardy-Weinberg equilibrium. Based on multivariate Cox regression analysis of post-transplant complications, we discovered that SLCO1B1 (521T > C) variant genotype was an independent protective factor for chronic GvHD (HR = 0.25, 95% confidence interval (CI) (0.08–0.84)). For viral infection, CYP2C8 (1291 + 106T > C) variant genotype was an independent risk factor for cytomegalovirus infection (HR = 2.98, 95% CI (1.18–7.53)). As to hemorrhagic cystitis, SLCO1B1 (1865 + 4846T > C) variant genotype was an independent protective factor, while older age was considered as an independent risk factor (HR = 0.41, 95% CI (0.19–0.85); HR = 2.52, 95% CI (1.14–5.54), respectively). No statistical significance was discovered between common clinical characteristics and MMF-related SNPs with other complications, including grade II-IV/III-IV acute GvHD, Epstein-Barr virus infection, peri-engraftment syndrome, and capillary leak syndrome. We also discovered SLCO1B1 (597 C > T) and SLC29A1 (-162 + 228 A > C) variant genotypes are both independent factors for cumulative incidence of relapse after haplo-HSCT (HR = 4.02, 95% CI (1.42–11.44); HR = 0.18, 95% CI (0.07–0.43), respectively).ConclusionsOur findings highlight the significance of MMF-related transporters and metabolic enzymes SNPs in the development of post-transplant complications, contributing to facilitating personalized risk assessment and improving the clinical management in haplo-HSCT patients.

Bortezomib induces Rho-dependent hyperpermeability of endothelial cells synergistically with inflammatory mediators

BackgroundBortezomib (BTZ), a selective 26 S proteasome inhibitor, is clinically useful in treating multiple myeloma and mantle cell lymphoma. BTZ exerts its antitumor effect by suppressing nuclear factor-B in myeloma cells, promoting endothelial cell apoptosis, and inhibiting angiogenesis. Despite its success, pulmonary complications, such as capillary leak syndrome of the vascular hyperpermeability type, were reported prior to its approval. Although the incidence of these complications has decreased with the use of steroids, the underlying mechanism remains unclear. This study aims to investigate how BTZ influences endothelial cell permeability.MethodsWe examined the impact of BTZ on vascular endothelial cells, focusing on its effects on RhoA and RhoC proteins. Stress fiber formation, a known indicator of increased permeability, was assessed through the Rho/ROCK pathway.ResultsBTZ was found to elevate the protein levels of RhoA and RhoC in vascular endothelial cells, leading to stress fiber formation via the Rho/ROCK pathway. This process resulted in enhanced vascular permeability in a Rho-dependent manner. Furthermore, the stress fiber formation induced by BTZ had synergistic effects with the inflammatory mediator histamine.ConclusionsOur findings suggest that BTZ accumulates RhoA and RhoC proteins in endothelial cells, amplifying the inflammatory mediator-induced increase in the active GTP-bound state of Rho, thereby exaggerating vascular permeability during pulmonary inflammation. This study provides novel insights into the molecular mechanism underlying the pulmonary complications of BTZ, suggesting that BTZ may enhance inflammatory responses in pulmonary endothelial cells by increasing RhoA and RhoC protein levels.

Capillary leak phenotype as a major cause of death in patients with POEMS syndrome.

Cause of death (COD) in POEMS (polyneuropathy, organomegaly, endocrinopathies, monoclonal protein and skin changes) syndrome is not well described. We investigated COD in patients with POEMS syndrome treated at Mayo Clinic between 2000 and 2022. Of the 89 deaths, 49 patients had known COD and were the subject of this study. Seventeen patients died of unrelated causes, while 32 patients (65%) died from causes related to POEMS syndrome including secondary malignancies like myelodysplastic syndrome and acute leukemia (n = 5) and complications from active therapy (n = 5). Notably, 19 patients died with a stereotypic syndrome we termed capillary leak phenotype (CLP), which was characterized by refractory ascites, effusions and/or anasarca that ultimately resulted in hypotension, renal failure and cardiopulmonary arrest. Alternate causes for these symptoms, such as cardiac and hepatic etiologies, were excluded. CLP as a COD was an earlier event with a median time from diagnosis to death of 2.5 years compared to 12.0 years for all other deceased patients (p = <0.0001). By definition, treatment of terminal CLP was unsuccessful with median survival of only 4 months after CLP onset. The driver of CLP is unknown, but recognition as an entity should allow for systematic study.

Hemodynamic Management with Vasopressin for Cardiovascular Surgery.

Background and Objectives: Vasopressin increases blood pressure through aquaporin-2-mediated water retention and is useful for managing hemodynamics after surgery. However, even after decades of study, clear clinical guidelines on doses and ideal use cases after cardiovascular surgery remain unclear. Here, the existing literature is synthesized on vasopressin use for cardiac surgeries and coupled with real-world clinical experience to outline a clearer clinical path for vasopressin use. Materials and Methods: Literature from 1966 to the present was searched, and information on surgical outcomes for cardiovascular surgery was extracted. Clinicians from the University of Tsukuba with extensive vasopressin experience in pediatric cardiovascular patients were consulted for general use guidelines. Results: Vasopressin response after cardiovascular surgery is multifaceted, and low-power trials, plus conflicting study reports, generally render it as a secondary choice behind norepinephrine. Clinical experience indicates that low doses of 0.2-0.3 mU/kg/min with constant blood pressure and oxygen monitoring for response are required. Although sole use is not recommended, vasopressin may aid in controlling hemodynamics when given with other volemic or osmolal drugs. Conclusions: Vasopressin may work in a select population of first-line non-responders, but relevant response factors remain unanalyzed and clear guidelines for use remain unestablished. Future, large-scale studies are needed to delineate temporal and demographic characteristics that affect response to vasopressin for the purpose of managing post-surgical capillary leakage and hemodynamics.

Evaluation of Metastasis Inhibition by ABD-IL-2 Compared to Human IL-2 in a Breast Cancer Mouse Model.

Interleukin-2 (IL-2) is a well-known cytokine that plays a crucial role in stimulating immune cells, including natural killer (NK) cells and cytotoxic T cells. It has been studied as an immunotherapy for a variety of diseases, including cancer. However, due to its short serum half-life, high doses of IL-2 are required which can result in systemic toxicities like capillary leak syndrome. To demonstrate the enhanced antitumor efficacy of Albumin Binding Domain-conjugated IL-2 (ABD-IL-2) at a lower dose compared to IL-2. IL-2 and ABD-IL-2 were purified using Ni-NTA resin with a histidine sequence added to their C-terminal region for purification purpose. Peripheral blood lymphocytes were stimulated with IL-2 and ABD-IL-2 to assess their function. 4T1 cells were injected into BALB/c mice to establish a breast cancer model with metastasis evaluated in the lungs. Both recombinant proteins significantly stimulated T lymphocyte proliferation compared to the negative control (P=0.000, P=0.001). Administration of both proteins reduced the size of isolated tumors in the breast cancer mouse model. The control group had more nodules and larger lung metastatic centers (P=0.000). Metastasis to secondary lymphoid organs occurred only in the control group. By using ABD-IL-2 at a one-third concentration compared to IL-2, we aimed to reduce administration toxicity associated with high doses of IL-2 in immunotherapy. This approach shows potential for improving IL-2-based treatments while minimizing adverse effects.

Mortality Predictors in Children with Severe Dengue at Dhaka Shishu (Children) Hospital

Background: There are many tropical areas where dengue is a significant mosquito borne disease and causes substantial global mortality. Despite the high burden of dengue virus (DENV) infections, severe dengue remains fatal in Bangladesh. Nevertheless, few risk factors are known for death in cases of severe dengue. Being aware of these predictors are crucial to advance patient management and provide counseling for clinical decisions. Methods: This cross sectional analytical study was conducted at Dhaka Shishu (Children) Hospital from May 2019 to February 2020. Using convenient sampling the study enrolled a total of 350 children with severe dengue. Of these 16 died, and 334 survived. Comparisons of physiologic, clinical and laboratory parameters between survival and mortality groups were performed to identify predictors of death. Results: The majority (81%) of incidents were in children aged 5 to 10 years who attended. There was no significant differences in gender of the patients. The clinical predictors of mortality were major bleeding, plasma leakage (P &gt;20% rise in hematocrit, ascites, pleural effusion), hepatomegaly, and refractory shock (p&lt;0.05). Laboratory findings in the group with high mortality were thrombocytopenia (&lt;15,000/mm³), elevated liver enzymes (ALT, AST), prolonged PT/INR, hypoalbuminemia and high ferritin values (p&lt;0.001). Conclusion: In children with severe dengue, major bleeding, plasma leakage, refractory shock, severe thrombocytopenia, and raised ferritin were significant predictors of mortality. Knowing early the presence of these risk factors will enable timely and judicious management in at risk children to improve outcomes.

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 &lt;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

Chikungunya infection in children: clinical profile and outcome.

The clinical profile and outcomes of children with chikungunya infection differ from those observed in adults. As there is a paucity of data on chikungunya infection in children, this study aimed to find the clinical course, complications, and mortality rates of chikungunya infection in children. This was a combined retrospective and prospective observational study. Children aged 1 month to 15 years who tested positive for chikungunya infection by IgM enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction in serum or body fluids were included. The demographic details, clinical presentation, laboratory parameters, treatment given, and outcomes were recorded in a structured proforma. Fifty-eight cases (41 retrospective and 17 prospective) were recruited, out of which 30 (52%) were males. The median age was 8 (3-11) years. The most common clinical feature at admission was fever observed in 55 patients (94.8%), followed by vomiting [25 (43.1%)] and myalgia [23 (39.7%)]. Commonly observed clinical signs were skin rash [32 (55.2%)], hepatomegaly [25 (43.1%)], and anemia [22 (37.9%)]. Frequently observed acute complications were lymphopenia [46 (79.3%)], hyponatremia [32 (55.2%)], capillary leak [27 (46.6%)], and thrombocytopenia [26 (44.8%)]. Of 58 cases, 8 (13.8%) children had co-infection with other microbes. Overall, 55 (94.8%) children had complete recovery, 2 (3.4%) children died of complications (one with acute encephalitis and one child with acute respiratory distress syndrome), and 5 children had prolonged arthralgia. Children with chikungunya had more skin manifestations and neurological manifestations than arthralgia. Also, a significant proportion of children developed serious complications like a capillary leak.

Dengue virus non-structural protein 1 binding to thrombin as a dengue severity marker: Comprehensive patient analysis in south Taiwan.

Previously we identified a complex of non-structural protein (NS) 1 - Thrombin (NST) in dengue infected patients. Here, we investigated how the concentration of NS1 and NST differ in various dengue severity levels as well as their demographic and clinical features. Several comorbid (hypertension, diabetes, and chronic renal failure) often found in dengue patients were also measured and analyzed. A total of 86 dengue patients (52 not severe and 34 severe), were enrolled and had their blood taken. Blood samples were further verified for clinical blood parameters, including liver and renal function tests and serologic assays (NS1 and NST). Patients' severity was grouped based on WHO 2009 classification, which separates patients into dengue without warning signs (DNWS), dengue with warning signs (DWWS), and severe dengue (SD). DWWS is explained as DNWS with warning signs (persistent abdominal pain, persistent vomiting, liver enlargement, bleeding (any kind), fatigue, and restlessness). SD are those with severe plasma leakage, severe bleeding, or severe organ impairment. Multivariate regression analysis was used to predict the role of NST on the dengue severity development and receiver operating characteristic (AUROC) test was utilized to evaluate separability. The analysis revealed that NS1 significantly impacts the disease outcome (p 0.018, OR=2.467 (1.171-5.197)) but not beyond the effect through NST (p 0.108, OR=0.085 (0.004-1.719)). We also prove that NST was a better severity biomarker compared to NS1, as it can predict progression from DNWS to DWWS (AUC: NS1=0.771∗∗, NST=0.81∗∗) and SD (AUC: NS1=0.607, NST=0.754∗) significantly. This finding suggests the importance of NST in mediating the NS1 effect to promote dengue severity progression and its promising capability as an acute stage dengue severity biomarker.

THE EFFECT OF THE INFLAMMATORY RESPONSE ON THE DEVELOPMENT OF PREGNANCY COMPLICATED BY PREECLAMPSIA

Preeclampsia remains one of the main causes of obstetric and perinatal complications. The frequency of preeclampsia in the structure of pregnancy complications varies from 6 % to 12 % in healthy pregnant women and from 20 % to 40 % in pregnant women with extragenital pathology. There is growing interest in investigating the exact pathophysiological mechanism of the preeclampsia process as this may identify new potential screening biomarkers. There is evidence that inflammatory mechanisms are a key link between placental ischemia and endothelial dysfunction. It has been hypothesized that impaired regulatory systems are unable to regulate the resolution of inflammatory pathways, contributing to an exaggerated immune response. It is appropriate to call pregnancy a unique immune state that is modulated, but not suppressed. Modulation of the immune system leads to differentiated reactions depending on the stage of pregnancy. Each stage of pregnancy is characterized by a unique inflammatory state. The first and third trimesters are pro-inflammatory, while the second trimester is an anti-inflammatory phase. Proinflammatory mediators, such as IL-6, directly and indirectly through TNF-α, bradykinin, thrombin cause degradation of the endothelial glycocalyx, which leads to an increase in the permeability of the vascular wall with the progression of capillary leakage into the interstitial space. Inflammatory damage to the glycocalyx that occurs during preeclampsia increases intercellular permeability associated with leakage of fluid and albumin into the interstitial space. As a result of damage to the endothelium, there is an increase in the volume of extracellular fluid, which is manifested in women with severe preeclampsia in the form of edema with pathological fluid retention. Further studies are needed to clarify the role of inflammatory mediators in predicting the risk of developing preeclampsia. Further study of the problem will reveal potential targets for treatment, primarily related to inhibition of inflammatory processes and prevention of damage to the endothelial glycocalyx.

Síndrome de fuga capilar por mordedura de serpiente en la Amazonía. Reporte de un caso

Capillary leak syndrome is a unique complication characterized by extravasation of liquids in the interstitial space due to protein loss caused by snakebite envenoming. We describe the case of a 12-year-old boy from the district of Napo in the city of Iquitos in the Peruvian Amazon, who had edema and increased face volume due to the bite of a snake of the Bothrops genus in the lateral aspect of the right leg; he was the hospitalized and diagnosed with severe ophidism complicated with face edema. The patient received eight vials of antivenin, antibiotics and analgesics. Finally, the patient was discharged from the hospital after eight days of hospitalization, with favorable evolution and recovery.