Retos y estrategias en el manejo de la trombosis de la vena porta / Challenges and strategies in the management of portal vein thrombosis

La trombosis de la vena porta (TVP) en pacientes con o sin cirrosis hepática (CH) se define como una obstrucción de la vena porta debido a la formación de un trombo que puede extenderse a las venas mesentéricas superiores y esplénica. Esta es una complicación común de la enfermedad hepática avanzada. Se creía que la TVP se producía predominantemente debido al potencial protrombótico del paciente con CH, ya que se observaba una mayor incidencia de TVP en CH con una puntuación MELD y Child-Pugh más altas, con una prevalencia informada del 10 % al 25%.

Portal vein thrombosis (PVT) in patients with or without hepatic cirrhosis (CH) is defined as an obstruction of the portal vein due to the formation of a thrombus that may extend to the superior mesenteric and splenic veins. This is a common complication of advanced liver disease. It was believed that PVT predominantly occurred due to the prothrombotic potential of the patient with CH, as a higher incidence of PVT was observed in CH with higher MELD and Child-Pugh scores, with a reported prevalence of 10% to 25%.

Caracterización de pacientes con trombosis portal sobre hígado no cirrótico en un hospital universitario de Medellín, Colombia / Characterization of patients with portal vein thrombosis on non-cirrhotic liver at a university hospital in Medellín, Colombia

Introducción. La trombosis de la vena porta es la oclusión parcial o completa de la luz de la vena porta o sus afluentes por la formación de trombos. Se asocia a desenlaces adversos y a un peor pronóstico. La frecuencia de aparición viene en aumento, a menudo de manera incidental, debido al uso cada vez mayor de imágenes diagnósticas. Metodología. Estudio observacional de una serie de casos de pacientes mayores de 18 años a quienes se les documentó trombosis venosa portal en hígado no cirrótico en el periodo comprendido entre enero de 2012 y diciembre de 2019 en un hospital de cuarto nivel de la ciudad de Medellín, Colombia. Resultados. Se documentaron 94 trombosis portales, la media de edad fue 44 ± 15 años, el 56 % eran mujeres. El promedio de aparición de síntomas fue de 14 días. La presentación de la trombosis fue aguda en un 41 %, crónica en 44 % y de instauración aguda sobre una trombosis crónica en un 15 %. La presentación clínica fue asintomática en el 33 %, el dolor abdominal fue la presentación más común con el 62 %. La trombofilia adquirida de mayor ocurrencia fueron las neoplasias mieloproliferativas crónicas en un 18 %, seguida del síndrome antifosfolípido en un 6 %. El método diagnóstico más usado fue la TAC trifásica en un 58 % seguido de la ultrasonografía en un 35 %. El 66 % de los pacientes fueron anticoagulados, siendo la warfarina el principal anticoagulante usado en un 56 %. El 16 % presento algún tipo de sangrado, aunque ninguno fue sangrado mayor. Conclusiones. La trombosis portal sigue siendo en muchos casos un hallazgo incidental. Se encontró un número inusual de neoplasias mieloproliferativas crónicas. La anticoagulación es segura y eficaz, aunque los anticoagulantes orales directos aún tienen un uso restringido.

Introduction. Portal vein thrombosis is the partial or complete occlusion of the lumen of the portal vein or its tributaries by thrombus formation. It is associated with adverse outcomes and a poorer prognosis. Its frequency is increasing, often incidentally, due to the growing use of diagnostic imaging. Methodology. This is an observational study of a case series of patients over 18 years old who were documented with portal vein thrombosis in a non-cirrhotic liver between January 2012 and December 2019 in a fourth-level hospital in the city of Medellín, Colombia. Results. Ninety-four cases of portal vein thrombosis were documented. The mean age was 44 ± 15 years, and 56 % were women. The average onset of symptoms was 14 days. Thrombosis presentation was acute in 41 %, chronic in 44 %, and acute on chronic in 15 %. Clinically, 33 % were asymptomatic, and abdominal pain was the most common presentation at 62 %. The most common acquired thrombophilia was chronic myeloproliferative neoplasms at 18 %, followed by antiphospholipid syndrome at 6 %. The most used diagnostic method was triphasic CT at 58 %, followed by ultrasonography at 35 %. Sixty-six percent of the patients received anticoagulation, with warfarin being the main anticoagulant used at 56 %. Sixteen percent experienced some type of bleeding, although none were major. Conclusions. Portal vein thrombosis remains, in many cases, an incidental finding. An unusual number of chronic myeloproliferative neoplasms were found. Anticoagulation is safe and effective, although the use of direct oral anticoagulants remains restricted.

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

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

Bariatric and general surgical procedures in obese patients with a history of venous thromboembolism and concurrent anticoagulation therapy.

OBJECTIVE: The objective of this study was to examine the use and outcomes of perioperative anticoagulation (AC) in obese patients with a known history of venous thromboembolism event (VTE). METHOD: A retrospective review of a prospective database for patients with a VTE history undergoing bariatric and general surgery at a single center (1/2008-12/2017) was performed. Factors assessed included demographics, surgical details, and outcomes. RESULTS: Sixty-five patients underwent 76 procedures: 46 females (71%); mean age 51 years (range 26-73), mean weight 284 pounds (range 110-558), mean body mass index 45 (range 19-87). Comorbidities include hypertension (60%), gastroesophageal reflux disease (54%), osteoarthritis (49%), obstructive sleep apnea (45%), and diabetes (37%). Operations: 22 general surgeries (29%), 20 sleeve gastrectomies (26%), 12 revisions/conversions (16%), 12 Roux-en-Y gastric bypasses (16%), and 10 gastric bands (13%). Modalities: 67% laparoscopic, 28% robotic, and 5% open. Twenty-two patients (34%) had a pre-operative inferior vena cava filter placed with no complications. The mean length of stay was 4.4 days (range 1-31). Complications: seven 30-day readmissions (9%), one 30-day reoperation (1%), and two 90-day VTEs (3%). Thirty-day readmissions: four for inability to tolerate PO, two for small bowel obstruction, and one for symptomatic anastomotic ulcer. CONCLUSIONS: In our patients, post-operative AC could be started without an increased risk of bleeding in patients with a history of VTE undergoing bariatric surgery.

OBJETIVO: Examinar el uso y los resultados de la anticoagulación perioperatoria en pacientes bariátricos con antecedentes de tromboembolia venosa (TEV). MÉTODO: Revisión retrospectiva (base de datos prospectiva) de pacientes sometidos a cirugía general y bariátrica (1/2008-12/2017). Se evaluaron datos demográficos, detalles quirúrgicos y resultados. RESULTADOS: Sesenta y cinco pacientes se sometieron a 76 procedimientos: 46 mujeres (71%), edad media 51 años (rango: 26-73), peso medio 284 libras (rango: 110-558), índice de masa corporal medio 45 (rango: 19-87). Comorbilidad: hipertensión (60%), enfermedad por reflujo gastroesofágico (54%), osteoartritis (49%), apnea obstructiva del sueño (45%), diabetes (37%). Operaciones: 22 cirugía general (29%), 20 gastrectomías en manga (26%), 12 revisiones/conversiones (16%), 12 Y-de-Roux (16%), 10 bandas gástricas (13%). Modalidades: 67% laparoscópica, 28% robótica, 5% abierta. A 22 pacientes (34%) se les colocó un filtro de vena cava inferior preoperatorio sin complicaciones. La estancia media fue de 4.4 días (rango: 1-31). Complicaciones: 7 reingresos a los 30 días (9%), 1 reoperación a los 30 días (1%), 2 TEV a los 90 días (3%). Reingresos a los 30 días: 4 por incapacidad para tolerar la vía oral, 2 obstrucciones de intestino delgado y 1 úlcera anastomótica sintomática. CONCLUSIONES: En nuestros casos, la anticoagulación posoperatoria pudo iniciarse sin aumento del riesgo de sangrado en pacientes con antecedentes de TVE sometidos a cirugía bariátrica.

Thromboprophylaxis in varicose veins surgery: The everyday concern.

Venous thromboembolic disease (VTE) occupies an important place as a cause of morbidity and mortality in surgical patients in all specialties. Despite the existence of guidelines for thrombo prophylaxis in surgery, it is not clear due to the lack of current evidence, how to develop antithrombotic prophylaxis in varicose vein surgery and many questions arise when the surgeon is faced with a patient to be operated on. A comprehensive review of the literature was conducted to examine the evidence about the prevention of the venous thromboembolism in varicose veins surgery patients, and aims to guide the reader through questions that arise in daily practice, discussing the different scenarios presented in the literature for the choice of the most appropriate prophylaxis for each case. The lack of conclusive literature determines that risk should be individualized using available scales and other procedure-related factors, so that the type and duration of prophylaxis can be determined on a case-by-case basis.

Prevalence of PICC-related thrombosis in patients with hematological malignancies: a systematic review.

PURPOSE: To estimate the prevalence of peripherally inserted central catheter (PICC)-related venous thrombosis in patients with hematological malignancies. METHODS: A systematic review of observational studies that evaluated the occurrence of PICC-related venous thrombosis in children, adults, and older people with hematological malignancies was conducted. Searches were carried out on June 12th, 2023 on PubMed, CINAHL, Embase, Web of Science Core Collection, Scopus, and LILACS, and to gray literature on Google Scholar, and ProQuest Dissertations and Theses Global. Eligibility criteria were applied independently by two reviewers, first on the titles and abstracts on the Rayyan platform and then on the full text of eligible studies. Risk of bias was assessed by the JBI checklist. Data were summarized descriptively, and the meta-analysis was carried out using the MetaXL 5.3 software. The review followed JBI guidelines and PRISMA for reporting. RESULTS: In the 40 studies included, prevalence of PICC-related venous thrombosis was 9% in general, 9% in adults, and 6% in children with hematological malignancies. Most studies only evaluated cases of symptomatic thrombosis (n = 25; 64%). CONCLUSION: Patients with hematological malignancies using PICC have an estimated prevalence of PICC-related venous thrombosis of 9%, and this rate may be underestimated due to the consideration of mostly symptomatic cases.

Immune checkpoint inhibitors-associated thrombosis in patients with head and neck cancer: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group.

PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with Immune Checkpoint Inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS: /Patients. This retrospective, multicenter study was promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with head and neck cancer who initiated ICI between 01/01/2015 and 31/12/2021 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT, with secondary objectives including the analysis of their impact on survival and the identification of variables predictive of VTE/AT. RESULTS: A total of 143 patients with head and neck cancer were enrolled. The incidence of VTE/AT during follow-up (median 8.6 months) was 2.8%. Survival analysis showed no significant differences (p = 0.644) between the group that developed VTE/AT (median 7.13 months, 95% CI 0-22.9) and the group that did not (median 9.86 months, 95% CI 6.3-13.4). The presence of liver metastases was predictive of VTE/AT (p < 0.05). CONCLUSIONS: Thromboembolic disease associated with immunotherapy in patients with head and neck neoplasia does not significantly impact survival. The presence of liver metastases can predict these events.

Altered dynamics of calcium fluxes and mitochondrial metabolism in platelet activation-related disease and aging.

Understanding the mechanisms controlling platelet function is crucial for exploring potential therapeutic targets related to atherothrombotic pathologies and primary hemostasis disorders. Our research, which focuses on the role of platelet mitochondria and Ca2+ fluxes in platelet activation, the formation of the procoagulant phenotype, and thrombosis, has significant implications for the development of new therapeutic strategies. Traditionally, Ca2+-dependent cellular signaling has been recognized as a determinant process throughout the platelet activation, controlled primarily by store-operated Ca2+ entry and the PLC-PKC signaling pathway. However, despite the accumulated knowledge of these regulatory mechanisms, the effectiveness of therapy based on various commonly used antiplatelet drugs (such as acetylsalicylic acid and clopidogrel, among others) has faced challenges due to bleeding risks and reduced efficacy associated with the phenomenon of high platelet reactivity. Recent evidence suggests that platelet mitochondria could play a fundamental role in these aspects through Ca2+-dependent mechanisms linked to apoptosis and forming a procoagulant phenotype. In this context, the present review describes the latest advances regarding the role of platelet mitochondria and Ca2+ fluxes in platelet activation, the formation of the procoagulant phenotype, and thrombosis.

Analysis of completion intraoperative venography during first rib resection for venous thoracic outlet syndrome.

BACKGROUND: We evaluated the impact of completion intraoperative venography on clinical outcomes for axillosubclavian vein (AxSCV) thrombosis owing to venous thoracic outlet syndrome (vTOS). METHODS: We performed a retrospective, single-center review of all patients with vTOS treated with first rib resection (FRR) and intraoperative venography from 2011 to 2023. We reviewed intraoperative venographic films to classify findings and collected demographics, clinical and perioperative variables, and clinical outcomes. Primary end points were symptomatic relief and primary patency at 3 months and 1 year. Secondary end points were time free from symptoms, reintervention rate, perioperative complications, and mortality. RESULTS: Fifty-one AxSCVs (49 patients; mean age, 31.3 ± 12.6 years; 52.9% female) were treated for vTOS with FRR and external venolysis followed by completion intraoperative venography with a mean follow up of 15.5 ± 13.5 months. Before FRR, 32 underwent catheter-directed thrombolysis (62.7%). Completion intraoperative venography identified 16 patients with no stenosis (group 1, 31.3%), 17 with no stenosis after angioplasty (group 2, 33.3%), 10 with residual stenosis after angioplasty (group 3, 19.7%), and 8 with complete occlusion (group 4, 15.7%). The overall symptomatic relief was 44 of 51 (86.3%) and did not differ between venographic classifications (group 1, 14 of 16; group 2, 13 of 17; group 3, 10 of 10; and group 4, 7 of 8; log-rank test, P = .5). The overall 3-month and 1-year primary patency was 42 of 43 (97.7%) and 32 of 33 (97.0%), respectively (group 1, 16 of 16 and 9 of 9; group 2, 16 of 17 and 12 of 13; group 3, 10 of 10, 5 of 5; group 4, primary patency not obtained). There was one asymptomatic rethrombosis that resolved with anticoagulation, and three patients underwent reintervention with venous angioplasty for significant symptom recurrence an average 2.89 ± 1.7 months after FRR. CONCLUSIONS: Our single-center retrospective study demonstrates that FRR with completion intraoperative venography has excellent symptomatic relief and short- and mid-term patency despite residual venous stenosis and complete occlusion. Although completion intraoperative venographic classification did not correlate with adverse outcomes, this protocol yielded excellent results and provides important clinical data for postoperative management. Our results also support a conservative approach to AxSCV occlusion identified after FRR.

Left Gastric Vein Direct Anastomosis as Alternative to Portal Flow Reconstruction in Liver Transplantation.

Introduction: The most relevant limiting factor for performing end-to-end anastomosis is portal vein thrombosis (PVT), which leads to challenging vascular reconstructions. This study aimed to analyze a single center's experience using the left gastric vein (LGV) for portal flow reconstruction in liver transplantation (LT). Methods: This retrospective observational study reviewed laboratory and imaging tests, a description of the surgical technique, and outpatient follow-up of patients with portal system thrombosis undergoing LT with portal flow reconstruction using the LGV. This study was conducted at a single transplant reference center in the northeast region of Brazil from January 2016 to December 2021. Results: Between January 2016 and December 2021, 848 transplants were performed at our center. Eighty-two patients (9.7%) presented with PVT, most of whom were treated with thrombectomy. Nine patients (1.1% with PVT) had extensive thrombosis of the portal system (Yerdel III or IV), which required end-to-side anastomosis between the portal vein and the LGV without graft, and had no intraoperative complications. All patients had successful portal flow in Doppler ultrasound control evaluations. Discussion: The goal was to reestablish physiological flow to the graft. A surgical strategy includes using the LGV graft. According to our reports, using LGV fulfilled the requirements for excellent vascular anastomosis and even allowed the dispensing of venous grafts. This is the largest case series in a single center of reconstruction of portal flow with direct anastomosis with the LGV without needing a vascular graft.

Thrombosis and infections associated with PICC in onco-hematological patients, what is their relevance?

PURPOSE: Peripherally inserted central venous catheters (PICC) in the onco-hematological patients may be associated with thrombosis or infections that may have short- to medium-term repercussions. MATERIAL AND METHODS: Single-centre retrospective analysis of a prospectively collected cohort. Primary objective was to establish the PICC-thrombosis and infections incidence. Secondary objectives were to analyze profile of patients suffering from these complications and variables associated with an increased likelihood of developing these events. RESULTS: 549 patients were recruited. 58.5% (n = 321) were oncology patients and 41.5% (n = 228) hematology patients. The incidence of PICC-associated thrombosis was 3.5% (n = 19). Thrombosis was associated with progression of the underlying malignant pathology in 10.6% (n = 2) of cases. No association was found between clinical variables analysed and development of thrombosis. Incidence of PICC-associated infections was 7.65% (n = 42). In the 30 days prior to PICC infection, 57.1% (n = 24) had a febrile syndrome of another focus, 73.8% (n = 11) had been hospitalized, 49.5% (n = 25) had a neutrophil count of 0-500 cells/mm3 and 47.6% (n = 20) had an episode of neutropenic fever. Variables significantly associated with the development of infection were hematological patients, high-flow PICC, 3-lm PICC or PICC insertion because of administration of vesicant therapy. CONCLUSIONS: Incidence of PICC-associated thrombosis is low and apparently less prognostically aggressive than other forms of thrombosis associated with cancer, without identify predictive factors. Infection was more prevalent and the identification of risk factors in our series could facilitate its prevention.

Circ-USP9X accelerates deep vein thrombosis after fracture by acting as a miR-148b-3p sponge and upregulates SRC kinase signaling inhibitor 1.

OBJECTIVES: This study aims to elucidate the role of circUSP9X (Circular RNA Ubiquitin Specific Peptidase 9 X-Linked) in the development of venous thrombosis in the lower extremities. METHODS: An animal model of Deep Vein Thrombosis (DVT) and a hypoxic model of Human Umbilical Vein Endothelial Cells (HUVECs) treated with Cobalt (II) Chloride (CoCl2) were developed. The expression levels of circUSP9X, microRNA-148b-3p (miR-148b-3p), and SRC Kinase Signaling Inhibitor 1 (SRCIN1) were quantified using quantitative reverse transcription Polymerase Chain Reaction and Western blot analysis. Cell cytotoxicity, viability, apoptosis, and inflammation in HUVECs were assessed via Lactate Dehydrogenase (LDH) assay, MTT assay, flow cytometry, Enzyme-Linked Immunosorbent Assay, and Western blot, respectively. Hematoxylin and Eosin staining were employed for histopathological examination of the venous tissues in the animal model. The interaction between circUSP9X, miR-148b-3p, and SRCIN1 was further explored through dual-luciferase reporter assays and RNA Immunoprecipitation experiments. RESULTS: The present findings reveal a significant upregulation of circUSP9X and SRCIN1 and a concurrent downregulation of miR-148b-3p in DVT cases. Knockdown of circUSP9X or overexpression of miR-148b-3p ameliorated CoCl2-induced apoptosis in HUVECs, reduced LDH release, enhanced cellular viability, and mitigated inflammation. Conversely, overexpression of circUSP9X intensified CoCl2's cytotoxic effects. The effects of manipulating circUSP9X expression were counteracted by the corresponding modulation of miR-148b-3p and SRCIN1 levels. Additionally, circUSP9X knockdown effectively inhibited the formation of DVT in the mouse model. A competitive binding mechanism of circUSP9X for miR-148b-3p, modulating SRCIN1 expression, was identified. CONCLUSION: circUSP9X promotes the formation of DVT through the regulation of the miR-148b-3p/SRCIN1 axis.

Magnetic Resonance Imaging Features of Plantar Vein Thrombosis.

Plantar vein thrombosis (PVT) is an underdiagnosed condition affecting the deep plantar veins, with challenging clinical diagnosis, often presenting with non-specific symptoms that mimic other foot pathologies. This study assessed the magnetic resonance imaging (MRI) features of patients diagnosed with PVT to contribute to the understanding of this condition. We performed the comprehensive analysis of a substantial dataset, including 112 patients, with a total of 130 positive MRI scans (86 of the forefoot and 44 of the ankle) presenting with PVT. Upon evaluating all the veins of the feet, we observed a higher frequency of involvement of the lateral plantar veins (53.1%) when compared to the medial veins (3.8%). The most affected vascular segments in the forefeet were the plantar metatarsal veins (45.4%), the plantar venous arch (38.5%), and the plantar communicating veins (25.4%). The characteristic findings on MRI were perivascular edema (100%), muscular edema (86.2%), venous ectasia (100%), perivascular enhancement (100%), and intravenous filling defects (97.7%). Our study provides valuable insights into the imaging evaluation of PVT and shows that MRI is a reliable resource for such diagnosis.

Incremento del riesgo hemorrágico en pacientes con fibrilación auricular y enfermedad renal crónica en hemodiálisis tratados con anticoagulantes. Serie de cuatro centros / Increased risk of bleeding in patients with atrial fibrillation and chronic kidney disease on hemodialysis treated with anticoagulants. A four center series

Resumen Objetivo: El objetivo de este estudio fue estimar si el uso de anticoagulantes se asociaba con una diferencia en la frecuencia de trombosis de cualquier sitio, hemorragia mayor y mortalidad en adultos con coexistencia de ambas patologías. Método: Se realizó un estudio de cohorte retrospectivo en cuatro centros de alta complejidad. Se incluyeron mayores de 18 años con ERC en hemodiálisis y FA no valvular, con indicación de anticoagulación (CHA2DS2VASc ≥ 2). El desenlace primario fue la ocurrencia de sangrado mayor, evento trombótico (accidente vascular cerebral, infarto agudo al miocardio o enfermedad tromboembólica venosa) o muerte. Se realizó ajuste por variables de confusión por regresión logística. Resultados: De los 158 pacientes incluidos, el 61% (n = 97) recibieron anticoagulante. El desenlace principal se encontró en el 84% de quienes recibieron anticoagulación y en el 70% de quienes no la recibieron (OR: 2.12, IC95%: 0.98-4.57; luego del ajuste OR: 2.13, IC95%: 1.04-4.36). De los desenlaces mayores se presentaron sangrado en el 52% vs. el 34% (OR: 2.03; IC95%: 1.05-3.93), trombosis en el 35% vs. el 34% (OR: 1.03; IC95%: 0.52-2.01) y muerte en el 46% vs. el 41% (OR: 1.25; IC95%: 0.65-2.38). Conclusiones: Los resultados de este estudio sugieren un incremento en el riesgo de sangrado en los pacientes con FA y ERC en hemodiálisis que reciben anticoagulación, sin disminución del riesgo de eventos trombóticos ni de muerte.

Abstract Objective: The aim of this study was to estimate whether the consumption of anticoagulants was associated with a difference in the frequency of thrombosis of any site, major bleeding and mortality, in adults with both diseases. Method: A retrospective cohort study was carried out in four high complexity centers. Patients older than 18 years with CKD on hemodialysis and non-valvular AF, with an indication for anticoagulation (CHA2DS2VASc ≥ 2), were included. The primary outcome was the occurrence of: major bleeding, thrombotic event (cerebrovascular accident, acute myocardial infarction or venous thromboembolic disease) or death. Adjustment for confounding variables was performed using logistic regression. Results: From 158 patients included, 61% (n = 97) received an anticoagulant. The main outcome was found in 84% of those who received anticoagulation and 70% of those who did not (OR: 2.12, 95%CI: 0.98-4.57; after the adjusted analysis OR: 2.13, 95%CI: 1.04-4.36). Separate outcomes were bleeding in 52% vs. 34% (OR: 2.03; 95%CI: 1.05-3.93), thrombosis in 35% vs. 34% (OR: 1.03; 95%CI: 0.52-2-01) and death in 46% vs. 41% (OR: 1.25; 95%CI: 0.65-2.38). Conclusions: The results of this study suggest an increased risk of bleeding in patients with AF and CKD on hemodialysis receiving anticoagulation, without a decrease in the risk of thrombotic events or all-cause mortality.

Compressão intermitente imediata sobre anastomose vascular: Uma nova técnica para prevenir trombose? / Immediate intermittent compression over vascular anastomosis: a new technique to prevent thrombosis

Introdução: Este estudo tem o objetivo de avaliar o efeito da compressão intermitente imediata sobre anastomoses arteriais microcirúrgicas em comparação com compressão fixa e com utilização isolada de irrigação com soro fisiológico e heparina em laboratório experimental. Método: 12 ratos Wistar foram aleatoriamente divididos em três grupos para terem suas artérias femorais seccionas e anastomosadas de forma término-terminal, para comparação de patência com 30 minutos e 7 dias. Grupo I: foi realizada compressão intermitente imediata sobre a anastomose por 60 segundos; grupo II: uma compressão fixa foi mantida imediatamente após a anastomose, também por 60 segundos; grupo III, após o término da anastomose, não foi feita nenhuma intervenção adicional. Além da avaliação da patência, os animais foram pesados e medidos os diâmetros arteriais operados. Resultados: 24 artérias femorais foram abordadas. As médias de peso inicial dos ratos dos grupos I, II e III foram, respectivamente, de 243,8g, 254,6g e 260,4g, enquanto as finais foram de 264,4g, 281g e 282,1g (p<0,001). O diâmetro médio das artérias abordadas foi, respectivamente, de 0,89mm, 0,88mm e 0,90mm, e os tempos de anastomoses em minutos, de 25,6, 24,5 e 24,5, respectivamente; As patências finais após 7 dias foram, respectivamente, de 62,5% (p=0,07), 25% (p=0,48) e 50% (p=0,13). Conclusão: A compressão intermitente imediata pode ser realizada ao término de anastomoses arteriais microcirúrgicos sem prejuízo na patência final do procedimento.

Introduction: This study aims to evaluate the effect of immediate intermittent compression on microsurgical arterial anastomoses in comparison with fixed compression and only observation in an experimental laboratory. Methods: The two femoral arteries of twelve male Wistar rats were sectioned and reanastomosed to compare patency at 30 minutes and 7 days. Group I: immediate intermittent compression was performed over the anastomosis for 60 s; group II: a fixed compression was maintained immediately after the anastomosis for 60 s; group III: after completion of the anastomosis, no additional intervention was performed. In addition to the patency assessment, the animals were weighed and the operated arterial diameters were measured. Results: Twenty-four femoral arteries were examined. Initial average weights of the rats in groups I, II, and III were 243.8g, 254.6g, and 260.4g, respectively, while the final weights were 264.4g, 281g, and 282.1g (p<0.001), respectively; mean diameter of the approached arteries was 0.89, 0.88, and 0.90mm, respectively, and the anastomoses (time in minutes) were 25.6, 24.5, and 24.5, respectively; final patencies after 7 days were 62.5% (p=0.07), 25% (p=0.48), and 50% (p=0.13), respectively. Conclusion: Immediate intermittent compression can be performed at the end of microsurgical arterial anastomoses without affecting the final patency of the procedure.

Anticoagulantes Orais Diretos versus Antagonistas da Vitamina K para Trombo Ventricular Esquerdo: Uma Metanálise com Análise Sequencial de Ensaios / Direct Oral Anticoagulants versus Vitamin K Antagonists for Left Ventricular Thrombus: A Meta-Analysis with Trial Sequential Analysis

Resumo Fundamento Os antagonistas da vitamina K (AVKs) são o tratamento de primeira linha recomendado para trombo ventricular esquerdo (TVE); entretanto, os anticoagulantes orais diretos (AODs) têm sido considerados uma terapia alternativa. Objetivos Avaliar a eficácia e a segurança dos AODs em comparação com a terapia com AVKs em pacientes com TVE. Métodos PubMed, Embase e Cochrane foram sistematicamente pesquisados em busca de ensaios clínicos randomizados ou estudos de coorte que comparassem AODs versus AVKs para TVE. As razões de risco (RR) foram calculadas para desfechos binários, com intervalos de confiança (IC) de 95%. A significância estatística foi definida como valor de p < 0,05. Resultados Foram incluídos um total de 4 ensaios clínicos randomizados e 29 estudos de coorte, com 4.450 pacientes designados para AODs ou AVKs. Não houve diferença significativa entre os grupos para acidente vascular cerebral ou eventos embólicos sistêmicos (AVC/EES) (RR 0,84; IC 95% 0,65 a 1,07; p = 0,157), acidente vascular cerebral (RR 0,73; IC 95% 0,48 a 1,11; p = 0,140), eventos embólicos sistêmicos (EES) (RR 0,69; IC 95% 0,40 a 1,17; p = 0,166), resolução do trombo (RR 1,05; IC 95% 0,99 a 1,11; p = 0,077), qualquer sangramento (RR 0,78; IC 95% 0,60 a 1,00; p = 0,054), sangramento clinicamente relevante (RR 0,69; IC 95% 0,46 a 1,03; p = 0,066), sangramento menor (RR 0,73; IC 95% 0,43 a 1,23; p = 0,234), sangramento maior (RR 0,87; IC 95% 0,42 a 1,80; p = 0,705) e mortalidade por todas as causas (RR 1,05; IC 95% 0,79 a 1,39; p = 0,752). Em comparação com AVKs, a rivaroxabana reduziu significativamente AVC/EES (RR 0,35; IC 95% 0,16 a 0,91; p = 0,029) e EES (RR 0,39; IC 95% 0,16 a 0,95; p = 0,037). Conclusões Os AODs tiveram uma taxa semelhante de eventos tromboembólicos e hemorrágicos, bem como de resolução do trombo, em comparação com os AVKs no tratamento de TVE. A terapia com rivaroxabana teve uma redução significativa nos eventos tromboembólicos, em comparação com os AVKs.

Abstract Background Vitamin K antagonists (VKAs) are the recommended first-line treatment for left ventricular thrombus (LVT); however, direct oral anticoagulants (DOACs) have been considered an alternative therapy. Objectives To evaluate the efficacy and safety of DOACs compared with VKAs therapy in patients with LVT. Methods PubMed, Embase, and Cochrane were systematically searched for randomized clinical trials or cohort studies that compared DOACs versus VKAs for LVT. Risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (95% CIs). Statistical significance was defined as p value < 0.05. Results A total of 4 randomized clinical trials and 29 cohort studies were included, with 4,450 patients assigned to either DOACs or VKAs. There was no significant difference between groups for stroke or systemic embolic (SSE) events (RR 0.84; 95% CI 0.65 to 1.07; p = 0.157), stroke (RR 0.73; 95% CI 0.48 to 1.11; p = 0.140), systemic embolic (SE) events (RR 0.69; 95% CI 0.40 to 1.17; p = 0.166), thrombus resolution (RR 1.05; 95% CI 0.99 to 1.11; p = 0.077), any bleeding (RR 0.78; 95% CI 0.60 to 1.00; p = 0.054), clinically relevant bleeding (RR 0.69; 95% CI 0.46 to 1.03; p = 0.066), minor bleeding (RR 0.73; 95% CI 0.43 to 1.23; p = 0.234), major bleeding (RR 0.87; 95% CI 0.42 to 1.80; p = 0.705), and all-cause mortality (RR 1.05; 95% CI 0.79 to 1.39; p = 0.752). Compared with VKAs, rivaroxaban significantly reduced SSE events (RR 0.35; 95% CI 0.16 to 0.91; p = 0.029) and SE events (RR 0.39; 95% CI 0.16 to 0.95; p = 0.037). Conclusions DOACs had a similar rate of thromboembolic and hemorrhagic events, as well as thrombus resolution, compared to VKAs in the treatment of LVTs. Rivaroxaban therapy had a significant reduction in thromboembolic events, compared to VKAs.

Primary hyperparathyroidism in pregnancy: a case report highlighting uncommon complication / Hiperparatiroidismo primario en el embarazo: reporte de caso destacando una complicación infrecuente

Abstract Primary hyperparathyroidism (PHPT) is characterized by elevated levels of calcium and parathyroid hormone (PTH). However, the interpretation of diagnostic tests, such as serum calcium and PTH levels, is complex in pregnant women. The aim of this report is to present a case of PHTP in a pregnant adolescent, with a special emphasis on an uncommon complication, as well as diagnostic and treatment strategies. A 17-year-old pregnant female presented with hyper emesis gravidarum and neurological symptoms, leading to the diagnosis of cerebral venous thrombosis. Further investigations revealed hypercalcemia and persistently elevated PTH levels, consistent with PHPT. After local ization studies, the patient underwent an emergency parathyroidectomy with a diagnosis of parathyroid ad enoma. During follow-up, intrauterine growth restric tion and severe preeclampsia developed, necessitating an emergency cesarean section. Both the mother and neonate had favorable outcomes. PHPT is an infrequent condition in the pregnant population, and its diagnosis can be challenging due to the overlap of symptoms with normal physiological changes during pregnancy. The occurrence of uncom mon complications, such as thrombotic phenomena, highlights the need for a comprehensive approach to ensure early detection and management. In most cases, parathyroidectomy is the treatment of choice.

Resumen El hiperparatiroidismo primario (HPTP) se caracteriza por niveles elevados de calcio y hormona paratiroidea (PTH). Sin embargo, la interpretación de pruebas diag nósticas, como los niveles de calcio sérico y PTH, es compleja en mujeres embarazadas. El objetivo de este re porte es presentar un caso de HPTP en una adolescente embarazada, con especial hincapié en una complicación infrecuente, así como en las estrategias diagnósticas y de tratamiento. Una mujer embarazada de 17 años presentó hiperé mesis gravídica y síntomas neurológicos, lo que llevó al diagnóstico de trombosis venosa cerebral. Posterio res investigaciones revelaron hipercalcemia y niveles persistentemente elevados de PTH, consistentes con HPTP. Tras la realización de estudios de localización, la paciente fue sometida a una paratiroidectomía de emergencia con diagnóstico de adenoma de paratiroi des. Durante el seguimiento, se desarrolló restricción del crecimiento intrauterino y preeclampsia grave, lo que resultó en la necesidad de realizar una cesárea de emergencia. Tanto la madre como el neonato evolucio naron favorablemente. El HPTP es una condición infrecuente en la población embarazada y su diagnóstico puede ser desafiante por la superposición de síntomas con los cambios fisiológicos normales del embarazo. La aparición de complicaciones infrecuentes, como fenómenos trombóticos, resalta la necesidad de un abordaje integral para garantizar la detección y el manejo temprano. En la mayoría de los casos, la paratiroidectomía es el tratamiento de elección.

Trombosis espontánea de plexo pampiniforme: Reporte de un caso y revisión de literatura

Introducción: La trombosis de plexo pampiniforme es una entidad poco conocida, solo existen 31 casos reportados a la fecha. Objetivo: Presentación de un caso de una patología poco frecuente, descripción de las publicaciones anteriores y revisión de la literatura. Reporte de caso: Paciente de 20 años, sin antecedentes, con trombosis de plexo pampiniforme derecho. Sospecha inicial de hernia inguinal derecha complicada, el diagnóstico se realizó con ecografía Doppler y recibió tratamiento con anticoagulantes. Se complementó con tomografía y estudio de trombofilias. Discusión: El estudio y manejo ha sido variable, antes prevalecía la estrategia quirúrgica. Actualmente, algunos autores recomiendan el manejo conservador y otros proponen diferenciar el tratamiento según segmento anatómico comprometido. Conclusión: Al ser una entidad poco frecuente, el tratamiento es una decisión que debe ser tomada según cada caso, ya que no existen pautas de tratamiento, pero la tendencia es cada vez mayor hacia el tratamiento conservador. El rol de la anticoagulación está por definir. Es importante realizar un adecuado diagnóstico diferencial y búsqueda de causas subyacentes.

Introduction: Pampiniform plexus thrombosis is a rare entity, with only 31 cases reported to date. Aim: Presentation of a case of a rare disease, description of previous publications and review of the literature. Case report: 20-year-old patient, with no history, with right pampiniform plexus thrombosis. Initial suspicion was complicated right inguinal hernia, diagnosis was made with Doppler ultrasound and treatment with anticoagulation. It was complemented with tomography and study of thrombophilias. Discussion: The study and management has been variable, where the surgical strategy prevailed. Currently some authors recommend conservative management and others differentiate the treatment according to the compromised anatomical segment. Conclusion: Being a rare entity, conservative treatment or surgery continues to be a decision that must be made according to each case since there are no treatment guidelines, but the trend is increasing towards conservative treatment. The role of anticoagulation remains to be defined. It is important to carry out an adequate differential diagnosis and search for underlying causes.

El papel del estetrol en la anticoncepción: una revisión integral / The role of estetrol in contraception: a comprehensive review

Esta revisión narrativa explora el papel potencial del estetrol (E4), un esteroide estrogénico natural, en la anticoncepción, analizando sus propiedades farmacológicas, su efectividad y su seguridad. Se revisaron estudios preclínicos, ensayos clínicos y evaluaciones de seguridad del E4 como anticonceptivo oral combinado (AOC). Se investigó el impacto en parámetros endocrinos, metabólicos y hemostáticos, así como su tolerabilidad. En los resultados, el E4 tiene menor afinidad por el receptor de estrógeno-α de membrana, pero mantiene la actividad agonista en los receptores nucleares. E4/DRSP (drospirenona) demostró ser un AOC eficaz, con ciclos de sangrado regulares y predecibles en la mayoría de las mujeres. La tolerabilidad fue favorable, con eventos adversos leves o moderados y bajas tasas de interrupción. El sangrado fue el evento adverso más común, y se reportaron casos raros de migrañas con aura, trombosis venosa profunda, hiperpotasemia y depresión. E4/DRSP tuvo mínimo impacto en los parámetros lipídicos, hepáticos, de globulina fijadora de hormonas sexuales y de metabolismo de hidratos de carbono, y efecto neutral o mínimo en los parámetros hemostáticos. Se concluye que E4/DRSP parece ser una opción anticonceptiva eficaz y segura, con reducido riesgo trombótico y mínimo impacto en los parámetros endocrinos y metabólicos. Se requiere más investigación para confirmar su seguridad y eficacia a largo plazo.

This narrative review explores the potential role of estetrol (E4), a natural estrogenic steroid, in contraception, analyzing its pharmacological properties, effectiveness, and safety. Preclinical studies, clinical trials, and safety assessments of E4/DRSP (drospirenone) as a combined oral contraceptive (COC) were reviewed. The impact on endocrine, metabolic, and hemostatic parameters, as well as tolerability, was investigated. In results, E4 exhibits lower affinity for estrogen transmembrane receptor-α but maintains agonistic activity on nuclear receptors. E4/DRSP proved to be an effective COC with regular and predictable bleeding cycles in most women. Tolerability was favorable with mild or moderate adverse events and low discontinuation rates. Bleeding was the most common adverse event, and rare cases of aura migraines, deep vein thrombosis, hyperkalemia, and depression were reported. E4/DRSP had minimal impact on lipid, hepatic, sex hormone-binding globulin, and carbohydrate metabolism parameters, with a neutral or minimal effect on hemostatic parameters. The conclusion is that E4/DRSP seems to be an effective and safe contraceptive option, with reduced thrombotic risk and minimal impact on endocrine and metabolic parameters. Further research is needed to confirm long-term safety and efficacy.

Catheter-related thrombosis in a neonatal intensive care unit: a case-control study / Trombose relacionada a cateter em unidade de terapia intensiva neonatal: um estudo de caso-controle

INTRODUCTION: Catheter-related thrombosis (CRT) accounts for most thrombotic events in the neonate. OBJECTIVE: Investigate CRT frequency, association with days of catheter use until diagnosis, and number of catheters used, in a single-center Neonatal Intensive Care Unit. METHODS: A case-control study that included 14 cases and 42 controls. Data collection occurred between January 2017 and December 2020 in a public NICU. Crude odds ratios (COR) were calculated. The study complied with ethical standards from national guidelines. RESULTS: Two hundred and ninety-four neonates used central venous catheters, of which 14 (4.7%) were diagnosed with CRT. Catheter in use when diagnosis was made was centrally inserted central catheters in 8 (57.1%). Before diagnosis, the cumulative duration of catheter use was 34.5 days and the median number of catheters used was three. A higher SNAPPE-II (COR 1.03; 95% CI 1.01-1.06; p=0.03), cumulative days of catheter use >30 (COR 19.11; 95% CI 2.28-160.10; p=0.007) and number of catheters used ≥3 (COR 7.66; 95% CI 1.51-38.70; p=0.01) were associated with CRT. CONCLUSION: CRT cases were associated with clinical severity; number of catheters and cumulative days of catheter use. We suggest that screening for thrombosis should be performed in neonates who need a long time of catheter use and more than three catheters. Reducing the duration and number of venous catheters used will help to reduce CRT.

INTRODUÇÃO: A trombose relacionada ao cateter (TRC) é responsável pela maioria dos eventos trombóticos no neonato. OBJETIVO: Investigar a frequência da TRC, a associação com os dias de uso do cateter até o diagnóstico e o número de cateteres utilizados em uma Unidade de Terapia Intensiva Neonatal unicêntrico. MÉTODOS: Estudo caso-controle que incluiu 14 casos e 42 controles. A coleta de dados ocorreu entre janeiro de 2017 e dezembro de 2020 em uma UTIN pública. Foram calculadas razões de chances brutas (COR). O estudo respeitou os padrões éticos das diretrizes nacionais. RESULTADOS: Duzentos e noventa e quatro neonatos utilizaram cateter venoso central, dos quais 14 (4,7%) foram diagnosticados com TRC. O cateter em uso no momento do diagnóstico foi o cateter central inserido centralmente em 8 (57,1%). Antes do diagnóstico, o tempo acumulado de uso do cateter foi de 34,5 dias e a mediana do número de cateteres utilizados foi de três. Um maior número de dias de uso do cateter >30 (COR 19,11; IC 95% 2,28-160,10; p=0,007) e número de cateteres utilizados >3 (COR 7,66; IC 95% 1,51-38,70; p=0,01). CONCLUSÃO: Os casos de TRC foram associados à gravidade clínica; número de cateteres e dias cumulativos de uso do cateter. Sugerimos que o rastreamento de trombose seja realizado em neonatos que necessitem de longo tempo de uso do cateter e mais de três cateteres. Reduzir a duração e o número de cateteres venosos usados ajudará a reduzir a TRC.