Evaluation of soluble P-selectin as a predictive biomarker in acute symptomatic pulmonary embolism: Insights from a prospective observational study.

BACKGROUND: Soluble P-selectin (sP-selectin) has been proposed as a potential biomarker for venous thromboembolism (VTE) diagnosis with interesting results. However, its role in predicting early mortality in pulmonary embolism (PE) remains unexplored. METHODS: This observational, prospective, single-center study enrolled consecutive patients aged 18 or older with confirmed acute symptomatic PE and no prior anticoagulation. The study aims to assess the prognostic capacity of sP-selectin measured at the time of PE diagnosis for short-term mortality and major bleeding. RESULTS: A total of 196 patients, with a mean age of 69.1 years (SD 17), were included, of whom 52.6% were male. Within 30 days, 9.7% of patients (n = 19) died, and 5.1% (n = 10) suffered major bleeding. PE risk stratification revealed 4.6% (n = 9) with high-risk PE, 34.7% (n = 68) with intermediate-high-risk PE, 38.3% (n = 75) with intermediate-low-risk PE, and 22.5% (n = 44) with low-risk PE according to the European Society of Cardiology score. Mean plasma sP-selectin levels were comparable between survivors and non-survivors (489.7 ng/mL ±63 vs. 497.3 ng/mL ±51; p = .9). The ROC curve for 30-day all-cause mortality and major bleeding yielded an AUC of 0.49 (95% CI 0.36-0.63) and 0.46 (95% CI 0.24-0.68), respectively. Multivariate and survival analyses were precluded due to lack of significance. CONCLUSIONS: sP-selectin was not useful for predicting short-term mortality or major bleeding in patients with acute symptomatic pulmonary embolism. Further studies are required to clarify the role of sP-selectin in VTE, particularly in prognosticating PE outcomes.

The prognostic value of blood cellular indices in pulmonary embolism.

Prognostication in acute pulmonary embolism (PE) requires reliable markers. While cellular indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) appear promising, their utility in PE prognostication needs further exploration. We utilized data from the RIETE registry and the Loyola University Medical Center (LUMC) to assess the prognostic value of NLR, PLR, and SII in acute PE, using logistic regression models. The primary outcome was 30-day all-cause mortality. We compared their prognostic value versus the simplified Pulmonary Embolism Severity Index (sPESI) alone. We included 10 085 patients from RIETE and 700 from the LUMC. Thirty-day mortality rates were 4.6% and 8.3%, respectively. On multivariable analysis, an elevated NLR (>7.0) was associated with increased mortality (adjusted odds ratio [aOR]: 3.46; 95% CI: 2.60-4.60), outperforming the PLR > 220 (aOR: 2.36; 95% CI: 1.77-3.13), and SII > 1600 (aOR: 2.52; 95% CI: 1.90-3.33). The c-statistic for NLR in patients with low-risk PE was 0.78 (95% CI: 0.69-0.86). Respective numbers were 0.66 (95% CI: 0.63-0.69) and 0.68 (95% CI: 0.59-0.76) for intermediate-risk and high-risk patients. These findings were mirrored in the LUMC cohort. Among 9810 normotensive patients in RIETE, those scoring 0 points in sPESI and with an NLR ≤ 7.0 (35% of the population) displayed superior sensitivity (97.1%; 95% CI: 95.5-98.7) and negative predictive value (99.7%; 95% CI: 99.5-99.8) than sPESI alone (87.1%; 95% CI: 83.9-90.3, and 98.7%; 95% CI: 98.4-99.1, respectively) for 30-day mortality. The NLR is a significant prognostic marker for 30-day mortality in PE patients, especially useful to identify patients with very low-risk PE.

Comparative analysis of COVID-19-associated venous thromboembolism outcomes: evolution from 2020 to 2021-2022.

Patients with COVID-19 are at an increased risk for venous thromboembolism (VTE). With the advent of vaccinations and novel treatments from 2020 through 2022, the landscape of COVID-19 has evolved. Notably, the effects of such interventions on the outcomes of COVID-19-associated VTE have not been thoroughly examined. Data from the RIETE registry were analyzed to evaluate 90-day VTE-related outcomes (all-cause mortality, major bleeding, and VTE recurrences) in patients with COVID-19-associated VTE. We compared the periods before and after the widespread introduction of COVID-19 vaccines: March to December 2020 (pre-vaccine period) and March 2021 to December 2022 (post-vaccine period). Statistical analysis included mixed-effects parametric survival-time models. Among 1,620 patients with COVID-19-associated VTE, most (74.1%) were identified during 2020 period. The analysis revealed a more than two-fold increase in the risk of death within 90 days (adjusted hazard ratio [HR]: 2.27; 95% confidence interval, CI: 1.18-4.38) and major bleeding (adjusted HR: 2.91; 95%CI: 1.08-7.84) for patients from the 2020 period compared to those from the 2021-2022 period. Inpatient subgroup analysis confirmed the observed mortality differences. The frequency of recurrent VTE was low (1.1 vs. 0.7%, respectively), and did not show significant variation between the two periods. Our research provides a comparative perspective on the clinical outcomes of COVID-19-associated VTE before and after the introduction of vaccines. Our findings reveal a significant decrease in the incidence of 90-day mortality and major bleeding in patients with COVID-19-associated VTE in the 2021-2022 period.

Use of Oral Anticoagulant Drugs in Patients with Pulmonary Hypertension.

Pulmonary hypertension (PH), in particular pulmonary arterial hypertension and chronic thromboembolic PH, burdens patients with relevant morbidity and mortality. The use of oral anticoagulants (OACs) seems able to mitigate the risk of adverse outcomes and death in these patients. Despite scarce evidence, the use of OAC is recommended to treat PH patients, mainly based on observational data. So far, data are still unclear about the impact of direct oral anticoagulant (DOACs), whereas vitamin K antagonists are the main drugs recommended. More data are needed to fully clarify the role of OAC and DOACs in PH patients.

Arterial and venous involvement in Behçet's syndrome: a narrative review.

Behçet syndrome (BS) is a unique type of vasculitis that affects veins and arteries of all sizes, leading to recurrent vascular events, mostly venous thrombosis. The prevalence of venous thromboembolism in BS patients ranges between 15 and 40%. Thrombosis is usually an early manifestation leading to diagnosis of BS in up to 40% of patients. BS is per se a model of inflammation-induced thrombosis. The primary autoimmune response activates lymphocytes that in turn produce a cytokine cascade that activates neutrophils, which modify the secondary structure of fibrinogen making it less susceptible to plasmin-induced lysis. This leads to endothelial dysfunction, platelet activation and overexpression of tissue factor leading to inflammatory thrombi, usually attached to the wall. The pathogenesis of thrombosis is especially relevant to direct the specific treatment, that is based on immunosuppression rather than anticoagulation. Superficial vein thrombosis (SVT) and deep vein thrombosis (DVT) are the most common form of thrombosis in BS, but thrombosis in atypical sites (cava vein, suprahepatic veins, intracardiac thrombus) and arterial involvement can also occur. We assessed the latest update of the European League Against Rheumatism recommendations for the management of BS. Vascular Behçet treatment is usually based of immunosuppressants, and the role of anticoagulation remains controversial. The use of interventional and surgical procedures should be carefully evaluated, due to the risk of triggering a vascular pathergy phenomenon.

Long-term follow-up of patients with venous thromboembolism and COVID-19: Analysis of risk factors for death and major bleeding.

INTRODUCTION: COVID-19 predisposes patients to a higher risk of venous thromboembolism (VTE), although the extent of these implications is unclear and the risk of bleeding has been poorly evaluated. To date, no studies have reported long-term outcomes of patients with COVID-19 and VTE. METHOD: Prospective observational study to evaluate long-term (90 days or more) outcomes of patients diagnosed with VTE (PE, DVT of the extremities, or both) in the setting of COVID-19. The main outcome of the study was a compound of major bleeding and death. RESULTS: The study comprised 100 patients (mean age 65 ± 13.9 years). At the time of VTE diagnosis, 66% patients were hospitalized, 34.8% of them in the ICU. Mean follow-up was 97.9 ± 23.3 days. During the study period, 24% patients died and median time to death was 12 (IQR: 2.25-20.75) days, 11% patients had major bleeding and median time to event was 12 (IQR: 5-16) days. The cause of death was PE in 5% and bleeding in 2% of patients. There were no VTE recurrences. The main study outcome occurred in 29% patients. Risk of death or major bleeding was independently associated with ICU admission (HR 12.2; 95% CI 3.0-48.3), thrombocytopenia (HR 4.5; 95% CI 1.2-16.5), and cancer (HR 21.6; 95% CI 1.8-259). CONCLUSION: In patients with COVID-19 and VTE, mortality and major bleeding were high and almost a third of deaths were VTE-related. The majority of complications occurred in the first 30 days. ICU admission, thrombocytopenia, and cancer are risk factors for poor prognosis.

Inflammatory Biomarkers in the Short-Term Prognosis of Venous Thromboembolism: A Narrative Review.

The relationship between inflammation and venous thrombosis is not well understood. An inflammatory response may be both the cause and consequence of venous thromboembolism (VTE). In fact, several risk factors of VTE modulate thrombosis through inflammatory markers. Acute pulmonary embolism (PE) is burdened by a remarkable mortality rate, up to 34% in severely ill patients presenting with hemodynamic instability. Initial mortality risk stratification is based on hemodynamic instability. Patients with a situation of hemodynamic stability require immediate further risk assessment based on clinical, imaging, and circulating biomarkers, as well as the presence of comorbidities. Some inflammatory biomarkers have shown potential usefulness in the risk stratification of patients with VTE, especially acute PE. C-reactive protein on admission is associated with 30-day mortality and bleeding in VTE patients. P-selectin is associated with right ventricle dysfunction in PE patients and might be associated with VTE recurrences and the extension of thrombosis. Tissue factor microparticles are associated with VTE recurrence in cancer-associated thrombosis. Other inflammatory biomarkers present scarce evidence (inflammatory cytokines, erythrocyte sedimentation rate, fibrinogen, leukocyte count). In this manuscript, we will review the prognostic role of different inflammatory biomarkers available both for clinical practice and research in VTE patients.

Pulmonary Embolism: A Practical Guide for the Busy Clinician.

Acute pulmonary embolism (PE) is the third most common acute cardiovascular condition, and its prevalence increases over time. D-dimer has a very high negative predictive value, and if normal levels of D-dimer are detected, the diagnosis of PE is very unlikely. The final diagnosis should be confirmed by computed tomographic scan. However, echocardiography is the most available, bedside, low-cost, diagnostic procedure for patients with PE. Risk stratification is of utmost importance and is mainly based on hemodynamic status of the patient. Patients with PE and hemodynamic stability require further risk assessment, based on clinical symptoms, imaging, and circulating biomarkers.

Cervical and Oropharyngeal Lymphogranuloma Venereum: Case Report and Literature Review.

Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by invasive serovars of Chlamydia trachomatis. There have been only a few case reports of oropharyngeal C. trachomatis infection complicated with cervical LGV. We report a case of a HIV-positive male patient with cervical LGV that presented a poor evolution despite appropriate treatment.

Idiopathic versus Provoked Renal Infarction: Characteristics and Long-Term Follow-Up of a Cohort of Patients in a Tertiary Hospital.

BACKGROUND: There is limited evidence on the etiology and outcomes of renal infarction. A provoking factor is identified only in one- to two-thirds of patients. METHODS: This is a retrospective observational study. The clinical characteristics and outcomes of patients with acute renal infarction were studied; the sample was divided into two groups according to the presence of at least one provoking factor at the time of diagnosis (atrial fibrillation, flutter, major thrombophilia, or renal artery malformations). RESULTS: The study comprised 59 patients with a mean age of 63 (±16.7) years and a follow-up period of 3.1 (±2.8) years. An identifiable provoking factor was found for 59.3% of the renal infarctions at the time of diagnosis, and atrial fibrillation was the most frequent one (in 49.2% of all patients). Renal impairment was found in 49.2% of the patients at diagnosis and in 50.8% of the patients 6 months after the event (p = 0.525). When compared with the idiopathic group, the patients with provoked infarction were older (69.8 vs. 57.9 years, p = 0.014) and had a higher rate of recurrence of arterial thrombosis during follow-up (18.8 vs. 0%, p = 0.028), but there were no differences in the rest of the baseline characteristics or in mortality rates. Six patients (10.2%) in the idiopathic group were diagnosed with atrial fibrillation during follow-up. CONCLUSIONS: Atrial fibrillation, both at diagnosis and at follow-up, is the most common identifiable cause of renal infarction; however, a significant number of patients are idiopathic, and these are younger, but they have a similar burden of cardiovascular disease and a lower risk of arterial recurrence.

Hemolytic Anemia as a Provoking Factor for Recurrent Venous Thromboembolism: A Case Report.

Warm antibody autoimmune hemolytic anemia (WAIHA) is a rare disease that leads to the destruction of red blood cells in the reticuloendothelial system through the mediation of agglutinins (immunoglobulin G (IgG) type in most cases) that attach to the erythrocyte wall at 37 °C. The association of WAIHA and venous thromboembolism (VTE) seems to be higher than other hemolytic disorders classically associated with VTE and there is a current investigation aimed at clarifying this association and establishing some criteria to use anticoagulant treatment in patients with WAIHA. Despite this, WAIHA is a rare cause for the development of recurrent VTE under secondary prophylactic anticoagulant treatment, with only a few cases described in the literature. We present the case of a patient who developed a recurrence of deep vein thrombosis during a WAIHA episode despite treatment with acenocoumarol and a review of the literature.

Prognostic Significance of Heart Failure in Acute Pulmonary Embolism: A Comprehensive Assessment of 30-Day Outcomes.

INTRODUCTION: Patients with heart failure (HF) are known to have an increased risk of pulmonary embolism (PE), but there is limited evidence regarding the prognostic implications of HF in patients with acute PE and the relationship between PE prognosis and left ventricular ejection fraction (LVEF). The primary objective of this study was the development of a composite outcome (mortality, major bleeding, and recurrence) within the first 30 days. The secondary objective was to identify the role of LVEF in predicting the development of early complications in patients with both HF and reduced LVEF. MATERIAL AND METHODS: A prospective study was conducted at two tertiary hospitals between January 2012 and December 2022 to assess differences among patients diagnosed with acute PE based on the presence or absence of a history of HF. Cox regression models were employed to assess the impact of HF and reduced LVEF on the composite outcome at 30 days. RESULTS: Out of 1991 patients with acute symptomatic PE, 7.13% had a history of HF. Patients with HF were older and had more comorbidities. The HF group exhibited higher mortality (11.27% vs. 4.33%, p < 0.001) and a higher incidence of major bleeding (9.86% vs. 4.54%, p = 0.005). In the multivariate analysis, HF was an independent risk factor for the development of the composite outcome (HR 1.93; 95% CI 1.35-2.76). Reduced LVEF was independently associated with a higher risk of major bleeding (HR 3.44; 95% CI 1.34-8.81). CONCLUSION: In patients with acute pulmonary embolism, heart failure is independently associated with a higher risk of early complications. Additionally, heart failure with reduced LVEF is an independent risk factor for major bleeding.

Platypnea-Orthodeoxia Syndrome and COVID-19 Successfully Treated With Percutaneous Patent Foramen Ovale Closure: A Report of Two Cases and Literature Review.

Platypnea-orthodeoxia syndrome (POS) is a rare clinical condition characterized by positional dyspnea and/or hypoxia. We report two cases of patients with COVID-19 bronchopneumonia with a torpid evolution. Due to clinical suspicion of POS, a diagnostic workup was performed, including a bubble echocardiography, which revealed a patent foramen ovale (PFO) with early and massive passage of bubbles to the left cavities. Both patients underwent percutaneous PFO closure with a resolution of POS. Here, we present the second and third cases of POS associated with PFO successfully closed during the acute phase of COVID-19. This suggests that PFO closure could be a potential treatment option for this condition.

Incidence and long-term outcomes of upper limb deep vein thrombosis associated with intracardiac devices: analysis of bleeding, recurrence, and sequelae.

Pacemakers (PM) and implantable cardioverter-defibrillators are vital devices in contemporary clinical practice, but their growing adoption poses challenges. Complications, including lead migration, infections, and post-implantation venous thrombosis, underscore the importance of comprehensive investigation. This retrospective observational study enrolled patients diagnosed with upper limb deep vein thrombosis (DVT) secondary to intracardiac devices at a tertiary hospital from 2015 to 2022. The aim of the study was to determine the incidence and long-term outcomes (bleeding, DVT recurrence and sequelae) in these patients. Across the study period, 2681 intracardiac devices were implanted, with 12 cases of upper limb DVT documented. The majority of patients were male (91.7%), with a mean age of 63.92 years. DVT occurred in patients with PM (50%), implantable cardioverter-defibrillators (25%) and implantable cardioverter-defibrillators with Cardiac Resynchronization Therapy (25%). Treatment encompassed low-molecular-weight heparin (91.7%) during the acute episode and long-term anticoagulation with direct oral anticoagulants (75%) or vitamin K antagonists (25%). Over a mean follow-up period of 33.17 months, half of the patients exhibited long-term sequelae, notably collateral circulation (66.7%). Remarkably, no thrombosis recurrences were observed during follow-up. However, one patient (8.3%) experienced a major bleeding event during treatment, and one patient (8.3%) required device removal (PM) due to persistent symptoms. This study revealed upper limb DVT occurred in 0.45% of patients after intracardiac device implantation. Rate of thrombosis recurrence was low during follow-up. Although half of the patients developed long-term sequelae, the need for prolonged anticoagulant therapy in these cases remains uncertain.

The Potential Role of CA-125 as a Biomarker for Short-Term Mortality Risk in Patients with Acute Symptomatic Pulmonary Embolism.

Background: Antigen carbohydrate 125 (CA-125) is a complex glycoprotein extensively studied as a prognostic biomarker in heart failure, yet its potential role in the short-term prognosis of an acute pulmonary embolism (PE) remains unexplored. Methods: In this observational, prospective, single-center study, consecutive patients aged 18 and older with a confirmed acute symptomatic PE and no history of prior anticoagulant therapy were enrolled. Primary and secondary objectives aimed to assess the prognostic capacity of CA-125 at PE diagnosis for 30-day mortality and major bleeding, respectively. Results: A total of 164 patients were included (mean age 69.8 years, SD 17), with 56.1% being male. Within 30 days, 17 patients (10.4%) died and 9 patients (5.5%) suffered major bleeding. ROC curve analysis for 30-day mortality yielded an area under the curve of 0.69 (95% CI 0.53-0.85) with an optimal CA-125 cut-off point of 20 U/mL and a negative predictive value of 96%. Multivariate analysis revealed a significant association between CA-125 levels exceeding 20 U/mL and 30-day mortality (adjusted odds ratio 4.95; 95% CI 1.61-15.2) after adjusting for age, cancer, NT-proBNP > 600 ng/mL, and the simplified pulmonary embolism severity index score. Survival analysis for 30-day mortality exhibited a hazard ratio of 5.47 (95% CI 1.78-16.8). No association between CA-125 levels and 30-day major bleeding was found. Conclusions: CA-125 emerges as a promising surrogate biomarker for short-term mortality prediction in an acute symptomatic PE. Future investigations should explore the integration of CA-125 into PE mortality prediction scores to enhance the prognostic accuracy in this patient population.

External validation of a prognostic score to identify low-risk outpatients with acute deep venous thrombosis in the lower limbs.

BACKGROUND: Current clinical guidelines suggest home treatment for patients diagnosed with acute deep venous thrombosis (DVT). A prognostic score has been proposed to identify low-risk patients; however, its validation remains limited. METHOD: This prospective observational study aimed to externally validate the prognostic score in selecting low-risk outpatients with acute DVT in the lower limbs. Consecutive outpatients diagnosed with acute DVT in a tertiary hospital were included. The score included 6 variables: heart failure, kidney failure, recent major bleeding, altered platelet count, immobilization, and cancer. The primary outcome was the incidence of a composite outcome, including confirmed diagnosis of PE, major bleeding, or all-cause death at 7 days. Patients meeting zero criteria were considered low risk. RESULTS: Among the 1035 patients included, 485 (46.9 %) met zero criteria. Of these, 0.2 % (95 % CI 0.0-1.1 %) and 0.4 % (95 % CI, 0.0-1.5 %) patients experienced the composite outcome at 7 and 30 days, respectively. Among patients who met 1 or more criteria for admission, 344 patients (62.5 %) were discharged. Among these, the composite outcome at 7 and 30 days occurred in 2 (0.6 %) and 5 (1.4 %) patients, respectively. The C-statistics of the score were 0.68 (95 % CI, 0.57-0.79) and 0.69 (95 % CI, 0.64-0.76) at 7 and 30 days, respectively. CONCLUSION: This study demonstrates the efficacy of the prognostic score in identifying low-risk outpatients with acute DVT. It also suggests that a considerable proportion of patients with acute DVT may benefit from outpatient treatment despite having some risk criteria, highlighting the potential for optimizing ambulatory care pathways.

Soluble urokinase type plasminogen activator receptor (suPAR) and mortality in acute pulmonary embolism.

INTRODUCTION: The soluble urokinase-type plasminogen activator receptor (suPAR) potentially plays a role in immune-thrombosis, possibly by modulating plasmin activity or contributing to chemotaxis in a complex, poorly understood context. The role of suPAR levels in the short-term prognostic of patients with pulmonary embolism (PE) has not been evaluated. MATERIAL AND METHODS: This observational, prospective, single-center study enrolled consecutive patients aged 18 and above with confirmed acute symptomatic PE and no prior anticoagulant therapy. The primary objective was to assess the prognostic capacity of suPAR levels measured at the time of diagnosis in terms of mortality. RESULTS: Fifty-two patients, with a mean age of 73.8 years (±17), were included, with gender distribution evenly split at 50%. Seven (13.5%) patients died. The ROC curve for mortality yielded an AUC of 0.72 (95% CI 0.48-0.96), with an optimal suPAR cut-off of 5.5ng/mL. Bivariate analysis for suPAR>5.5ng/mL was associated with a crude odds ratio of 10 (95% CI 1.63-61.27; p=0.01) for 30-day mortality. Survival analysis showed a 30-day mortality hazard ratio of 8.33 (95% CI 1.69-40.99; p<0.01). CONCLUSION: suPAR emerges as a potential biomarker for short-term mortality prediction and holds the potential for enhanced stratification in patients with acute symptomatic PE.

A Rare Case of Stroke as a Complication After Percutaneous Mechanical Thrombectomy in a Patient with Intermediate-High Risk Pulmonary Embolism and Patent Foramen Ovale.

We present an extremely rare case of a patient with intermediate-high risk pulmonary embolism treated with percutaneous mechanical thrombectomy, complicated with stroke as a form of paradoxical embolism through a previously unknown patent foramen ovale. We reviewed the literature for indications, efficacy, and safety of this procedure, as well as for experience on this technique in patients with patent foramen ovale. LEARNING POINTS: Some authors propose percutaneous mechanical thrombectomy as an aggressive treatment of intermediate-high risk pulmonary embolism.Pending clinical trials, percutaneous mechanical thrombectomy seems to reduce right ventricle overload in these patients, with rare adverse effects.To our knowledge, this is the first reported case of stroke as a complication of the procedure. These patients should be screened for patent foramen ovale before the procedure.