Risks of venous thromboembolic complications in related to combined oral contraceptives

Hormonal contraception is the most popular and effective reversible method for preventing unwanted pregnancy exerting multiple prophylactic and therapeutic effect along with contraceptive activity. The main adverse coupled to combined oral contraceptives (COCs) is its impact on the hemostasis and increased risk of venous thromboembolic complications. A great evolutionary path has been travelled after beginning application of hormonal contraception to reduce dose of its estrogen component and improving quality of gestagen component. Nevertheless, thrombotic complications related to COCs use still remain a pressing issue not only due to disease severity and high mortality rate from pulmonary embolism (PE), but also due to the difficulties in its timely diagnostics. Here we describe a clinical case of a 19-year-old patient suffering from vena cava inferior thrombosis complicated by PE after using COCs.

Successful Secondary Endovascular Intervention in Pediatric Patients with Venous Thromboembolic Events

Background In the past, pediatric patients with venous thromboembolic events (VTE) were treated with low-molecular-weight heparin (LMWH) which was successful in around 70% of the cases. However, anticoagulation alone might not restore patency in all patients, and advanced therapeutic options to prevent postthrombotic syndrome are needed. During recent years, endovascular interventions have become a treatment option for pediatric patients with persistent thrombotic occlusion, not only in life- or limb-threatening VTE. Methods We evaluated 12 consecutive patients (11–17 years) with newly diagnosed VTE being treated at our department during the last 4 years (2017–2020). In case follow-up examination showed persistent venoocclusion under anticoagulation, patients received secondary interventional therapy like recanalization, percutaneous transluminal angioplasty with or without catheter-directed thrombolysis, and stenting. Patients with no clinical signs of venoocclusion or regredient thrombosis in imaging examination received anticoagulation alone. Results Six of 12 (50%) patients underwent catheter intervention. Median time from diagnosis to intervention was 4 months (0–12 months). Reintervention was necessary in one (8%) case and complete recanalization failed in one (8%) case. There were no major bleeding events or other major postinterventional complications, no acute or late local recurrence, and all patients reported clinical improvement after the procedure. Conclusion If endovascular intervention is used in teenage patients with persistent symptomatic VTE, reduction of postthrombotic symptoms is possible, even if intervention is performed secondary to failure of anticoagulation. Multidisciplinary treatment decisions can be based on the clinical course and follow-up imaging.

COVID-19 is associated with higher risk of venous thrombosis, but not arterial thrombosis, compared with influenza: Insights from a large US cohort

Introduction Infection with SARS-CoV-2 is typically compared with influenza to contextualize its health risks. SARS-CoV-2 has been linked with coagulation disturbances including arterial thrombosis, leading to considerable interest in antithrombotic therapy for Coronavirus Disease 2019 (COVID-19). However, the independent thromboembolic risk of SARS-CoV-2 infection compared with influenza remains incompletely understood. We evaluated the adjusted risks of thromboembolic events after a diagnosis of COVID-19 compared with influenza in a large retrospective cohort. Methods We used a US-based electronic health record (EHR) dataset linked with insurance claims to identify adults diagnosed with COVID-19 between April 1, 2020 and October 31, 2020. We identified influenza patients diagnosed between October 1, 2018 and April 31, 2019. Primary outcomes [venous composite of pulmonary embolism (PE) and acute deep vein thrombosis (DVT); arterial composite of ischemic stroke and myocardial infarction (MI)] and secondary outcomes were assessed 90 days post-diagnosis. Propensity scores (PS) were calculated using demographic, clinical, and medication variables. PS-adjusted hazard ratios (HRs) were calculated using Cox proportional hazards regression. Results There were 417,975 COVID-19 patients (median age 57y, 61% women), and 345,934 influenza patients (median age 47y, 66% women). Compared with influenza, patients with COVID-19 had higher venous thromboembolic risk (HR 1.53, 95% CI 1.38–1.70), but not arterial thromboembolic risk (HR 1.02, 95% CI 0.95–1.10). Secondary analyses demonstrated similar risk for ischemic stroke (HR 1.11, 95% CI 0.98–1.25) and MI (HR 0.93, 95% CI 0.85–1.03) and higher risk for DVT (HR 1.36, 95% CI 1.19–1.56) and PE (HR 1.82, 95% CI 1.57–2.10) in patients with COVID-19. Conclusion In a large retrospective US cohort, COVID-19 was independently associated with higher 90-day risk for venous thrombosis, but not arterial thrombosis, as compared with influenza. These findings may inform crucial knowledge gaps regarding the specific thromboembolic risks of COVID-19.

Comparison of Anti-factor Xa Levels in Female and Male Patients with Obesity After Enoxaparin Application for Thromboprophylaxis

Purpose Venous thromboembolic events (VTEs) are common complications after bariatric surgery, and enoxaparin is commonly used to prevent VTEs. The risk for VTEs is sex-specific. Whether enoxaparin application results in similar anti-factor Xa activities (aFXa) in males and females with obesity remains to be determined. We investigated whether our dosage regimen of enoxaparin resulted in similar serum aFXa levels in female and male patients undergoing bariatric surgery. Materials and Methods We administered enoxaparin twice daily in patients undergoing bariatric surgery. Patients with a body mass index (BMI) > 60 kg/m2 (n = 11) received 60 mg enoxaparin (group 2), and patients with lower BMI (n = 86) received 40 mg per dose (group 1). Peak aFXa levels were measured 3 days after surgery. The primary outcome was the aFXa level. As a secondary outcome, we detected VTEs and major bleeding events and explored the possible influencing factors of aFXa. Results Women had higher aFXa than men, but after matching for anthropometric values, the two groups were similar (females: 0.17 ± 0.08 U/ml; males: 0.18 ± 0.08 U/ml). Linear regression revealed a moderate relationship between weight and aFXa levels. The 3-month follow-up was attended by 94.9%, at which one patient had pulmonary embolism. Conclusion Individual enoxaparin dosage regimens for men and women do not seem to be required. Weight-based dosing regimen seems to be a more reasonable choice. Graphical abstract

Predictors of recurrence of venous thromboembolic disease after discontinuing of anticoagulation: a prospective cohort study

Objective We aim to evaluate factors associated with the recurrence of thromboembolic episodes among patients with a first episode of venous thromboembolic disease during anticoagulation treatment and at least one year after treatment suspension. Methods A prospective cohort of patients with a first episode of deep vein thrombosis confirmed by Doppler ultrasound and initiated anticoagulation treatment. Participants were registered in the Institutional Registry of Thromboembolic Disease between June 2015 and March 2019. Patients with cancer, with permanent inferior vena cava filter implant, and those who refused to participate or did not provide informed consent were excluded. All patients were evaluated within treatment at 30 days and at least one year after the suspension of anticoagulation with a D-dimer study and an ultrasound. All patients were evaluated for recurrence, bleeding (major and minor), and death. Results A total of 304 patients were recruited during the study period. Seventy-three percent were female, and the median age was 80 years. The rate of recurrence rate during anticoagulation treatment was 5% (N = 16/303; 95% confidence interval: 3 to 8), and 5% during post-suspension follow-up (N = 11/202; 95%CI: 3 to 9). The overall bleeding rate was 13% (N = 39; 95%CI: 9 to 17), and 5% for major bleeding. Patients who recurred had higher basal D-dimer mean, higher neutrophils and monocytes, and a higher prevalence of age-adjusted D-dimer ratio greater than 0.5 before discontinuation. In addition, they more frequently had complete leg involvement by ultrasound and received a shorter treatment. Conclusions Although some baseline and pre-suspension parameters had a higher recurrence incidence, statistical significance was not reached, probably due to small statistical power and a short-term follow-up.

Laelia furfuracea Lindl.: an Endemic Mexican Orchid with Anticoagulant Activity

Laelia furfuracea is an endemic orchid from Mexico, with antioxidant activity. The objective of this study was to evaluate the effect of hydroethanolic extract and fractions obtained from the orchid leaves on the clotting times of patients with venous thromboembolic disease (VTD) and to identify their tentative compounds. The anticoagulant activity was evaluated by determining prothrombin (PT), thrombin (TT) and, activated partial thromboplastin (APTT) times. Identification of the compounds was carried out using a chromatographic technique with an ultra-high-performance liquid chromatographic analyzer coupled with electrospray ionization with quadrupole time of flight-mass-mass spectrometry. The extract prolonged the clotting times depending on the concentration-response (5-60 mg / mL); 25 mg/mL prolonged the PT (33.2 ± 2.3 s) and TT (33.1 ± 0.3 s); and APTT (61.8 ± 3.4 s) at a concentration of 15 mg/mL. The main groups tentatively identified were xanthine, carboxylic acid, amino acid, and phenolic compounds. These compounds or the synergy between them prolong clotting times. Laelia furfuracea is an orchid with research potential in the search for new anticoagulant agents. Resumen. Laelia furfuracea es una orquídea endémica de México, la cual posee actividad antioxidante. El objetivo de este estudio fue evaluar el efecto del extracto hidroetanólico y fracciones obtenidas de hojas de la orquídea sobre los tiempos de coagulación de pacientes con enfermedad tromboembólica venosa (ETV) e identificar sus posibles compuestos. La actividad anticoagulante se evaluó determinando los tiempos de protrombina (TP), trombina (TT) y tromboplastina parcial activada (TTPA). La identificación de los compuestos se realizó usando una técnica cromatográfica con un analizador cromatográfico líquido de Ultra Alta Resolución con Ionización por electroespray acoplado a espectrometría de masas con Cuadrupolo y Tiempo de Vuelo. El extracto prolongó los tiempos de coagulación dependiente de la concentración-respuesta (5-60 mg/mL); 25 mg/mL prolongó el TP (33.2±2.3 s) y TT (33.1±0.3 s); y TTPA (61.8±3.4 s) a una concentración de 15 mg/mL. Los principales grupos de posibles compuestos identificados fueron xantina, ácido carboxílico, aminoácido y compuestos fenólicos. Estos compuestos o la sinergia entre ellos prolongan los tiempos de coagulación. Laelia furfuracea es una orquídea con potencial en investigación para la búsqueda de nuevos agentes anticoagulantes.

SARS-CoV-2 Virus Infection-Related Arterial Thromboembolism Leading to Critical Limb Ischemia and Amputation

COVID-19 infection has been shown to increase risk for thromboembolism. With most studies reporting mainly venous thromboembolic events, there is a lack of literature regarding the incidence of arterial thromboses in patients with COVID-19 infection. We report a dramatic case of a 55-year-old male with confirmed COVID-19 infection who presented with acute left critical limb ischemia leading to amputation as a result of thromboembolism from a distal abdominal aortic thrombus. Our case report contributes to the limited body of literature on COVID-19-related arterial thromboembolism. The patient consented to publish this case.

Immobility due to COVID-19 confinement, use of contraceptives and presence of the G20210A mutation. Validity of the Virchow triad for the presentation of Deep Venous Thrombosis and Pulmonary Thromboembolism.

Venous thromboembolic disease is a complex and multifactorial pathology, the result of the interaction of both genetic and environmental factors. The Virchow triad, first described in 1859, is still valid to explain the pathogenesis of thrombosis, where three main factors are reflected: a) hypercoagulable state; b) impaired blood flow; c) endothelial injury. The outbreak of a new COVID-19 pandemic has led to drastic confinement measures, with the consequent syndrome of immobility, as occurred in Spain between the months of March to June 2020. Pregnancy and hormonal contraception have proven to be an environmental factor predisposing to venous thrombosis. The presence of genetic factors, such as the mutation of the prothrombin gene G20210A, has been shown to be a risk factor for the presentation of venous thrombosis. We present the case of a 23-year-old non-smoking woman, a heterozygous carrier of a prothrombin gene mutation G20210A (hypercoagulability), who after confinement due to COVID-19 (impaired blood flow due to immobility) and use of hormonal patch contraceptives (endothelial abnormality), triggered deep vein thrombosis (DVT) / pulmonary thromboembolism (PE) that required hospital admission; and who, after rapid withdrawal of anticoagulant treatment, presented a second and a third episode of DVT. We highlight the usefulness of evaluating risk factors in G20210A heterozygous patients and the proper management of anticoagulation to avoid recurrences in patients susceptible to DVT / PE.