Rivaroxabana para profilaxia de tromboembolismo venoso em abdominoplastia após grande perda ponderal: 396 casos / Rivaroxaban for venous thromboembolism prophylaxis in abdominoplasty after massive weight loss: 396 cases

Introdução: Abdominoplastia consiste em um dos procedimentos estéticos mais populares realizados no Brasil. Pacientes pósbariátricos representam um desafio peculiar ao cirurgião plástico, uma vez que não só requerem reconstruções complexas, mas também apresentam comorbidades residuais e deficiências nutricionais. O tromboembolismo venoso (TEV) constitui uma complicação grave e potencialmente fatal da abdominoplastia. Apesar da pequena frequência desta complicação, os métodos aceitos como padrões para prevenção de TEV em pacientes após abdominoplastia, incluindo quimioprofilaxia, permanecem controversos. Objetivo: Avaliar a experiência do autor com rivaroxabana para profilaxia de TEV em pacientes submetidos a abdominoplastia após grande perda ponderal. Métodos: Uma série de 396 casos foi conduzida retrospectivamente. Todos os pacientes submetidos à abdominoplastia após cirurgia bariátrica que receberam rivaroxabana foram incluídos. A dose profilática foi de 10mg por dia. Dados demográficos, comorbidades, tipo de cirurgia e complicações foram registrados. Resultados: 396 casos de pacientes pós-bariátricos (356 mulheres e 40 homens) foram submetidos à abdominoplastia e receberam rivaroxabana no pós-operatório, de julho de 2015 a julho de 2018. A média de idade dos pacientes foi de 39,1 anos. O índice de massa corporal médio no momento da abdominoplastia foi de 27,2kg/m². Houve apenas um caso de tromboembolismo venoso (0,25%). Treze pacientes apresentaram hematoma com necessidade de drenagem. Conclusões: A quimioprofilaxia de rotina com rivaroxabana para pacientes submetidos à abdominoplastia após grande perda ponderal revela uma baixa incidência de TEV. Esta medicação oral é bem tolerada e apresenta um perfil de complicação aceitável.

Introduction: Abdominoplasty is one of the most popular aesthetic procedures performed in Brazil. Postbariatric patients present a challenge to the plastic surgeon as not only do they have complex reconstructive challenges but also they have residual medical comorbidities and nutritional deficiencies. A serious and potentially fatal complication of abdominoplasty is venous thromboembolism (VTE). Despite the frequency of this serious complication, the accepted standard methods to prevent VTE in abdominoplasty patients, including chemoprophylaxis, remain controversy. Objective: To evaluate the author experience with rivaroxaban, for VTE prophylaxis in abdominoplasty patients after massive weight loss. Methods: A retrospective 396 cases series were conducted. All patients who underwent abdominoplasty after bariatric surgery and received rivaroxaban were included. The prophylactic dose was 10 mg daily for 30 days, beginning 24 hours postoperatively. Patient demographics, comorbidities, type of surgery and complications were recorded. Results: From July 2015 until July 2018, 396 post bariatric patients (356 women and 40 men) underwent abdominoplasty and received rivaroxaban postoperatively. The mean body mass index prior to their weight loss procedure was 43.8kg/m2 (range, 37.3- 61.9kg/m2) and mean BMI was 27.2kg/m² at the time of the abdominoplasty. Mean patient age was 39.1 years. Only one patient had a symptomatic PTE event. Thirteen patients had a hematoma requiring operative evacuation, and all went on to heal without sequel. Conclusions: Routine chemoprophylaxis with rivaroxaban for abdominoplasty patients after massive weight loss has a low rate of VTE events. This oral medication is well tolerated and has an acceptable complication profile.

Viscoelastic properties of plasma fibrin clots are similar in patients on rivaroxaban and vitamin K antagonists.

Unfavorable fibrin clot features have been observed in patients with venous thromboembolism (VTE). We investigated whether rivaroxaban, a direct factor Xa inhibitor, and vitamin K antagonists (VKAs) can improve plasma clot viscoelastic properties. We studied four age- and sex-matched groups: 25 healthy controls, 15 VTE patients taking rivaroxaban 20 mg/day (blood concentration, 145 (67 - 217) ng/ml), 15 VTE patients taking VKA (INR: 2 - 3), and 15 VTE patients who stopped oral anticoagulant therapy (OAT). Using a hybrid rheometier the storage (G') and loss (G") moduli were evaluated in citrated plasma after addition of 5 pmol/l tissue factor. Fiber thickness within clots was assessed using scanning electron microscopy. Higher G' but not G" was observed for VTE patients taking rivaroxaban (+34%; post hoc, P = 0.029) compared to controls. As reflected by lower G' and G", patients taking rivaroxaban (-19% and -30%; post hoc, P = 0.0013 and P < 0.0001, respectively) formed less stiff and viscous clots compared to VTE patients after OAT withdrawal, also after adjustment for fibrinogen. VTE patients treated with rivaroxaban and VKA had similar clot viscoelastic properties (post hoc, P = 0.85 for G' and P = 0.29 for G"). G' and G" correlated with plasma rivaroxaban concentrations (r = -0.67, P = 0.005 and r = -0.59, P = 0.021, respectively), and the time from the last dose of rivaroxaban intake (r = 0.59, P = 0.02 and r = 0.58, P = 0.022, respectively). G' and G" showed no association with INR in patients on VKAs. G' or G" were not associated with fibrin diameter on scanning electron microscopy images in either group. Our preliminary study shows that both rivaroxaban and VKA improve clot viscoelastic properties in VTE patients, which might contribute to their antithrombotic effects. G' and G" may reflect specific clot physical features, beyond key plasma clot characteristics, which highlights benefits from comprehensive plasma clot analysis in patients with thrombotic diseases.

[Current study aimed to highlight extent of clot resolution in deep veins and its association with anticoagulation pattern in VTE patients]. / Stepen' rekanalizatsii glubokikh ven nizhnikh konechnostei v zavisimosti ot vybrannoi skhemy antikoaguliantnoi terapii.

MATERIAL AND METHODS: Data of 70 patients with acute VTE of lower extremities (iliofemoral level) was analyzed. There were 42 patients in the study group which were treated with rivaroxaban (15 mg BID for 21 days, 20 mg od from day 22); 28 patients were in control group treated with conventional therapy (LMWH/VKA). Extent of clot resolution was assessed on ultrasound. Data was collected at a day of VTE diagnosis and further at 1, 3, 6 month. RESULTS: The results of the study demonstrated, that patients treated with rivaroxaban had earlier recanalization and extent of clot resolution was higher than in patients treated with conventional therapy. After one year of treatment 73,8% of patients in the study group had total or good recanalization compared to 37% of patients in the control group.

Safety ad efficacy of direct oral anticoagulants for extended treatment of venous thromboembolism.

Currently available anticoagulants have limitations for long-term treatment of venous thromboembolism (VTE). We have evaluated the efficacy and safety of direct oral anticoagulants (DOACs) for extended treatment of VTE. Four randomized controlled trials (RCTs) comparing DOACs (apixaban, rivaroxaban, and dabigatran) with placebo or warfarin for extended treatment of VTE were published. Primary efficacy outcome was recurrent VTE or VTE-related death, and primary safety outcome was major bleeding. DOACs significantly lower the risk of recurrent VTE or VTE-related death compared to placebo/warfarin, as well as all-cause mortality. Risk of major bleeding is not different with DOACs compared to placebo/warfarin. However, DOACs are associated with a significantly higher rate of the composite of major and clinically relevant bleeding compared to placebo. In conclusion, DOACs are effective and safe for the extended treatment of VTE, and may reduce the risk of all-cause mortality.

Potential role of electrostimulation in augmentation of venous blood flow after total knee replacement: A pilot study.

AIM: To investigate the potential role of a novel electrostimulation device in augmenting the femoral vein venous blood flow following total knee replacement surgery. MATERIAL AND METHODS: A total of 30 consecutive patients undergoing total knee replacement were allocated to receive either peroneal nerve electrostimulation plus low molecular weight heparin and below-knee compression stockings (Group 1, electrostimulation group, n = 15, mean age: 63.40 ± 5.91 years, male: female ratio 9:6) or low molecular weight heparin and below-knee compression stockings alone (Group 2, control group, n = 15, mean age: 63.86 ± 7.47 years, male: female ratio 8:7). Electrostimulation was performed for 1 h in every 4 h after the operation. Peak blood velocity in the femoral vein was evaluated with Duplex ultrasonongraphy in supine position. Presence of leg edema and calf diameter was also taken into consideration as outcome measures, which were recorded both before surgery and at the time of discharge from hospital. RESULTS: Postoperative peak blood flow velocity in the femoral vein was significantly higher in electrostimulation group compared to control group (17.46 ± 2.86 cm/s vs. 13.84 ± 3.58 cm/s, p < 0.02). Electrostimulation group achieved a significant increase in peak blood flow velocity in the femoral vein after the operation (mean increase 67.48 ± 17.38%, p < 0.001). CONCLUSION: Electrostimulation of the common peroneal nerve enhanced venous flow in the lower limb and may potentially be of use as a supplementary technique in deep venous prophylaxis following lower limb orthopedic operations.

Evaluation of time in therapeutic range in anticoagulated patients: a single-center, retrospective, observational study.

BACKGROUND: The percentage of time during which the patients have the INR within the target values (i.e. Time in Therapeutic Range [TTR]) is a measure of anticoagulation quality with Vitamin K Antagonists (VKA). To evaluate the quality of anticoagulation using TTR according to the Rosendaal method, we performed an observational, retrospective study. We included all outpatients who attended the cardiology anticoagulation clinic of a Portuguese hospital (2011-2013), whose target INR was 2.0-3.0. RESULTS: 377 VKA-treated patients were evaluated. Of these, 72.4% had non-valvular atrial fibrillation. Patients were followed for a mean period of 471 days. The mean TTR was 60.3% (SD 19.3%) and 44.3% of the patients had a mean TTR<60%. Patients were at high risk of bleeding (INR>4.5) and at high thrombotic risk (INR<1.5) during, respectively, 1.7% and 4.7% of the time. CONCLUSIONS: Anticoagulation control needs to be improved. These results are informative for all stakeholders: patients, health care professionals, and policymakers.

Rivaroxaban for treatment of venous thromboembolism in older adults.

Rivaroxaban is a factor Xa inhibitor recently approved for use in the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). Older adults are at an increased risk for venous thromboembolism (VTE), and rivaroxaban offers an alternative to standard treatment including vitamin K antagonists. This review evaluates the literature supporting this new indication with a focus on the safety and efficacy in older adults as well as those with renal insufficiency and fragility, which the EINSTEIN-PE study defined as those older than 75 years of age, weighing 50 kg or less, or with a creatine clearance (Clcr) of less than 50 mL/min. Three large studies (EINSTEIN-PE, -DVT, -EXT) provide an evaluation of recurrent VTE and bleeding events with the use of rivaroxaban. EINSTEIN-DVT and EINSTEIN-PE showed rivaroxaban to be equivalent to standard treatment in the overall population as well as in older adults and those with renal insufficiency and fragility. Further, EINSTEIN-EXT showed benefit of rivaroxaban over placebo for extended VTE protection (i.e., longer than 6 to 12 months of treatment), both overall and in the subgroups of those older than 75 years of age and with a Clcr of 50 mL/min to < 80 mL/min..

Phase III trials of new oral anticoagulants in the acute treatment and secondary prevention of VTE: comparison and critique of study methodology and results.

The traditional treatment of venous thromboembolism (VTE) has been use of heparin and vitamin K antagonists (VKA), and although shown to be effective, they have numerous limitations. New oral anticoagulants (NOACs) including direct thrombin (factor IIa) inhibitors (dabigatran) and selective factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) have emerged as promising alternatives with the potential to overcome the limitations of traditional treatments. Clinical trials have been performed with a view to making significant changes to the acute, long-term and extended treatment of VTE. Data are now available on the efficacy and safety, including bleeding rates, of the NOACs in comparison with VKA in the acute treatment and secondary prevention of VTE as well as in comparison with placebo extended VTE treatment. This review compares and contrasts the design and results of the Phase III trials of NOACs in VTE and discusses the implications of the NOACs in terms of treatment strategies in VTE patients.

Electrical calf muscle stimulation with Veinoplus device in postoperative venous thromboembolism prevention.

AIM: The aim of this pilot study was to evaluate the potential effect of electrical calf muscle stimulation (EMS) in the prevention of postoperative deep vein thrombosis (DVT) in high risk patients and to assess efficacy and safety of EMS in patients with calf DVT. METHODS: This was a prospective non-randomized controlled study involving 80 patients over the age of 40 having major surgery (44 abdominal and 36 cranial or spinal surgery; duration more than 60 min under general anesthesia). Patients were divided into 2 comparable groups: main (N.=40) and control (N.=40). In both groups graduated middle stretch compression bandage with compression level 20-40 mmHg was applied and low dose unfractioned heparin (LDUH) injections (5000 U s.c. 3 t.i.d) were started on 1st or 2-5th day after surgery and continued until discharge. The time of starting LDUH was comparable in both groups. In addition, electrical calf muscle stimulation (EMS) with Veinoplus device was performed for not less than 5 periods of 20 minutes per day (total >100 minutes) in the main group. Control of venous patency was performed with duplex ultrasound obligatory at baseline (first 24 h after surgery) and then every 3 days until discharge. RESULTS: The incidence of DVT was 2.5% in the main group and 25% in the control group (P=0.007). In patients without DVT at baseline it was 3% versus 21% (P=0.025). Patients with baseline thrombosis who underwent EMS did not have any new cases of DVT and PE, while in patients without EMS thrombosis progression was observed in 43% cases also without pulmonary embolism (not significant). CONCLUSION: EMS with Veinoplus device at >100 min per day (>5 sessions) can decrease the rate of postoperative DVT in high risk patients. Using of EMS in patients with calf DVT does not increase the rate of PE. These findings need to be confirmed in a randomized controlled trial.

[Haemodynamic and clinical efficacy of electric muscular stimulation of the venous outflow in prevention of postoperative venous thromboembolic complications].

The present clinical and experimental study was carried out in order to evaluate efficacy of electrical stimulation of the crural muscles with the purpose of preventing postoperative venous thromboembolic complications. At the first stage by means of ultrasonographic angioscanning in apparently healthy volunteers (n=21) we evaluated the linear velocity of blood flow on the popliteal vein on the background of using myostimulation and compression bandage with various levels of pressure applied either separately or in a combination with each other. It was revealed that electrical stimulation of the crural muscles led to a 2.8-4.5-fold increase in the peck velocity of blood flow, while the compression decreased the parameters of the venous outflow both at rest and during muscular contraction. By means of theoretical calculations it was determined that an optimal compression profile for a combination with electrical stimulation is a pressure under the bandage equalling 20-40 mm Hg, providing substantial acceleration of the venous outflow with the laminary blood flow preserved. At the second stage we assessed efficacy of comprehensive prevention of venous thromboembolism with the use of electromyostimulation, the respective compression bandage and direct anticoagulants in surgical-profile patients from a high-risk group (n=90) by means of ultrasound screening of the venous system during the whole postoperative period. When myostimulation was used in the regimen of 3-5 procedures a day, the frequency of venous thrombosis amounted to 40% (n=10) and did not significantly differ from that in patients not subjected to myostimulation (25%, n=40). When myostimulation was used in the regimen of 5-10 procedures per day, the frequency of venous thrombosis turned out to be considerably lower (2.5%, n=40). A conclusion was made on efficacy of using this method in the examined group of patients.

Proteomic analysis of venous thromboembolism: an update.

Venous thromboembolism is a complex, multifactorial disorder, the pathogenesis of which typically involves a variety of inherited or acquired factors. The multifactorial etiology of this disease and the partial correlation between genotype and prothrombotic phenotype limit greatly the value of genetic analysis in assessing thrombotic risk. The integration of several new 'omics' techniques enables a multifaceted and holistic approach to the study of venous thrombotic processes and pave the way to the search and identification of novel blood biomarkers and/or effectors of thrombus formation that can also be the possible future target of new anticoagulant and thrombolytic therapies for more personalized medicine. This review provides a comprehensive overview of the latest candidate proteomic biomarkers of venous thrombosis and of the proteomics studies relevant to its pathophysiology, some of which seem to confirm the existence of a common physiopathological basis for venous thromboembolism and atherothrombosis.

The emergency medicine approach to the evaluation and treatment of pulmonary embolism.

Each year in the United States, up to 900,000 individuals will suffer from acute pulmonary embolism, resulting in an estimated 200,000 to 300,000 hospital admissions. Despite decades of research on the topic, the diagnosis remains elusive in many situations and the fatality rate remains significant. This issue presents a review of the current evidence guiding the emergency medicine approach to the diagnosis and treatment of pulmonary embolism. Key to this approach is the concept of risk stratification: using factors from the history and physical examination, plus ancillary tests, to guide clinical decision making. The pathophysiology of pulmonary embolism and decision-support tools are reviewed, and emergency department management strategies are described.

Warfarin therapy in patients with venous thromboembolism: patterns of use and predictors of clinical outcomes.

INTRODUCTION: Few studies have investigated current practices in the USA relating to warfarin use and monitoring, or the effects of warfarin discontinuation on risk of venous thromboembolism (VTE) and bleeding complications. This study investigated the effect of warfarin discontinuation on rates of VTE recurrence in a real-world setting. METHODS: Integrated Healthcare Information Services database records from January 2003 to September 2007 from patients aged at least 18 years, hospitalized for VTE, and with at least two prescriptions or 60 days of warfarin treatment were reviewed, with warfarin discontinuation and international normalized ratio (INR) data collated. RESULTS: A total of 1027 of 8380 (12.3%) patients discontinued warfarin within 3 months. Overall, 1656 (19.8%) patients had no INR monitoring, with 38.1% of INR values being inside the therapeutic range (INR 2-3). Recurrent VTE was observed in 915 (10.9%) patients. Significant predictors of recurrent VTE (at any time) included discontinuation of warfarin within 3 months, time from index VTE to warfarin initiation, previous VTE-related hospitalization, and duration of index hospitalization. CONCLUSION: This study found that in a real-world population, less than 50% of warfarin patients achieved INR values within the therapeutic range. Warfarin discontinuation within 3 months was associated with a higher rate of recurrent VTE.

A pilot evaluation of a neuromuscular electrical stimulation (NMES) based methodology for the prevention of venous stasis during bed rest.

Bed rest poses an increased risk factor for a potentially fatal venous thromboembolism (VTE). Lack of activation of the calf muscle pump during this resting period gives rise to venous stasis which may lead to deep vein thrombosis (DVT) development. Our aim was to investigate the effects that 4h of bed rest have on the lower limb hemodynamics of healthy subjects and to what extent electrically elicited contractions of the calf muscles can alleviate these effects. Outcome variables included popliteal vein blood flow and heart rate. Primary results indicated that the resting group experienced a significant decline in popliteal venous blood flow of approximately 47% with approximately 13% decrease in heart rate. The stimulated groups maintained a significantly higher venous blood flow and heart rate. Volume flow in the contralateral limb remained constant throughout the study and was comparable to that of the stimulated limb's recovery flow. The results suggest that even short periods of bed rest can significantly reduce lower limb blood flow which could have implications for DVT development. Electrically elicited calf muscle contractions significantly improve lower limb blood flow and can alleviate some debilitating effects of bed rest.

Prevention of venous stasis in the lower limb by transcutaneous electrical nerve stimulation.

OBJECTIVES: This study aims to investigate the effects of thromboprophylactic transcutaneous electrical nerve stimulation (TpTENS) of the peroneal nerve on venous blood flow in the limbs of volunteers. TpTENS might be considered for use in preventing venous stasis during surgical treatment. METHODS: In 10 volunteers, peak venous velocity (PV) and flow volume (FV) in the popliteal vein were measured using duplex ultrasonography during calf-muscle stimulation. The effects of TpTENS of the peroneal nerve were compared with those of other mechanical methods, including electrical muscle stimulation, intermittent pneumatic compression, active ankle motion and calf squeeze, used to prevent venous stasis and achieve thromboprophylaxis. RESULTS: TpTENS had similar effects on popliteal vein blood flow in comparison with other established methods of thromboprophylaxis. The PV increased its basal flow by 3.9 times (p < 0.01) and FV by 2.7 times (p < 0.01), respectively, compared with baseline values. CONCLUSIONS: TpTENS is as effective as other electrical and mechanical methods of calf-muscle pump activation in achieving acceleration of venous flow in the lower limb.

Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention.

Due to the aging of the populations of developed countries and a common occurrence of risk factors, it is increasingly probable that a patient may have both cancer and cardiovascular disease. In addition, cytotoxic agents and targeted therapies used to treat cancer, including classic chemotherapeutic agents, monoclonal antibodies that target tyrosine kinase receptors, small molecule tyrosine kinase inhibitors, and even antiangiogenic drugs and chemoprevention agents such as cyclooxygenase-2 inhibitors, all affect the cardiovascular system. One of the reasons is that many agents reach targets in the microenvironment and do not affect only the tumor. Combination therapy often amplifies cardiotoxicity, and radiotherapy can also cause heart problems, particularly when combined with chemotherapy. In the past, cardiotoxic risk was less evident, but it is increasingly an issue, particularly with combination therapy and adjuvant therapy. Today's oncologists must be fully aware of cardiovascular risks to avoid or prevent adverse cardiovascular effects, and cardiologists must now be ready to assist oncologists by performing evaluations relevant to the choice of therapy. There is a need for cooperation between these two areas and for the development of a novel discipline, which could be termed cardio-oncology or onco-cardiology. Here, we summarize the potential cardiovascular toxicities for a range of cancer chemotherapeutic and chemopreventive agents and emphasize the importance of evaluating cardiovascular risk when patients enter into trials and the need to develop guidelines that include collateral effects on the cardiovascular system. We also discuss mechanistic pathways and describe several potential protective agents that could be administered to patients with occult or overt risk for cardiovascular complications.