Effects of Ranolazine and Ivabradine on Pulmonary Microhemodynamics in Experimental Model of Pulmonary Thromboembolism.

We studied changes of pulmonary microhemodynamics when modeling pulmonary artery thromboembolism on perfused isolated rabbit lungs after pretreatment with ranolazine and ivabradine. The increase in pulmonary artery pressure, pulmonary vascular resistance, and pre- and postcapillary resistance was less pronounced than in control animals, but was close to that in case of pulmonary thromboembolism after pretreatment with voltage-gated Na+ channel blockers lidocaine and ropivacaine. The increase of capillary filtration coefficient inversely correlated with values of capillary hydrostatic pressure. Thus, ranolazine and ivabradine exhibit the properties of voltage-gated Na+ channel blockers mainly in smooth muscles of pulmonary arterial vessels and promote the decrease in endothelial permeability.

Statins during Anticoagulation for Emergency Life-Threatening Venous Thromboembolism: A Review.

Venous thromboembolism (VTE) is the leading cause of morbidity and death worldwide, after cancer and cardiovascular diseases. VTE is defined to include pulmonary embolism (PE) and/or deep vein thrombosis (DVT). Approximately 25% of PE patients experience sudden death as an initial symptom of VTE, and between 10% and 30% of patients die within the first month after diagnosis. Currently, the only drugs approved for the treatment of both acute and chronic VTE are vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). However, their effectiveness is limited due to their associated risk of bleeding. Ideally, therapy should be able to treat VTE and limit the risk of VTE recurrence without increasing the risk of bleeding. Several studies have shown that the use of statins during anticoagulation for VTE reduces the risk of death and VTE recurrence. However, to date, there are conflicting data on the impact of statins during anticoagulation for VTE. A biological protective function of statins during anticoagulation has also been reported. Statins affect D-dimer levels; tissue factor (TF) gene expression; and VIII, VII, and Von Willebrand clotting factors-the major clotting factors they are able to affect. However, the usefulness of statins for the treatment and prevention of VTE is currently under debate, and they should not be substituted for guideline-recommended VTE prophylaxis or anticoagulation treatment. In this review of the literature, we illustrate the advances on this topic, including data on the role of statins in primary VTE prevention and secondary VTE prevention, related biological mechanisms, the risk of bleeding during their use, and their ability to reduce the risk of death.

Risk factors for acute kidney injury and impact of earlier anticoagulation on renal function in patients with normotensive pulmonary embolism: a retrospective cohort study.

OBJECTIVE: We aimed to investigate the risk factors for acute kidney injury (AKI) after normotensive pulmonary embolism (PE) and the impact of anticoagulation on renal recovery. DESIGN: Multicentred, retrospective cohort study. SETTING: Data from four tertiary hospitals in China were captured. All available measurements of serum creatinine (SCr) during hospitalisation and follow-up were collected. PARTICIPANTS: Patients with acute PE and those without haemodynamic instability were enrolled. All recruited patients were followed up for up to 2 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the occurrence of AKI, defined by the Kidney Disease Improving Global Outcomes criteria. The secondary outcome was the recovery of renal function. The time interval between PE onset and the initiation of anticoagulation was analysed to obtain its influence on the recovery of renal function. RESULTS: A total of 461 patients with acute normotensive PE were enrolled. A transient elevation of SCr during hospitalisation was observed. The incidence of AKI among normotensive patients was 18.9%. Brain natriuretic peptide (BNP) NT-proBNP elevation (adjusted HR (aHR) 2.27, 95% CI 1.33 to 3.86) and history of chronic kidney disease (aHR 4.81, 95% CI 2.44 to 9.48) were associated with the development of AKI during hospitalisation. Earlier initiation of anticoagulation therapy (within 5 days after PE onset, compared with over 6 days) promoted an early recovery of renal function (adjusted OR 0.26, 95% CI 0.08 to 0.84, p=0.025). CONCLUSIONS: Renal impairment and AKI were highly prevalent among patients with normotensive patients. The occurrence of AKI was associated with right heart function. Patients who developed AKI after PE would benefit from earlier anticoagulation therapy for an early recovery of renal function.

Dispensed prescription medications and short-term risk of pulmonary embolism in Norway and Sweden.

Scandinavian electronic health-care registers provide a unique setting to investigate potential unidentified side effects of drugs. We analysed the association between prescription drugs dispensed in Norway and Sweden and the short-term risk of developing pulmonary embolism. A total of 12,104 pulmonary embolism cases were identified from patient- and cause-of-death registries in Norway (2004-2014) and 36,088 in Sweden (2005-2014). A case-crossover design was used to compare individual drugs dispensed 1-30 days before the date of pulmonary embolism diagnosis with dispensation in a 61-90 day time-window, while controlling for the receipt of other drugs. A BOLASSO approach was used to select drugs that were associated with short-term risk of pulmonary embolism. Thirty-eight drugs were associated with pulmonary embolism in the combined analysis of the Norwegian and Swedish data. Drugs associated with increased risk of pulmonary embolism included certain proton-pump inhibitors, antibiotics, antithrombotics, vasodilators, furosemide, anti-varicose medications, corticosteroids, immunostimulants (pegfilgrastim), opioids, analgesics, anxiolytics, antidepressants, antiprotozoals, and drugs for cough and colds. Mineral supplements, hydrochlorothiazide and potassium-sparing agents, beta-blockers, angiotensin 2 receptor blockers, statins, and methotrexate were associated with lower risk. Most associations persisted, and several additional drugs were associated, with pulmonary embolism when using a longer time window of 90 days instead of 30 days. These results provide exploratory, pharmacopeia-wide evidence of medications that may increase or decrease the risk of pulmonary embolism. Some of these findings were expected based on the drugs' indications, while others are novel and require further study as potentially modifiable precipitants of pulmonary embolism.

Fault in Our Genes: A Case of Pulmonary Thromboembolism in Young.

Methylenetetrahydrofolate reductase (MTHFR) enzyme is one of the key enzymes involved in the metabolism of folate. Mutations in this enzyme can lead to a procoagulant state. We present a case of a 20-year-old male with no known comorbidities, who presented with fever and hemoptysis and was diagnosed as a case of pulmonary embolism. He was found to have a homozygous mutation in the MTHFR gene that was responsible for his disease state. He was started on unfractionated heparin infusion and underwent catheter-directed thrombolysis. He showed marked improvement in his condition and was discharged on oral anticoagulants with an advice to follow-up.

RésuméL'enzyme méthylènetétrahydrofolate réductase (MTHFR) est l'une des enzymes clés impliquées dans le métabolisme du folate. Les mutations de cette enzyme peuvent conduire à un état procoagulant. Nous présentons le cas d'un homme de 20 ans sans comorbidités connues, qui s'est présenté avec de la fièvre et une hémoptysie et a été diagnostiqué comme un cas d'embolie pulmonaire. Il s'est avéré qu'il présentait une mutation homozygote du gène MTHFR responsable de son état pathologique. Il a commencé une perfusion d'héparine non fractionnée et a subi une thrombolyse dirigée par cathéter. Il a montré une nette amélioration de son état et a été libéré sous anticoagulants oraux avec un conseil de suivi.

Medication adherence, related factors and outcomes among patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension: a systematic review.

INTRODUCTION: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are life-threatening conditions that can progress to death without treatment. Although strong medication adherence (MA) is known to enhance outcomes in chronic illnesses, its association with PAH and CTEPH was sporadically explored. This study aims to examine the MA of patients with PAH or CTEPH, identify factors associated with low adherence and explore the resulting outcomes. METHODS: A systematic review was conducted by searching multiple databases (Medline, Embase, Cochrane Central, ClinicalTrials.gov, Scopus, Web of Science and Google Scholar) from 6 March 1998 to 6 July 2023. We included studies reporting MA as primary or secondary end-points. Study selection, data extraction and methodological quality assessment were performed in duplicate. RESULTS: 20 studies involving 22 675 patients met the inclusion criteria. Heterogeneity was observed, particularly in the methods employed. MA means ranged from 0.62 to 0.96, with the proportion of patients exhibiting high MA varying from 40% (95% CI 35-45%) to 94% (95% CI 88-97%). Factors associated with low adherence included increased treatment frequency, time since diagnosis and co-payment. High MA seems to be associated with reduced hospitalisation rates, inpatient stays, outpatient visits and healthcare costs. CONCLUSIONS: This systematic review underscores the heterogeneity of MA across studies. Nevertheless, the findings suggest that high MA could improve patients' clinical outcomes and alleviate the economic burden. Identifying factors consistently associated with poor MA could strengthen educational efforts for these patients, ultimately contributing to improved outcomes.

Lemierre Syndrome: Clinical Challenges And The Anticoagulation Dilemma In Adolescent Care.

Lemierre syndrome is a rare, life-threatening condition characterized by an acute otorhinolaryngologic infection with septic thrombophlebitis of the internal jugular vein and septic embolism, particularly to the lungs. We describe a case of a previously healthy 15-year-old female patient who initially presents fever and odynophagia but quickly develops neck and pleuritic chest pain. Computed tomography was performed and the radiological findings confirmed the diagnosis of a Lemierre syndrome. She was managed with antibiotics, anticoagulant for three days and symptomatic treatment, with a gradually improving condition. After 17 days of hospitalisation, due to reappearance of pleuritic pain, a new imaging assessment was performed and showed additional septic emboli in the lungs, which prompted the reintroduction of anticoagulant therapy. Awareness of the existence of this syndrome is essential to ensure a radiological evaluation with computed tomography and thus timely diagnosis and treatment.

Clinical usefulness of endothelial progenitor cells in predicting the efficacy of riociguat in chronic thromboembolic pulmonary hypertension.

Endothelial dysfunction is important in the pathology of pulmonary hypertension, and circulating endothelial progenitor cells (EPCs) have been studied to evaluate endothelial dysfunction. In patients with chronic thromboembolic pulmonary hypertension (CTEPH), riociguat reportedly increases the number of circulating EPCs. However, the relationship between EPC numbers at baseline and changes in clinical parameters after riociguat administration has not been fully elucidated. Here, we evaluated 27 treatment-naïve patients with CTEPH and analyzed the relationships between EPC number at diagnosis and clinical variables (age, hemodynamics, atrial blood gas parameters, brain natriuretic peptide, and exercise tolerance) before and after riociguat initiation. EPCs were defined as CD45dim CD34+ CD133+ cells and measured by flow cytometry. A low number of circulating EPCs at diagnosis was significantly correlated with increased reductions in mean pulmonary arterial pressure (mPAP) (correlation coefficient = 0.535, P = 0.004) and right atrial pressure (correlation coefficient = 0.618, P = 0.001) upon riociguat treatment. We then divided the study population into two groups according to the mPAP change: a weak-response group (a decrease in mPAP of 4 mmHg or less) and a strong-response group (a decrease in mPAP of more than 4 mmHg). The number of EPCs at diagnosis was significantly lower in the strong-response group than in the weak-response group (P = 0.022), but there were no significant differences in other clinical variables or in medication profiles. In conclusion, circulating EPC numbers could be a potential predictor of the therapeutic effect of riociguat in CTEPH patients.

Cerebrovascular events and thrombolysis in pulmonary embolism-induced cardiac arrest: a case series and key challenges.

BACKGROUND AND PURPOSE: Cerebrovascular events during thrombolysis in cardiac arrest (CA) caused by pulmonary embolism (PE) is a life-threatening condition. However, the balance between cerebrovascular events and thrombolytic therapy in PE-induced CA remains a great challenge. METHODS: In this study, we reported three unique cases regarding main concerns surrounding cerebrovascular events in thrombolytic therapy in PE-induced CA. RESULTS: The patient in the case 1 treated with thrombolysis during CPR and finally discharged neurologically intact. The patient in the case 2 received delayed thrombolysis and died eventually. The patient in the case 3 was contraindicated to thrombolysis due to the complication of subarachioid hemorrahage and died within days. CONCLUSIONS: Our case series highlights three proposed approaches to consider before administering thrombolysis as a treatment option in PE-induced CA patients: (1) prolonging the resuscitation, (2) administering thrombolysis promptly, and (3) ruling out cerebrovascular events.

Optimal long-term anticoagulation after acute pulmonary embolism: current state of the art and a look into the near future.

PURPOSE OF REVIEW: This review aims to summarize the current state of the art and future directions in optimal long-term anticoagulation following acute pulmonary embolism (PE). RECENT FINDINGS: Actual studies and guidelines underscore the preference for direct oral anticoagulants (DOAC) in standard therapeutic doses for maintenance therapy post-PE, while considering patient-specific factors and dose-reduction criteria. Risk stratification should always include the assessment of concomitant trigger- or risk factors regarding their strength and persistence. The use of tools like specific scores can facilitate the identification of optimal candidates for long-term therapy, emphasizing once more personalized approaches and strategies. Special patient groups, such as cancer associated thrombosis, chronic thromboembolic pulmonary hypertension or antiphospholipid syndrome require even more tailored therapy approaches. SUMMARY: Optimal long-term anticoagulation post-PE should be guided by straightforward and individual risk assessment strategies. The array of indications for DOACs has gotten wider in last years, also within special patient groups. Still, chronic thromboembolic pulmonary hypertension and antiphospholipid syndrome remains domain of vitamin K agonists.

Isolated Calf Muscle Venous Thrombosis: A Review of Anticoagulation Strategies.

Deep vein thrombosis (DVT) of the lower extremities is divided into 2 categories according to the extent of thrombosis involvement. Thrombosis involving the popliteal vein, femoral vein, and iliac vein is classified as proximal DVT, while thrombosis involving the anterior tibial vein, posterior tibial vein, peroneal vein, and calf muscles vein is regarded as distal DVT. There are updated guidelines for the anticoagulant treatment for proximal DVT, but the best anticoagulant treatment for distal DVT is still controversial, especially for isolated calf muscular vein thrombosis (CMVT). The risk of isolated CMVT extending to the proximal deep veins and developing into pulmonary embolism is lower than with distal DVT. Some scholars believe that isolated CMVT has the risk of evolving into proximal deep vein thrombosis and pulmonary embolism, and active early anticoagulation therapy can reduce the risk and benefit patients. In addition, based on the characteristics of CMVT and the bleeding risk of anticoagulation therapy, some studies have recommended use of non-anticoagulation methods such as compression therapy. There is still a lack of multicenter, big-data, randomized, controlled trials on the benefits or risks of anticoagulation therapy. Among scholars who support anticoagulation therapy, there is still a lack of consensus on the optimal duration. This article reviews the current evidence on anticoagulant therapy for patients with isolated CMVT and how long the anticoagulation course should be if anticoagulation is required. Our research will provide a theoretical basis for subsequent research. More prospective studies with larger sample sizes are needed to provide more clinical evidence.

[Catheter-assisted local lysis therapy for submassive pulmonary embolism]. / Kathetergestützte lokale Lysetherapie bei submassiven Lungenembolien.

BACKGROUND: Pulmonary embolism is the third most common cardiovascular disease. Interventional treatment options as an alternative to systemic lysis therapy of hemodynamically stable, submassive pulmonary embolisms have received an unprecedented boost in innovation in recent years. The treatment options are heterogeneous and can be roughly divided into local thrombolysis and local thrombectomy. For years in our center we have been carrying out catheter-assisted, locoregional lysis therapy with side-hole lysis catheters and a cumulative dose per pulmonary branch of 10 mg alteplase over 15 h for hemodynamically stable, submassive pulmonary emboli. AIM: The aim of this retrospective study was to review this therapeutic concept and to collect data on clinical endpoints and possible complications. METHODS: The study included data from 01/2018-03/2023. For this purpose, the patients were selected based on the OPS codes (8.838.60 and 1­276.0), and the data was collected using the medical records. Biometric data, data on previous illnesses and vital parameters, laboratory chemistry data, CT diagnostic data, echocardiographic data, data on drug treatment and data on complications were collected anonymously. RESULTS: There was a significant reduction in the strain on the right heart. Peripheral oxygen saturation also improved significantly and heart rate decreased significantly. The complication rate remained low and was almost exclusively limited to access-related problems. CONCLUSION: Catheter-assisted, locoregional lysis therapy is a safe and effective treatment method for submassive pulmonary embolism.

Phillyrin and its metabolites treat pulmonary embolism by targeting PLCß3 to inhibit platelet activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Lian Qiao (LQ), the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a well-documented traditional Chinese medicine known for its detoxifying and heat-clearing properties. Clinically, compounds containing LQ are widely used to treat thrombotic diseases, indicating that it may have antithrombotic effects. However, its exact mechanism of action remains unknown. AIM OF THE STUDY: This study aimed to verify the antithrombotic effect of LQ and further explore the material basis and target mechanism of its antithrombotic effect using various biological methods. MATERIALS AND METHODS: An epinephrine-collagen-thrombin-induced mouse model of acute pulmonary embolism (APE) was established to study the effects of LQ on thrombus development. A UPLC/Q/TOF-MS screening and identification system based on the inhibition of platelet aggregation and Ca2+ antagonism was established to determine the pharmacodynamic components of LQ that inhibit platelet activation. The inhibitory effect of active ingredients on platelet activation, and the determination of the target of their inhibitory effect on platelet activation have been studied using chemical proteomics. Furthermore, based on the structure and function of the target protein, a multidisciplinary approach was adopted to analyze the molecular mechanism of active ingredient binding to target proteins and to evaluate the effects of active ingredients on the downstream signaling pathways of target proteins. RESULTS: LQ showed significant anticoagulant effects in APE model mice. Phillyrin and phillygenin were the antiplatelet-activating components of LQ. PLCß3 was identified as a target for inhibiting platelet activation by phillyrin and its metabolites. The mechanism underlying the effect involves phillyrin and its metabolites inhibiting PLCß3 activity by blocking the binding of PLCß3 to Gαq through non-covalently targeting the ASN260 of PLCß3, thus inhibiting the downstream Gαq-PLCß3-Ca2+ signaling pathway, effectively hindering platelet activation and therefore playing an anticoagulant role. CONCLUSION: This study not only proposes and validates the antithrombotic effect of LQ for the first time but also finds that phillyrin and phillygenin are the main pharmacological substances through which LQ exerts antithrombotic activity and reveals a novel mechanism by which they exert antiplatelet activity by directly targeting and inhibiting PLCß3 activity. These findings significantly contribute to our understanding of the therapeutic potential of phillyrin and provide important clues for the discovery and development of new antiplatelet drugs.

Direct oral anticoagulants in the treatment of chronic thromboembolic pulmonary hypertension patients: A retrospective cohort study.

INTRODUCTION: Direct oral anticoagulants (DOACs) are increasingly prescribed for life-long anticoagulation in chronic thromboembolic pulmonary hypertension (CTEPH) patients, despite not being recommended in the guidelines. This study aims to evaluate the efficacy and safety of DOACs in CTEPH patients. METHODS: From May 2013 to December 2022, patients who were first diagnosed with CTEPH in Fuwai Hospital and started long-term anticoagulation treatment with warfarin or DOACs were retrospectively included and followed up until (1) death, (2) transition to other kinds of anticoagulants, or (3) discontinuation of anticoagulation. Propensity score matching was used to balance confounding bias of baseline characteristics. All-cause death, major bleeding, clinically relevant nonmajor bleeding and venous thromboembolism (VTE) recurrence were obtained and analysed. RESULTS: After propensity score matching, 115 patients taking warfarin and 206 patients taking DOACs were included in our study and followed up for 5.5 [3.4, 7.1] years. There was no significant difference of survival between the warfarin and the DOAC group (p = 0.77). The exposure adjusted event rate of major bleeding (0.3 %/person-year vs 0.4 %/person-year, p = 0.705) and clinically relevant nonmajor bleeding (3.1 %/person-year vs 3.2 %/person-year, p > 0.999) was similar between two groups. The exposure adjusted rate of VTE recurrence was significantly higher in the DOAC group (1.5 %/person-year vs 0.3 %/person-year, p = 0.030). CONCLUSION: In anticoagulation of CTEPH patients, DOACs have similar survival rate, similar risk of bleeding but higher risk of VTE recurrence than warfarin.

[Successful treatment of high-risk pulmonary embolism with low-dose anticoagulation: a case report].

Reperfusion is considered as the cornerstone of the treatment of high-risk pulmonary embolism (PE). However, when thrombolysis is contraindicated and surgery or interventional therapy is not available, the treatment of high-risk PE becomes very difficult. To our knowledge, there are no reports of successful treatment of high-risk PE with low-dose anticoagulation. On November 30, 2021, a 56-year-old male patient with subarachnoid hemorrhage was admitted to the emergency department of the First Affiliated Hospital of Chongqing Medical University. On the second day of admission, the patient suddenly went into shock during aneurysm clipping. After implementing D-dimer, markers of myocardial injury, echocardiography and computed tomography pulmonary angiography, a high-risk PE was diagnosed. Due to the contraindication of thrombolysis and the refusal of endovascular treatment, he was eventually cured with low-dose anticoagulation combined with vasopressors.

Risk of recurrent venous thromboembolism and bleeding in patients with acute isolated subsegmental pulmonary embolism.

INTRODUCTION: Approximately 10 % of all diagnosed pulmonary embolism are isolated to the subsegmental vessels. The risk of recurrent venous thromboembolism (VTE) in patients with an acute subsegmental pulmonary embolism (SSPE) managed with or without anticoagulant therapy remains poorly understood. METHODS: This is an observational cohort study including consecutive adult patients diagnosed with acute isolated SSPE between June 01, 2019, and August 31, 2022. We excluded patients with a concomitant diagnosis of deep vein thrombosis and those who had an indication for long-term anticoagulation. The primary outcome was objectively confirmed recurrent VTE. RESULTS: Overall, 118 patients with acute SSPE were included in the analysis. The mean (± standard deviation [SD]) age of the participants was 59 ± 17 years and 44 % of them had active cancer. Mean (±SD) duration of follow-up was 438 ± 426 days. Seventy-seven patients (65 %) were initially treated with anticoagulation, whereas 41 patients (35 %) were not. Of the 77 patients receiving anticoagulant therapy, 23 (30 %) received extended-duration anticoagulation (beyond 3 months) for secondary prevention. Overall, recurrent VTE events occurred in 6/118 (5 %, 95 % CI 2.4 to 10.7) patients. Four events (4/77 = 5.2 %, 95 % CI 2.0 to 12.6) occurred in initially treated patients. Two recurrent VTE occurred in patients initially left untreated (2/41 = 4.9 %, 95 % CI 1.4 to 16.1). Half of the recurrent VTE occurred in patients with active cancer. CONCLUSIONS: Most patients diagnosed with an acute SSPE received anticoagulation. The incidence of recurrent VTE detected over time was relatively high, especially in patients with cancer.

Clinical outcomes after discontinuing anticoagulant therapy in patients with first unprovoked venous thromboembolism.

BACKGROUND: The duration of anticoagulation for a first episode of unprovoked venous thromboembolism (VTE) should balance the likelihood of VTE recurrence against the risk of major bleeding. OBJECTIVES: Analyze rates and case-fatality rates (CFRs) of recurrent VTE and major bleeding after discontinuing anticoagulation in patients with a first unprovoked VTE after at least 3 months of anticoagulation. METHODS: We compared the rates and CFRs in patients of the Registro Informatizado Enfermedad Trombo Embólica (RIETE) and Contemporary management and outcomes in patients with venous thromboembolism registries. We used logistic regression models to identify predictors for recurrent pulmonary embolism (PE) and major bleeding. RESULTS: Of 8261 patients with unprovoked VTE in RIETE registry, 4012 (48.6%) had isolated deep vein thrombosis (DVT) and 4250 had PE. Follow-up (median, 318 days) showed 543 recurrent DVTs, 540 recurrent PEs, 71 major bleeding episodes, and 447 deaths. The Contemporary management and outcomes in patients with venous thromboembolism registry yielded similar results. Corresponding CFRs of recurrent DVT, PE, and major bleeding were 0.4%, 4.6%, and 24%, respectively. On multivariable analyses, initial PE presentation (hazard ratio [HR], 3.03; 95% CI, 2.49-3.69), dementia (HR, 1.47; 95% CI, 1.01-2.13), and anemia (HR, 0.72; 95% CI, 0.57-0.91) predicted recurrent PE, whereas older age (HR, 2.11; 95% CI, 1.15-3.87), inflammatory bowel disease (HR, 4.39; 95% CI, 1.00-19.3), and anemia (HR, 2.24; 95% CI, 1.35-3.73) predicted major bleeding. Prognostic scores were formulated, with C statistics of 0.63 for recurrent PE and 0.69 for major bleeding. CONCLUSION: Recurrent DVT and PE were frequent but had low CFRs (0.4% and 4.6%, respectively) after discontinuing anticoagulation. On the contrary, major bleeding was rare but had high CFR (24%). A few clinical factors may predict these outcomes.

Pulmonary Thromboembolism following Russell's Viper Bites.

Snakebite envenoming and its resulting complications are serious threats to the health of vulnerable people living in rural areas of developing countries. The knowledge of the heterogeneity of symptoms associated with snakebite envenoming and their management strategies is vital to treat such life-threatening complications to save lives. Russell's viper envenomation induces a diverse range of clinical manifestations from commonly recognised haemotoxic and local effects to several rare conditions that are often not reported. The lack of awareness about these unusual manifestations can affect prompt diagnosis, appropriate therapeutic approaches, and positive outcomes for patients. Here, we report pulmonary thromboembolism that developed in three patients following Russell's viper envenomation and demonstrate their common clinical features and diagnostic and therapeutic approaches used. All patients showed clinical signs of local (oedema) and systemic (blood coagulation disturbances) envenomation, which were treated using polyvalent antivenom. They exhibited elevated heart rates, breathlessness, and reduced oxygen saturation, which are non-specific but core parameters in the diagnosis of pulmonary embolism. The recognition of pulmonary embolism was also achieved by an electrocardiogram, which showed sinus tachycardia and computed tomography and echocardiogram scans further confirmed this condition. Anti-coagulant treatment using low-molecular-weight heparin offered clinical benefits in these patients. In summary, this report reinforces the broad spectrum of previously unreported consequences of Russell's viper envenomation. The constant updating of healthcare professionals and the dissemination of major lessons learned in the clinical management of snakebite envenoming through scientific documentation and educational programs are necessary to mitigate the adverse impacts of venomous snakebites in vulnerable communities.

Direct Oral Anticoagulants in Chronic Thromboembolic Pulmonary Hypertension: First Meta-Analysis of Prospective Studies.

Direct oral anticoagulants (DOACs) are becoming increasingly popular clinically, but their safety and effectiveness profile in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is not well-established. Literature from the PubMed and EMBASE databases was systematically screened up to February 2024 to identify relevant studies on the use of DOACs in CTEPH patients. The bias risk of RCTs was assessed using the Cochrane Risk of Bias Tool 2.0. The quality of observational prospective cohorts was assessed using the Newcastle-Ottawa Scale tool. Data pooled from different studies were analyzed. Results from 4 studies were gathered, including 2 randomized controlled trials and 2 prospective cohorts, with a total of 2038 patients, of which 751 were on DOACs and 1287 were on vitamin K antagonists (VKAs). Similar rates of all-cause mortality (3.33% vs 3.33%, RD = -0.01%, 95% CI [-0.02%, 0.00%], P = .17), VTE recurrence (1.46% vs 2.12%, RD = -0.00%, 95% CI [-0.01%, 0.01%], P = .92) were observed. DOACs were associated with a nonsignificant reduction in bleeding events including major bleeding (2.22% vs 3.71%, RD = -0.01%, 95% CI [-0.04%, 0.01%], P = .30), any bleeding (5.33% vs 9.94%, RD = -0.03%, 95% CI [-0.07%, 0.01%], P = .10), and minor bleeding (4.17% vs 13.3%, RD = -0.06%, 95% CI [-0.23%, 0.10%], P = .45). Data pooled from existing perspective trials suggests the use of DOACs in CTEPH patients as an effective and safe alternative to VKAs.