Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model.

Background: Acute pulmonary embolism (APE) is classified as a subset of diseases that are characterized by lung obstruction due to various types of emboli. Current clinical APE treatment using anticoagulants is frequently accompanied by high risk of bleeding complications. Recombinant hirudin (R-hirudin) has been found to have antithrombotic properties. However, the specific impact of R-hirudin on APE remains unknown. Methods: Sprague-Dawley (SD) rats were randomly assigned to five groups, with thrombi injections to establish APE models. Control and APE group rats were subcutaneously injected with equal amounts of dimethyl sulfoxide (DMSO). The APE+R-hirudin low-dose, middle-dose, and high-dose groups received subcutaneous injections of hirudin at doses of 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg, respectively. Each group was subdivided into time points of 2 h, 6 h, 1 d, and 4 d, with five animals per point. Subsequently, all rats were euthanized, and serum and lung tissues were collected. Following the assessment of right ventricular pressure (RVP) and mean pulmonary artery pressure (mPAP), blood gas analysis, enzyme-linked immunosorbnent assay (ELISA), pulmonary artery vascular testing, hematoxylin-eosin (HE) staining, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, immunohistochemistry, and Western blot experiments were conducted. Results: R-hirudin treatment caused a significant reduction of mPAP, RVP, and Malondialdehyde (MDA) content, as well as H2O2 and myeloperoxidase (MPO) activity, while increasing pressure of oxygen (PaO2) and Superoxide Dismutase (SOD) activity. R-hirudin also decreased wall area ratio and wall thickness to diameter ratio in APE rat pulmonary arteries. Serum levels of endothelin-1 (ET-1) and thromboxaneB2 (TXB2) decreased, while prostaglandin (6-K-PGF1α) and NO levels increased. Moreover, R-hirudin ameliorated histopathological injuries and reduced apoptotic cells and Matrix metalloproteinase-9 (MMP9), vascular cell adhesion molecule-1 (VCAM-1), p-Extracellular signal-regulated kinase (ERK)1/2/ERK1/2, and p-P65/P65 expression in lung tissues. Conclusion: R-hirudin attenuated pulmonary hypertension and thrombosis in APE rats, suggesting its potential as a novel treatment strategy for APE.

Pulmonary embolism after diagnostic curettage in patient with adenomyosis and hysteromyoma: A case report and brief review of literature.

RATIONALE: Pulmonary embolism (PE) is a common cause of cardiovascular death whose major acquired risk factors include postoperative states, pregnancy, malignancy, and age. We report a case of PE that occurred after diagnostic curettage for abnormal uterine bleeding, with a medical history of adenomyosis and hysteromyoma. PATIENT CONCERNS AND DIAGNOSES: A 31-year-old Han Chinese female was referred to our hospital with menstrual disorders, increased menstrual flow, and severe anemia. After admission, the patient was treated with a blood transfusion, iron supplementation, and erythropoietin, and diagnostic curettage was performed the following day. On the first postoperative day, the patient developed pulmonary embolism with dyspnea and fever diagnosed by CT pulmonary angiography and significantly elevated D-dimer. INTERVENTIONS AND OUTCOMES: Molecular weight heparin was administered for PE for 2 weeks, dyspnea was relieved significantly after 2 days of treatment and the uterine bleeding did not increase; and gonadotropin-releasing hormone agonists were administered for adenomyosis after 1 week of anticoagulant therapy to reduce bleeding. We followed up for 6 months, and the patient had no recurrence of thrombosis and uterine bleeding had improved. CONCLUSION: We speculate that the occurrence of pulmonary embolism was closely related to adenomyosis, hysteromyoma, and curettage in this patient. Treating the presence of both menstrual bleeding and thromboembolism is challenging, and careful management is necessary to avoid therapeutic contradictions.

Rare, fatal pulmonary fat embolism after acupuncture therapy: A case report and literature review.

BACKGROUND: Death from nontraumatic pulmonary fat embolism associated with minor soft tissue contusion, surgery, cancer chemotherapy, hematologic disorders and so on has been reported. Patients often present with atypical manifestations and rapid deterioration, making diagnosis and treatment difficult. However, there are no reported cases of death from pulmonary fat embolism after acupuncture therapy. This case emphasizes that the stress induced by acupuncture therapy, a mild soft tissue injury, plays an important role in pulmonary fat embolism. In addition, it suggests that in such cases, pulmonary fat embolism as a complication of acupuncture therapy needs to be taken seriously, and autopsy should be used to identify the source of fat emboli. CASE PRESENTATION: The patient was 72 years old female and experienced dizziness and fatigue after silver-needle acupuncture therapy. She experienced a significant drop in blood pressure and died 2 h later despite treatment and resuscitation. A systemic autopsy and histopathology examination (H&E and Sudan Ⅲ staining) were performed. More than 30 pinholes were observed in the lower back skin. Focal hemorrhages were seen surrounding the pinholes in the subcutaneous fatty tissue. Microscopically, numerous fat emboli were observed in the interstitial pulmonary arteries and alveolar wall capillaries, in addition to the vessels of the heart, liver, spleen and thyroid gland. The lungs showed congestion and edema. The cause of death was identified as pulmonary fat embolism. CONCLUSION: This article suggests that high vigilance for risk factors and the complication of pulmonary fat embolism following silver-needle acupuncture therapy should be exercised. In postmortem examinations, it should be pay attention that the peripheral arterial system and the venous system draining from non-injured sites should be examined for the formation of fat emboli, which can help distinguish posttraumatic and nontraumatic pulmonary fat embolism.

Central Retinal Vein Occlusion After Discontinuation of Rivaroxaban Therapy in a Young Patient with COVID-19 Pulmonary Embolism: A Case Report.

BACKGROUND We present the report of the first case, to the best of our knowledge, of central retinal vein occlusion (CRVO) that occurred 3 days after anticoagulation discontinuation in a patient with a history of pulmonary embolism in the course of COVID-19. CASE REPORT A previously healthy 38-year-old man was hospitalized in April 2021 with severe COVID-19 pneumonia, complicated by segmental and subsegmental pulmonary embolism. The patient was treated with a concurrent combination of remdesivir, dexamethasone, therapeutic enoxaparin, ceftriaxone, passive oxygen therapy, and convalescent plasma therapy, which led to pulmonary improvement. The treatment with therapeutic enoxaparin (80 mg/0.8 mL twice a day) was continued for 1 month after discharge, followed by 15 mg of rivaroxaban twice a day for 3 weeks and 20 mg of rivaroxaban once a day for 11 weeks. Within 3 days after rivaroxaban discontinuation, the patient experienced a decrease in visual acuity in his right eye, to the level of 5/25. Nonischemic CRVO with cystoid macular edema was diagnosed and an intravitreal injection of ranibizumab was performed. Common identifiable factors contributing to CRVO were excluded, and the treatment with prophylactic enoxaparin was initiated. Two weeks later, macular edema decreased significantly and visual acuity improved to 20/20. The treatment with enoxaparin was discontinued. CONCLUSIONS Rebound hypercoagulability after discontinuation of rivaroxaban therapy can manifest as CRVO in a young patient with a history of COVID-19 pulmonary embolism. It was successfully treated with an intravitreal injection of ranibizumab.

Comparison of real-world clinical and economic outcomes in patients receiving oral anticoagulants: A retrospective claims analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) have become widely used for the prevention of stroke in nonvalvular atrial fibrillation (AF) and for the treatment of venous thromboembolism (VTE). Warfarin, the standard of care prior to DOACs, requires monitoring and dose adjustment to ensure patients remain appropriately anticoagulated. DOACs do not require monitoring but are significantly more expensive. We sought to examine real-world effectiveness and costs of DOACs and warfarin in patients with AF and VTE. OBJECTIVE: To examine clinical and economic outcomes. The clinical objectives were to determine the bleeding and thrombotic event rates associated with DOACs vs warfarin. The economic objectives were to determine the cost associated with these events, as well as the all-cause medical and pharmacy costs associated with DOACs vs warfarin. METHODS: This analysis was an observational, propensity-matched comparison of retrospective medical and pharmacy claims data for members enrolled in an integrated health plan between October 1, 2015, and September 30, 2020. Members who were older than 18 years of age with at least 1 30-day supply of warfarin or a DOAC filled within 30 days of a new diagnosis of VTE or nonvalvular AF were eligible for the analysis. Cox hazard ratios were used to compare differences in clinical outcomes, where paired t-tests were used to evaluate economic outcomes. RESULTS: After matching, there were 893 patients in each group. Among matched members, warfarin was associated with increased risk of nonmajor bleeds relative to apixaban (hazard ratio [HR] = 1.526; P = 0.0048) and increased risk of pulmonary embolism relative to both DOACs (apixaban: HR = 1.941 [P = 0.0328]; rivaroxaban: HR = 1.833 [P = 0.0489]). No statistically significant difference was observed in hospitalizations or in length of stay between warfarin and either DOAC. The difference-in-difference (DID) in total costs of care per member per month for apixaban and rivaroxaban relative to warfarin were $801.64 (P = 0.0178) and $534.23 (P = 0.0998) more, respectively. DID in VTE-related cost for apixaban was $177.09 less, relative to warfarin (P = 0.0098). DID in all-cause pharmacy costs for apixaban and rivaroxaban relative to warfarin were $342.47 (P < 0.0001) and $386.42 (P < 0.001) more, respectively. CONCLUSIONS: Warfarin use was associated with a significant decrease in total cost of care despite a significant increase in VTE-related costs vs apixaban. Warfarin was also associated with a significant increase in other nonmajor bleeds relative to apixaban, as well as a significant increase in pulmonary embolism relative to both DOACs. Warfarin was associated with a significant reduction in all-cause pharmacy cost compared with either DOAC. DISCLOSURES: The authors of this study have nothing to disclose.

Impact of sex, race and socioeconomic status on survival after pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension.

OBJECTIVES: Pulmonary thromboendarterectomy (PTE) is a definitive treatment for chronic thromboembolic pulmonary hypertension. Demographic-based disparities in PTE outcomes have not been well-studied. METHODS: We reviewed all patients who underwent PTE for chronic thromboembolic pulmonary hypertension between 2009 and 2019 at our institution, tracking demographic information including self-identified race, preoperative characteristics and 2-year survival. Socioeconomic status was assessed using the zip code-linked Distressed Communities Index, a validated holistic measure of community well-being. Survival was estimated using Kaplan-Meier method and factors associated with mortality were estimated using Cox regression. RESULTS: Of 235 PTE patients, 101 (42.9%) were white and 87 (37.0%) were black. White patients had a higher median age at surgery (57 vs 51 years, P = 0.035) and a lower degree of economic distress (33.6 vs 61.2 percentile, P < 0.001). Regarding sex, 106 (45.1%) patients were male and 129 (53.6%) were female. Male patients had a higher median age (59 vs 50 years, P = 0.004), greater rates of dyslipidaemia (34% vs 20.2%, P = 0.025), a lower ejection fraction (55% vs 57%, P = 0.046) and longer cross-clamp (77 vs 67.50 min, P = 0.004) and circulatory arrest times (42 vs 37.50 min, P = 0.007). No difference was observed in unadjusted 2-year survival after PTE between patients stratified by race and sex (P = 0.35). After adjustment for clinically relevant variables, neither socioeconomic status, sex nor race were associated with mortality in Cox proportional hazard analysis. CONCLUSIONS: Sex, socioeconomic status and race were not associated with adverse outcomes after PTE in our single-centre experience.

Do Antiangiogenics Promote Clot Instability? Data from the TESEO Prospective Registry and Caravaggio Clinical Trial.

BACKGROUND: Venous thromboembolism (VTE) is a common complication in cancer patients. Much of its morbidity stems from the development of fatal pulmonary embolisms (PE). Little is known about the factors involved in clot stability, with angiogenesis possibly being implicated. METHODS: The database is from the TESEO prospective registry that recruits cancer patients with VTE from 41 Spanish hospitals. Independent validation was conducted in a cohort from the Caravaggio trial. The objective is to evaluate the association between exposure to antiangiogenic therapies and the PE/VTE proportion in oncological patients. RESULTS: In total, 1,536 subjects were evaluated; 58.4% (n = 894) had a PE and 7% (n = 108) received antiangiogenic therapy (bevacizumab in 75%). The PE/VTE proportion among antiangiogenic-treated individuals was 77/108 (71.3%) versus 817/1,428 (57.2%) among those receiving other alternative therapies (p = 0.004). The effect of the antiangiogenics on the PE/VTE proportion held up across all subgroups except for active smokers or those with chronic obstructive pulmonary disease. Exposure to antiangiogenics was associated with increased PEs, odds ratio (OR) 2.27 (95% CI, 1.42-3.63). In the Caravaggio trial, PE was present in 67% of the individuals treated with antiangiogenics, 50% of those who received chemotherapy without antiangiogenic treatment, and 60% without active therapy (p = 0.0016). CONCLUSION: Antiangiogenics are associated with increased proportion of PE in oncological patients with VTE. If an effect on clot stability is confirmed, the concept of thrombotic risk in cancer patients should be reconsidered in qualitative terms.

A multiscale model of vascular function in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by recurrent or unresolved pulmonary thromboemboli, leading to perfusion defects and increased arterial wave reflections. CTEPH treatment aims to reduce pulmonary arterial pressure and reestablish adequate lung perfusion, yet patients with distal lesions are inoperable by standard surgical intervention. Instead, these patients undergo balloon pulmonary angioplasty (BPA), a multisession, minimally invasive surgery that disrupts the thromboembolic material within the vessel lumen using a catheter balloon. However, there still lacks an integrative, holistic tool for identifying optimal target lesions for treatment. To address this insufficiency, we simulate CTEPH hemodynamics and BPA therapy using a multiscale fluid dynamics model. The large pulmonary arterial geometry is derived from a computed tomography (CT) image, whereas a fractal tree represents the small vessels. We model ring- and web-like lesions, common in CTEPH, and simulate normotensive conditions and four CTEPH disease scenarios; the latter includes both large artery lesions and vascular remodeling. BPA therapy is simulated by simultaneously reducing lesion severity in three locations. Our predictions mimic severe CTEPH, manifested by an increase in mean proximal pulmonary arterial pressure above 20 mmHg and prominent wave reflections. Both flow and pressure decrease in vessels distal to the lesions and increase in unobstructed vascular regions. We use the main pulmonary artery (MPA) pressure, a wave reflection index, and a measure of flow heterogeneity to select optimal target lesions for BPA. In summary, this study provides a multiscale, image-to-hemodynamics pipeline for BPA therapy planning for patients with inoperable CTEPH. NEW & NOTEWORTHY This article presents novel computational framework for predicting pulmonary hemodynamics in chronic thromboembolic pulmonary hypertension. The mathematical model is used to identify the optimal target lesions for balloon pulmonary angioplasty, combining simulated pulmonary artery pressure, wave intensity analysis, and a new quantitative metric of flow heterogeneity.

[Thromboembolic event and metabolic hyperhomocysteinemia: A case report and review of literature]. / Événement thromboembolique et hyperhomocystéinémie métabolique : case-report et revue de la littérature.

INTRODUCTION: Venous thromboembolic diseases have an incidence of 1.57/1000. Among patients under 50 years old, thrombophilia is assessed, the indications for which are increasingly stringent. Today, the need of plasma homocysteine assay is uncertain. OBSERVATION: Our case is a 42 year-old man, in whom a pulmonary embolism associated with macrocytosis made us discover a B12 deficiency secondary to Biermer's disease. In the literature, patients are men with an average age limit to the realisation of the assessment of thrombophilia. Not all of these patients had any causal other than hyperhomocysteinemia secondary to Biermer's disease. The support is not detailed. CONCLUSION: Hyperhomocysteinemia is probably not the only thromboembolic factor. The patient received anticoagulation and vitamin B12 supplementation. A good reading of the complete blood count is essential.

Right Ventricular Extracellular Volume with Dual-Layer Spectral Detector CT: Value in Chronic Thromboembolic Pulmonary Hypertension.

Background Right ventricular (RV) extracellular volumes (ECVs), as a surrogate for histologic fibrosis, have not been sufficiently investigated. Purpose To evaluate and compare RV and left ventricular (LV) ECVs obtained with dual-layer spectral detector CT (DLCT) in chronic thromboembolic pulmonary hypertension (CTEPH) and investigate the clinical importance of RV ECV. Materials and Methods Retrospective analysis was performed on data from 31 patients with CTEPH (17 were not treated with pulmonary endarterectomy [PEA] or balloon pulmonary angioplasty [BPA] and 14 were) and eight control subjects who underwent myocardial delayed enhancement (MDE) DLCT from January 2019 to June 2020. The ECVs in the RV and LV walls were calculated by using iodine density as derived from spectral data pertaining to MDE. Statistical analyses were performed with one-way repeated analysis of variance with the Tukey post hoc test or the Kruskal-Wallis test with the Steel-Dwass test and linear regression analysis. Results The PEA- and BPA-naive group showed significantly higher ECVs than the PEA- or BPA-treated group and control group in the septum (28.2% ± 2.9 vs 24.3% ± 3.6, P = .005), anterior right ventricular insertion point (RVIP) (32.9% ± 4.6 vs 25.3% ± 3.6, P < .001), posterior RVIP (35.2% ± 5.2 vs 27.3% ± 4.2, P < .001), mean RVIP (34.0% ± 4.2 vs 26.3% ± 3.4, P < .001), RV free wall (29.5% ± 3.3 vs 25.9% ± 4.1, P = .036), and mean RV wall (29.1% ± 3.0 vs 26.1% ± 3.1, P = .029). There were no significant differences between the PEA- or BPA-treated group and control subjects in these segments (septum, P = .93; anterior RVIP, P = .38; posterior RVIP, P = .52; mean RVIP, P = .36; RV free wall, P = .97; and mean RV, P = .33). There were significant correlations between ECV and mean pulmonary artery pressure (PAP) or brain natriuretic peptide (BNP) in the mean RVIP (mean PAP: R = 0.66, P < .001; BNP: R = 0.44, P = .014) and the mean RV (mean PAP: R = 0.49, P = .005; BNP: R = 0.44, P = .013). Conclusion Right ventricular and right ventricular insertion point extracellular volumes could be noninvasive surrogate markers of disease severity and reverse tissue remodeling in chronic thromboembolic pulmonary hypertension. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Sandfort and Bluemke in this issue.

Efficacy and Safety of Rivaroxaban versus Warfarin for the Treatment of Acute Pulmonary Embolism: A Real-World Study.

BACKGROUND: Pulmonary embolism (PE) is a life-threatening disease. Target-specific anticoagulant rivaroxaban is a direct factor Xa inhibitor that can be safely used without laboratory monitoring. OBJECTIVE: To investigate the efficacy and safety of rivaroxaban versus warfarin for the treatment of acute pulmonary thromboembolism in real-world clinical practice. METHOD: This was a semiretrospective, semiprospective, and real-world trial involving 128 patients with acute symptomatic pulmonary embolism with or without active tumor or frailty. We compared rivaroxaban to the standard therapy consisting of low-molecular-weight heparin combined with warfarin. The primary efficacy outcome was absorption of thrombus. The principal safety outcome was bleeding episode. RESULTS: There was no significant difference in thrombus absorption between rivaroxaban and standard therapy after 3-month treatment (P = 0.798, 95% confidence interval (CI) 0.686 to 1.336) or more than 6-month treatment (P = 0.534, 95% confidence interval (CI) 0.795 to 1.556). There was no decline in efficacy (including computed tomographic pulmonary angiography and recurrence) when the rivaroxaban dose was reduced to 10 mg once daily after 3 months of administration. The ratio of patients without bleeding was 48.84% for rivaroxaban and 19.05% for standard therapy (P = 0.001). There was no significant difference in rivaroxaban monotherapy subgroups (including frail patients, tumor patients, and thrombolysis or nonthrombolysis at intermediate-high-risk patients). CONCLUSION: In this real-world study, the efficacy and safety of rivaroxaban alone was not different to standard therapy for pulmonary emboli absorption. With an extension in treatment duration, the rivaroxaban regimen had a higher efficacy and safety than standard therapy and there was no decline in treatment efficacy when the rivaroxaban dose was reduced to 10 mg once daily.

A Rare Case of Submassive Pulmonary Embolism with a Right Aberrant Subclavian Artery and Thrombosed Kommerell Diverticulum.

An 81-year-old man presented with shortness of breath and was referred to our hospital with suspected acute pulmonary embolism. Enhanced computed tomography revealed a right aberrant subclavian artery with a thrombosed Kommerell diverticulum (KD), as well as deep vein thrombosis in the left leg and bilateral pulmonary artery thrombosis. Thrombosis in the KD disappeared after one month of anticoagulation treatment with rivaroxaban. Thrombosis of a KD is a rare condition that may cause distal emboli and subclavian steal syndrome, although this syndrome was not present in this case. Rivaroxaban is an effective anticoagulant for treating thrombosis of a KD.

Controlled Delivery of 80 mg Aerosol Furosemide Does Not Achieve Consistent Dyspnea Relief in Patients.

PURPOSE: Aerosol furosemide may be an option to treat refractory dyspnea, though doses, methods of delivery, and outcomes have been variable. We hypothesized that controlled delivery of high dose aerosol furosemide would reduce variability of dyspnea relief in patients with underlying pulmonary disease. METHODS: Seventeen patients with chronic exertional dyspnea were recruited. Patients rated recently recalled breathing discomfort on a numerical rating scale (NRS) and the multidimensional dyspnea profile (MDP). They then performed graded exercise using an arm-ergometer. The NRS was completed following each exercise grade, and the MDP was repeated after a pre-defined dyspnea threshold was reached. During separate visits, patients received either aerosol saline or 80 mg of aerosol furosemide in a randomized, double-blind, crossover design. After treatment, graded exercise to the pre-treatment level was repeated, followed by completion of the NRS and MDP. Treatment effect was defined as the difference between pre- and post-treatment NRS at end exercise, expressed in absolute terms as % Full Scale. "Responders" were defined as those showing treatment effect ≥ 20% of full scale. RESULTS: Final analysis included 15 patients. Neither treatment produced a statistically significant change in NRS and there was no significant difference between treatments (p = 0.45). There were four "responders" and one patient whose dyspnea worsened with furosemide; two patients were responders with saline, of whom one also responded to furosemide. No adverse events were reported. CONCLUSIONS: High dose controlled delivery aerosol furosemide was not statistically different from saline placebo at reducing exercise-induced dyspnea. However, a clinically meaningful improvement was noted in some patients.

A Retrospective Study on Efficacy and Safety of Rivaroxaban and Dalteparin for Long-Term Treatment of Venous Thromboembolism in Patients with Lung Cancer.

BACKGROUND: Standard therapy for cancer-associated venous thromboembolism (VTE) is low-molecular-weight heparin. The use of direct oral anticoagulants for cancer-associated VTE has increased; however, their efficacy and safety in lung cancer patients remain unclear. OBJECTIVES: We examined the efficacy and safety of rivaroxaban compared with dalteparin for cancer-associated VTE in patients with primary lung cancer. METHODS: A single-center retrospective study of 204 patients with primary lung cancer who were prescribed rivaroxaban (n = 131) or dalteparin (n = 73) for VTE was performed. The primary endpoint was a composite event including recurrence and major or clinically relevant nonmajor bleeding. Secondary endpoints included the incidence of recurrence, major and clinically relevant nonmajor bleeding, all-cause mortality, and bleeding or pulmonary embolism-related mortality. RESULTS: The composite event occurred in 38 (29.0) and 12 (16.4%) patients in the rivaroxaban and dalteparin (p = 0.045) groups, respectively. The multivariate Cox proportional hazards model for age, Eastern Cooperative Oncology Group performance score, and bleeding risk factors revealed the rivaroxaban group showed a 1.176-fold composite event risk without statistical significance (0.595-2.324, p = 0.641). There was no statistically significant intergroup difference for the incidence of VTE recurrence (5.3% in the rivaroxaban group versus 2.7% in the dalteparin group, p = 0.495) and major or clinically relevant nonmajor bleeding (23.7% in the rivaroxaban group versus 13.7% in the dalteparin group, p = 0.089). There was no significant difference in the all-cause mortality rate (hazard ratio 0.864, 95% CI 0.624-1.196, p = 0.337). CONCLUSIONS: There was no difference in the safety and efficacy profile of rivaroxaban compared with dalteparin. Therefore, rivaroxaban may be a valuable treatment option for lung cancer-associated VTE.

A case report of the successful administration of clozapine in the face of myocardial infarction, pulmonary embolism and hyperlipidaemia resulting in the termination of long-term seclusion.

BACKGROUND: Cardiometabolic health significantly impacts on the mortality of people with severe mental illness. Clozapine has the greatest efficacy for Treatment Resistant Schizophrenia (TRS) but the greatest negative impact on cardiometabolic health. Balancing the risks and benefits of treatment, dignity, autonomy, liberty, mental and physical health can be challenging, particularly when imposing interventions with potentially life threatening adverse events, such as clozapine. We describe the successful administration of clozapine in the face of myocardial infarction, pulmonary embolism and hyperlipidaemia resulting in the termination of long-term seclusion for a gentleman with TRS in high secure psychiatric services. CASE PRESENTATION: The impact of clozapine on a 44-year-old gentleman with TRS, extreme violence requiring physical restraint and long-term segregation, and numerous other significant physical health complications is described. He had metabolic syndrome; a poor diet, sedentary lifestyle, Body Mass Index (BMI) of 31.5, poorly controlled lipids and had smoked heavily since childhood. During preparations to initiate clozapine, he suffered a myocardial infarction and pulmonary embolism. His compliance with secondary prevention medications was poor due to paranoid persecutory and somatic delusions. Despite these concerns, nasogastric administration of clozapine was approved and prescribed within nine months of his myocardial infarction and a month from his pulmonary embolism but was ultimately not required. Accepting oral medication, his mental state made a rapid and dramatic improvement. After spending 1046 days in seclusion, this was terminated 94 days after clozapine initiation. He has been compliant with all medications for 24 months, had no incidents of violence or seclusion, and has been transferred to medium secure services. His physical health stabilised despite continuing to lead a sedentary lifestyle and remaining obese (BMI of 35). He developed hypertension, Type II Diabetes Mellitus and his triglycerides rose to 22.2 mmol/L in the same month after clozapine initiation. However, with pharmacological intervention, 24 months later these are controlled, and he has had no further thromboembolic events. CONCLUSIONS: We highlight that despite significant physical health concerns, clozapine can be successfully initiated and safely prescribed with a significantly positive effect on both the psychiatric and holistic care of patients with treatment resistant schizophrenia.

Rivaroxaban for the treatment of venous thromboembolism in real life: A single-center prospective study.

The clinical profile, evolution and complications of treatment with rivaroxaban in a cohort of patients presenting with venous thromboembolism (VTE) were analyzed in an observational, non-interventional and prospective study.A total of 111 patients were included in the study. Clinical data were collected from the medical history of the patients and recorded in a specific database.Mean age was 63.8 ±â€Š17.4 years, 53.2% of patients were men, 55.9% had at least another concomitant condition, and 40.9% at least 1 VTE risk factor. 54.1% of patients presented with deep venous thrombosis, 32.4% with pulmonary embolism and 13.5% with both conditions simultaneously. The 61% of patients were admitted to hospital and mean hospital length-of-stay was 8.8 ±â€Š9.9 days. After a mean follow-up 530 ±â€Š464 days (median follow-up of 405 days), 3.9% of patients died and VTE recurrence occurred in 2.9% of patients. While receiving rivaroxaban, a first bleeding complication occurred in 8.1%; all events were minor bleeding.Our study supports the current literature data and confirms the similar results of real-life VTE patients with those enrolled in the rivaroxaban pivotal clinical trials. Rivaroxaban may facilitate outpatient treatment and might be considered as a first-line therapy for the management of VTE patients.

Acute cytomegalovirus infection associated with pulmonary embolism treated successfully with rivaroxaban: case report.

Severe life-threatening thromboembolism may be caused exclusively by the presence of an acute CMV infection or due to the association of this agent and other thrombogenic factors. We report a case of an immunocompetent young female patient who presented a pulmonary embolism associated with acute CMV infection. The patient did not have any other apparent cause of thrombosis. She was successfully treated with rivaroxaban for 6 months without further episodes. To the best of our knowledge, this is the first report of a pulmonary embolism associated with CMV treated with a direct oral anticoagulant. The current case report calls attention to the importance of signs and symptoms of thromboembolism among patients with CMV. Direct oral anticoagulants can potentially bring the same benefits to treat pulmonary embolism associated with CMV as those observed in patients not infected.

Increasing Safe Outpatient Management of Emergency Department Patients With Pulmonary Embolism: A Controlled Pragmatic Trial.

Background: Many low-risk patients with acute pulmonary embolism (PE) in the emergency department (ED) are eligible for outpatient care but are hospitalized nonetheless. One impediment to home discharge is the difficulty of identifying which patients can safely forgo hospitalization. Objective: To evaluate the effect of an integrated electronic clinical decision support system (CDSS) to facilitate risk stratification and decision making at the site of care for patients with acute PE. Design: Controlled pragmatic trial. (ClinicalTrials.gov: NCT03601676). Setting: All 21 community EDs of an integrated health care delivery system (Kaiser Permanente Northern California). Patients: Adult ED patients with acute PE. Intervention: Ten intervention sites selected by convenience received a multidimensional technology and education intervention at month 9 of a 16-month study period (January 2014 to April 2015); the remaining 11 sites served as concurrent controls. Measurements: The primary outcome was discharge to home from either the ED or a short-term (<24-hour) outpatient observation unit based in the ED. Adverse outcomes included return visits for PE-related symptoms within 5 days and recurrent venous thromboembolism, major hemorrhage, and all-cause mortality within 30 days. A difference-in-differences approach was used to compare pre-post changes at intervention versus control sites, with adjustment for demographic and clinical characteristics. Results: Among 881 eligible patients diagnosed with PE at intervention sites and 822 at control sites, adjusted home discharge increased at intervention sites (17.4% pre- to 28.0% postintervention) without a concurrent increase at control sites (15.1% pre- and 14.5% postintervention). The difference-in-differences comparison was 11.3 percentage points (95% CI, 3.0 to 19.5 percentage points; P = 0.007). No increases were seen in 5-day return visits related to PE or in 30-day major adverse outcomes associated with CDSS implementation. Limitation: Lack of random allocation. Conclusion: Implementation and structured promotion of a CDSS to aid physicians in site-of-care decision making for ED patients with acute PE safely increased outpatient management. Primary Funding Source: Garfield Memorial National Research Fund and The Permanente Medical Group Delivery Science and Physician Researcher Programs.

Excited catatonia in a patient with fatal pulmonary embolism and a successful treatment strategy.

BACKGROUND: Patients with psychiatric disorders in critical condition are difficult to treat. In this study, we report on a patient with underlying schizoaffective disorder who developed catatonia, cardiac arrest, and pulmonary embolism, as well as a successful treatment strategy. CASE PRESENTATION: The inpatient is a 41-year-old morbidly obese male with schizoaffective disorder whose clozapine dosage was titrated from 100 mg to 175 mg due to auditory hallucination and agitation. The patient abruptly developed acute cardiopulmonary symptoms associated with an elevated troponin-I level. He was transferred to a cardiac intensive care unit, where he remained for 3 days. He was also found to have excited catatonic symptoms, and the lorazepam-diazepam protocol was initiated to quickly relieve the catatonia. Once the coronary angiogram was read as normal, the patient was transferred back to the psychiatric ward. However, the patient then suffered from in-hospital cardiac arrest. He was resuscitated and again transferred to the medical intensive care unit. Computed tomography confirmed the diagnosis of a pulmonary embolism. The patient was treated with Rivaroxaban 30 mg/d for the first 21 days, followed by 20 mg daily for 3 months. To control his severe and refractory psychotic symptoms, the patient was re-prescribed clozapine. During the 15-month follow-up period, the patient demonstrated a fair response and tolerability to clozapine 150 mg without symptoms relapse and no thromboembolic event. CONCLUSION: This report can serve to remind psychiatrists and physicians to be aware of fatal conditions in patients with psychiatric diseases and physical illnesses.