High Thromboembolic Risk Research Articles

Hemostasis and thrombosis risks and management in vascular anomalies.

The role of the hematologist in the management of vascular anomalies is evolving. Several vascular tumors and malformations are associated with complex coagulation derangements. Kaposiform hemangioendothelioma or tufted angiomas may present with a consumptive coagulopathy known as the Kasabach-Merritt phenomenon (KMP). The management of KMP is essential to reduce morbidity and mortality from this condition. Slow-flow vascular malformations (SFVM) are also frequently complicated by a coagulopathy requiring anticoagulation, especially during and after surgical procedures, and some of these conditions pose a high risk of venous thromboembolism. Pain in SFVM is also frequently responsive to anticoagulation as well. It is essential for a hematologist with expertise in vascular anomalies to assist in the management of these complex conditions as part of a multidisciplinary team to reduce morbidity and mortality. Through case-based discussions, we attempt to highlight the critical role of the hematologist in managing these anomalies.

Management of paroxysmal nocturnal hemoglobinuria with low-level hemolysis in pregnancy- a report of two cases.

Pregnant women with paroxysmal nocturnal hemoglobinuria (PNH) are at high risk for life-threatening thromboembolism. Therapy with the complement inhibitor eculizumab is able to mitigate thrombotic risks in PNH and to improve pregnancy outcomes. However, whether PNH with low-level hemolysis in pregnancy can be safely managed without complement inhibition is unclear.Here, we describe two pregnant patients with PNH in the setting of bone marrow failure and low-level hemolysis with lactate dehydrogenase (LDH) < 1.5 x upper limit of normal [ULN]. In both patients, management consisted solely of prophylactic anticoagulation, without the use of complement inhibition. Both pregnancies ended successfully without thromboembolic complications.We conclude that in pregnant patients with PNH and low-level hemolysis (i.e. LDH < 1.5 x ULN), management with close monitoring and prophylactic anticoagulation only, without use of complement inhibition, might be a reasonable strategy. More data to guide optimal management of pregnant women with PNH are needed.

Management strategies to prevent stroke in patients with atrial fibrillation and malignant left atrial appendage

BackgroundPatients with atrial fibrillation and malignant left atrial appendage (LAA) may benefit from LAA closure (LAAC); however, evidence is limited. ObjectiveThe purpose of this study was to determine management strategies and clinical outcomes in patients with atrial fibrillation and malignant LAA. MethodsMalignant LAA was defined as a history of ischemic stroke and/or evidence of LAA thrombus despite continuous oral anticoagulation (OAC) therapy (continuous for ≥3 weeks). We studied 80 patients with malignant LAA treated with LAAC. We compared these patients first against 44 patients with malignant LAA treated with OAC alone and second against 114 patients without malignant LAA who were treated with LAAC for conventional indications. ResultsAmong patients with malignant LAA (first comparison), those treated with LAAC had a higher 1-year cumulative incidence rate of ischemic stroke than did patients treated with OAC alone (6.3% vs 5.3%; log-rank, P = .09) whereas the difference in stroke risk while receiving OAC was comparable (2.7% vs 5.3%; log-rank, P = .84). Furthermore, all disabling stroke events in patients with malignant LAA treated with LAAC occurred only while not receiving OAC. Among patients treated with LAAC (second comparison), those with malignant LAA had a higher 1-year cumulative incidence rate of ischemic stroke (and ischemic stroke due to device-related thrombosis) than did those without malignant LAA (6.3% vs 2.2%; log-rank, P = .009 and 2.2% vs 0%; log-rank, P = .04, respectively). However, these differences in stroke risk were no longer significant while receiving OAC (2.7% vs 1.0%; log-rank, P = .11). ConclusionCombination performing LAAC and continuation of OAC may be options to prevent ischemic stroke in patients with high thromboembolic risk and malignant LAA.

The Value of Cardiac MRI in the Diagnosis of Left Intraventricular Apical Thrombus after Myocardial Infarction: A Case Report

Left ventricular thrombus is a dreadful complication in post-myocardial infarction and should be researched, especially in patients with ventricular dysfunction, given the high thromboembolic risk in these patients. Several studies have shown that transthoracic echocardiography (TTE) lacks specificity when compared with cardiac magnetic resonance imaging (MRI) in the discovery of intraventricular thrombus. However, MRI remains a costly and time-consuming examination, especially in developing countries. In our clinical case, cardiac MRI enabled us to diagnose an apical intra- LV thrombus in the post-infarction period, which guided us in the correct management of the patient and avoided any thromboembolic complications. Today, cardiac MRI confirms its value as a reference imaging tool in the management of ischemic heart disease.

Mobile health technology integrated care in atrial fibrillation patients according to polypharmacy: an analysis of the mAFA-II clinical trial

Abstract Background Polypharmacy is common in patients with multiple chronic long-term conditions and has been associated with adverse outcome in patients with Atrial Fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway has been proposed to streamline an integrated care management of AF patients, and the Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA-II) prospective cluster randomised trial showed the efficacy of a mobile health (mHealth) implemented ‘ABC’ pathway (mAFA intervention) in improving prognosis of AF patients. Whether these benefits apply also to AF patients with polypharmacy is unclear. Purpose To evaluate the effect of mAFA intervention according to the presence of polypharmacy at baseline. Methods In the mAFA-II cluster randomised trial, between June 2018 and August 2019 adults with AF were enrolled in 40 centres in China; clusters were randomised in a 1:1 ratio to mAFA intervention or usual care. In this analysis, we defined polypharmacy as being treated with 5 or more drugs at baseline. The primary outcome was the composite of stroke, thromboembolism, all-cause death and rehospitalisation. We evaluated the interaction between the effect of mAFA intervention and the presence of polypharmacy at baseline on the risk of the primary outcome using multivariable Cox-regression analysis; results were expressed as adjusted Hazard Ratio (aHR) and 95% Confidence Intervals (95%CI). We also evaluated individual components of the primary outcomes as exploratory secondary endpoints. Results 3,324 patients were enrolled in the trial and included in this analysis; of these, 558 (16.8%) patients were polymedicated at baseline (mean age 71.9±12.6 years, females 44.3%); of these, 303 (54.3%) were allocated to mAFA intervention. 2,766 patients were not polymedicated (mean age 67.9±14.4 years, females 36.7%), of these 1,343 (48.5%) were allocated to mAFA intervention. Overall, patients in the polypharmacy group were older and with higher prevalence of most comorbidities and higher thromboembolic risk. The effect of mAFA intervention was similar among patients with vs. without polypharmacy on the reduction of the primary composite outcome, although with a diluted effect among polymedicated patients (adjusted Hazard Ratio [aHR] and 95% Confidence Interval [CI]: 0.34 [0.22-0.53] vs. 0.73 [0.27-1.99], p for interaction=0.166, Figure 1); similar results were observed for all-cause death and rehospitalizations. Conclusions A mHealth-technology implemented ABC pathway showed a similar effect on the reduction of the primary composite outcome among patients with and without polypharmacy. These findings support a broad application of the ABC pathway to improve outcomes in AF patients.Figure 1

Anticoagulation status and left atrial appendage occlusion indications in hospitalized cardiology patients with atrial fibrillation: a Hellenic Cardiorenal Morbidity Snapshot (HECMOS) sub-study

Abstract Background Proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (NVAF) patients. Left atrial appendage occlusion (LAAC) may be considered for stroke prevention in patients with NVAF and contraindications for long-term anticoagulant treatment. Purpose We aimed to assess the anticoagulation status and LAAC indications in patients with NVAF from HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Methods HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on March 3, 2022, in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves and moderate to severe mitral valve stenosis. Patients with poor adherence to anticoagulants, high bleeding risk, previous major bleeding, and previous stroke were considered candidates for LAAC. Results Two hundred fifty-six patients (mean age 76.6±11.7, 148 males) were included in our analysis. Most of them (n=159; 62%) suffered from persistent AF. Mean CHA 2 DS 2 - VASc score was 4.28±1.7, while mean HAS-BLED score was 1.47±0.9. Three out of 3 patients with a CHA 2 DS 2 -VASc 0 or 1 (female) received improperly anticoagulants. Sixteen out of 18 patients with a CHA 2 DS 2 -VASc 1 or 2 (female) received anticoagulants. Thirty-three out of 235 patients with a CHA 2 DS 2 -VASc &amp;gt; 1 or 2 (for female) did not receive improperly anticoagulants. Among 221 under anticoagulant therapy, 191 (86.4%) received non-vitamin K antagonist oral anticoagulants (NOACs) and 30 (13.6%) received vitamin K antagonists. Relative indications for LAAC were present in 77 patients with NVAF (53 had only one risk factor, while 22 had two and 2 patients had three concurrent risk factors). In detail, 15 reported poor or no adherence to the anticoagulant therapy, 17 patients had a history of major bleeding, 36 had a prior stroke and 35 had a HAS-BLED score ≥3. No LAAC treatment was recorded. Conclusion Αnticoagulation status was nearly optimal in a high thromboembolic risk population of cardiology patients, mainly treated with NOACs. Three out of ten AF patients should be screened for LAAC.Anticoagulation by thrombotic riskPotential LAAC candidates

Clinical analysis of bleeding and thrombotic events in haematological-oncology patients with severe thrombocytopenia and a high risk of thrombosis

Background: Haematological patients with severe thrombocytopenia and high thrombotic risk face challenges related to balancing bleeding and thrombosis risks. This study investigated factors associated with bleeding and thrombosis in high-risk haematological oncology patients with severe thrombocytopenia not receiving anticoagulant therapy and characterized their clinical features when both events occurred. Methods: A total of 446 haematological oncology patients with Caprini scores ≥ 5 were included from July 2022 to June 2023 at Mianyang City Central Hospital. Those not receiving prophylactic anticoagulants due to an admission platelet count < 50 × 109/L were studied. Patients were categorized into bleeding/nonbleeding and thrombotic/nonthrombotic groups on the basis of hospital course. Relevant clinical data were collected, and univariate/multivariate logistic regression was used to analyse the influencing factors. The platelet count at admission was assessed via ROC curves for thrombosis prediction. Results: In the bleeding group, higher proportions of patients with leukaemia, myeloid tumours, lung infections, and a central venous catheter (CVC) with two lumens were observed, along with shorter catheter durations, lower initial and minimum platelet counts during hospitalization, and prolonged plasminogen times (all P < 0.05). The thrombotic group had a greater thrombosis history, initial platelet count, use of two venous catheter lumens, parenteral nutrition, sedation, and autologous haematopoietic stem cell transplantation (Auto-HSCT), with a lower leukaemia proportion (P < 0.05). Logistic regression identified lymphoma type and minimum platelet count as bleeding protective factors and the Charlson Comorbidity Index (CCI) score as an independent risk factor. Thrombosis history, two venous catheter lumens, and sedation were risk factors for thrombosis. The median platelet count was lower at bleeding and thrombosis than at admission (P = 0.007). The platelet count at admission had predictive value for thrombosis, especially severe thrombocytopenia, with an AUC of 0.735 (95% CI 0.613–0.858, P = 0.003) and a cut-off value of 42.5 × 109/L. Conclusions: For haematological neoplasm patients with a high risk of venous thromboembolism (VTE), severe thrombocytopenia and high CCI scores, risk prevention and control of bleeding take precedence over thrombosis prophylaxis. Prophylactic anticoagulation is still recommended for patients with lymphoma assessed at high risk for VTE and with platelet counts of at least 42.5 × 109/L.

Role of Tumor Microenvironment in the Risk of Thromboembolic Complications in Ovarian Cancer

Introduction. Incidence of ovarian cancer remains high in the overall prevalence of oncological pathology. Adjuvant chemotherapy refers to its treatment options. Patients with oncological pathology are faced with a high risk of thrombosis and thromboembolism, with up to 30% lethal outcome within a month of its development. A number of cancer cells are known to induce platelet aggregation, contributing to thrombosis and metastasis as a result of this interaction. Accordingly, the paper is aimed at presenting a clinical case for demonstrating the role of P-selectin expression in the complications in a patient with ovarian cancer. Materials and methods. The present paper evaluates platelet activation marker in a patient undergoing chemotherapy courses after cytoreductive surgery. Following the case conference and in accordance with the clinical recommendations of the Russian Oncology Association (AOR) and Russian Society of Clinical Oncology (RUSSCO), cytoreduction (CC-0), radical hysterectomy, transverse colectomy, left hemicolectomy with rectum resection were performed. The interventions included ascendostomy, pelvic, lateral right-sided and left-sided peritonectomy, pelvic lymphoadenectomy, total omentectomy, Renape-French HIPEC (hyperthermic intraperitoneal chemotherapy), abdominal and pelvic drainage. Expression of P-selectin on the platelet surface was measured as a marker of platelet activation. Results and discussion. At the time of admission, the patient had high CD62 expression activity compared to healthy volunteers (CD62 ADP- — 11.2%, CD62 ADP — 24.7% vs CD62 ADP- — 1.3%, CD62 ADP — 17.2%). During the complex treatment of ovarian cancer, the platelet activation increased (CD62 ADP- — 21.8 %, CD62 ADP+ — 30.1 %). At discharge, CD62 expression values reached the conditional norm, presumably indicating thrombosis development. Conclusion. Tumor microenvironment influences the hemostasis system. Detailed study into this issue obtains a high potential for the prevention of primary and secondary thromboembolic complications in oncologic patients.

Primary Prevention of Cancer-Associated Thrombosis: Current Perspectives.

Over the past two decades, the incidence of cancer-associated thrombosis (CAT) has increased. It is nowadays a common and often serious complication among patients with cancer. Although medical thromboprophylaxis is recommended for most surgical and nonsurgical cancer patients, it has been infrequently used in ambulatory patients with cancer because of the burden of treatment and concerns about bleeding. However, various risk assessment scores are now available and randomized placebo-controlled trials have established the efficacy of low-molecular-weight heparin or the direct oral Xa inhibitors rivaroxaban and apixaban in ambulatory patients with cancer at high risk of venous thromboembolism (VTE). This review provides an overview of (1) primary thromboprophylaxis in the setting of hospitalized surgical and medical patients, (2) extended thromboprophylaxis after hospital discharge, (3) performance of risk assessment tools for CAT, and (4) primary thromboprophylaxis in ambulatory patients with cancer. The aim is to provide support to physicians in identifying ambulatory patients with cancer at high VTE risk who benefit most from medical thromboprophylaxis according to current recommendations from international guidelines.

Transfer RNAs are Linked to Ischemic Stroke and Major Bleeding in Patients with End-Stage Kidney Disease.

Patients with end-stage kidney disease (ESKD) are at very high risk for thromboembolism and bleeding. This study aimed to identify small noncoding RNAs (sncRNAs), specifically microRNAs and transfer-RNA (tRNA)-derived fragments (tRFs), as potential novel biomarkers for predicting thromboembolism and bleeding in this high-risk population. In this sncRNA discovery research, we leveraged the VIVALDI cohort, consisting of 625 ESKD patients on hemodialysis, to conduct two nested case-control studies, each comprising 18 participants. The primary outcomes were ischemic stroke in the first study and major bleeding in the second. Plasma samples were processed using the miND pipeline for RNA-seq analysis to investigate differential expression of microRNAs and tRNA/tRFs between cases and their respective matched controls, with results stringently adjusted for the false discovery rate (FDR). No significant differential expression of microRNAs for either ischemic stroke or major bleeding outcomes was observed in the two nested case-control studies. However, we identified four tRNAs significantly differentially expressed in ischemic stroke cases and seven in major bleeding cases, compared with controls (FDR < 0.1). Coverage plots indicated that specific tRNA fragments (tRFs), rather than full-length tRNAs, were detected, however. Alternative mapping approaches revealed challenges and technical limitations that precluded in-depth differential expression analyses on these specific tRFs. Yet, they also underscored the potential of tRNAs and tRFs as markers for thromboembolism and bleeding. While microRNAs did not show significant differential expression, our study identifies specific tRNAs/tRFs as potential novel biomarkers for ischemic stroke and major bleeding in ESKD patients.

Heritable Thrombophilia and Increased Risk for Venous Thromboembolism Despite Thromboprophylaxis After Pelvis or Acetabulum Fracture.

Individuals with pelvic and acetabular fractures are at high risk of venous thromboembolism (VTE). The purpose of this study was to determine whether serum markers for thrombophilia and rapid thromboelastography (r-TEG) values correlate with increased VTE risk among patients with pelvic and acetabular fractures. . Prospective observational study. Two urban academic level 1 trauma centers. Adult patients with isolated pelvis and/or acetabulum fractures (OTA/AO 61 and 62) treated surgically placed on a standardized VTE chemoprophylaxis regimen with enoxaparin over a 5-year period were included. Serum r-TEG, coagulation laboratory values, and markers for heritable thrombophilia were drawn postoperatively and after completion of a 6-week course of enoxaparin. The primary outcome was VTE event (either deep venous thrombosis or pulmonary embolism) diagnosed using a Duplex ultrasound, chest computed tomography angiogram, or lung ventilation-perfusion ordered based on clinical suspicion of a VTE event. Laboratory markers and values were then compared between patients who went on to have a VTE event and those who did not and patients with and without markers of thrombophilia. One hundred thirty-three adult patients with isolated operative pelvic and/or acetabular fractures were enrolled in this study. The average age of patients at time of injury was 48.3 years (range 18-91). Sixty-seven percent of patients in the study were (n = 90) males. Sixty-three percent of patients (n = 84) completed both clinical and laboratory follow-up. Forty-one percent of patients (n = 54) had 1 or more markers of heritable thrombophilia. Twelve percent (n = 10) of patients who completed follow-up were diagnosed with VTE. Age, sex, and smoking status were not associated with VTE. Patients who developed VTE had a higher body mass index (P = 0.04). Having more than 1 marker of heritable thrombophilia (P = 0.004) and an r-TEG mean amplitude greater than 72 mm postoperatively was positively associated with VTE (P = 0.02). Among patients treated surgically for isolated pelvic and acetabular fractures who received enoxaparin prophylaxis, the presence of more than 1 marker of heritable thrombophilia or r-TEG mean amplitude value greater than 72 mm postoperatively was associated with an increased risk of VTE. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Validation of clinical risk assessment scores for venous thromboembolism in patients with cancer: a population-based cohort study

BackgroundGuidelines recommend using risk assessment tools to identify ambulatory patients with cancer at high risk of venous thromboembolism (VTE). ObjectiveWe aimed to validate a new cancer-associated thrombosis (CAT) risk score in a population-based healthcare setting. MethodsWe used healthcare registry data and electronic medical records from the Central Denmark Region to calculate the new CAT risk score and the guideline-recommended Khorana score in patients with a first-time cancer diagnosis who initiated systemic cancer therapy. Patients were followed for six months after initiation of therapy. The outcome was any VTE identified through hospital discharge diagnoses. Discrimination was assessed using c-statistics. ResultsWe included 12,471 patients from 2012 through 2020. Of these, 416 (3.3%) developed VTE. The c-statistic was 0.71 (95% confidence interval [CI]: 0.68–0.74) for the new CAT score and 0.66 (95% CI: 0.63–0.70) for the Khorana score. The six-month cumulative VTE incidence was 5.0% in 6,175 patients classified as high risk by the new CAT score, compared with 1.7% in 6,296 patients classified as low risk. The six-month cumulative VTE incidence was 5.2% in 4,263 patients classified as high risk by the Khorana score, compared with 2.4% in 8,208 patients classified as low risk. ConclusionThe new CAT score had a discriminatory ability similar to that reported in the derivation study. The c-statistic was numerically higher than that of the Khorana score. Our findings support implementation of the new CAT score to identify ambulatory patients with cancer who are at high risk of VTE.

Multiple myeloma: retrospective assessment of routine thromboprophylaxis and utility of thrombotic risk scores

BackgroundThe high risk of venous thromboembolism (VTE) in multiple myeloma (MM) warrants primary thromboprophylaxis for most patients. Myeloma-specific thrombotic risk scores (TRSs), such as IMPEDE-VTE, SAVED, and PRISM, were developed to improve risk assessment and guide antithrombotic strategies. Their performance is variable and has not yet been tested in Latin America. ObjectivesWe aimed to assess the use of primary thromboprophylaxis, the incidence of VTE and bleeding events, and the effectiveness of TRSs in patients with newly diagnosed MM. MethodsThis was a retrospective, single-center study. Cumulative VTE rates and TRS performance were analyzed using survival and receiver operating characteristic curves. ResultsThe study included 250 newly diagnosed MM patients; the vast majority (98.6%) received aspirin as thromboprophylaxis. VTE occurred in 8% within the initial 6 months, increasing to 14.8% over a median follow-up of 19 months. High rates of major bleeding (4.8%) and clinically relevant nonmajor bleeding (4.4%) events were documented. A minimal proportion (0.8%, 0.5%, and 1.2%) of patients were classified as low risk by IMPEDE-VTE, PRISM, and SAVED scores, respectively. Only IMPEDE-VTE exhibited a trend for distinguishing between intermediate-risk (7.14%) and high-risk (13.2%) groups (P = .09). PRISM and SAVED scores showed limited utility. VTE did not impact survival. ConclusionAspirin as primary thromboprophylaxis carries an unacceptable risk of VTE and bleeding in patients at intermediate or high thrombotic risk. The IMPEDE-VTE score performed best, although without reaching statistical significance. We confirm that VTE does not portend poor overall survival in MM.

Rate and predictors of thromboprophylaxis in internal medicine wards: Results from the AURELIO study

BackgroundRandomized controlled trials suggest that prophylactic doses of anticoagulants effectively prevent venous thromboembolism (VTE) in hospitalized medical patients with high thromboembolic risk. However, no prospective studies exist regarding the real-world prevalence of prophylactic anticoagulant use. This prospective study aimed to determine the rate and predictors of thromboprophylaxis in an unselected population of patients hospitalized in medical departments. MethodsWe conducted a multicenter prospective observational study (AURELIO – rAte of venous thrombosis in acutely iLl patIents hOspitalized) to assess the rate of deep vein thrombosis (DVT) in unselected acutely ill patients hospitalized in medical wards using compression ultrasound (CUS) at admission and discharge. Additionally, we evaluated the rate of pharmacological thromboprophylaxis administration in this population and analyzed the thrombotic risk by assessing RAMs (Risk Assessment Models) such as the IMPROVE-VTE and PADUA scores following the clinician's decision to administer thromboprophylaxis. Patients with IMPROVE-VTE scores ≥3 and/or PADUA scores ≥4 were classified as high thrombotic risk; those with IMPROVE-VTE scores <3 and/or PADUA scores <4 were classified as low risk. ResultsWe recruited 2371 patients (1233 males [52 %] and 1138 females [48 %]; mean age 72 ± 16 years). The median length of hospitalization was 13 ± 12 days. Overall, 442/2371 (18.6 %) patients received prophylactic parenteral anticoagulants (subcutaneous low weight molecular heparin or fondaparinux once daily) at admission. Assessing the thrombotic risk of the population recruited 1016 (42.9 %) patients were classified as high risk and 1354 (57.1 %) were low risk. Among high-risk patients, 339/1016 (33.4 %) received anticoagulant prophylaxis compared to 103/1354 (7.6 %) low-risk patients. During hospitalization, 9 patients developed DVT, comprising 7 asymptomatic and 2 symptomatic cases of proximal DVT. Of these, 3 patients were on anticoagulant prophylaxis, while 6 were not. Among the high-risk population, 7 out of 1016 patients (0.7 %) experienced proximal DVT during hospitalization, with 2 out of these 7 (28 %) receiving anticoagulant thromboprophylaxis. In the low-risk population, 2 out of 1354 patients (0.2 %) developed DVT, with 1 out of these 2 (50 %) receiving anticoagulant thromboprophylaxis. Age, heart or respiratory failure, pneumonia, active neoplasia, previous VTE, reduced mobility, and absence of kidney failure were more frequent in patients receiving prophylaxis. Multivariable logistic regression identified age (RR 1.010; CI 95 % 1002–1019; p = 0.015), heart/respiratory failure (RR 1.609; CI 95 % 1248–2075; p < 0.0001), active neoplasia (RR 2.041; CI 95 % 1222–2141; p < 0.0001), pneumonia (RR 1.618; CI 95 % 1557–2676; p < 0.0001), previous VTE (RR 1.954; CI 95 % 1222–3125; p < 0.0001), and reduced mobility (RR 4.674; CI 95 % 3700–5905; p < 0.0001) as independent predictors of thromboprophylaxis. ConclusionsThis study, conducted without pre-established thromboembolic risk scores, offers a comprehensive view of venous thromboembolism prophylaxis in medical patients with acute conditions hospitalized in internal medicine departments. It reveals that advanced age, heart or respiratory failure, active cancer, pneumonia, previous VTE, and reduced mobility are predictors that may influence the decision to administer thromboprophylaxis in these patients.

Janus kinase inhibitors versus tumor necrosis factor inhibitors in rheumatoid arthritis: meta-analytical comparison of efficacy and safety.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized by persistent inflammation leading to progressively worse disability. Janus kinase (JAK) inhibitors and tumor necrosis factor (TNF) inhibitors are pivotal in RA treatment, yet their comparative efficacy remains underexplored. This study aimed to compare the efficacy and safety of JAK inhibitors and TNF inhibitors in treating RA using data from randomized controlled trials (RCTs). A meta-analysis and outcomes analysis were based on results of the Health Assessment Questionnaire Disability Index (HAQ-DI), Clinical Disease Activity Index (CDAI), Visual Analogue Scale (VAS), and Patient Global Assessment Scale (PtGA) and other indices as incidences of venous thromboembolism (VTE) and malignancy. The JAK inhibitors caused a statistically significant improvement in the HAQ-DI score [MD = 0.08, 95% CI (0.03, 0.12), p = 0.0008] compared with the TNF inhibitors. However, no significant difference was observed between the two drug classes in the CDAI score [MD = -2.03, 95% CI (-9.27, 5.22), p = 0.58]. JAK inhibitors were associated with an increase in the VAS score [MD = 3.62, 95% CI (0.86, 6.38), p = 0.01], but there was no significant difference in the PtGA score [MD = 1.91, 95% CI (-3.25, 7.08), p = 0.47]. JAK inhibitors demonstrated superior efficacy in improving the functional status and reducing the disease activity in RA patients compared with TNF inhibitors. Both drug classes exhibited comparable safety profiles for VTE and malignancies, though JAK inhibitors had a higher risk for thromboembolism.

What Constitutes High Risk for Venous Thromboembolism? Comparing Approaches to Determining an Appropriate Threshold.

Guidelines recommend pharmacological venous thromboembolism (VTE) prophylaxis only for high-risk patients, but the probability of VTE considered "high-risk" is not specified. Our objective was to define an appropriate probability threshold (or range) for VTE risk stratification and corresponding prophylaxis in medical inpatients. Patients were adults admitted to any of 10 Cleveland Clinic Health System hospitals between December 2020 and August 2021 (N = 41,036). Hospital medicine physicians and internal medicine residents from included hospitals were surveyed between June and November 2023 (N = 214). We compared five approaches to determining a threshold: decision analysis, maximizing the sensitivity and specificity of a logistic regression model, deriving a probability from a point-based model, surveying physicians' understanding of VTE risk, and deriving a probability from physician behavior. For each approach, we determined the probability threshold above which a patient would be considered high-risk for VTE. We applied each threshold to the Cleveland Clinic VTE risk assessment model (CCM) and calculated the percentage of the 41,036 patients in our cohort who would be considered eligible for prophylaxis due to their high-risk status. We compared these hypothetical prophylaxis rates with physicians' observed prophylaxis rates. The different approaches yielded thresholds ranging from 0.3% to 5.4%, corresponding inversely with hypothetical prophylaxis rates of 0.2% to 75%. Multiple thresholds clustered between 0.52% to 0.55%, suggesting an average hypothetical prophylaxis rate of approximately 30%, whereas physicians' observed prophylaxis rates ranged from 48% to 76%. Multiple approaches to determining a probability threshold for VTE prophylaxis converged to suggest an optimal threshold of approximately 0.5%. Other approaches yielded extreme thresholds that are unrealistic for clinical practice. Physicians prescribed prophylaxis much more frequently than the suggested rate of 30%, indicating opportunity to reduce unnecessary prophylaxis. To aid in these efforts, guidelines should explicitly quantify high-risk.

The Efficacy and Safety of DOACs in Inherited Antithrombin Deficiency: A Cohort Study from a Tertiary Referral Center.

Individuals with inherited antithrombin deficiency (IATD) have a high risk of venous thromboembolism (VTE). Most VTEs are managed with direct oral anticoagulants (DOACs), but the utility of DOACs in antithrombin deficiency (ATD) is unreported. Patients with IATD treated with DOAC were identified from our institutions' IATD registry. We assessed patients' characteristics, ATD type, and initial VTE characteristics, thrombosis recurrence and bleeding rates. Thirty-three patients received DOACs for 73 (38.5-111.5) months (median (interquartile range)). Prior to taking DOACs, 12 (36%) patients had VTE recurrence: these occurred after anticoagulation was ceased (4), nonadherence to VKA prior to DOAC use (3), or during heparin use in pregnancy (5). There were no VTE recurrences on standard-dose DOAC, except in a noncompliant patient receiving dabigatran. There was one recurrence with compliant DOAC use-a patient receiving rivaroxaban 10 mg. Six (18%) patients experienced clinically relevant bleeding, which was predominantly menorrhagia (5/6). One major bleeding event, intracranial hemorrhage, occurred in a patient receiving full-dose rivaroxaban who had refractory hypertension (0.5 events/100 patient-years). In this cohort, compliant DOAC users had an overall VTE recurrence rate of 0.5/100 patient-years, whereas with low-dose DOACs the event rate was 3.5/100 patient-years. Standard-dose DOACs appear efficacious and relatively safe in IATD.

Atrial fibrillation management in older hospitalized patients: Evidence of a poor oral anticoagulants prescriptive attitude from the Italian REPOSI registry

Atrial fibrillation (AF) prevalence increases in older patients which also show a high thromboembolic risk. Oral anticoagulants (OACs) are recommended to prevent cardioembolic events and direct oral anticoagulants (DOACs) improved anti-thrombotic treatment. However, the benefits/risks of anticoagulant in older patients still need to be completely defined.This retrospective observational study aimed to describe the treatment with OACs in older AF hospitalized patients, and to identify factors influencing OAC therapy or discontinuation using the REgistro Politerapie SIMI.Univariate and multivariate logistic regression models were applied to identify predictors of OACs treatment and discontinuation. Cox proportional hazards models were performed to evaluate one-year mortality by treatment groups.AF patients were 1,128(26.5 %) at discharge and 1,098(97.3 %) required OAC treatment; about half of them (N = 528;48.1 %) were no-OACs users; 236(21.5 %) and 334(30.4 %) used DOACs and VKA, respectively.Increasing DOACs use was observed during the study period. Predictors of OACs treatment were: BMI (OR:1.04; 95 %CI:1.01–1.07), Barthel index (OR:1.01; 95 %CI:1.01–1.02), medications number (OR:1.07; 95 %CI:1.01–1.13). Conversely, a lower probability was found in patients with a high CIR.S (OR:0.59; 95 %CI:0.36–0.97) and neoplasm (OR:0.57; 95 %CI:0.37–0.88). Hospital stay (OR:1.02; 95 %CI:1.01–1.05), neoplasm (OR:2.25; 95 %CI:1.07–4.70) and INR (OR:1.21; 95 %CI:1.05–1.40) increased OACs discontinuation. A lower discontinuation was observed in dyslipidemic patients (OR:0.18; 95 %CI:0.04–0.82) and heart failure (OR:0.38; 95 %CI:0.21–0.70). Among AF patients, 157(14.3 %) died during the follow-up year. Age (HR = 1.05; 95 %CI = 1.03–1.08) and CIR.S (HR = 2.54; 95 %CI = 1.53–4.21) were associated with a greater mortality risk. In conclusion, critical issues related to the underuse and discontinuation of OACs therapy in hospitalized older patients were highlighted.

Comparative Analysis of Muscle Activity and Circulatory Dynamics: A Crossover Study Using Leg Exercise Apparatus and Ergometer.

Background and Objectives: Bedridden patients are at a high risk of venous thromboembolism (VTE). Passive devices such as elastic compression stockings and intermittent pneumatic compression are common. Leg exercise apparatus (LEX) is an active device designed to prevent VTE by effectively contracting the soleus muscle and is therefore expected to be effective in preventing disuse of the lower limbs. However, few studies have been conducted on the kinematic properties of LEX. Therefore, this study aimed to compare the exercise characteristics of LEX with those of an ergometer, which is commonly used as a lower-limb exercise device, and examine its effect on the two domains of muscle activity and circulatory dynamics. Materials and Methods: This study used a crossover design in which each participant performed both exercises to evaluate the exercise characteristics of each device. Fifteen healthy adults performed exercises with LEX and an ergometer (Terasu Erugo, SDG Co., Ltd., Tokyo, Japan) for 5 min each and rested for 10 min after each exercise. Muscle activity was measured using surface electromyography (Clinical DTS, Noraxon, Scottsdale, AZ, USA), and circulatory dynamics were recorded using a non-invasive impedance cardiac output meter (Physioflow Enduro, Manatec Biomedical, Paris, France). The primary outcome was the mean percentage of maximum voluntary contraction (%MVC) of the soleus muscle during exercise. Results: The mean %MVC of the soleus muscle was significantly higher in the LEX group, whereas no significant differences were observed across the periods and sequences. Heart rate, stroke volume, and cardiac output increased during exercise and decreased thereafter; however, the differences between the devices were not significant. Conclusions: LEX may not only have a higher thromboprophylaxis effect, but also a higher effect on preventing muscle atrophy as a lower-extremity exercise device. Additionally, LEX could potentially be used safely in patients who need to be monitored for changes in circulatory dynamics.

The burden of atrial fibrillation on emergency medical services: A population-based cohort study

BackgroundAtrial fibrillation (AF) is a growing burden on healthcare resources, despite improvements in prevention and management. AF is a common cause of hospitalisation, and Emergency Medical Services (EMS) use. However, there is a paucity of data describing the burden of AF on EMS. We aimed to determine the prevalence, characteristics, and outcomes of patients presenting with AF to EMS using a large population-based sample. MethodsConsecutive attendances for AF in Victoria, Australia (January 2015–June 2019) were included if patients had a diagnosis of “AF” or “arrhythmia” with AF on electrocardiogram. Data were individually linked to emergency, hospital, and mortality records. ResultsOf 2,613,056 EMS attendances, 16,525 were a first attendance for AF and linked to hospital records. Median (IQR) age was 76 (67,84) years (43% female). Seventy-eight percent had high thromboembolic risk (CHA2DS2-VASc score ≥ 2), and 72% had a heart rate ≥ 100 bpm. Forty-two percent of patients received no treatment by paramedics and 99.4% were transported to hospital. Fifty-three percent were discharged from ED. Median length of hospital stay was 2 days. Of 2542 cases reattended for AF, 19% occurred within 30 days, with increased odds for females and those of low socioeconomic status. Overall, 24% died during the study period, 12% within 30 days. Increasing age, heart failure, stroke, COPD, and low socioeconomic status increased the odds of 30-day mortality. ConclusionsEMS utilisation for AF is common and associated with frequent reattendance. Further studies are required to investigate novel pathways of care to reduce AF burden on healthcare systems.