Benefits and harms of direct oral anticoagulation and low molecular weight heparin for thromboprophylaxis in patients undergoing non-cardiac surgery: systematic review and network meta-analysis of randomised trials.

OBJECTIVE: To systematically compare the effect of direct oral anticoagulants and low molecular weight heparin for thromboprophylaxis on the benefits and harms to patients undergoing non-cardiac surgery. DESIGN: Systematic review and network meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL), up to August 2021. REVIEW METHODS: Randomised controlled trials in adults undergoing non-cardiac surgery were selected, comparing low molecular weight heparin (prophylactic (low) or higher dose) with direct oral anticoagulants or with no active treatment. Main outcomes were symptomatic venous thromboembolism, symptomatic pulmonary embolism, and major bleeding. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for network meta-analyses. Abstracts and full texts were screened independently in duplicate. Data were abstracted on study participants, interventions, and outcomes, and risk of bias was assessed independently in duplicate. Frequentist network meta-analysis with multivariate random effects models provided odds ratios with 95% confidence intervals, and GRADE (grading of recommendations, assessment, development, and evaluation) assessments indicated the certainty of the evidence. RESULTS: 68 randomised controlled trials were included (51 orthopaedic, 10 general, four gynaecological, two thoracic, and one urological surgery), involving 45 445 patients. Low dose (odds ratio 0.33, 95% confidence interval 0.16 to 0.67) and high dose (0.19, 0.07 to 0.54) low molecular weight heparin, and direct oral anticoagulants (0.17, 0.07 to 0.41) reduced symptomatic venous thromboembolism compared with no active treatment, with absolute risk differences of 1-100 per 1000 patients, depending on baseline risks (certainty of evidence, moderate to high). None of the active agents reduced symptomatic pulmonary embolism (certainty of evidence, low to moderate). Direct oral anticoagulants and low molecular weight heparin were associated with a 2-3-fold increase in the odds of major bleeding compared with no active treatment (certainty of evidence, moderate to high), with absolute risk differences as high as 50 per 1000 in patients at high risk. Compared with low dose low molecular weight heparin, high dose low molecular weight heparin did not reduce symptomatic venous thromboembolism (0.57, 0.26 to 1.27) but increased major bleeding (1.87, 1.06 to 3.31); direct oral anticoagulants reduced symptomatic venous thromboembolism (0.53, 0.32 to 0.89) and did not increase major bleeding (1.23, 0.89 to 1.69). CONCLUSIONS: Direct oral anticoagulants and low molecular weight heparin reduced venous thromboembolism compared with no active treatment but probably increased major bleeding to a similar extent. Direct oral anticoagulants probably prevent symptomatic venous thromboembolism to a greater extent than prophylactic low molecular weight heparin. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018106181.

How can Secondary Thromboprophylaxis in High-Risk Pregnant Patients be Improved?

Low-molecular-weight heparin (LMWH) is suggested for thromboprophylaxis in pregnant women with previous venous thromboembolism (VTE). Anyway, there is only limited amount of studies evaluating the effect of LMWH on hemostatic parameters during pregnancy of patients with previous VTE and the need of secondary thromboprophylaxis. We therefore provide results of prospective and longitudinal assessment of changes in hemostasis in high-risk pregnant women at four times during pregnancy (T1-T4) and one time after the postpartum period (T5) used for individualized modification of thromboprophylaxis. In this study, the results of coagulation factor VIII (FVIII) and protein S (PS) activity, ProC Global ratio and anti-Xa activity were evaluated. Despite the thromboprophylaxis, an increased predisposition to thromboembolic complications was detected (significant increase in FVIII activity and decrease in PS function, ProC Global ratio not normalized even after the postpartum period - p < .0001 between controls and T5 for PS and ProC Global). These results indicate that hemostasis may not be restored even 6 to 8 weeks after delivery and pose the question when is it safe to withdraw the anticoagulant thromboprophylaxis in high-risk patients with prior VTE.

Use of direct oral anticoagulants for postoperative venous thromboembolism prophylaxis after surgery for gynecologic malignancies.

Venous thromboembolism is a preventable cause of postoperative mortality in patients undergoing surgery for malignancy. Current standard of care based on international guideline recommends 28 days of extended thromboprophylaxis after major abdominal and pelvic surgery for malignancies with unfractionated heparin or low molecular weight heparin. Direct oral anticoagulants have been approved for the treatment of venous thromboembolism in the general population. This regimen has a significant advantage over other types of anticoagulation regimens, particularly being administered by non-parenteral routes and without the need for laboratory monitoring. In this review, we evaluate the role of direct anticoagulation and provide an update on completed and ongoing clinical trials.

Mechanisms of COVID-19-induced kidney injury and current pharmacotherapies.

The COVID-19 pandemic created a worldwide debilitating health crisis with the entire humanity suffering from the deleterious effects associated with the high infectivity and mortality rates. While significant evidence is currently available online and targets various aspects of the disease, both inflammatory and noninflammatory kidney manifestations secondary to COVID-19 infection are still largely underrepresented. In this review, we summarized current knowledge about COVID-19-related kidney manifestations, their pathologic mechanisms as well as various pharmacotherapies used to treat patients with COVID-19. We also shed light on the effect of these medications on kidney functions that can further enhance renal damage secondary to the illness.

Evaluating compliance of extended venous thromboembolism prophylaxis following abdominopelvic surgery for cancer: A multidisciplinary quality improvement project.

BACKGROUND AND OBJECTIVES: Despite quality evidence supporting postoperative extended venous thromboembolism prophylaxis (eVTEp) following abdominopelvic cancer surgery, baseline use of eVTEp at our institution was 3%. Our project aim was to improve the proportion of patients prescribed eVTEp following surgery for gynecologic, hepatobiliary, and colorectal cancers by a 30% absolute increase. METHODS: We performed an interrupted time series study using quality improvement methodology. Postoperative order sets, pre-printed prescriptions, process checklists, and multimodal education were introduced. Process and outcome data were collected and analyzed on statistical process control charts. RESULTS: We included 324 patients with gynecologic and hepatobiliary cancers. Despite efforts to include them, the colorectal team did not participate. The monthly mean order set-use was 58% (SD = 14%), by specialty: gynecology 79%, hepatobiliary 47%. The proportion of patients prescribed eVTEp increased from 3% to 70% (SD = 14%). The target goal was surpassed and sustained by both cohorts. Patient compliance was 73% (n = 117/160, SD = 16%). Of those who stopped eVTEp early, 45% (n = 14/31) objected because of the injectable nature. Bleeding events were infrequent (0.6%, n = 2/324). CONCLUSIONS: Three process changes and multimodal education resulted in a significant increase in eVTEp use. Failure to identify improvement champions limited project expansion to colorectal patients. Patient compliance was largely limited by the injectable nature of the medication.

Dual mechanical and pharmacological thromboprophylaxis decreases risk of pulmonary embolus after laparotomy for gynecologic malignancies.

OBJECTIVES: Patients with gynecologic malignancies have high rates of post-operative venous thromboembolism. Currently, there is no consensus for peri-operative thromboprophylaxis specific to gynecologic oncology. We aimed to compare rates of symptomatic pulmonary embolus within 30 days post-operatively, and to identify risk factors for pulmonary embolus. METHODS: The Division of Gynecologic Oncology at Sunnybrook Health Sciences Centre implemented dual thromboprophylaxis for laparotomies in December 2017. We conducted a prospective study of laparotomies for gynecologic malignancies from December 2017 to October 2018, with comparison to historical cohort from January 2016 to November 2017 using the institutional National Surgical Quality Improvement Program database (NSQIP). Pre-intervention, patients received low molecular weight heparin during admission and extended 28-day prophylaxis was continued at the surgeon's discretion. Post-intervention, all patients received both mechanical thromboprophylaxis with sequential compression devices during admission and 28-day prophylaxis with low molecular weight heparin. RESULTS: There were 371 and 163 laparotomies pre- and post-intervention, respectively. Patient characteristics (age, body mass index, diabetes, smoking, tumor stage), rate of malignant cases, operative blood loss and duration, and length of stay were similar between groups. After implementation, pulmonary emboli rates decreased from 5.1% to 0% (p=0.001). There were more cytoreductive procedures pre-intervention (p≤0.0001) but surgical complexity scores were similar (p=0.82). Univariate analysis revealed that surgery pre-intervention (OR 4.25, 95% CI 1.04 to 17.43, p=0.04), length of stay ≥5 days (OR 11.94, 95% CI 2.65 to 53.92, p=0.002), and operative blood loss ≥500 mL (OR 2.85, 95% CI 1.05 to 7.8, p=0.04) increased risk of pulmonary embolus. On multivariable analysis, surgery pre-intervention remained associated with more pulmonary emboli (OR 4.16, 95% CI 1.03 to 16.79, p=0.045), when adjusting for operative blood loss. CONCLUSION: Dual thromboprophylaxis after laparotomy significantly reduced rates of pulmonary embolus in this high-risk patient population.

Early Chemoprophylaxis Against Venous Thromboembolism in Patients With Traumatic Brain Injury.

INTRODUCTION: Timing to start of chemoprophylaxis for venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) remains controversial. We hypothesize that early administration is not associated with increased intracranial hemorrhage. METHODS: A retrospective study of adult patients with TBI following blunt injury was performed. Patients with penetrating brain injury, any moderate/severe organ injury other than the brain, need for craniotomy/craniectomy, death within 24 hours of admission, or progression of bleed on 6 hour follow-up head computed tomography scan were excluded. Patients were divided into early (≤24 hours) and late (>24 hours) cohorts based on time to initiation of chemoprophylaxis. Progression of bleed was the primary outcome. RESULTS: 264 patients were enrolled, 40% of whom were in the early cohort. The average time to VTE prophylaxis initiation was 17 hours and 47 hours in the early and late groups, respectively (P < .0001). There was no difference in progression of bleed (5.6% vs. 7%, P = .67), craniectomy/-craniotomy rate (1.9% vs. 2.5%, P = .81), or VTE rate (0% vs. 2.5%, P = .1). CONCLUSION: Early chemoprophylaxis is not associated with progression of hemorrhage or need for neurosurgical intervention in patients with TBI and a stable head CT 7 hours following injury.

The therapeutic efficacy and safety of traditional Chinese medicine injection combined with low-molecular-weight heparin on the acute lower extremity deep venous thrombosis: A protocol for systematic review and network meta-analysis.

BACKGROUND: Lower extremity deep venous thrombosis (LEDVT) of lower extremities is one of the common clinical diseases. Lack of a timely treatment in the acute stage easily causes pulmonary embolism, thus seriously threatening patients' life. Low-molecular-weight heparin (LMWH), as a new generation of heparin-based anticoagulant and antithrombotic drug, is now commonly used in the clinical treatment of acute lower extremity deep venous thrombosis (ALEDVT). Relevant randomized controlled trials (RCTs) have reported the therapeutic efficacy and safety of Traditional Chinese medicine injection (TCMJ) combined with LMWH on ALDVT, although their conclusions remain controversial. In addition, the efficacy of various TCMJs has rarely been analyzed and compared. This study aims to evaluate the therapeutic efficacy and safety of TCMJ combined with LMWH on ALEDVT through a network meta-analysis. METHODS: RCTs reporting TCMJ combined with LMWH and LMWH along for the treatment of ALEDVT published before November 2021 will be searched in online databases, including the Cochrane Library, Embase, PubMed, Web of Science, Wanfang, Chongqing VIP Chinese Science and Technology Periodical Database, Chinese Biomedical Literature Database, and Chinese National Knowledge Infrastructure. Two investigators will be independently responsible for literature screening, data extraction, and quality evaluation according to Cochrane's risk of bias assessment tool. R software will be used to perform a network Meta-analysis. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide high-quality, evidence-based medical evidence for comparing the therapeutic efficacy and safety of TCMJ combined with LMWH and LMWH alone on ALEDVT.

PICO Questions and DELPHI Methodology for the Management of Venous Thromboembolism Associated with COVID-19.

Patients with coronavirus disease 2019 (COVID-19) have a higher risk of venous thromboembolic disease (VTE) than patients with other infectious or inflammatory diseases, both as macrothrombosis (pulmonar embolism and deep vein thrombosis) or microthrombosis. However, the use of anticoagulation in this scenario remains controversial. This is a project that used DELPHI methodology to answer PICO questions related to anticoagulation in patients with COVID-19. The objective was to reach a consensus among multidisciplinary VTE experts providing answers to those PICO questions. Seven PICO questions regarding patients with COVID-19 responded with a broad consensus: 1. It is recommended to avoid pharmacological thromboprophylaxis in most COVID-19 patients not requiring hospital admission; 2. In most hospitalized patients for COVID-19 who are receiving oral anticoagulants before admission, it is recommended to replace them by low molecular weight heparin (LMWH) at therapeutic doses; 3. Thromboprophylaxis with LMWH at standard doses is suggested for COVID-19 patients admitted to a conventional hospital ward; 4. Standard-doses thromboprophylaxis with LMWH is recommended for COVID-19 patients requiring admission to Intensive Care Unit; 5. It is recommended not to determine D-Dimer levels routinely in COVID-19 hospitalized patients to select those in whom VTE should be suspected, or as a part of the diagnostic algorithm to rule out or confirm a VTE event; 6. It is recommended to discontinue pharmacological thromboprophylaxis at discharge in most patients hospitalized for COVID-19; 7. It is recommended to withdraw anticoagulant treatment after 3 months in most patients with a VTE event associated with COVID-19. The combination of PICO questions and DELPHI methodology provides a consensus on different recommendations for anticoagulation management in patients with COVID-19.

Anticoagulation for COVID-19 Patients: A Bird's-Eye View.

Coronavirus disease 2019 (COVID-19) is a systemic disease that can be life-threatening involving immune and inflammatory responses, and that can result in potentially lethal complications, including venous thrombo-embolism (VTE). Forming an integrative approach to thrombo-prophylaxis and coagulation treatment for COVID-19 patients ensues. We aim at reviewing the literature for anticoagulation in the setting of COVID-19 infection to provide a summary on anticoagulation for this patient population. COVID-19 infection is associated with a state of continuous inflammation, which results in macrophage activation syndrome and an increased rate of thrombosis. Risk assessment models to predict the risk of thrombosis in critically ill patients have not yet been validated. Currently published guidelines suggest the use of prophylactic intensity over intermediate intensity or therapeutic intensity anticoagulant for patients with critical illness or acute illness related to COVID-19 infection. Critically ill COVID-19 patients who are diagnosed with acute VTE are considered to have a provoking factor, and, therefore, treatment duration should be at least 3 months. Patients with proximal deep venous thrombosis or pulmonary embolism should receive parenteral over oral anticoagulants with low-molecular-weight heparin or fondaparinux preferred over unfractionated heparin. In patients with impending hemodynamic compromise due to PE, and who are not at increased risk for bleeding, reperfusion may be necessary. Internists should remain updated on new emerging evidence regarding anticoagulation for COVID-19 patients. Awaiting these findings, we invite internists to perform individualized decisions that are unique for every patient and to base them on clinical judgment for risk assessment.

Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19: The HEP-COVID Randomized Clinical Trial.

Importance: Hospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown. Objective: To evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19. Design, Setting, and Participants: The HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US. Interventions: Patients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m2) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status. Main Outcomes and Measures: The primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imaging, laboratory, and health record data. Results: Of 257 patients randomized, 253 were included in the analysis (mean [SD] age, 66.7 [14.0] years; men, 136 [53.8%]; women, 117 [46.2%]); 249 patients (98.4%) met inclusion criteria based on D-dimer elevation and 83 patients (32.8%) were stratified as ICU-level care. There were 124 patients (49%) in the standard-dose vs 129 patients (51%) in the therapeutic-dose group. The primary efficacy outcome was met in 52 of 124 patients (41.9%) (28.2% VTE, 3.2% ATE, 25.0% death) with standard-dose heparins vs 37 of 129 patients (28.7%) (11.7% VTE, 3.2% ATE, 19.4% death) with therapeutic-dose LMWH (relative risk [RR], 0.68; 95% CI, 0.49-0.96; P = .03), including a reduction in thromboembolism (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; P < .001). The incidence of major bleeding was 1.6% with standard-dose vs 4.7% with therapeutic-dose heparins (RR, 2.88; 95% CI, 0.59-14.02; P = .17). The primary efficacy outcome was reduced in non-ICU patients (36.1% vs 16.7%; RR, 0.46; 95% CI, 0.27-0.81; P = .004) but not ICU patients (55.3% vs 51.1%; RR, 0.92; 95% CI, 0.62-1.39; P = .71). Conclusions and Relevance: In this randomized clinical trial, therapeutic-dose LMWH reduced major thromboembolism and death compared with institutional standard heparin thromboprophylaxis among inpatients with COVID-19 with very elevated D-dimer levels. The treatment effect was not seen in ICU patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04401293.

Microneedle based transcutaneous delivery of low molecular weight heparin.

This study aimed to fabricate and characterize polymeric microneedle patches for rapid and non-invasive administration of enoxaparin across skin layers. The patches comprising of PVA, sorbitol and enoxaparin sodium were prepared by employing micromolding technique. Formulated patches were characterized physicochemically by folding endurance, dimensional analysis and swelling study, morphologically by optical and scanning electron microscopy and thermally by thermogravimetric analysis. Moreover, performance efficiency of prepared polymeric device was analyzed by in-vitro drug release study and piercing ability. Prepared patches showed appropriate dimensions and folding endurance (i.e., ~1100) indicating satisfactory integrity of polymeric device. Patches exhibited appropriately distanced needles with pointed tips in optical and scanning electron microscopy analysis. Thermogravimetric analysis proved thermal stability of formulation ingredients and prepared patches. Swelling percentage was >110 % suggesting that prepared formulation would allow penetration of physiological fluids in its polymeric network. Maximum (~89%) drug was released within ~2 hours during in-vitro release study. In-vitro piercing ability experiments suggested that prepared patches successfully breached skin barrier stratum corneum. It is concluded that prepared microneedle device can serve as a potential alternative of currently employed invasive parenteral route for rapid and efficient administration of enoxaparin sodium in the systemic circulation.

Meta-analysis of Different Pressing Time on the Incidence of Subcutaneous Hemorrhage of Low Molecular Weight Heparin Administration.

To investigate the effect of different pressing time on the incidence of subcutaneous hemorrhage of low molecular weight heparin (LMWH) administration by meta-analysis. Cochrane Library, PubMed, MEDLINE, CINAHL, EMbase, Springer, EBSCO, China Biomedical Literature Database, CNKI, Wanfang Database, and VIP Database were searched. To screen the literature of randomized controlled trials with different pressing time in patients with subcutaneous LMWH injection from the establishment of the database to December 2020. The quality of the literature was evaluated and the data were extracted. Meta-analysis was performed by RevMan 5.3. A total of 17 randomized controlled trials were included. Meta-analysis showed that the bleeding rate of pressing for 5 min odds ratio (OR = 3.89, 95% confidence interval [CI]: 2.68-5.64, P < .05) or pressing for 10 min (OR = 1.99, 95% CI: 1.34-2.95) was significantly lower than that of pressing for 3 min. Moreover, the bleeding rate was significantly lower in the 5 min pressing (OR = 1.47, 95% CI: 1.18-1.82) and 10 min pressing(OR = 2.12, 95% CI: 1.61-2.77) than in the no compression group. It is the most suitable time to press 5 min after subcutaneous LMWH injection, which can better control the incidence of bleeding.

[Superficial Vein Thrombosis]. / Oberflächliche Venenthrombose.

EPIDEMIOLOGY AND RISK FACTORS: A large German registry on superficial vein thrombosis (SVT) documents that risk profiles, clinical presentation and treatment patterns are highly variable in patients with SVT, including a large variation in anticoagulation treatment modalities, intensities and durations. Inspite of a high percentage of initial anticoagulation there is a substantial risk of subsequent venous thromboembolism (VTE), recurrences or extension after three months. Inspite of current guideline recommendations, one third of the patients receives heparins, oral anticoagulants or no anticoagulation at all. At initial presentation about one quarter of the patients with SVT have a concomitant, frequently asymptomatic VTE. Risk factors for this complication include prior hospitalization, immobilization, prior VTE, autoimmune disorders, higher age, cancer and SVT occurring in a non-varicose veins or SVT-extension into the perforator veins. These risk factors are also associated with thromboembolic complications during follow-up. TREATMENT: Based on a large placebo-controlled trial with clinical endpoints (The CALISTO-Study), guidelines recommend Fondaparinux 2.5 mg once daily administered over 4 to 6 weeks. Alternatively, an intermediate dose of low molecular weight heparin can be considered. In high-risk patients, rivaroxaban 10 mg once daily was noninferior compared to Fondaparinux. A rebound of VTE recurrences was observed in both study arms after treatment had been discontinued after 45 days. Further studies are required to determine whether treatment needs to be extended beyond 45 days in high-risk patients.

Comparison of standard prophylactic and preemptive therapeutic low molecular weight heparin treatments in hospitalized patients with COVID-19.

NTRODUCTION: Anticoagulant treatment approach in patients with COVID-19 is not well studied and not standardized. We aimed to compare the effects of standard prophylactic and pre-emptive therapeutic Low-Molecular-weight Heparin (LMWH) treatment approaches on mortality in patients with COVID-19. PATIENTS AND METHODS: This retrospective and single-centre study includes patients aged ≥ 18 years, who were diagnosed with COVID-19 and treated with LMWH during the hospital stay. Therapeutic dose of LMWH was defined as 1 mg/kg subcutaneously twice daily and prophylactic dose of LMWH was defined as 40 mg subcutaneously once daily. RESULTS: Among the 336 patients diagnosed with COVID-19 pneumonia, 115 patients, who received LMWH were included in the study. The mean age was 58.6 ± 13.3 and 58 (50.4 %) of the patients were male. Sixty-nine (60 %) of the patients were treated with prophylactic and 46 (40 %) therapeutic LMWH.In-hospital mortality was not different between patients treated therapeutic LMWH and prophylactic LMWH by the multivariate regression analysis (OR=2.187, 95% CI 0.484-9.880, p=0.309) and the propensity score modelling (OR=1.586, 95% CI 0.400-6.289, p=0.512.)CONCLUSION: Clinicians should consider the potential risks and benefits of standard prophylactic and pre-emptive therapeutic LMWH. Therefore, anticoagulant therapy should be individualized in patients with COVID-19 (Tab. 3, Ref. 28).

Association of Parenteral Anticoagulation Therapy With Outcomes in Non-ST-Segment Elevation Acute Coronary Syndrome Patients Without Invasive Therapy: Findings from the Improving Care for Cardiovascular Disease in China (CCC) project.

Our previous study showed that parenteral anticoagulation therapy (PACT) in the context of aggressive antiplatelet therapy failed to improve clinical outcomes in patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome (NSTE-ACS). However, the role of PACT in patients managed medically remains unknown. This observational cohort study enrolled patients with NSTE-ACS receiving medical therapy from November 2014 to June 2017 in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. Eligible patients were included in the PACT group and non-PACT group. The primary outcomes were in-hospital all-cause mortality and major bleeding. The secondary outcome included minor bleeding. Among 23,726 patients, 8,845 eligible patients who received medical therapy were enrolled. After adjusting the potential confounders, PACT was not associated with a lower risk of in-hospital all-cause mortality (adjusted odds ratio (OR), 1.25; 95% confidence interval (CI), 0.92-1.71; P = 0.151). Additionally, PACT did not increase the incidence of major bleeding or minor bleeding (major bleeding: adjusted OR, 1.04; 95% CI, 0.80-1.35; P = 0.763; minor bleeding: adjusted OR, 1.27; 95% CI, 0.91-1.75; P = 0.156). The propensity score analysis confirmed the primary analyses. In patients with NSTE-ACS receiving antiplatelet therapy, PACT was not associated with a lower risk of in-hospital all-cause mortality or a higher bleeding risk in patients with NSTE-ACS receiving non-invasive therapies and concurrent antiplatelet strategies. Randomized clinical trials are warranted to reevaluate the safety and efficacy of PACT in all patients with NSTE-ACS who receive noninvasive therapies and current antithrombotic strategies.

Early prophylactic anticoagulation after subarachnoid hemorrhage decreases systemic ischemia and improves outcome.

BACKGROUND: In neurosurgical perioperative treatment, especially in connection with subarachnoid hemorrhage (SAH), the prophylactic anticoagulation (AC) regimen is still considered controversial. The goal of this retrospective study was to assess how the time point of low-molecular-weight heparin (LMWH) initiation (ToH) affects ischemic and hemorrhagic events after SAH. METHODS: 370 patients who received acute treatment for non-traumatic SAH between 2011 and 2018 were included, and 208 patients were followed up after 12 months. We assessed how the ToH affects ischemic and hemorrhagic events as well as outcome scores. Statistical analysis was performed using the Mann-Whitney U-Test, the chi-squared test, Fisher's exact test, and univariate binomial logistic regression. P-values below 0.05 were considered statistically significant. RESULTS: The incidence of systemic ischemia was 4.6%, cerebral ischemia 33.5%, and intracranial rebleeding 14.6%. Delaying ToH (measured in hours) increases systemic ischemia (p = 0.009). The odds ratio for the impact of delayed anticoagulation on systemic ischemia is 1.013 per hour (95%CI of OR 1.001-1.024). ToH has no influence on cerebral ischemia or intracranial rebleeding. Early anticoagulation was associated with a more favorable Glasgow Outcome Score 12 months after discharge (ToH within 48 h: p = 0.006). ToH did not affect mortality or readmission rates. CONCLUSIONS: Initiating prophylactic AC with LMWH later than 48 h after aneurysm repair or admission impairs outcomes 12 months after discharge. It might be safe for patients with non-traumatic SAH to be anticoagulated with prophylactic doses of heparin within 24 h after admission or the treatment of source of bleeding (SoB). Early AC with prophylactic LMWH does not promote rebleeding.

Venous Thromboembolic Prophylaxis After Total Hip and Knee Arthroplasty.

➤: The selection of an agent for prophylaxis against venous thromboembolism (VTE) is a balance between efficacy and safety. The goal is to prevent symptomatic VTE while limiting the risk of bleeding. ➤: The optimal agent for VTE prophylaxis has not been identified. The American College of Chest Physicians guidelines recommend that, after total hip or total knee arthroplasty, patients receive at least 10 to 14 days of 1 of the following prophylaxis agents: aspirin, adjusted-dose vitamin K antagonist, apixaban, dabigatran, fondaparinux, low-molecular-weight heparin, low-dose unfractionated heparin, rivaroxaban, or portable home mechanical compression. ➤: The use of aspirin for VTE prophylaxis has increased in popularity over the past decade because it is effective, and it is an oral agent that does not require monitoring. The true efficacy of aspirin needs to be determined in multicenter randomized clinical trials. ➤: Validated risk stratification protocols are essential to identify the safest and most effective regimen for VTE prophylaxis for individual patients. There is no consensus regarding the optimal method for risk stratification; the selection of a prophylaxis agent should be determined by shared decision-making with the patient to balance the risk of thrombosis versus bleeding. ➤: Patients with atrial fibrillation being treated with chronic warfarin therapy or direct oral anticoagulants should stop the agent 3 to 5 days prior to surgery. Patients do not typically require bridging therapy prior to surgery.