Validation of the IMPEDE VTE score for prediction of venous thromboembolism in Chinese patients with multiple myeloma: A single-center retrospective cohort study.

Multiple myeloma (MM) significantly increases the risk of venous thromboembolism (VTE) within 6 months of treatment initiation. The IMPEDE VTE score is a VTE risk prediction model which is recently incorporated into the National Comprehensive Cancer Network (NCCN) guidelines, but it lacks validation among Asians, including Chinese MM patients. We performed a retrospective chart review of 405 Chinese with newly diagnosed MM who started therapy at Beijing Jishuitan Hospital between April 2013 to October 2022. The 6-month cumulative incidence of VTE was 3.8 % (95 % CI:1.6-7.6), 8.6 % (95 % CI: 5.3-21.9) and 40.5 % (95 % CI: 24.9-55.7) in the low-, intermediate- and high-risk groups (P < 0.001), respectively. The C-statistic of the IMPEDE VTE scores for predicting VTE within 6 months of treatment initiation was 0.74 (95 % CI: 0.65-0.83). Of note, in this single-center cohort study, we propose that the anticoagulant LMWH may be more effective than the antiplatelet aspirin in potentially preventing VTE in newly diagnosed MM patients. Our findings suggest that the IMPEDE VTE score is a valid evidence-based risk stratification tool in Chinese patients with newly diagnosed MM.

Effectiveness of Taohong Siwu decoction in the prevention of deep vein thrombosis in hip surgery patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the effects of Taohong Siwu Decoction (THSWD) combined with low molecular weight heparin (LMWH), as well as THSWD alone, on the incidence of Deep vein thrombosis (DVT), D-dimer levels, prothrombin time (PT), activated partial thromboplastin time (APTT), visual analogue scale (VAS) pain score, and calf swelling in patients undergoing hip fracture or replacement surgery, compared to LMWH. METHODS: According to the predefined inclusion criteria, we conducted a comprehensive search for randomized controlled trials (RCTs) examining the efficacy of THSWD combined with LMWH or THSWD compared to LMWH in patients with hip fractures or undergoing replacement surgery. The search was performed across multiple databases including China National Knowledge Internet, WanFang, Sinomed, Duxiu, PubMed, Embase, Google Scholar, Cochrane, and Web of Science from their inception until December 2023. Additionally, relevant literature references were retrieved and hand searching of pertinent journals was conducted. The methodological quality assessment of the included trials was carried out following the guidelines outlined in the Cochrane Handbook. Review Manager 5.4 was applied in analyzing and synthesizing. RESULTS: A total of 18 RCTs with 1353 patients were included. The results of meta-analysis showed that compared with the control group, the combined group had a better effect on the incidence of DVT [RR = 0.32, 95% CI(0.17, 0.58; P = .0002], D-dimer [SMD = -5.88, 95% CI(-7.66, -4.11); P < .00001], VAS [MD = -1.16, 95% CI(-1.81, -0.50); P = .0005], Calf circumference difference [MD = -0.56, 95% CI(-1.05, -0.08); P = .02]. There was no significant difference in PT and APTT between the combined group and the control group. Meta-analysis results show that the D-dimer, incidence of DVT, PT, and APTT did not significantly differ between the THSWD and the LMWH groups. CONCLUSION: This meta-analysis shows that compared with LMWH, THSWD combined with LMWH has a better efficacy in the treatment of DVT after hip surgery, without a significant increase in the incidence of adverse events. Additionally, the combined therapy can also reduce D-dimer, VAS, and swelling. However, due to the limitations of the included studies (such as small sample size and low-quality evidence), the results need to be further verified in more rigorous multicenter clinical trials with a large sample size.

Treatment of cancer-associated venous thromboembolism: A focus on special populations.

Current evidence-based clinical practice guidelines recommend the use of both low-molecular-weight heparin (LMWH) and direct factor Xa inhibitors (apixapan, edoxaban and rivaroxaban) as first-line options for the treatment of venous thromboembolism (VTE) in patients with cancer. However, most of these guidelines refer to the general cancer patient population and provide limited guidance for specific subgroups of patients at particularly high risk of bleeding, such as those with gastrointestinal cancers, primary or metastatic brain tumors, thrombocytopenia, or renal impairment. In these complex populations, the management of cancer-associated thrombosis (CAT) poses unique challenges and requires a nuanced approach based on the primum non nocere principle. This comprehensive review critically examines the relevant literature and discusses the therapeutic options currently available for the management of CAT in these special situations.

An Update in Anticoagulant Therapy for Patients with Cancer-Associated Venous Thromboembolism.

PURPOSE OF REVIEW: This review aims to assess the treatment options for cancer-associated venous thromboembolism (VTE) based on the most robust level of evidence recommendations and suggestions based on expert opinion. RECENT FINDINGS: Several classes of anticoagulants have been studied in the treatment of cancer-associated thrombosis (CAT). Since the CLOT trial, guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of this condition. However, since 2018, some direct oral anticoagulants became an alternative first-line treatment for CAT. Three Xa antagonists (rivaroxaban, apixaban, and edoxaban) proved to be at least as effective as the LMWH strategy for the short-term prevention of VTE recurrence. The right choice of treatment in the context of anticoagulation strategy, thrombo-hemorrhagic risk management, and a patient's comorbidities represents a challenge. The correct management of CAT and a more individualized approach are needed to identify risk factors and offer the best treatment for each patient.

Network pharmacology- and molecular simulation-based exploration of therapeutic targets and mechanisms of heparin for the treatment of sepsis/COVID-19.

Critically infected patients with COVID-19 (coronavirus disease 2019) are prone to develop sepsis-related coagulopathy as a result of a robust immune response. The mechanism underlying the relationship between sepsis and COVID-19 is largely unknown. LMWH (low molecular weight heparin) exhibits both anti-inflammatory and anti-coagulating properties that result in a better prognosis of severely ill patients with COVID-19 co-associated with sepsis-induced coagulopathy or with a higher D-dimer value. Heparin-associated molecular targets and their mechanism of action in sepsis/COVID-19 are not well understood. In this work, we characterize the pharmacological targets, biological functions and therapeutic actions of heparin in sepsis/COVID-19 from the perspective of network pharmacology. A total of 38 potential targets for heparin action against sepsis/COVID-19 and 8 core pharmacological targets were identified, including IL6, KNG1, CXCL8, ALB, VEGFA, F2, IL10 and TNF. Moreover, enrichment analysis showed that heparin could help in treating sepsis/COVID-19 through immunomodulation, inhibition of the inflammatory response, regulation of angiogenesis and antiviral activity. The pharmacological effects of heparin against these targets were further confirmed by molecular docking and simulation analysis, suggesting that heparin exerts effective binding capacity by targeting the essential residues in sepsis/COVID-19. Prospective clinical practice evaluations may consider the use of these key prognostic indicators for the treatment of sepsis/COVID-19.Communicated by Ramaswamy H. Sarma.

Comparative effectiveness of prophylactic strategies for preeclampsia: a network meta-analysis of randomized controlled trials.

OBJECTIVE: Preeclampsia is a common disease during pregnancy that leads to fetal and maternal adverse events. Few head-to-head clinical trials are currently comparing the effectiveness of prophylactic strategies for preeclampsia. In this network meta-analysis, we aimed to compare the efficacy of prophylactic strategies for preventing preeclampsia in pregnant women at risk. DATA SOURCES: Articles published in or before September 2021 from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, references of key articles, and previous meta-analyses were manually searched. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing prophylactic strategies preventing preeclampsia with each other or with negative controls were included. METHODS: Two reviewers independently extracted data, assessed the risk of bias, and assessed evidence certainty. The efficacy of prophylactic strategies was estimated by frequentist and Bayesian network meta-analysis models. The primary composite outcome was preeclampsia/ pregnancy-induced hypertension. RESULTS: In total, 130 trials with a total of 112,916 patients were included to assess 13 prophylactic strategies. Low-molecular-weight heparin (0.60; 95% confidence interval, 0.42-0.87), vitamin D supplementation (0.65; 95% confidence interval, 0.45-0.95), and exercise (0.68; 95% confidence interval, 0.50-0.92) were as efficacious as calcium supplementation (0.71; 95% confidence interval, 0.62-0.82) and aspirin (0.79; 95% confidence interval, 0.72-0.86) in preventing preeclampsia/pregnancy-induced hypertension, with a P score ranking of 85%, 79%, 76%, 74%, and 61%, respectively. In the head-to-head comparison, no differences were found between these effective prophylactic strategies for preventing preeclampsia and pregnancy-induced hypertension, except with regard to exercise, which tended to be superior to aspirin and calcium supplementation in preventing pregnancy-induced hypertension. Furthermore, the prophylactic effects of aspirin and calcium supplementation were robust across subgroups. However, the prophylactic effects of low-molecular-weight heparin, exercise, and vitamin D supplementation on preeclampsia and pregnancy-induced hypertension varied with different risk populations, dosages, areas, etc. The certainty of the evidence was moderate to very low. CONCLUSION: Low-molecular-weight heparin, vitamin D supplementation, exercise, calcium supplementation, and aspirin reduce the risk of preeclampsia/pregnancy-induced hypertension. No significant differences between effective prophylactic strategies were found in preventing preeclampsia. These findings raise the necessity to reevaluate the prophylactic effects of low-molecular-weight heparin, vitamin D supplementation, and exercise on preeclampsia.

Anticoagulant Therapy for Cancer-Associated Thrombosis : A Cost-Effectiveness Analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) offer an alternative to low-molecular-weight heparin (LMWH) and warfarin for treating cancer-associated thrombosis (CAT). OBJECTIVE: To determine the cost and effectiveness of DOACs versus LMWH. DESIGN: Cohort-state transition decision analytic model. DATA SOURCES: Network meta-analysis comparing DOACs versus LMWH. TARGET POPULATION: Adult patients with cancer at the time they develop thrombosis. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: Strategies of 1) enoxaparin, 2) apixaban, 3) edoxaban, and 4) rivaroxaban for treatment of CAT. OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER) in 2022 U.S. dollars per quality-adjusted life-year (QALY) gained. RESULTS OF BASE-CASE ANALYSIS: In the base-case scenario, using drug prices from the U.S. Department of Veterans Affairs Federal Supply Schedule, apixaban dominated enoxaparin and edoxaban by being less costly and more effective. Rivaroxaban was slightly more effective than apixaban, with an ICER of $493 246. In a scenario analysis using "real-world" drug prices from GoodRx, rivaroxaban was cost-effective with an ICER of $50 053 per QALY. RESULTS OF SENSITIVITY ANALYSIS: Results were highly sensitive to monthly drug costs. Probabilistic sensitivity analyses showed that at a willingness-to-pay threshold of $50 000 per QALY, apixaban was preferred in 80% of simulations. However, sensitivity analyses also demonstrated that apixaban only remained cost-effective if monthly medication costs were below $530. Above this, rivaroxaban became cost-effective. LIMITATIONS: An assumption was made that patients would continue anticoagulation indefinitely unless they suffered a major bleed. Nonmedical costs such as patient and caregiver loss of productivity were not accounted for, and long-term thrombotic complications were not explicitly modeled. CONCLUSION: The 3 DOACs are more effective and more cost-effective than LMWH. The most cost-effective DOAC depends on the relative cost of each of these agents. These are important considerations for treating physicians and health policymakers. PRIMARY FUNDING SOURCE: None.

Successful Treatment of Splenic Vein Thrombosis Secondary to Acute Pancreatitis with Oral Anticoagulants: A Pediatric Case Series.

BACKGROUND Two Pediatric Patients with Splanchnic Venous Thrombosis as a Complication of Acute Pancreatitis Successfully Treated with Low-Molecular-Weight Heparin and Rivaroxaban CASE REPORT Case 1: A 13-year-old girl presented with a second attack of acute pancreatitis. She developed a non-occlusive splenic vein thrombosis diagnosed by CT scan on the sixth day of hospitalization. Injectable low-molecular-weight heparin was started during hospitalization and switched to oral rivaroxaban at discharge. Imaging at follow-up showed resolution of thrombosis. Case 2: A 9-year-old girl with history of acute recurrent pancreatitis presented with a third attack of acute pancreatitis. An occlusive splenic vein thrombosis with extension into the portal vein and superior mesenteric vein and necrotizing pancreatitis was seen on CT scan on the third day of hospitalization. Low-molecular-weight heparin was initiated during hospitalization and was switched to oral rivaroxaban at discharge. Imaging at follow-up demonstrated nearly complete resolution of the extensive thrombosis. CONCLUSIONS Splanchnic venous thrombosis remains a rare complication of pediatric pancreatitis. Anticoagulant use in patients with these complications remains controversial. Direct oral anticoagulants are as safe and effective as low-molecular-weight heparin and should be considered for use in children instead of low-molecular-weight heparin due to its advantages, including the availability of enteral forms of administration.

Micellar nanoparticles inhibit breast cancer and pulmonary metastasis by modulating the recruitment and depletion of myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSCs) are notorious for their pathological characteristics of immunosuppression and their promoting effect on cancers. They can induce the formation of pre-metastatic niche (PMN) characterized by inflammation, immunosuppression and vascular leakage, and promote pulmonary metastasis of breast cancer. Herein, a tumor targeting c(RGDfk) peptide modified low molecular-weight-heparin-all-trans-retinoic-acid (LMWH-ATRA) micellar nanoparticle loaded with chemotherapeutic drug doxorubicin (DOX) and immune adjuvant α-galactosylceramide (αGC) (RLA/DOX/αGC NP) was developed. The hydrophilic segment LMWH inhibited the recruitment of MDSCs by competitively binding with P-selectin on the surface of vascular endothelial cells (VECs), while the hydrophobic segment ATRA promoted the depletion of MDSCs by inducing their differentiation. Through the modulation of MDSCs, micelles can significantly improve the inflammatory and immunosuppressive microenvironment of the lung and tumor sites, and inhibit the formation of PMN. Not only this, the micelles also produced a synergistic effect with αGC, which effectively improved the anti-tumor immunity of tumor bearing mice and provided a promising therapeutic strategy for breast cancer and pulmonary metastasis.

Direct Oral Anticoagulants for the Prevention and Acute Treatment of Cancer-Associated Thrombosis.

Cancer is a major risk factor for venous thromboembolism (VTE), and cancer-associated thrombosis (CAT) constitutes approximately 15-25% of all VTE cases. For decades, the standard treatment for CAT used to be daily subcutaneous low molecular weight heparin (LMWH). Data on the safety and efficacy of the direct oral anticoagulants (DOACs) in this population emerged only in recent years and specific DOACs were included into recent guidelines recommendations. In this narrative review of the literature, we reported the results of the phase III randomized controlled trials that evaluated the DOACs for the prevention and the acute treatment of CAT. For the acute phase treatment, the anti-Xa inhibitors (apixaban, edoxaban, rivaroxaban) showed better efficacy than LMWH in preventing VTE recurrence; however, rivaroxaban and edoxaban were also associated with an increased risk of bleeding events. For primary prevention of CAT in ambulatory cancer patients starting chemotherapy, apixaban and rivaroxaban showed better efficacy than placebo but a trend towards higher bleeding rates. Recent guidelines suggest the DOACs for the treatment of CAT in selected cancer patients (eg, low bleeding risk, no luminal gastrointestinal or genitourinary malignancies, no interfering medications). The DOACs are also suggested for primary thromboprophylaxis in selected ambulatory cancer patients at high risk of VTE (eg, Khorana score ≥2 prior to starting new chemotherapy, low bleeding risk, no interfering medications).

Significant Tumor Reduction With Traditional Chinese Medicine in a Patient With Advanced Prostate Cancer: A Case Report.

Prostate cancer (PC) is the most common malignancy of the male genitourinary system. For patients with advanced progressive PC, the treatment strategies include second-line endocrine therapy, chemotherapy, and immunotherapy. Such therapeutic techniques are either too expensive or too toxic for some patients, and traditional Chinese medicine (TCM) has become an alternative for its low cost and low toxicity. The application of Shi-pi-san and Gui-zhi-Fu-ling-wan in PC has never been reported. We report their application on a 71-year-old male patient, who was diagnosed with PC and was undergoing endocrine therapy. He originally chose chemotherapy, and experienced acute renal failure, which required hemodialysis during hospitalization. He felt weak and opted for Chinese herbal medicine treatment. After treatment with Shi-pi-san and Gui-zhi-Fu-ling-wan, the patient's tumor and other symptoms were significantly reduced, and he reported feeling "refreshed." This case indicates that TCM treatment has unique advantages and is more tolerable than endocrine therapy and chemotherapy. Considering that the patient was undergoing hemodialysis treatment and using low-molecular-weight heparin (LMWH) to prevent blood coagulation while taking TCM, whether LMWH has a synergistic anticancer effect remains to be explored.

Safflor yellow treating angina pectoris: A pharmacoeconomic evaluation and network meta-analysis.

BACKGROUND: Coronary heart disease (CHD) is a cardiovascular disease caused by myocardial ischemia. In China, safflor yellow and artemisinin-based combination therapies have been extensively used to treat angina pectoris. METHODS: Efficacies were provided by a network meta-analysis following the PRISMA 2020 checklist. Cost-effectiveness analysis was based on patient perspectives. Two-way and probabilistic sensitivity analyses were conducted to assess the robustness of the study results. RESULTS: Conventional treatment combined with safflower is a better choice against angina pectoris. Sensitivity analysis showed that the model was sensitive to the treatment efficacy rather than the drug cost. CONCLUSION: Conventional treatment combined with safflower injection is suggested to treat angina pectoris. Low molecular weight heparin or compound Danshen-dropping pills can be used to increase the recovery rate of angina pectoris, according to conventional treatment combined with safflower injection.

A review of latest clinical practice guidelines for the management of cancer-associated thrombosis.

The management of cancer-associated thrombosis (CAT) poses unique challenges to healthcare professionals. While low-molecular weight heparins (LMWHs) have long been the gold standard for both the primary and secondary prevention of CAT, results from large randomized controlled trials assessing the benefit of direct oral anticoagulants (DOACs) in both settings have resulted in some paradigm shifts. Herein, we review and compare recommendations from the latest authoritative clinical practice guidelines (CPGs) for the management of CAT and summarize the most recent evidence on available treatment options. A rigorous methodology was used to select high quality CPGs and compare the recommendations across CPGs. Only CPGs focusing on the management of CAT developed by a multidisciplinary international working group and issued or endorsed by national or international scientific societies, or government organizations were eligible for inclusion. The quality of selected CPGs was assessed using the Appraisal of Guidelines, Research, and Evaluation II (AGREE II) tool. Four CPGs met the inclusion criteria, including the International Initiative on Thrombosis and Cancer (ITAC), the American Society of Clinical Oncology (ASCO), the American Society of Hematology (ASH), and the National Comprehensive Cancer Network (NCCN).

Prevention of Deep Vein Thrombosis by Panax Notoginseng Saponins Combined with Low-Molecular-Weight Heparin in Surgical Patients.

OBJECTIVE: To evaluate the efficacy of deep vein thrombosis (DVT) prevention among real-world surgical inpatients who received panax notoginseng saponins (PNS) combined with low-molecular-weight heparin (LMWH). METHODS: A prospective cohort study was conducted among surgical patients between January 2016 and November 2018 in Xuanwu Hospital, Capital Medical University, Beijing, China. Participants received LMWH alone or PNS combined with LMWH for preventing DVT. The primary outcome was incidence of lower extremity DVT, which was screened once a week. Participants in the LMWH group were given LMWH (enoxaparin) via hypodermic injection, 4000-8000 AxalU once daily. Participants in the exposure group received PNS (Xuesaitong oral tablets, 100 mg, 3 times daily) combined with LMWH given the same as LMWH group. RESULTS: Of the 325 patients screened for the study, 281 participants were included in the final analysis. The cohort was divided into PNS + LMWH group and LMWH group with 134 and 147 participants, respectively. There was a significant difference of DVT incidence between two groups (P=0.01), with 21 (15.7%) incident DVT in the PNS + LMWH group, and 41 (27.9%) incident DVT in the LMWH group. Compared with participants without DVT, the participants diagnosed with DVT were older and had higher D-dimer level. The multivariate logistic regression model showed a significant lower risk of incident DVT among participants in the PNS + LMWH group compared with the LMWH group (odds ratio 0.46, 95% confidence interval, 0.25-0.86). There were no significant differences in thromboelaslography values (including R, K, Angle, and MA) and differences in severe bleeding between two groups. No symptomatic pulmonary embolism occurred during the study. CONCLUSION: Combined application of PNS and LMWH can effectively reduce the incidence of DVT among surgical inpatients compared with LMWH monotherapy, without increased risk of bleeding.

Antithrombin supplementation for prevention of vascular thrombosis after pediatric liver transplantation.

AIMS: After liver transplantation (LT), synthesis of coagulation factors by the graft recovers faster for pro thrombotic than anti thrombotic factors, resulting in a potential pro thrombotic imbalance. We studied the thrombotic and hemorrhagic complications in our pediatric LT series, providing supplementation of fresh frozen plasma (FFP) and/or antithrombin (AT) in the prophylactic antithrombotic regimen. METHODS: This was a retrospective observational single center study. All isolated pediatric LTs performed between 1/11/2009 and 31/12/2019 (n = 181) were included. Postoperatively, in addition to low molecular weight heparin, 22 patients (12%) received FFP (10 ml/kg twice daily for 10 days), 27 patients (15%) were given FFP (reduced duration) and AT (50-100 IU/kg/day if AT activity remained <70%), and 132 (73%) received AT only. Complications, outcome, and coagulation profiles in postoperative days 0-10 were analyzed. RESULTS: In all three treatment groups, AT activity normalized by day 4 while prothrombin remained <70% of normal until day 9. Hepatic artery thrombosis (HAT), portal vein thrombosis (PVT), and hemorrhagic complications occurred in 2.8%, 3.3%, and 3.9% of LTs. One- and 5-year patient and graft survival were 88% (±2.4% Standard Error) and 84% (±2.5%), and 86% (±2.6%) and 84% (±2.7%), respectively, without difference between groups. HAT were associated with low AT on days 0 and 1, and PVT with low AT on day 0. CONCLUSIONS: Low antithrombin activity after LT was associated with postoperative thromboses. FFP and/or AT supplementation allowed early normalization of AT activity, while thrombotic or hemorrhagic complications were rare, suggesting efficient and safe management of post-LT coagulopathy.

Distinct Approaches to Perioperative Management of Anticoagulation and Antiplatelet Therapy among Providers Performing Cutaneous Surgery.

BACKGROUND: Despite increasing cross-collaboration between providers who perform cutaneous surgery, a disparity still exists in the current practices regarding perioperative management. This could lead to treatment delays, patient confusion, and increased morbidity, such as clotting, infection, and discomfort of patients. OBJECTIVE: To characterize the management practices of different providers in regards to perioperative anticoagulation and antiplatelet therapy for cutaneous surgery. METHODS AND MATERIALS: This study used an electronic survey to assess current perioperative management practices of dermatologic surgeons and plastic and reconstructive surgeons. RESULTS: 177 physicians (115 dermatologic surgeons and 62 plastic and reconstructive surgeons) responded to the survey. For all therapeutic agents, dermatologic surgeons were significantly more likely than their plastic and reconstructive surgery colleagues to continue all anticoagulant and antiplatelet agents perioperatively for cutaneous surgery (vitamin K antagonists, antiplatelets, LMWH, direct Xa inhibitors, direct thrombin inhibitors, NSAIDS: P<0.001; fish oil, vitamin E: P<0.01). CONCLUSION: Our data highlight the significant practice gaps that exist between dermatologic surgeons and plastic and reconstructive surgeons. Reducing this disparity will facilitate improved continuity of care, especially when patients are referred from dermatologic surgeons to plastic and reconstructive surgeons for more complex repairs, and potentially reduce morbidity and mortality associated with medication discontinuation. J Drugs Dermatol. 2022;21(7):766-772. doi:10.36849/JDD.6726.

ISTH guidelines for antithrombotic treatment in COVID-19.

Antithrombotic agents reduce risk of thromboembolism in severely ill patients. Patients with coronavirus disease 2019 (COVID-19) may realize additional benefits from heparins. Optimal dosing and timing of these treatments and benefits of other antithrombotic agents remain unclear. In October 2021, ISTH assembled an international panel of content experts, patient representatives, and a methodologist to develop recommendations on anticoagulants and antiplatelet agents for patients with COVID-19 in different clinical settings. We used the American College of Cardiology Foundation/American Heart Association methodology to assess level of evidence (LOE) and class of recommendation (COR). Only recommendations with LOE A or B were included. Panelists agreed on 12 recommendations: three for non-hospitalized, five for non-critically ill hospitalized, three for critically ill hospitalized, and one for post-discharge patients. Two recommendations were based on high-quality evidence, the remainder on moderate-quality evidence. Among non-critically ill patients hospitalized for COVID-19, the panel gave a strong recommendation (a) for use of prophylactic dose of low molecular weight heparin or unfractionated heparin (LMWH/UFH) (COR 1); (b) for select patients in this group, use of therapeutic dose LMWH/UFH in preference to prophylactic dose (COR 1); but (c) against the addition of an antiplatelet agent (COR 3). Weak recommendations favored (a) sulodexide in non-hospitalized patients, (b) adding an antiplatelet agent to prophylactic LMWH/UFH in select critically ill, and (c) prophylactic rivaroxaban for select patients after discharge (all COR 2b). Recommendations in this guideline are based on high-/moderate-quality evidence available through March 2022. Focused updates will incorporate future evidence supporting changes to these recommendations.

Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy: Results from a Randomized Clinical Trial.

PURPOSE: Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD. DESIGN: Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis. PARTICIPANTS: Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry. METHODS: Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy. MAIN OUTCOME MEASURES: Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon. RESULTS: A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified. CONCLUSIONS: Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.

Cost-effectiveness of direct oral anticoagulants compared to low-molecular-weight-heparins for treatment of cancer associated venous thromboembolism in Spain.

AIM: Recent studies have compared the efficacy and safety of direct-acting oral anticoagulants (DOAC) and low-molecular-weight heparin (LMWH) for cancer-associated venous thromboembolism (VTE). However, there is no available cost-effectiveness analysis comparing DOAC and LMWH. The study aimed to conduct a cost-effectiveness analysis of DOAC (apixaban, edoxaban, and rivaroxaban) vs. LMWH for the treatment of cancer-associated VTE in Spain from the Spanish healthcare system perspective. METHODS: We developed a Markov model with a 12-month time horizon. The states included pulmonary embolism, deep vein thrombosis, major and non-major bleeding, chronic thromboembolic pulmonary hypertension, post-thrombotic syndrome, and death. The use of medical resources and drug costs were obtained from the 2021 Spanish Ministry of Health database, and the main references for obtaining the outcomes were derived from Caravaggio, Hokusai VTE Cancer, ADAM VTE, and SELECT-D trials. We performed a deterministic and probabilistic sensitivity analysis to validate the robustness. The Incremental Cost-Effectiveness Ratio (ICER) scores cost per life-year (€/LY) gained and cost per quality-adjusted life-year (€/QALY) gained. RESULTS: The 12-month cost of DOAC was 1,994€ (apixaban 1,944€, edoxaban 1,968€, rivaroxaban 2,122€) and 2,152€ for LMWH. The amount of QALY for DOAC was 0.54 (apixaban 0.55, rivaroxaban 0.53, and edoxaban 0.52) and 0.53 for LMWH. We observed similar results for LYs. ICER scores in terms both of €/LY and €/QALY show that DOAC is dominant over LMWH and apixaban showed the best profile. LIMITATIONS: Our research is based on an indirect comparison of a short-term clinical trial. CONCLUSION: Our results suggest that DOAC is cost-effective and cost-saving compared to LMWH in treating VTE.

Comparison of Managing Factor Xa Inhibitor to Unfractionated Heparin Transitions by aPTT Versus a Treatment Guideline Utilizing Heparin Anti-Xa Levels.

BACKGROUND: There are inadequate data on the optimal strategy for transitioning factor Xa inhibitors (FXai; apixaban, rivaroxaban) to unfractionated heparin (UFH) infusions. OBJECTIVE: In patients transitioning from an FXai to an UFH infusion, this study compared the safety and efficacy of monitoring UFH infusions using an activated partial thromboplastin time (aPTT) titration scale versus utilizing an UFH-calibrated anti-Xa titration scale aided by a novel institutional guideline. METHODS: A retrospective cohort analysis was conducted on adult patients transitioning from an FXai to an UFH infusion at 2 medical centers from June 1, 2018, to November 1, 2020. One institution utilized aPTT while the other institution primarily used UFH-calibrated anti-Xa. The primary endpoint was a composite of death, major bleeding, or new thrombosis during the hospitalization with a planned noninferiority analysis. Secondary outcomes were also collected including the amount and duration of UFH administered between cohorts. RESULTS: The incidence rate of the primary composite endpoint was 6.3% in the anti-Xa group and 11% in the aPTT group (P < 0.001 for noninferiority, P = 0.138 for superiority) meeting noninferiority criteria. No statistical differences were seen in new thrombosis, major bleeding, or any bleeding. CONCLUSION AND RELEVANCE: This represents the first report of a comparison between aPTT versus anti-Xa monitoring in relation to clinical outcomes for patients transitioning from an FXai to an UFH infusion. A transition guideline primarily utilizing an UFH-calibrated anti-Xa assay appears to be a safe alternative to aPTT monitoring and can aid facilities in the management of patients during these complex transitions.