Anticoagulant prescribing patterns in patients with primary central nervous system malignancies and secondary metastases.

To evaluate the safety of direct oral anticoagulants (DOACs) versus low-molecular weight heparin (LMWH) in patients with central nervous system (CNS) malignancies and secondary metastases. All adult patients with CNS malignancies and secondary metastases who were treated with a DOAC or LMWH for any indication from 2018 to 2022 were included. The primary outcome was the incidence of any intracranial hemorrhage (ICH) after anticoagulation initiation. Secondary outcomes included non-ICH bleeding events and thromboembolic events. Tolerability was assessed by any changes in anticoagulant therapy during study period. 153 patients were included; 48 patients received enoxaparin and 105 received DOACs, of which apixaban was used most commonly. The population was predominantly White (74%) and male (59%) with a median age of 65. Data was censored for immortal time bias for outcomes evaluated beyond 3 months. ICH occurred in 7.7% of the population, more frequently in the enoxaparin group (DOACs 4, 4% vs. enoxaparin 7, 16%, p = 0.037). Non-ICH bleeds were predominantly minor and more common in the DOAC group (DOACs 13, 13% vs. enoxaparin 1, 2%, p = 0.037). Thromboembolic events were not different between groups (DOACs 9. 9% vs, enoxaparin 2, 4%, p = 0.503). Anticoagulant switches occurred more in the enoxaparin group (DOACs 12, 12.4% vs. enoxaparin, 37.8%, p < 0.001), primarily due to patient or provider preference. Our data supports DOACs to be preferred over LMWH for the treatment of VTE or for stroke prevention with AF to prevent ICH in patients with brain tumors or metastases.

Superior sagittal sinus thrombosis in the course of mixed phenotype acute leukaemia treated with acute lymphoblastic leukaemia-like therapy-a case report.

Mixed phenotype acute leukaemia (MPAL) is associated with worse overall survival, compared with other acute leukaemias in adults. Lack of clear treatment guidelines makes the therapy challenging. ALL-like induction and consolidation treatment followed by allo-HSCT is the preferred first-line treatment. We present a case of a 36-year-old woman diagnosed with MPAL (EGIL Myelo/B) with KMT2A rearrangement, treated with the PALG-ALL-7 (including PEG-asparaginase) protocol. On day 25 after the induction therapy initiation, numbness of limbs and dizziness were observed. Therefore, the imaging studies (CT and MRI) were performed and a diagnosis of thrombosis of superior sagittal sinus of the brain was established. Routinely performed blood coagulation tests showed prolonged APTT and PT, decreased antithrombin III activity and decreased free protein S concentration. LMWH treatment and substitutional therapy with antithrombin III were started, which resulted in a significant reduction in the thrombosis associated symptoms and improvement of the neurological status after 3 days. After induction and consolidation therapy, the patient obtained complete haematological remission and negative measurable residual disease. Six months after the diagnosis, allo-HSCT was successfully performed. During the 4 months follow-up, the patient remained MRD negative and thrombotic symptoms free. To the best of our knowledge, our communication has been the first report of such complication in an MPAL patient treated with PEG-asparaginase containing protocol in adults. We recommend increased vigilance in patients manifesting any mild neurological symptoms and early decision about the MRI study performance.

The effect of renal impairment and obesity on anti-Xa peak and trough levels in patients receiving therapeutic doses of nadroparin: a comparison with control patients.

PURPOSE: Anti-Xa peak level monitoring is recommended during LMWH treatment in renal impairment or obesity. The trough level has been proposed as marker for bleeding. We studied the influence of renal impairment and obesity on anti-Xa levels. METHODS: Peak and trough levels were collected during therapeutic nadroparin treatment in patients with renal impairment, obese patients, and controls. 27 patients (n = 68 samples) were evaluated and combined with published data (n = 319 samples from 35 patients) using population pharmacokinetic (popPK) modelling. RESULTS: Median peak level was 0.44 and 0.95 IU/mL in renal impairment with and without dose reduction and 0.60 and 0.43 IU/mL in obesity and controls, respectively. Trough levels were < 0.5 IU/mL in all patients with renal impairment with dose reduction and in 5/6 control patients. In the popPK model, total body weight and eGFR were covariates for clearance and lean body weight for distribution volume. Model-based evaluations demonstrated peak levels below the therapeutic window in controls and increased levels in renal impairment. Dose reductions resulted in a different effect on peak and trough levels. Obese patients (BMI up to 32 kg/m2) had similar levels upon weight-based dosing. CONCLUSION: In renal impairment, anti-Xa peak levels after dose reduction are comparable to those in controls. Weight-based dosing is suitable for obese patients. Aiming for peak levels between 0.6 and 1.0 IU/mL in these patients would result in overexposure compared to controls. Considering the association of trough levels and bleeding risk and our findings, trough monitoring seems to be a suitable parameter to identify nadroparin accumulation.

Evaluation of direct oral anticoagulants versus low molecular weight heparins for venous thromboembolism treatment in patients with gastrointestinal malignancies.

BACKGROUND: Direct oral anticoagulant (DOAC) use in cancer-associated venous thromboembolism (CA-VTE) has increased due to updates in recent guidelines and literature. However, select guidelines caution against DOAC use in patients with gastrointestinal (GI) malignancies due to reported increased bleeding events. The objective of this study was to compare the safety and effectiveness of DOACs versus low-molecular-weight heparins (LMWHs) for CA-VTE treatment in patients with GI malignancies. PATIENTS AND METHODS: This multicenter, retrospective cohort study included patients with primary GI malignancies who received therapeutic anticoagulation with a DOAC or LMWH for CA-VTE between January 1, 2018, and December 31, 2019. The primary outcome was the incidence rate of bleeding events (major, clinically relevant non-major, or minor bleeding events) within a 12-month period following the initiation of therapeutic anticoagulation. The secondary endpoint was the incidence rate of recurrent VTE events within a 12-month period following the start of therapeutic anticoagulation. RESULTS: After screening, 141 patients met inclusion criteria. The incidence rate of all bleeding events significantly differed between DOAC (4.98 events/100 person-months) and LWMH (10.2 events/100 person-months) recipients. The corresponding incidence rate ratio (IRR) with the DOAC group serving as the reference was 2.05 (p = 0.01), with the majority of bleeds in both groups presenting as minor bleeds. No difference was found between the incidence rate of recurrent VTE within a 12-month period of starting therapeutic anticoagulation between groups (IRR 3.08, p = 0.06). CONCLUSION: Our results suggest that DOACs do not pose an additional bleeding risk compared to LMWH in patients with certain GI malignancies. Careful selection of DOAC therapy with respect to bleeding risk is still warranted.

The Effect of Heparin Full-Dose Anticoagulation on Survival of Hospitalized, Non-critically Ill COVID-19 Patients: A Meta-analysis of High Quality Studies.

BACKGROUND: International COVID-19 guidelines recommend thromboprophylaxis for non-critically ill inpatients to prevent thrombotic complications. It is still debated whether full-dose thromboprophylaxis reduces all-cause mortality. The main aim of this updated systematic review and meta-analysis is to evaluate the effect of full-dose heparin-based thromboprophylaxis on survival in hospitalized non-critically ill COVID-19 patients. METHODS: A systematic review was performed across Pubmed/Medline, EMBASE, Cochrane Central Register of clinical trials, Clinicaltrials.gov, and medRxiv.org from inception to November 2022. We conducted a meta-analysis of randomized clinical trials (RCTs) comparing full-dose heparin-based anticoagulation to prophylactic or intermediate dose anticoagulation or standard treatment in hospitalized non-critically ill COVID-19 patients. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials and Grading of Recommendations Assessment, Development and Evaluation was applied. The primary outcome was all-cause mortality at the longest follow-up available. RESULTS: We identified 6 multicenter RCTs involving 3297 patients from 13 countries across 4 continents. The rate of all-cause mortality was 6.2% (103/1662) in the full-dose group vs 7.7% (126/1635) in the prophylactic or intermediate dose group (Risk Ratio [RR] = 0.76; 95% confidence interval [CI] = 0.59-0.98; P = 0.037). The probabilities of any mortality difference and of NNT ≤ 100 were estimated at 98.2% and 84.5%, respectively. The risk of bias was low for all included RCTs and the strength of the evidence was "moderate." CONCLUSION: Our meta-analysis of high-quality multicenter RCTs suggests that full-dose anticoagulation with heparin or low molecular weight heparin reduces all-cause mortality in hospitalized non-critically ill COVID-19 patients. STUDY REGISTRATION: PROSPERO, review no. CRD42022348993.

Scientific considerations in the regulatory approval of generic (or biosimilar) version of enoxaparin sodium - A lifesaving carbohydrate polymer.

Enoxaparin sodium (Clexane®/Klexane®/Lovenox®) is one amongst the few drugs that have assumed a central role as drug of treatment and/or prevention against thromboembolic complications during COVID-19. The increase in demand resulting in many generic (or biosimilar) versions entering the market has increased the risks of quality and safety (including immunogenicity) related issues. Under the circumstances, development of stringent regulatory approaches has received much attention as investigation of new drug delivery systems for improved therapeutic activity. As one of the measures to increase quality testing and ensure uninterrupted supply of this life-saving drug globally, determination of enoxaparin molecular weight (MW) has been added in the United States Pharmacopoeia (USP) monograph for enoxaparin sodium. In addition, the presence of a unique 1,6-anhydro-ring structure at the reducing end of about 15-25% of the poly (oligo) saccharide chains of the generic (or biosimilar) product has been set as a mandatory requirement. This article presents an overview of the scientific considerations in the quality manufacturing and testing of the generic (or biosimilar) enoxaparin for regulatory review and approval. In certain cases of strong analytical similarity (structural and functional), abandonment of in vivo testing in animals and humans represents a major advancement in the approval of generic (or biosimilar) version of innovator enoxaparin sodium (lovenox®, injections).

Does COVID-19 infection acquired in different pregnancy trimester influence placental pathology?

OBJECTIVES: To determine the morphological characteristics of the placentas from COVID-19 positive mothers in regard to the trimester of COVID-19 infection onset and low weight molecular heparin (LMWH) treatment. METHODS: Placentas were collected in the period April 1st till September 1st 2021 after delivery at Department of Obstetrics and Gynecology University Hospital Split, Croatia, and sent for pathological examination. Medical history and pathology reports were used to collect the data. Pregnant women were divided based on the onset of COVID-19 infection and stratified into low molecular weight heparin (LMWH)+ or LMWH-. Depending on the data distribution, the following test were used: chi-squared test. Student's t-test, Mann-Whitney U test, ANOVA and Kruskal-Wallis test. RESULTS: In 38% of patients the onset of COVID-19 infection was the 1st trimester of pregnancy, in 27% in the 2nd and 35% of women were infected in the 3rd trimester The fetal vascular malperfusion (FVM) occurrence was statistically significantly higher in the LMWH- group and if the onset of infection was in the 2nd trimester, while the perivillous fibrin deposition was most likely to happen if the COVID-19 infection that occured in the 1st trimester of pregnancy. CONCLUSIONS: The onset of COVID-19 infection has the influence on trophoblast damage and subsequent morphological appearance of the placenta. LMWH use in COVID positive pregnant women decreases the rate of the FVM in examined placentas.

Comparison of 90-Day Adverse Events Associated With Aspirin and Potent Anticoagulation Use for Venous Thromboembolism Prophylaxis: A Cohort Study of 72,288 Total Knee and 35,142 Total Hip Arthroplasty Patients.

BACKGROUND: While aspirin is acceptable for venous thromboembolism (VTE) prophylaxis following total joint arthroplasty in most patients, more potent agents are used in patients considered higher risk for VTE. We evaluated the efficacy and safety of aspirin versus potent anticoagulation agents following total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: A cohort study of 72,288 TKA and 35,142 THA from the Kaiser Permanente Total Joint Replacement Registry was performed (2009 to 2019). Identified medications were aspirin, factor Xa inhibitors, low-molecular-weight heparin (LMWH), and warfarin. A validated VTE risk score was assigned to each patient. Propensity score-weighted logistic regressions were used to evaluate 90-day VTEs. Noninferiority testing was performed with a margin of 1.25 using the upper bound (UB) of the 1-sided 95% CI. RESULTS: For TKA, aspirin was not inferior to LMWH (odds ratio [OR] = 0.77, UB = 1.09) and warfarin (OR = 0.64, UB = 0.90); there was no evidence to support noninferiority of aspirin compared to factor Xa inhibitors. Findings were consistent for THA (LMWH: OR = 0.59, UB = 0.75; warfarin: OR = 0.69, UB = 0.89). TKA was considered higher risk for VTE, whereas aspirin use demonstrated noninferiority compared to warfarin (OR = 0.54, UB = 0.81), we lacked evidence of noninferiority when compared to LMWH and factor Xa inhibitors. We lacked evidence of noninferiority of aspirin versus any potent anticoagulation in higher-risk THA. CONCLUSION: Aspirin was found to be effective and safe for VTE prevention in primary total joint arthroplasty, including in patients considered higher risk for VTE. LEVEL OF EVIDENCE: III.

The Hemostatic System in Newborns and the Risk of Neonatal Thrombosis.

Newborns are the most vulnerable patients for thrombosis development among all children, with critically ill and premature infants being in the highest risk group. The upward trend in the rate of neonatal thrombosis could be attributed to progress in the treatment of severe neonatal conditions and the increased survival in premature babies. There are physiological differences in the hemostatic system between neonates and adults. Neonates differ in concentrations and rate of synthesis of most coagulation factors, turnover rates, the ability to regulate thrombin and plasmin, and in greater variability compared to adults. Natural inhibitors of coagulation (protein C, protein S, antithrombin, heparin cofactor II) and vitamin K-dependent coagulation factors (factors II, VII, IX, X) are low, but factor VIII and von Willebrand factor are elevated. Newborns have decreased fibrinolytic activity. In the healthy neonate, the balance is maintained but appears more easily converted into thrombosis. Neonatal hemostasis has less buffer capacity, and almost 95% of thrombosis is provoked. Different triggering risk factors are responsible for thrombosis in neonates, but the most important risk factors for thrombosis are central catheters, fluid fluctuations, liver dysfunction, and septic and inflammatory conditions. Low-molecular-weight heparins are the agents of choice for anticoagulation.

Tumour cell-activated platelets modulate the immunological activity of CD4+, CD8+, and NK cells, which is efficiently antagonized by heparin.

Platelets, key players in haemostasis, are progressively investigated with respect to their role in immunity and inflammation. Although the platelet support to haematogenous cancer cell metastasis has been the subject of multiple studies, their impact on anti-cancer immunity remains unaddressed. Here, we investigated the immunomodulatory potential of platelets upon their activation by MDA-MB-231 breast cancer cells in various in vitro approaches. We provide evidence that platelets as well as their tumour cell-induced releasates increased the ratio of regulatory T cells, shaping an immunosuppressive phenotype in isolated CD4+ cultures. The influence on CD8+ T cells was assessed by detecting the expression of activation markers CD25/CD69 and release of cytolytic and pro-inflammatory proteins. Notably, the platelet preparations differentially influenced CD8+ T cell activation, while platelets were found to inhibit the activation of CD8+ T cells, platelet releasates, in contrast, supported their activation. Furthermore, the NK cell cytolytic activity was attenuated by platelet releasates. Low molecular weight heparin (LMWH), the guideline-based anticoagulant for cancer-associated thrombotic events, is known to interfere with tumour cell-induced platelet activation. Thus, we aimed to investigate whether, unfractionated heparin, LMWH or novel synthetic heparin mimetics can also reverse the immunosuppressive platelet effects. The releasate-mediated alteration in immune cell activity was efficiently abrogated by heparin, while the synthetic heparin mimetics partly outperformed the commercial heparin derivatives. This is the first report on the effects of heparin on rebalancing immunosuppression in an oncological context emerging as a novel aspect in heparin anti-tumour activities.

Cerebral venous sinus thrombosis caused by traumatic brain injury complicating thyroid storm: a case report and discussion.

INTRODUCTION: Cerebral venous sinus thrombosis (CVST) is an uncommon cerebrovascular disease with diverse predisposing factors. We report a case of CVST caused by a thyroid storm induced by traumatic brain injury. CASE PRESENTATION: A 29-year-old male patient with a history of Graves' disease with hyperthyroidism presented to our hospital with head trauma of cerebral contusion and laceration in both frontal lobes confirmed by admission CT scan. He received mannitol to lower intracranial pressure, haemostatic therapy, and antiepileptic treatment. Eight days later, he presented with signs of thyroid storms, such as tachycardia, hyperthermia, sweating and irritation, and his thyroid function tests revealed high levels of TPO-Ab, TR-Ab, TG-Ab, FT3 and FT4. Then, he entered a deep coma. His brain CT showed a thrombosis of multiple venous sinuses, along with the opening of peripheral collateral vessels, congestive infarction with haemorrhage and brain swelling. He regained consciousness after treatment with antithyroid drugs, anticoagulants, respiratory support and a regimen of sedation/analgesia. After a half-year follow-up, most of the patient's blocked cerebral venous sinuses had been recanalized, but there were still some sequelae, such as an impaired fine motor performance of the right hand and verbal expression defects. CONCLUSIONS: CVST can be induced by thyroid storms, and trauma-related thyroid storms can develop on the basis of hyperthyroidism. The purpose of this case report is to raise clinicians' awareness and improve their ability to diagnose CVST early in patients with traumatic brain injury complicating thyroid storms to improve the neurological prognosis among similar patients.

The Association of Low Molecular Weight Heparin Use and In-hospital Mortality Among Patients Hospitalized with COVID-19.

PURPOSE: To determine the association between low molecular weight heparin (LMWH) use and mortality in hospitalized COVID-19 patients. METHODS: We conducted a retrospective study of patients consecutively enrolled from two major academic hospitals exclusively for COVID-19 in Wuhan, China, from January 26, 2020, to March 26, 2020. The primary outcome was adjusted in-hospital mortality in the LMWH group compared with the non-LMWH group using the propensity score. RESULTS: Overall, 525 patients with COVID-19 enrolled with a median age of 64 years (IQR 19), and 49.33% men. Among these, 120 (22.86%) were treated with LMWH. Compared with the non-LMWH group, the LMWH group was more likely to be older and male; had a history of hypertension, diabetes, coronary heart disease (CHD), or stroke; and had more severe COVID-19 parameters such as higher inflammatory cytokines or D-dimer. Compared with non-LMWH group, LMWH group had a higher unadjusted in-hospital mortality rate (21.70% vs. 11.10%; p = 0.004), but a lower adjusted mortality risk (adjusted odds ratio [OR], 0.20; 95% CI, 0.09-0.46). A propensity score-weighting analysis demonstrated similar findings (adjusted OR, 0.18; 95% CI, 0.10-0.30). Subgroup analysis showed a significant survival benefit among those who were severely (adjusted OR, 0.07; 95% CI, 0.02-0.23) and critically ill (adjusted OR, 0.32; 95% CI, 0.15-0.65), as well as among the elderly patients' age > 65, IL-6 > 10 times upper limit level, and D-dimer > 5 times upper limit level. CONCLUSIONS: Among hospitalized COVID-19 patients, LMWH use was associated with lower all-cause in-hospital mortality than non-LMWH users. The survival benefit was particularly significant among more severely ill patients.

Therapeutically dosed low molecular weight heparins in renal impairment: a nationwide survey.

PURPOSE: International guidelines vary in their recommendations whether or not to reduce the therapeutic dose of low molecular weight heparins (LMWHs) in renal impairment. The use of anti-Xa monitoring as a basis of dose adjustments is also a matter of debate. As this may lead to variations in treatment policies, we aimed to study the treatment policies of therapeutically dosed LMWHs in renal impairment in Dutch hospitals. METHODS: An 11-item survey was distributed between June 2020 and March 2021 to hospital pharmacists, representing Dutch hospital organisations. Primary outcomes were the dosing regimens of therapeutically dosed LMWHs in renally impaired patients. Secondary outcomes were the proportion of hospitals that used anti-Xa monitoring and the anti-Xa target range used. RESULTS: There was a response from 56 of 69 (81%) Dutch hospital organisations where in each case a hospital pharmacist completed the survey. In these hospitals, 77 LMWH regimens were in use. In 76 of 77 (99%) regimens, a regular dose reduction was used at the start of treatment. Fifty-five of these hospitals used a dose reduction if estimated glomerular filtration rate (eGFR) < 50 ml/min and 17 used a dose reduction if eGFR < 30 ml/min. Anti-Xa levels were not routinely monitored in 40% of regimens, while 22% monitored anti-Xa if eGFR < 50 ml/min, 27% if eGFR < 30 ml/min and 10% in other eGFR cutoff values. Target ranges of 1.0-2.0 IU/ml (once daily) and 0.5/0.6-1.0 IU/ml (twice daily) were used in 69% of regimens that included monitoring of anti-Xa. CONCLUSION: Treatment policies show substantial diversity in therapeutically dosed LMWHs in renally impaired patients. The most commonly used treatment regimen was a regular dose reduction if eGFR is < 50 ml/min, without anti-Xa monitoring.

Can thromboprophylaxis build a link for cancer patients undergoing surgical and/or chemotherapy treatment? The MeTHOS cohort study.

BACKGROUND: Patients with active cancer have a 4-sevenfold increased risk for venous thromboembolism (VTE) especially during systematic anticancer treatment. Simultaneously, surgery is an additional risk factor. METHODS: The Metaxas's Hospital THromboprophylaxis program in Oncological & Surgical Patients (MeTHOS) is a prospective, phase IV, observational, non-interventional cohort study, aiming to record the thromboprophylaxis practice patterns in high-risk active cancer patients undergoing surgical and/or chemotherapy treatment. RESULTS: We are reporting results from 291 ambulatory patients (median age: 67 years, Q1-Q3: 59-73 years, 54.6% males) who received anti-neoplastic treatment and administered thromboprophylaxis. 59.8% had cardiovascular disease (mostly hypertension), 76.6% were reported as having at least one comorbidity, while 27.5% and 15.8% accumulated two and three comorbidities, respectively. 94.9% of the patients were receiving highly thrombogenic agents such as platinum-based agents, 5-FU, immunotherapy, antiangiogenics/anti-VEGF, or erythropoietin. 26.5% of the patients were initially surgically treated. In terms of anticoagulation, all patients were treated with tinzaparin (fixed dose, 10,000 Anti-Xa IU, OD). The median anticoagulation duration was 6.2 months. Six thrombotic events were observed (2.06%, 95% CI: 0.76-4.43%): 5 were DVT, and one PE. With respect to safety, 7 bleeding events occurred (2.6%, 95% CI: 1.0-5.3%); 6 of them were minor. CONCLUSIONS: Thromboprophylaxis with LMWH in patients with active cancer and high thrombotic burden was safe and effective. Intermediate dose of tinzaparin seems to be an appropriate agent for cancer-associated thromboprophylaxis management. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT04248348.

Efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients: a meta-analysis of multicenter randomized controlled trials.

Arterial and venous thrombotic events in COVID-19 cause significant morbidity and mortality among patients. Although international guidelines agree on the need for anticoagulation, it is unclear whether full-dose heparin anticoagulation confers additional benefits over prophylactic-dose anticoagulation. This systematic review and meta-analysis aimed to investigate the efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients. We searched Pubmed/Medline, EMBASE, Clinicaltrials.gov, medRxiv.org and Cochrane Central Register of clinical trials dated up to April 2022. Randomized controlled trials (RCTs) comparing full-dose heparin anticoagulation to prophylactic-dose anticoagulation or standard treatment in hospitalized non-critically ill COVID-19 patients were included in our pooled analysis. The primary endpoint was the rate of major thrombotic events and the co-primary endpoint was the rate of major bleeding events. We identified 4 studies, all of them multicenter, randomizing 2926 patients. Major thrombotic events were 23/1524 (1.5%) in full-dose heparin anticoagulation versus 57/1402 (4.0%) in prophylactic-dose [relative risk (RR) 0.39; 95% confidence interval (CI) 0.25-0.62; p˂0.01; I2 = 0%]. Clinical relevant bleeding events occurred in 1.7% (26/1524) among patients treated with heparin full anticoagulation dose compared to 1.1% (15/1403) in prophylactic-dose group (RR 1.60; 95% CI 0.85-3.03; p = 0.15; I2 = 20%). Mortality was 6.6% (101/1524) versus 8.6% (121/1402) (RR 0.63; 95% CI 0.33-1.19; p = 0.15). In this meta-analysis of high quality multicenter randomized trials, full-dose anticoagulation with heparin was associated with lower rate of major thrombotic events without differences in bleeding risk and mortality in hospitalized non critically ill COVID-19 patients.Study registration PROSPERO, review no. CRD42022301874.

Thromboprophylaxis after knee arthroscopy does not decrease the risk of deep vein thrombosis: a network meta-analysis.

PURPOSE: The primary aim of this network meta-analysis (NMA) is to compare the incidence of venous thromboembolisms (VTE) and bleeding risk following the use of pharmacological and non-pharmacological thromboprophylaxis for arthroscopic knee surgery (AKS). This study assumed the null hypothesis which was that there will be no difference in the incidence of VTE and bleeding risk when comparing no treatment, pharmacological treatment, and non-pharmacological treatment for preventing VTE events following AKS. METHODS: A systematic electronic search of CENTRAL, Medline, Embase, and ClinicalTrials.gov was carried out. All English language prospective randomized clinical trials published from date of database inception to November 21, 2021 were eligible for inclusion. All papers addressing arthroscopic knee surgery were eligible for inclusion regardless of timing of surgery, operation, surgical technique, or rehabilitation. Multiple random effects NMAs were conducted to compare all treatments for each outcome. The primary outcome was the incidence of pulmonary embolism (PE) and secondary outcomes consisted of overall deep vein thrombosis (DVT), symptomatic DVT, asymptomatic DVT, and all-cause mortality. Adverse outcomes consisted of major and minor bleeding, as well as adverse events. RESULTS: A total of nine studies with 4526 patients were included for analysis. There were 1054 patients in the no treatment/placebo group (NT/Placebo), 1646 patients in the graduated compression stockings, 810 patients in the extended-duration (> 10 days) low molecular weight heparin (Ext-LMWH) group, 650 patients in the short-duration (< 10 days) LMWH group (Short-LMWH), and 356 patients in the rivaroxaban group. GCS, Ext-LMWH, Short-LMWH and rivaroxaban all demonstrated low risks of PE, symptomatic DVT, asymptomatic DVT, combined DVT and all-cause mortality. Similarly, all interventions demonstrated a low risk of major bleeding. CONCLUSION: There is no significant difference in the risk reduction of PEs, symptomatic DVTs, major/minor bleeding, and/or all-cause mortality when using LWMH (including short or extended regimens), rivaroxaban, graduated compression stockings or no treatment following arthroscopic knee surgery. Future primary research on the efficacy of thromboprophylaxis following arthroscopic knee surgery should stratify outcomes based on key patient (i.e., age, sex, comorbidities) and surgical (i.e., major vs. minor surgery) characteristics and should include acetylsalicylic acid as an intervention. LEVEL OF EVIDENCE: I, network meta-analysis of Level I studies.

Enoxaparin Versus Direct Oral Anticoagulants for Venous Thromboembolism in Asians Undergoing Total Knee Arthroplasty: A Meta-Analysis and Systematic Review.

BACKGROUND: The introduction of direct oral anticoagulants (DOACs) shows promise for their role as a chemoprophylaxis agent after total knee arthroplasty (TKA) for the prevention of venous thromboembolism (VTE). However, existing studies are largely based on Western populations that do not account for the different risk profiles and lower rates of VTE in Asians. This systematic review and meta-analysis aimed to evaluate the efficacy of DOACs compared with enoxaparin in an Asian-based population study. METHODS: The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All studies that compared outcomes between enoxaparin and DOACs as VTE prophylaxis after TKA in the Asian population were included. RESULTS: Five studies with 121,153 patients were included. DOACs demonstrated a convincing benefit over enoxaparin in overall VTE prevention (odds ratio [OR] = 0.42, 95% confidence interval [CI]: 0.24-0.74). However, although the OR trended in favor of DOACs for the reduction of deep vein thrombosis events (OR = 0.54, 95% CI: 0.20-1.48) and pulmonary embolism (OR = 0.75, 95% CI: 0.07-8.20), statistical significance was not reached. In terms of bleeding complications, both arms had similar rates of major (0.91% vs 0.20%), clinically relevant nonmajor (3.28% vs 2.94%), and minor bleeding complications (12.8 vs 13.3%). A nonsignificance advantage of enoxaparin over DOACs was revealed in the OR for major bleeding (OR = 3.17; 95% CI: 0.81-12.43), whereas DOACs were favored to reduce risk of clinically relevant nonmajor (OR = 0.82; 95% CI: 0.01-91.51) and minor bleeding (OR = 0.76; 95% CI: 0.11-5.33). CONCLUSION: DOACs confer a significantly reduced rate of overall VTE compared with enoxaparin in Asians after TKA. No significant differences in deep vein thrombosis, pulmonary embolism, and rates of bleeding complications exist.

Sequential low molecular weight heparin and rivaroxaban for venous thromboprophylaxis in pelvic and acetabular trauma.

INTRODUCTION: Patients with pelvic trauma are at high risk of thromboembolic complications, but effective methods of prophylaxis are still to be accepted widely. The incidence of venous thromboembolism (VTE) has been reported to be as high as 61%, which represents the commonest cause of morbidity and mortality in this cohort. New oral anticoagulants are now available and may be used instead of LMWH injections for extended prophylaxis. Rivaroxaban has not been comprehensively considered in the previous pelvic and acetabular trauma literature, but its known benefits include increased patient compliance, especially in the minority of patients who are unable to self-administer injections, and that it does not require monitoring. MATERIALS AND METHODS: All patients referred to our pelvic trauma service between 2015 and 2020 were considered for this study, exclusion criteria involved those patients who had contraindications to rivaroxaban, those who were referred to our service but were never managed at our centre and those managed by other teams (e.g. neurosurgery). Operative patients were initially managed with LMWH until 24 h post-operatively when they started rivaroxaban. Conservatively managed patients started Rivaroxaban straight away. Data were collected on demographics, injury mechanism, fracture classification and clinically relevant VTE and bleeding events up until 3 months post discharge. RESULTS: The overall incidence of VTE was 2%. These represented 3 DVTs and 3 PEs, and occurred in patients who were managed operatively. No major bleeding events were observed. There were two minor bleeding events, both occurring in patients who were managed conservatively with rivaroxaban alone, and they did not require further intervention. 90% of patients surveyed expressed preference for oral prophylaxis. Reported compliance with rivaroxaban was 100%. CONCLUSION: Our data show that this VTE regimen protocol is safe and effective in this group of injured patients and is at least non-inferior to the standard prophylaxis of LMWH alone.

Should Emergency Physicians and Nurses Direct Their Patients to YouTube for Heparin Self-Injection Training? A Systematic Review of Social Media Videos.

BACKGROUND: The aim of this study was to examine the content, reliability, popularity, and quality of YouTube videos for patients learning how to self-administer subcutaneous low molecular weight heparin injections. METHODS: A systematic review of YouTube videos was conducted on August 20, 2021, using the keywords of "Low-molecular-weight heparin injection," "Enoxaparin injection," "Heparin injection," "Dalteparin injection," and "Tinzaparin injection." Two independent emergency physicians evaluated included videos separately with 5 different score systems (1- Journal of American Medical Association Score, 2-The Video Power Index, 3- Global Quality Scale, 4- Modified 5 Point DISCERN, 5- Total Comprehensiveness Score). RESULTS: Of 458 videos, a total of 161 unique videos were included. Of these, 94 (58.4%) were classified as useful and 67 (41.6%) as containing misleading information. The total number of views was 6,245,284 in useful information videos. DISCERN score (median 4, P < .001), Global Quality Score (median 4, P < .001), Journal of American Medical Association Score (median 4, P < .001), and Total Comprehensiveness Score (median 6, P < .001) were higher in the Useful Information Group. CONCLUSIONS: Nurse and physician prescreening and prescoring the accuracy and quality of specific low molecular weight heparin injection self-administration videos before recommending YouTube to patients is warranted. Policies to limit the spread of health misinformation through credibility scoring and evaluation are needed on social media sites such as YouTube.

Immune checkpoint inhibitors and potential risk of thromboembolic events: Analysis of the WHO global database of individual case safety reports.

Introduction: Thromboembolic events with the use of immune checkpoint inhibitors (ICIs) in patients with cancer have been reported in few studies. However, the detailed profile of these cases remains mostly uncertain. Method: A descriptive analysis of Thromboembolic events associated with ICIs retrieved from the VigiBase, between 1967 to November 2020. We extracted the data using the terms of 'pulmonary embolism' OR 'deep vein thrombosis' OR 'acute coronary syndrome' OR 'myocardial infarction' OR 'ischemic stroke' (preferred term (PT) (MedDRA). Results: We included 161 cases from 26 countries in our descriptive analysis. Patients' ages were reported in 141 (87.6%) cases, with a median of 68 years (interquartile range 61-74), and 63.4% of the patients were male. Indications for ICIs were reported in 151 (93.8%) cases, as follows: lung cancer (n = 85, 52.8%), renal cell carcinoma (n = 24, 14.9%), melanoma (n = 20, 12.4%), urethral carcinoma (n = 12, 7.45%), breast cancer (n = 4, 2.48%), adenocarcinoma of the gastroesophageal junction (n = 3, 1.9%), gastric cancer (n = 2, 1.24%), and skin cancer (n = 1, 0.62%). Nivolumab was reported as a suspected drug in 76 cases (47%), pembrolizumab in 46 cases (28.5%), atezolizumab in 21 cases (13%), durvalumab in 14 cases (8.6%), and avelumab in four cases (2.4%).The time to onset of thromboembolic events was reported in 127 (78.8%) cases. Most of these patients (n = 109, 85.8%) reported thromboembolic events within the first six months. The causality assessment of included cases showed that 50.3% of reported thromboembolic events were possibly related to the suspected reported medication, 13.7% were probably related, 13% were unlikely to be related, and 23% were not assessable due to insufficient information. Conclusion: This study demonstrates a possible association between the use of ICIs and thromboembolic events. Further epidemiological studies are needed to assess this association and to elucidate the underlying mechanism.