Symptomatic Venous Thromboembolic Events Research Articles

Evaluation of the Padua Prediction Score ability to predict venous thromboembolism in Israeli non-surgical hospitalized patients using electronic medical records

Venous thromboembolism (VTE) is considered a leading safety concern during hospitalization. The Padua Predication Score (PPS) is a risk model conceived to predict VTE among non-surgical hospitalized patients. The study aim was to evaluate the PPS ability to predict VTE in Israeli non-surgical hospitalized patients using data from electronic medical records. A single center, large-scale, historic cohort study of hospitalized non-surgical patients was conducted. Outcomes included clinically diagnosed symptomatic VTE events, bleeding events, and mortality during hospitalization and up to 90 days thereafter, and readmission up to 90 days after discharge. 5117 patient records were analyzed after screening and validation. 1120 (22%) patients were defined per PPS as high-risk, of which 277 (24.7%) were prophylactically treated. The low-risk group included 3997 (78%) patients. Prevalence of symptomatic VTE was low. Overall, 14 (0.27%) VTE events were diagnosed: 3 cases in the high-risk group (0.27%) and 11 (0.28%) in the low-risk group, with no significant difference, p = 0.768. Prophylactic treatment among the high-risk patients did not significantly improve VTE incidence: 1/277 (0.36%) treated vs. 2/843 (0.24%), p = 0.343. There was no significant difference between the study groups regarding the rates of bleeding, unexplained mortality or readmission. PPS was not found to be an efficient tool for identification of non-surgical hospitalized patients with high risk for clinically significant VTE.

Successful Secondary Endovascular Intervention in Pediatric Patients with Venous Thromboembolic Events.

In the past, pediatric patients with venous thromboembolic events (VTE) were treated with low-molecular-weight heparin (LMWH) which was successful in around 70% of the cases. However, anticoagulation alone might not restore patency in all patients, and advanced therapeutic options to prevent postthrombotic syndrome are needed. During recent years, endovascular interventions have become a treatment option for pediatric patients with persistent thrombotic occlusion, not only in life- or limb-threatening VTE. We evaluated 12 consecutive patients (11-17 years) with newly diagnosed VTE being treated at our department during the last 4 years (2017-2020). In case follow-up examination showed persistent venoocclusion under anticoagulation, patients received secondary interventional therapy like recanalization, percutaneous transluminal angioplasty with or without catheter-directed thrombolysis, and stenting. Patients with no clinical signs of venoocclusion or regredient thrombosis in imaging examination received anticoagulation alone. Six of 12 (50%) patients underwent catheter intervention. Median time from diagnosis to intervention was 4 months (0-12 months). Reintervention was necessary in one (8%) case and complete recanalization failed in one (8%) case. There were no major bleeding events or other major postinterventional complications, no acute or late local recurrence, and all patients reported clinical improvement after the procedure. If endovascular intervention is used in teenage patients with persistent symptomatic VTE, reduction of postthrombotic symptoms is possible, even if intervention is performed secondary to failure of anticoagulation. Multidisciplinary treatment decisions can be based on the clinical course and follow-up imaging.

Factors Associated With Risk of Postdischarge Thrombosis in Patients With COVID-19

COVID-19 is associated with a high incidence of thrombotic events; however, the need for extended thromboprophylaxis after hospitalization remains unclear. To quantify the rate of postdischarge arterial and venous thromboembolism in patients with COVID-19, identify the factors associated with the risk of postdischarge venous thromboembolism, and evaluate the association of postdischarge anticoagulation use with venous thromboembolism incidence. This is a cohort study of adult patients hospitalized with COVID-19 confirmed by a positive SARS-CoV-2 test. Eligible patients were enrolled at 5 hospitals of the Henry Ford Health System from March 1 to November 30, 2020. Data analysis was performed from April to June 2021. Anticoagulant therapy after discharge. New onset of symptomatic arterial and venous thromboembolic events within 90 days after discharge from the index admission for COVID-19 infection were identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. In this cohort study of 2832 adult patients hospitalized with COVID-19, the mean (SD) age was 63.4 (16.7) years (IQR, 53-75 years), and 1347 patients (47.6%) were men. Thirty-six patients (1.3%) had postdischarge venous thromboembolic events (16 pulmonary embolism, 18 deep vein thrombosis, and 2 portal vein thrombosis). Fifteen (0.5%) postdischarge arterial thromboembolic events were observed (1 transient ischemic attack and 14 acute coronary syndrome). The risk of venous thromboembolism decreased with time (Mann-Kendall trend test, P < .001), with a median (IQR) time to event of 16 (7-43) days. There was no change in the risk of arterial thromboembolism with time (Mann-Kendall trend test, P = .37), with a median (IQR) time to event of 37 (10-63) days. Patients with a history of venous thromboembolism (odds ratio [OR], 3.24; 95% CI, 1.34-7.86), peak dimerized plasmin fragment D (D-dimer) level greater than 3 μg/mL (OR, 3.76; 95% CI, 1.86-7.57), and predischarge C-reactive protein level greater than 10 mg/dL (OR, 3.02; 95% CI, 1.45-6.29) were more likely to experience venous thromboembolism after discharge. Prescriptions for therapeutic anticoagulation at discharge were associated with reduced incidence of venous thromboembolism (OR, 0.18; 95% CI, 0.04-0.75; P = .02). Although extended thromboprophylaxis in unselected patients with COVID-19 is not supported, these findings suggest that postdischarge anticoagulation may be considered for high-risk patients who have a history of venous thromboembolism, peak D-dimer level greater than 3 μg/mL, and predischarge C-reactive protein level greater than 10 mg/dL, if their bleeding risk is low.

Extended Thromboprophylaxis in Patients with COVID-19

IntroductionPatients hospitalized with COVID-19 have an increased incidence of venous thromboembolism (VTE) and arterial thromboembolism (ATE) events. These thrombotic events increase readmission and mortality rate in COVID-19 survivors who are recently discharged from hospital. To lower the risk of VTE, a short course of post-discharge anticoagulation at either prophylactic or therapeutic dose has been variably prescribed among different facilities to COVID-19 patients. This practice, however, is challenged by less than 3% incidence of VTE in unselected patients. The net clinical benefit of extended thromboprophylaxis beyond hospitalization remains unclear.MethodsWe conducted a retrospective multicenter observational study of 5613 hospitalized COVID-19 patients. After applying the inclusion and exclusion criteria, 2838 patients were included in statistical analysis. Patients were excluded if they had negative SARS-CoV-2 PCR, remained hospitalized at the time of analysis, or were discharged to hospice service. The first symptomatic ATE and VTE events up to 90 days after patients' discharge from their index admission for COVID-19 were identified using ICD-10 codes, and subsequently validated by chart review. The predictors for post-discharge VTE were identified using multivariate logistic regression. The average protective effect of anticoagulation was assessed using inverse propensity score weighting.ResultsThe mean age (SD) of our cohort was 63.4 (16.7) years old and 47.6% were male. Black, white and other races were 38.9%, 50.7% and 10.3%, respectively. Thirty-six (1.3%) patients developed post-discharge VTE events that require hospital visits (18 deep vein thromboses, 16 pulmonary embolisms and 2 portal vein thromboses). Fifteen (0.5%) patients developed post-discharge ATE events (14 acute coronary syndromes and 1 transient ischemic attack). The incidence of VTE decreased with time (p <.001) with the median event time of 16 days (Figure 1). The incidence of ATE was unchanged with time (p =.369) with the median event time of 37 days (Figure 1). Patients who had a history of VTE (OR=3.24, 95% CI 1.34-7.86), peak D-dimer >3 µg/mL (OR=3.76, 95% CI 1.86-7.57), and predischarge C-reactive protein >10 mg/dL (OR=3.02, 95% CI 1.45-6.29) were at a high risk of developing VTE after hospital discharge (Figure 2). A short course of prophylactic or therapeutic anticoagulation after hospital discharge markedly reduced VTE (OR=0, 95% CI 0-0, p<.001, and OR=0.176, 95% CI 0.04-0.75, p=.02, respectively).ConclusionsAlthough extended thromboprophylaxis in unselected COVID-19 patients is not recommended, post-discharge anticoagulation may be considered in high-risk patients who have a history of VTE, peak D-dimer >3 µg/mL and predischarge C-reactive protein >10 mg/dL if their bleeding risk is low. Our study has provided the first evidence to guide the selection of hospitalized COVID-19 patients who may benefit from post-discharge anticoagulation. [Display omitted] DisclosuresKaatz: Gilead: Consultancy; Novartis: Consultancy; CSL Behring: Consultancy; Bristol Myer Squibb: Consultancy, Research Funding; Alexion: Consultancy; Pfizer: Consultancy; Janssen: Consultancy, Research Funding; Osmosis Research: Research Funding.

Thrombin Generation As a Predictive Biomarker for Venous Thromboembolism in Patients with Pancreatic and Lung Cancer Undergoing Systemic Therapy

Introduction: Venous thromboembolism (VTE) is a leading cause of death in cancer patients, but routine thromboprophylaxis is untenable due to an unacceptably high rate of bleeding complications and judicious patient selection is critical. The Khorana score (KS) predicts the risk for chemotherapy-associated VTE, but the score has limitations because it is assessed only at one time point prior to initiation of treatment. Thrombin generation (TG) is a novel biomarker that assesses global coagulation activation and predicted increased VTE risk in cancer patients in the Vienna Cancer and Thrombosis Study (CATS). In CATS, patients with high peak TG had a 3- fold increased risk for VTE compared to those with low peak TG. A limitation of the study was that it enrolled a heterozygous cancer patient population, and peak TG was not reported by tumor type. Additionally, TG was only measured at enrollment into the study, not over time. The primary aim of our study was to determine if assessment of TG (both peak TG and endogenous thrombin potential (ETP)) improves VTE risk prediction compared to the KS alone during systemic therapy for lung and pancreas cancer. A secondary objective was to evaluate the impact of systemic therapy on peak TG and ETP over time.Methods: This is an ongoing prospective study enrolling adults with newly diagnosed locally advanced or metastatic adenocarcinoma of the lung or pancreas who will receive their cancer therapy at Dartmouth Hitchcock Medical Center. Those with a history of active VTE or use of full dose anticoagulant medication within 30 days prior to enrollment are excluded. After informed consent, KS is calculated and blood is collected in sodium citrate tubes at 3 different time points (at initiation of therapy, and at the beginning of the 2nd and 3rd cycles of systemic therapy). Platelet-poor plasma is prepared by centrifugation and stored at -80°C until analysis by calibrated automated thrombogram (CAT; Thrombinoscope BV, Maastricht, Netherlands) using 1 pM tissue factor and 4 uM phospholipids to trigger coagulation reactions. Measurements are performed in triplicate for each specimen, and raw data are converted to peak TG and ETP. Information about symptomatic VTE events within 6 months of study entry is collected from the medical record.Results: We present the results for 15 patients who have completed study-related procedures to date, including 6 lung and 9 pancreatic cancer patients with a median age 61 and 69 years, respectively. The majority of patients had metastatic disease and all patients received systemic therapy. The KS breakdown for the cohort is: KS1, 7%; KS2, 60%; KS3 27%; KS4 7%. Mean peak TG were 341, 324, 641 and 890 nmole, and mean ETP were 1459, 1685, 2155, 2051 nmole/min for KS 1,2,3 and 4, respectively, and both peak TG and ETP decreased over time after cancer therapy. VTE occurred in 4 patients (27%), and the median KS was 2 for patients with and without VTE. Mean peak TG prior to initiation of chemotherapy was similar in patients with and without VTE (359 and 389 nmole, respectively) but mean ETP was higher in patients with VTE (1959 vs 1760 nmole/min, respectively).Conclusions: Though our sample size to date is small, preliminary results suggest that there is a direct correlation between KS and peak TG and ETP, and that ETP at diagnosis may be a more reliable predictor VTE than KS in lung and pancreatic cancer patients. Peak TG and ETP decreased progressively after initiation of systemic therapy, suggesting that the degree of coagulation activation is proportional to tumor burden. Though preliminary, these data suggest that TG is a promising biomarker of VTE risk. Enrollment to the study is continuing.Funding: This study was funded by Northern New England Clinical Oncology Society. DisclosuresNo relevant conflicts of interest to declare.

Thromboembolic risk stratification by TRiP(cast) score to rationalise thromboprophylaxis in patients with lower leg trauma requiring immobilisation: a study protocol of the casting stepped-wedge cluster randomised trial

IntroductionPatients with lower limb trauma requiring orthopaedic immobilisation may be at risk of venous thromboembolism but opinions differ about who may benefit from thromboprophylactic anticoagulant treatment.The aim of this CASTING...

Post-acute conditions of patients with COVID-19 not requiring hospital admission

Post-acute conditions of patients with COVID-19 not requiring hospital admission

Incidence and clinical profile of venous thromboembolism in hospitalized COVID-19 patients from Madrid region

BackgroundCOVID-19 related in-hospital venous thromboembolism (VTE) incidence is high but data reported vary significantly. Some studies show that up to half of the events are diagnosed early after admission. ObjectivesTo study symptomatic VTE incidence in acute COVID-19 hospitalized patients and to describe timing of VTE diagnosis. MethodsMulticenter cohort of 5966 patients hospitalized with acute COVID-19. Multicenter Registry of 844 hospitalized patients with acute COVID-19 and associated acute VTE. ResultsBy the time of cohort data collection, 68 patients (1.14%) were still hospitalized, 19.8% had died, and 5.4% required ICU. During a median follow-up of 6 days (IQR, 4–12), 183 patients (3.07%; 95% CI, 2.64–3.55) presented a symptomatic VTE event. The cumulative incidences of VTE at 7, 14 and 21 days in wards [2.3% (95% CI, 1.9–2.7), 3.6% (95% CI, 3.0–4.3), and 4.3% (95% CI, 3.5–5.1)] were similar to the ones reported in ICU [2.2% (95% CI, 1.0–4.4), 2.9% (95% CI, 1.5–5.3), and 4.1% (95% CI, 2.2–6.8)], but at 30 and 60 days were higher in ICU [6.9% (95% CI, 4.2–10.5), and 12.8% (95% CI, 8.1–18.5)] than in wards. Eighty-eight VTE events (48%) were diagnosed early, within 48 h of admission. VTE was not associated with death (HR, 0.79; 95% CI, 0.55–1.12). ConclusionsIncidence of symptomatic VTE in our COVID-19 cohort is consistent with that of other real-life studies recently published. Early VTE events are, along with COVID-19, the reason for admission rather than an in-hospital complication.

Andexanet Alfa or Prothrombin Complex Concentrate for Factor Xa Inhibitor Reversal in Acute Major Bleeding: A Systematic Review and Meta-Analysis.

To combine evidence on andexanet alfa and prothrombin complex concentrates for factor Xa inhibitor-associated bleeding to guide clinicians on reversal strategies. Embase, Pubmed, Web of Science, and the Cochrane Library. Observational studies and randomized clinical trials studying hemostatic effectiveness of andexanet alfa or prothrombin complex concentrate for acute reversal of factor Xa inhibitor-associated hemorrhage. Two independent reviewers extracted the data from the studies. Visualization and comparison of hemostatic effectiveness using Sarode et al or International Society of Thrombosis and Hemostasis Scientific and Standardization Committee criteria at 12 and 24 hours, (venous) thrombotic event rates, and inhospital mortality were performed by constructing Forest plots. Exploratory analysis using a logistic mixed model analysis was performed to identify factors associated with effectiveness and venous thromboembolic event. A total of 21 studies were included (andexanet: 438 patients; prothrombin complex concentrate: 1,278 patients). The (weighted) mean effectiveness for andexanet alfa was 82% at 12 hours and 71% at 24 hours. The (weighted) mean effectiveness for prothrombin complex concentrate was 88% at 12 hours and 76% at 24 hours. The mean 30-day symptomatic venous thromboembolic event rates were 5.0% for andexanet alfa and 1.9% for prothrombin complex concentrate. The mean 30-day total thrombotic event rates for andexanet alfa and prothrombin complex concentrate were 10.7% and 3.1%, respectively. Mean inhospital mortality was 23.3% for andexanet versus 15.8% for prothrombin complex concentrate. Exploratory analysis controlling for potential confounders did not demonstrate significant differences between both reversal agents. Currently, available evidence does not unequivocally support the clinical effectiveness of andexanet alfa or prothrombin complex concentrate to reverse factor Xa inhibitor-associated acute major bleeding, nor does it permit conventional meta-analysis of potential superiority. Neither reversal agent was significantly associated with increased effectiveness or a higher rate of venous thromboembolic event. These results underscore the importance of randomized controlled trials comparing the two reversal agents and may provide guidance in designing institutional guidelines.

PO-81 Predicting symptomatic venous thromboembolic events in hospitalised children with cancer: prospective validation of a risk assessment model

PO-81 Predicting symptomatic venous thromboembolic events in hospitalised children with cancer: prospective validation of a risk assessment model

COVID-19 Infection in Critically Ill Patients Carries a High Risk of Venous Thrombo-embolism

ObjectiveThe coronavirus disease of 2019 (COVID-19) due to SARS-CoV-2 infection has been found to cause an increased risk of venous thrombo-embolism (VTE). The aims of the study were to determine the frequency of VTE in critically ill patients with COVID-19 and its correlation with D dimer levels and pharmacological prophylaxis.MethodsThis was a cohort study of critically ill patients due to COVID-19. All patients admitted to the intensive care unit on the same day of April 2020 were selected, regardless of length of stay, and a single bilateral venous duplex ultrasound in the lower extremities was performed up to 72 hours later. Pulmonary embolism (PE) was diagnosed by computed tomography angiography. Asymptomatic and symptomatic VTE were registered, including pre-screening in hospital VTE. Characteristics of patients, blood test results, doses of thromboprophylaxis received, VTE events, and mortality after seven day follow up were recorded.ResultsA total of 230 critically ill patients were studied. The median intensive care unit stay of these patients was 12 days (interquartile range [IQR] 5 – 19 days). After seven days follow up, the frequency of patients with VTE, both symptomatic and asymptomatic, was 26.5% (95% confidence interval [CI] 21% – 32%) (69 events in 61 patients): 45 with DVT and 16 with PE (eight of them with concomitant DVT). The cumulative frequency of symptomatic VTE was 8.3% (95% CI 4.7% – 11.8%). D dimer values ≥ 1 500 ng/mL were diagnostic of VTE, with a sensitivity of 80% and a specificity of 42%. During follow up after screening, six patients developed new VTE. Three of them developed a recurrence after a DVT diagnosed at screening, despite receiving therapeutic doses of heparin. Mortality rates at seven day follow up were the same for those with (6.6%) and without (5.3%) VTE.ConclusionPatients with severe COVID-19 infection are at high risk of VTE, and further new symptomatic VTE events and recurrence can occur despite anticoagulation. The prophylactic anticoagulant dose may need to be increased in patients with a low risk of bleeding.

Safety and effectiveness of biosimilar enoxaparin (Inhixa) for the prevention of thromboembolism in medical and surgical inpatients.

In 2016, biosimilar enoxaparin (Inhixa®, Techdow) was introduced in European markets with the same indications as branded enoxaparin (Clexane®, Sanofi). Its use is constantly increasing in clinical practice, however, little information from post-marketing clinical trials is available on its safety and effectiveness. We conducted an observational, retrospective study to assess the safety and effectiveness of Inhixa in preventing venous thromboembolism (VTE) in medically ill patients and in patients undergoing major abdominal surgery. We then compared our results with the incidence of symptomatic VTE and bleeding events during treatment with Clexane by pooling the results of clinical studies carried out in the same settings. We enrolled 381 patients, 189 admitted to a Medical Department and 192 to a Surgical Department from two single institutions. The incidence of major bleeding events was 1.8% globally (95% IC 0.7-3.8), 1.6% in medical patients (95% IC 0.3-4.6) and 2.1% in surgical patients (95% IC 0.6-5.3). VTE rate was 0.5% in the whole population (95% IC 0.1-1.9) and 0.5% (95% IC 0.01-2.9) in each group, respectively. The pooled estimate of the incidence of major bleeding with Clexane was 0.5% (IC 95%: 0.2-1.1) in medical patients and 2.6% (IC 95% 1.3-5.1) in surgical patients. The incidence of thrombotic events was 0.6% (IC 95%: 0.2-1.8) and 0.7% (CI95% 0.3-1.6), respectively. The incidence of bleeding and thrombosis in medical and surgical patients receiving Inhixa was low suggesting biosimilar enoxaparin is a valid alternative to branded enoxaparin.

Ambulatory Portable Pneumatic Compression Device as Part of a Multimodal Aspirin-Based Approach in Prevention of Venous Thromboembolism in Outpatient Total Knee Arthroplasty.

BackgroundThe purpose of this study is to review the incidence of symptomatic venous thromboembolism (VTE) in patients undergoing outpatient primary total knee arthroplasty (TKA) who used a portable pneumatic compression device as part of their VTE prophylaxis protocol.MethodsA retrospective review of all outpatient primary TKA procedures in which patients used ambulatory pneumatic compression pumps as part of their multimodal VTE prophylaxis was performed from 2016 through 2018. This yielded a cohort of 1131 patients (1453 TKAs). An aspirin (ASA)-based protocol was used in patients with standard VTE risk receiving either 81 mg or 325 mg of ASA twice daily for 6 weeks postoperatively. High-risk patients received a stronger chemoprophylaxis for 2 weeks followed by ASA for 4 weeks. Pneumatic compression pumps were worn for 23 hours/day for 14 days.ResultsVTE prophylaxis medication was 81-mg ASA in 56% of patients, 325-mg ASA in 10% of patients, and stronger chemoprophylaxis in 34% of patients. Patients were considered morbidly obese (body mass index >40 kg/m2) in 267 (18.4%) procedures. Ninety-seven (6.7%) patients had a preoperative history of VTE event. Forty-nine duplex ultrasounds were performed (3.3% of TKAs). Confirmed VTE events were documented in only 5 (0.3%) patients. All VTEs occurred in high-risk patients who were discharged on stronger chemoprophylaxis. The time (days) to VTE was 3, 3, 7, 45, and 88 days.ConclusionThe use of portable pneumatic compression pumps as part of a multimodal VTE prophylaxis protocol aided in a very low rate of symptomatic VTE events in patients undergoing outpatient primary TKA.

Intravenous Tranexamic Acid Safely and Effectively Reduces Transfusion Rates in Revision Total Knee Arthroplasties.

The efficacy and safety of tranexamic acid (TXA) in primary total knee arthroplasty (TKA) have been well established. However, there have been limited data for revision TKAs. The primary aim was to assess the impact of intravenous TXA on transfusion rates and symptomatic venous thromboembolic events (VTEs) in a large revision TKA cohort with or without intravenous TXA utilization. A retrospective review of revision TKAs performed from 2005 to 2014 was performed, identifying 2,951 procedures (2,219 patients), in which TXA was utilized in 1,144 procedures (39%). The mean age was 65 years with 52% female patients in the TXA revision group and 67 years with 52% female patients in the non-TXA revision group. Transfusion rates and symptomatic VTEs were the primary outcomes assessed. Comparisons were performed between cohorts, utilizing a unique propensity model to mitigate bias, on the basis of TXA use and subsequently for aseptic or septic revision etiology. Significant reductions in transfusion rates with use of TXA were identified in revision TKAs overall (13% compared with 39%; p < 0.001 [adjusted relative risk, 1.7]), including revisions for both aseptic etiology (6% with TXA compared with 28% without TXA; p < 0.001) and septic etiology (31% with TXA compared with 54% without TXA; p < 0.001). The risk of a postoperative symptomatic VTE was not significantly different (adjusted p = 0.63) with use of TXA at 11 events (1.0%) compared with 24 events (1.3%) in the non-TXA group). Intravenous TXA significantly reduced transfusion rates in revision TKAs by approximately twofold, including cohorts revised for aseptic and septic etiologies. There was a very low rate of VTEs (1.2%) with no significant difference in the number of VTEs between groups after adjusting risk utilizing propensity modeling. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Rivaroxaban and Extended Thromboprophylaxis in Acutely Ill Medical Patients with History of Cancer: Insights from the Magellan and Mariner Studies

Rivaroxaban and Extended Thromboprophylaxis in Acutely Ill Medical Patients with History of Cancer: Insights from the Magellan and Mariner Studies

Symptomatic Thromboembolic Complications After Shoulder Arthroplasty: An Update.

Venous thromboembolism (VTE) complications, including deep vein thrombosis and pulmonary embolism, are dreaded complications of orthopaedic surgical procedures that can result in substantial morbidity and mortality. There is a paucity of data examining risk factors for VTE in shoulder arthroplasty. The purpose of the present study was to review the rate of symptomatic VTE, determine patient and operative risk factors for VTE, and report on complications associated with VTE following shoulder arthroplasty. Over a 16-year period, 5,906 patients underwent primary anatomic total shoulder arthroplasty, reverse total shoulder arthroplasty, or hemiarthroplasty. Symptomatic VTE events were identified in 24 shoulders within 90 days of surgery. Patient records were reviewed for surgical indication, patient and operative risk factors, and management of VTE. The rate of symptomatic VTE following shoulder arthroplasty was 0.41%. There were no deaths resulting from VTE events. Compared with patients who did not have VTE, those with symptomatic VTE events were found to be older (74.75 versus 68.51 years; p = 0.0028) and more likely to have had arthroplasty for a traumatic indication (3.31% versus 0.33%; p < 0.001). Age of >70 years and arthroplasty for a traumatic indication were found to be independent risk factors on multivariate nominal logistic regression analysis, whereas body mass index, sex, operative time, and type of arthroplasty performed were not found to be independent risk factors. There were 11 readmissions resulting directly from the VTE events, and patients diagnosed with VTE as inpatients had longer hospital stays than outpatients (13.71 versus 1.94 days; p = 0.0002). The risk of VTE following shoulder arthroplasty is low, and routine use of pharmacologic VTE prophylaxis may not be necessary. However, VTE complications can lead to substantial morbidity, longer hospital stays, readmission to the hospital, and further complications. Therefore, patients with multiple risk factors for VTE such as prior history of VTE, active malignancy, age of >70 years, or arthroplasty for traumatic indications should be considered for pharmacologic VTE prophylaxis. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Intravenous tranexamic acid safely and effectively reduces transfusion rates in revision total hip arthroplasty.

Tranexamic acid (TXA) has been shown to significantly reduce transfusion rates in primary total hip arthroplasties (THAs), but high-quality evidence is limited in the revision setting. The purpose of the current study was to compare the rate of blood transfusions and symptomatic venous thromboembolic events (VTEs) in a large cohort of revision THAs treated with or without intravenous (IV) TXA. We performed a retrospective review of 3264 revision THAs (2645 patients) between 2005 and 2014, of which 1142 procedures received IV TXA (1 g at incision and 1 g at closure). The mean age in the revision group with TXA was 65 years (28 to 95), with 579 female patients (51%). The mean age in the revision group treated without TXA was 67 years (21 to 98), with 1160 female patients (55%). Outcomes analyzed included rates of transfusion and symptomatic VTEs between procedures undertaken with and without TXA. These comparisons were performed for the overall cohort, as well as within cases subcategorized for aseptic or septic aetiologies. A propensity score was developed to minimize bias between groups and utilized age at revision THA, sex, body mass index, American Society of Anesthesiologists (ASA) score, preoperative anticoagulation, and year of surgery. Tranexamic acid significantly and substantially reduced the rate of blood transfusions after revision THA overall from 54% to 26% (p < 0.001; adjusted relative risk (RR) 1.6; 95% confidence interval (CI) 1.3 to 1.9), with a significant reduction in both aseptic (49% to 18%; p < 0.001) and septic (73% to 53%; p = 0.04) revisions. The rate of VTE was minimal overall, with three events (0.3%) in the TXA group and four events (0.2%) in the non-TXA group. There were no significant differences in VTE rates based on TXA use or aetiology of revision. Intravenous TXA significantly reduced transfusion rates during all-cause revision THAs, including a subgroup analysis of both aseptic and septic cohorts. Adjusted risk using propensity modelling showed no statistical difference in rates of VTEs between either group. Cite this article: Bone Joint J 2019;100-B(6 Supple B):104-109.

Safety of low-dose subcutaneous recombinant interleukin-2: systematic review and meta-analysis of randomized controlled trials

Standard-dose intravenous recombinant interleukin-2 (rIL-2) is indicated for the treatment of some subtypes of cancer; however, severe adverse events, including venous thromboembolism (VTE), may complicate its administration. Low-dose subcutaneous rIL-2 is being studied for the management of immune-mediated diseases, since it can modulate the immunological response by specifically targeting T regulatory (Treg) cells; importantly, it is supposed to cause fewer or no complications. In this systematic review and meta-analysis of phase II-III randomized controlled trials (RCTs), we investigated the safety of low-dose (<6 Million International Unit [MIU]/day) and ultra-low-dose (≤1 MIU/day) rIL-2 for severe adverse events (grade III-V) with a focus on VTE. Data of 1,321 patients from 24 RCTs were analysed: 661 patients were randomized to the rIL-2 arm (on top of standard of care) and 660 patients to standard of care alone or placebo. Two studies reported higher rates of thrombocytopenia in the low-dose rIL-2 arm. Ultra-low-dose rIL-2 was reported to be well tolerated in 6 studies with a negligible rate of severe adverse events. Symptomatic VTE events were not reported in any of the study arms (absolute risk difference 0% [95%CI −0.1%; +0.1%]). Our results may facilitate the study and introduction in clinical practice of low-dose rIL-2 for potentially new indications.

Extended prophylaxis for venous thromboembolism after hospitalization for medical illness: A trial sequential and cumulative meta-analysis.

BackgroundThe efficacy, safety, and clinical importance of extended-duration thromboprophylaxis (EDT) for prevention of venous thromboembolism (VTE) in medical patients remain unclear. We compared the efficacy and safety of EDT in patients hospitalized for medical illness.Methods and findingsElectronic databases of PubMed/MEDLINE, EMBASE, Cochrane Central, and ClinicalTrials.gov were searched from inception to March 21, 2019. We included randomized clinical trials (RCTs) reporting use of EDT for prevention of VTE. We performed trial sequential and cumulative meta-analyses to evaluate EDT effects on the primary efficacy endpoint of symptomatic VTE or VTE-related death, International Society on Thrombosis and Haemostasis (ISTH) major or fatal bleeding, and all-cause mortality. The pooled number needed to treat (NNT) to prevent one symptomatic or fatal VTE event and the number needed to harm (NNH) to cause one major or fatal bleeding event were calculated.Across 5 RCTs with 40,247 patients (mean age: 67–77 years, proportion of women: 48%–54%, most common reason for admission: heart failure), the duration of EDT ranged from 24–47 days. EDT reduced symptomatic VTE or VTE-related death compared with standard of care (0.8% versus 1.2%; risk ratio [RR]: 0.61, 95% confidence interval [CI]: 0.44–0.83; p = 0.002). EDT increased risk of ISTH major or fatal bleeding (0.6% versus 0.3%; RR: 2.04, 95% CI: 1.42–2.91; p < 0.001) in both meta-analyses and trial sequential analyses. Pooled NNT to prevent one symptomatic VTE or VTE-related death was 250 (95% CI: 167–500), whereas NNH to cause one major or fatal bleeding event was 333 (95% CI: 200–1,000). Limitations of the study include variation in enrollment criteria, individual therapies, duration of EDT, and VTE detection protocols across included trials.ConclusionsIn this systematic review and meta-analysis of 5 randomized trials, we observed that use of a post-hospital discharge EDT strategy for a 4-to-6-week period reduced symptomatic or fatal VTE events at the expense of increased risk of major or fatal bleeding. Further investigations are still required to define the risks and benefits in discrete medically ill cohorts, evaluate cost-effectiveness, and develop pathways for targeted implementation of this postdischarge EDT strategy.Trial registrationPROSPERO CRD42018109151.

Incidence of Symptomatic Venous Thromboembolism in Patients with Hemophilia Undergoing Hip and Knee Joint Replacement without Chemoprophylaxis: A Retrospective Study.

ObjectiveTo establish the prevalence of clinically significant venous thromboembolic events (VTE) in hemophilia patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) without chemoprophylaxis and a modified coagulation factor substitution.MethodsA cohort of patients who underwent THA and TKA from June 2002 to April 2017 were included. Based on World Federation of Hemophilia (WFH) guidelines, a modified coagulation factor substitution regimen was adopted. All patients were under a standardized postoperative protocol with routine mechanical prophylaxis against VTE. None of the patients received prophylactic anticoagulation. Only symptomatic patients were referred for radiological examination to exclude VTE. We evaluated the patient demographics and calculated the prevalence of VTE in our cohort.ResultsA total of 98 patients were reviewed. The patients were all men. Thirty‐one patients underwent primary THA with 39 hip arthroplasties (only 1 case with hemophilia B) and 67 patients underwent primary TKA with 101 knee arthroplasties (5 cases with hemophilia B). The mean age was 34.2 ± 7.8 years. The mean body mass index was 21.2 ± 5.7 kg/m2. There was 100% compliance to mechanical prophylaxis. The mean time to ambulation was 6.8 days (±2.5 days), and the mean hospital stay was 32.4 days (±7.1 days). There was only 1 hemophilia B patient with clinically significant VTE. None of the other 97 surgical cases had symptomatic VTE within 6 months after the procedure. This translates to a prevalence of 1.02%.ConclusionGiven the low incidence (1.02%) of clinically significant VTE in our cohort, routine chemoprophylaxis in hemophilia patients undergoing THA and TKA may not be needed.