Duration Of Thromboprophylaxis Research Articles

Examining postpartum anticoagulation practices: An international survey of healthcare providers

BackgroundThe risk of venous thromboembolism (VTE) is 15 to 35-fold higher in the postpartum period compared to non-pregnant individuals. Clinical practice guidelines recommend the use of postpartum thromboprophylaxis with low molecular weight heparin (LMWH) for 6 weeks in individuals at high risk of developing VTE. However, a marked reduction in the risk of VTE risk occurs beyond the third week of the postpartum period. ObjectiveWe sought to characterize practice patterns of clinicians who manage postpartum individuals at high risk of VTE. MethodsWe conducted a cross-sectional study using a self-administered electronic questionnaire. The survey explored the use of postpartum thromboprophylaxis in high-risk individuals. Descriptive statistics were used to summarize survey responses. ResultsOf the 113 participants that responded to the initial invitation, 78 completed the survey (Europe (53.9 %); North America (23.2 %); Australia and New Zealand (19.0 %)). For individuals with a prior unprovoked or provoked deep venous thrombosis or pulmonary embolism, cerebral vein thrombosis and splanchnic vein thrombosis, 97.4 %, 93.5 %, 91.0 % and 88.5 % of the respondents recommended six weeks of postpartum thromboprophylaxis using LMWH, respectively. The recommendation for 6 weeks of thromboprophylaxis in patients with sickle cell disease and obstetric APS was comparatively lower (70.5 and 78.2 % respectively). Respondents with higher practice volumes and more years of experience in clinical practice were more likely to recommend a shorter duration of thromboprophylaxis. ConclusionOur study highlights the variability in clinician recommendations and the acceptability of treatment durations for postpartum thromboprophylaxis in high-risk conditions. Prospective studies are needed to determine optimal duration and establish evidence-based management.

Enhancing thromboprophylaxis after colorectal cancer surgery in China: Bridging the gap between evidence and implementation through pathway optimization.

The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.

Pancreatic Cancer and Venous Thromboembolism.

Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of all pancreatic cancers and is the most fatal of all cancers. The treatment response from combination chemotherapies is far from satisfactory and surgery remains the mainstay of curative strategies. These challenges warrant identifying effective treatments for combating this deadly cancer. PDAC tumor progression is associated with the robust activation of the coagulation system. Notably, cancer-associated thrombosis (CAT) is a significant risk factor in PDAC. CAT is a concept whereby cancer cells promote thromboembolism, primarily venous thromboembolism (VTE). Of all cancer types, PDAC is associated with the highest risk of developing VTE. Hypoxia in a PDAC tumor microenvironment also elevates thrombotic risk. Direct oral anticoagulants (DOACs) or low-molecular-weight heparin (LMWH) are used only as thromboprophylaxis in PDAC. However, a precision medicine approach is recommended to determine the precise dose and duration of thromboprophylaxis in clinical setting.

Efficacy and Safety of Extended Duration Postoperative Thromboprophylaxis with Low-Molecular-Weight-Heparin Among Subgroups of Patients Undergoing Surgical Resection of Colorectal Cancer: A Post-Hoc Analysis of the Periop-01 Trial

Background: Clinical practice guidelines suggest the use of extended duration of postoperative thromboprophylaxis to prevent venous thromboembolic (VTE) complications after any cancer-related major abdominal or pelvic surgeries. However, recent trials including patients undergoing surgical resection of colorectal cancer have reported relatively low rates of symptomatic VTE. Hence, the risk and benefits of extended postoperative thromboprophylaxis need to be carefully assessed in this patient population. We sought to determine the impact of extended duration thromboprophylaxis with low-molecular-weight-heparin on VTE and bleeding events among different subgroups of patients undergoing surgical resection of localized colorectal cancer. Methods: This is a pre-planned post-hoc analysis of the PERIOP-01 randomized controlled trial which compared extended (up to 6 weeks) to standard duration (in hospital only) of perioperative thromboprophylaxis with tinzaparin (4500 IU SC daily) in patients undergoing surgical resection of localized colorectal cancer. Subgroup analyses were performed based on different baseline characteristics. The primary efficacy and safety outcomes were objectively documented major VTE and combination of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) events, respectively. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using the Cox proportional hazards model to compare the treatment effect accounting for clustering at study center level. Results: A total of 614 patients were randomized in the PERIOP-01 trial (307 in the extended and 307 in the standard duration thromboprophylaxis groups). Overall, the mean age of the participants was 61 years, 41% of them were women, and most patients were white (90%). Type of primary cancer was well-balanced with 311 patients having rectal cancer (51%), whereas 303 (49%) had primary colon cancer. During the study period, major VTE events occurred in 2% and 1% of the extended- and standard-duration prophylaxis groups, respectively (P=0.8). Combination of MB and CRNMB events occurred in 3% of each group. No specific characteristics were found to be associated with a decreased risk of major VTE among patients on extended duration thromboprophylaxis (Figure 1). Patients with colon cancer resection receiving extended thromboprophylaxis were at an increased risk of bleeding complication compared to patients with rectal cancer (HR 2.57, 95%CI 1.25-5.3) (Figure 1). Other characteristics that may be associated with an increased risk of bleeding among patient on extended thromboprophylaxis included age >= 75 (HR 2.37, 95%CI 0.47-11.98) and male sex (HR 2.13, 95%CI 0.2-23.17), although these characteristics were not statistically significant. Conclusions: In the PERIOP-01 trial, extended thromboprophylaxis didn't reduce the risk of major VTE in any subgroups of patients. On the other hand, extended duration of thromboprophylaxis may be associated with an increased bleeding risk among male, elderly patients, and those with colon cancer.

Real world data for venous thromboembolisms (VTEs) in patients with active cancer: Thromboprophylaxis pooled analysis from GMaT and ACT4CAT studies.

6637 Background: Venous Thromboembolisms (VTEs) lead to many negative consequences for patients with active cancer and are reported up to 20%. They affect anticancer treatment plan, increase morbidity, mortality, economic burden, and escalate psychological drain. Current guidelines recommend pharmacologic prophylaxis for thrombosis in ambulatory cancer patients with Khorana score ≥2. Methods: GMaT and ACT4CAT are prospective observational phase IV studies conducted by HeSMO in Greece. The aim was to record the clinical practice for ambulatory patients with active cancer who received thromboprophylaxis and enrolled after signing informed consent. Studies were approved by the bioethics committee. Results: 1157 patients from 26 oncology clinics enrolled who received thromboprophylaxis. Tumor types: gastrointestinal 38.5%, lung 24.8%, urological 12.2%, gynecological 6.9%, breast 6.1% and others 11.5%. Treatment lines: 1st 62.5%, 2nd 15.1%, 3rd 4%, adjuvant 9.7% and neoadjuvant 5.9%. Age ≥65 in 55.2%, BMI ≥30 in 17.8% and males 59.9%. High-Risk for Thrombosis Agents (HRTAs) received 82.3%: platinum agents (52.9%), antimetabolites (49.0%) and immunotherapy (10.2%). Notably, 52.7% of anticancer agents had potential drug-drug interactions (DDIs) with Direct Oral Anticoagulants (DOACs). High thrombotic risk factors presented in table. Thromboprophylaxis duration was 5.1±3.3 months with: tinzaparin 91.2%, fondaparinux 4.6%, bemiparin 2.3%, enoxaparin 1.2%, rivaroxaban 0.4% and apixaban 0.3%. Intermediate thromboprophylaxis doses of Low Molecular Weight Heparins (LMWHs) received 62% of patients; 50% in adjuvant setting & 72.6% in metastatic. 32 thrombotic events reported (efficacy: 97.2%, 95%CI: 96.3-98.2%) and 26 grade 1 or minor bleedings (2.2%, 95%CI:1.4-3.1%). Patients receiving intermediate doses of LMWHs had less risk for thrombosis (p=0.0308). Conclusions: VTEs prophylaxis in ambulatory patients with active cancer was found safe and effective. Apart from Khorana score, metastasis, HRTAs and DDIs seem to affect clinical decision for thromboprophylaxis mainly with LMWHs and often using intermediate doses irrelevant of clinical setting. Cancer Associated Thrombosis (CAT) is not negligible risk for patients and oncologists appeared to be aware about this. Clinical trial information: NCT03292107 , NCT03909399 . [Table: see text]

Impact of thromboprophylaxis on hospital acquired thrombosis following discharge in patients admitted with COVID-19: Multicentre observational study in the UK.

Post-discharge thromboprophylaxis in patients admitted with COVID-19 remains controversial. We aimed to determine the impact of thromboprophylaxis on hospital acquired thrombosis (HAT) in patients (≥18 years) discharged following admission for COVID-19 in an observational study across 26 NHS Trusts in the UK (01.04.2020-31.12.2021). Overall, 8895 patients were included to the study: 971 patients were discharged with thromboprophylaxis and propensity score matched (PSM) with a desired ratio of 1:1, from patients discharged without thromboprophylaxis. Patients with heparin induced thrombocytopenia, major bleeding during admission and pregnant women were excluded. As expected from 1:1 PSM, no difference was observed in parameters between the two groups, including duration of hospital stay, except the thromboprophylaxis group had a significantly higher proportion who had received therapeutic dose anticoagulation during admission. There were no differences in the laboratory parameters especially D-dimers between the two groups at admission or discharge. Median duration of thromboprophylaxis following discharge from hospital was 4 weeks (1-8 weeks). No difference was found in HAT in patients discharged with TP versus no TP (1.3% vs. 0.92%, p = 0.52). Increasing age and smoking significantly increased the risk of HAT. Many patients in both cohorts had raised D-dimer at discharge but D-dimer was not associated with increased risk of HAT.

Effect of extended duration of thromboprophylaxis for medically ill patients

BackgroundThere are knowledge gaps regarding the comparative efficacy and safety of various venous thromboprophylaxis regimens with extended timing in patients hospitalized for acute medical illnesses. This study aims to investigate the optimal regimen for the prevention of venous thromboembolism in these patients. MethodsWe conducted a Bayesian network meta-analysis of randomized controlled trials (RCTs) comparing different venous thromboprophylaxis regimens for acutely ill medical patients. Outcomes included venous thromboembolism, major bleeding, and all-cause mortality. Risk ratios (RR) and associated 95% credible interval (CrI) were estimated. In addition, we assessed the most effective interventions in a subgroup of patients with stroke. ResultsWe identified five RCTs involving 40,124 patients. Extended thromboprophylaxis with direct oral anticoagulant (DOAC) (RR 0.78, 95% CrI 0.68 to 0.89) and low molecular weight heparin (LMWH) (RR 0.62, 95% CrI 0.45 to 0.84) were superior to standard therapy in the prevention of venous thromboembolism. However, both of them (DOAC: RR 1.99, 95% CrI 1.38 to 2.92; LMWH: RR 2.56, 95% CrI 1.26 to 5.68) lead to a significant increase in major bleeding). Moreover, both LMWH (RR 0.76, 95% CrI 0.57 to 1.00) and DOAC (RR 0.86, 95% CrI 0.76 to 0.98) with extended thromboprophylaxis showed favorable net clinical benefit compared to standard therapy. ConclusionsExtended thromboprophylaxis, especially with LMWH, showed better efficacy in venous thromboembolism reduction with increased risk of major bleeding. The beneficial effect of LMWH with extended timing has also been shown in stroke patients. Overall, extended thromboprophylaxis is associated with a positive net clinical benefit.

Time to rethink extended thromboprophylaxis after cancer surgery?

Venous thromboembolism (VTE) is an important cause of perioperative morbidity and mortality in patients with cancer [1,2]. Thromboprophylaxis initiated in the postoperative period and continued until hospital discharge can reduce the risk of symptomatic VTE by up to 70% [3,4]. However, the risk of VTE may be sustained beyond hospitalization especially in patients undergoing cancer-related surgeries [5]. Hence, current clinical practice guidelines recommend extended duration of thromboprophylaxis for up to 4 weeks after cancer-related major abdominal or pelvic surgery [6–8].

The early and long-term occurrence of symptomatic venous thromboembolism after lung cancer surgery without extended thromboprophylaxis-a single center experience with 435 patients.

The incidence of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), after lung cancer resections varies in the literature, and there is limited evidence regarding the optimal duration of thromboprophylaxis. This study aimed at determining the early and long-term occurrence of thromboembolic complications in patients who received in-hospital thromboprophylaxis and underwent resective surgery for lung cancer. The study included all patients who underwent lung cancer surgery at Tampere University Hospital between 2004 and 2016. Postoperative thromboprophylaxis was administered for the duration of the hospitalization. Data on subsequent episodes of VTE and survival were obtained from national registries. The results were compared to a demographically matched reference population. The study comprised 435 patients and 4,338 individuals in the reference population. The overall occurrence of VTE in patients and the reference group was 0.3% vs. 0.2% at 90 days (P=0.56), 3.5% vs. 0.7% at 1 year (P<0.001), 9.2% vs. 2.2% at 3 years (P<0.001), and 18.7% and 3.9% at 5 years (P<0.001), respectively. The majority of cases represented PE. The overall mortality at 5 years was 44.4% vs. 11.6% (P<0.001). No associations between patient characteristics and the occurrence of VTE during follow-up were detected. Patients undergoing lung cancer surgery and who receive in-hospital medical thromboprophylaxis do not seem to be in high risk for symptomatic VTE during the early postoperative period. However, during long-term follow-up the occurrence of symptomatic VTE was significant.

Association between duration of anticoagulant thromboprophylaxis and revision rate in primary total hip arthroplasty: a Danish and Norwegian nationwide cohort study.

There are concerns that bleeding following primary total hip arthroplasty (THA) contributes to prolonged wound drainage and prosthetic joint infection (PJI). We examined whether short (1-5 days), medium (6-14 days), and extended (≥ 15 days) duration of thromboprophylaxis is associated with the 5-year revision rate after THA due to osteoarthritis. We performed a cohort study based on data from hip arthroplasty and administrative registries in Denmark and Norway (2008-2014). The outcome was revision surgery due to PJI, aseptic loosening or any cause, and patient mortality. Adjusted cause-specific hazard ratios (HRs) were analyzed with Cox regression analyses. Among 50,482 THA patients, 8,333 received short, 17,009 received medium, and 25,140 received extended thromboprophylaxis. The HRs for revision due to PJI within 5 years were 1.0 (95%CI 0.7-1.3) and 1.1 (CI 0.9-1.3) for short and extended vs. medium treatment, whereas HR for extended vs. medium prophylaxis was 1.5 (CI 1.2-2.0) within 3 months. The HRs for revision due to aseptic loosening within 5 years were 1.0 (CI 0.7-1.4) and 1.1 (CI 0.9-1.4) for short and extended vs. medium treatment. The HRs for any revision within 5 years were 0.9 (CI 0.8-1.1) and 0.9 (CI 0.8-1.0) for short and extended vs. medium treatment. Extended vs. medium prophylaxis was associated with a decreased 0-3 month mortality. The absolute differences at 5 years were ≤ 1%. Our data suggests no association between duration of anticoagulant thromboprophylaxis and revision rate within 5 years of primary THA. The extended thromboprophylaxis might be associated with early increased revision rate due to PJI but also with lower mortality; however, the clinical relevance of this finding requires further research.

Risk of venous thromboembolism and bleeding after major surgery for ovarian cancer: standard in-hospital versus extended duration of thromboprophylaxis

BackgroundVenous thromboembolism (VTE) is a frequent complication in patients with ovarian cancer after major surgery. Based on limited data, international guidelines recommend extended thromboprophylaxis for up to 28 days. ObjectivesTo assess the incidence of VTE and bleeding within 30 days following major surgery in patients with ovarian cancer and to evaluate the association between VTE and thromboprophylaxis duration. MethodsThis was a single-center, retrospective, “before-after” cohort study in patients with ovarian cancer undergoing major surgery. Before July 2019, the local protocol mandated a standard course of thromboprophylaxis during hospital stay only. From July 2019 onward, patients received extended thromboprophylaxis for 28 days. The cumulative incidences of VTE and major bleeding within 30 days after surgery were estimated using the Kaplan-Meier method, with 95% confidence intervals (CIs). Cox regression analysis was performed to evaluate the association between thromboprophylaxis duration and VTE incidence. ResultsBetween January 2018 and December 2020, 250 women were included, of which 118 (47.2%) received extended and 132 (52.8%) standard thromboprophylaxis. During follow-up, 12 patients developed VTE (cumulative incidence, 4.8%; 95% CI, 2.1–7.4) and 2 major bleeding (cumulative incidence 0.8%; 95% CI, 0.0–1.9). Compared with standard thromboprophylaxis, VTE incidence was numerically lower with extended duration of thromboprophylaxis (5/118 [4.2%] vs 7/132 [5.3%]) but not significantly different (hazard ratio, 0.80; 95% CI, 0.25–2.52). The risk of major bleeding was similar in both groups (1/118 [0.8%] vs 1/132 [0.8%]; hazard ratio, 1.12; 95% CI, 0.07–17.89). ConclusionsThe cumulative VTE incidence in patients with ovarian cancer following major surgery was considerable. Extended thromboprophylaxis was safe and associated with a numerically lower risk of VTE but not significantly different.

Thromboprophylaxis for venous thromboembolism prevention in hospitalized patients with cirrhosis: Guidance from the SSC of the ISTH

Hospital‐associated venous thromboembolism (HA‐VTE) is a major cause of morbidity and mortality and is internationally recognized as a significant patient safety issue. While cirrhosis was traditionally considered to predispose to bleeding, these patients are also at an increased risk of VTE, with an associated increase in mortality. Hospitalization rates of patients with cirrhosis are increasing, and decisions regarding thromboprophylaxis are complex due to the uncertain balance between thrombosis and bleeding risk. This is further accentuated by derangements of hemostasis in patients with cirrhosis that are often considered contraindications to pharmacological thromboprophylaxis. Due to the strict inclusion and exclusion criteria of seminal studies of VTE risk assessment and thromboprophylaxis, there is limited data to guide decision making in this patient group. This guidance document reviews the incidence and risk factors for HA‐VTE in patients with cirrhosis, outlines evidence to inform the use of thromboprophylaxis, and provides pragmatic recommendations on VTE prevention for hospitalized patients with cirrhosis. In brief, in hospitalized patients with cirrhosis:1.We suggest inclusion of portal vein thrombosis as a distinct clinically important endpoint for future studies.2.We recommend against the use of thrombocytopenia and/or prolongation of prothrombin time/international normalized ratio as absolute contraindications to anticoagulant thromboprophylaxis.3.We suggest anticoagulant thromboprophylaxis in line with local protocols and suggest low molecular weight heparin (LMWH) or fondaparinux over unfractionated heparin (UFH). In renal impairment, we suggest LMWH over UFH. For critically ill patients, we suggest case‐by‐case consideration of thromboprophylaxis.4.We recommend research to refine VTE risk stratification, and to establish the optimal dosing and duration of thromboprophylaxis.

The Duration and Magnitude of Postdischarge Venous Thromboembolism Following Colectomy.

Objective:To assess the impact of current guidelines by reporting weekly postoperative postdischarge venous thromboembolism (VTE) rates.Summary Background Data:Disparity exists between the postoperative thromboprophylaxis duration colectomy patients receive based on surgical indication, where malignant resections routinely receive 28 days extended thromboprophylaxis into the postdischarge period and benign resections do not.Methods:English national cohort study of colectomy patients between 2010 and 2019 using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Stratified by admission type and surgical indication, absolute incidence rates (IRs) per 1000 person-years and adjusted incidence rate ratios (aIRRs) for postdischarge VTE were calculated for the first 4 weeks following resection and postdischarge VTE IRs for each postoperative week to 12 weeks postoperative.Results:Of 104,744 patients, 663 (0.63%) developed postdischarge VTE within 12 weeks after colectomy. Postdischarge VTE IRs per 1000 person-years for the first 4 weeks postoperative were low following elective resections [benign: 20.66, 95% confidence interval (CI): 13.73–31.08; malignant: 28.95, 95% CI: 23.09–36.31] and higher following emergency resections (benign: 47.31, 95% CI: 34.43–65.02; malignant: 107.18, 95% CI: 78.62–146.12). Compared with elective malignant resections, there was no difference in postdischarge VTE risk within 4 weeks following elective benign colectomy (aIRR=0.92, 95% CI: 0.56–1.50). However, postdischarge VTE risks within 4 weeks following emergency resections were significantly greater for benign (aIRR=1.89, 95% CI: 1.22–2.94) and malignant (aIRR=3.13, 95% CI: 2.06–4.76) indications compared with elective malignant colectomy.Conclusions:Postdischarge VTE risk within 4 weeks of colectomy is ∼2-fold greater following emergency benign compared with elective malignant resections, suggesting emergency benign colectomy patients may benefit from extended VTE prophylaxis.

Should all patients receive extended thromboprophylaxis after resection of primary lung cancer?

ObjectiveThe optimal duration of thromboprophylaxis in patients undergoing resection of primary lung cancer is not known. We investigated the incidence of pulmonary emboli and venous thromboembolism in patients undergoing early-stage lung cancer resection and the impact of change from short duration to extended thromboprophylaxis. MethodsWe reviewed the outcomes of consecutive patients who underwent resection of early-stage primary lung cancer following a change in protocol from inpatient-only to extended thromboprophylaxis to 28 days. Propensity-score matching of control (routine inpatient pharmacologic thromboprophylaxis) and treatment group (extended pharmacologic thromboprophylaxis) was performed. Adjustment for covariates based on the Caprini risk assessment model was undertaken. Thromboembolic outcomes were compared between the 2 groups. ResultsSeven hundred fifty consecutive patients underwent resection of primary lung cancer at Oxford University Hospitals NHS Foundation Trust between January 2013 and December 2018. Six hundred patients were included for analysis and propensity-score matching resulted in 253 matched pairs. Extended prophylaxis was associated with a significant reduction in pulmonary emboli (10 of 253 patients [4%] vs 1 of 253 patients [0.4%], P = .01). One patient (0.4%) developed a bleeding complication within the treatment cohort. Multivariable logistic regression model demonstrated that extended thromboprophylaxis was independently associated with a reduction in postoperative pulmonary emboli. ConclusionsPatients undergoing lung cancer resection surgery are at moderate-to-high risk of postoperative thromboembolic disease. Extended dalteparin for 28 days is safe and is associated with reduced incidence of pulmonary embolus in patients undergoing resection of early-stage primary lung cancer.

Thromboprophylaxis for children hospitalized with COVID‐19 and MIS‐C

BackgroundLimited data exist about effective regimens for pharmacological thromboprophylaxis in children with acute coronavirus disease 2019 (COVID‐19) and multisystem inflammatory syndrome in children (MIS‐C). ObjectivesStudy the outcomes of institutional thromboprophylaxis protocol for primary venous thromboembolism (VTE) prevention in children hospitalized with acute COVID‐19/MIS‐C. MethodsThis single‐center retrospective cohort study included consecutive children (aged less than 21 years) with COVID‐19/MIS‐C who received tailored intensity thromboprophylaxis, primarily with low‐molecular‐weight heparin, from April 2020 through October 2021. Thromboprophylaxis was given to those with moderate to severe disease based on the World Health Organization scale and exposure to two or more VTE risk factors. Therapeutic intensity was considered for severe illness. Clinical recovery along with D‐dimer improvement determined thromboprophylaxis duration. Outcomes were incident VTEs, bleeding, and mortality. ResultsAmong 211 hospitalizations, 45 (21.3%) received thromboprophylaxis (COVID‐19, 16; MIS‐C, 29). Median age was 14.8 years (interquartile range [IQR], 8.9–16.1). Among 35 (77.8%) with severe illness, 27 (60.0%) required respiratory support, and 19 (42.2%) required an intensive care unit stay. Median hospitalization was 6 days (IQR, 5.0–10.5). Median thromboprophylaxis duration was 19 days (IQR, 6.0–31.0) with therapeutic intensity in 24 (53.3%) and prophylactic in 21 (46.7%). Outcomes were as follows: VTE, 1 (2.2%); death, 1 (2.2%, unrelated to bleeding/thrombosis); major/clinically relevant nonmajor bleeding, 0; and minor bleeding, 7 (15.5%). D‐dimer was elevated in a majority at diagnosis (median, 2.3; IQR, 1.2–3.3 mg/ml fibrinogen‐equivalent units) and was noninformative in assessing disease severity. D‐dimer normalized at thromboprophylaxis discontinuation. ConclusionsOur experience of using clinically directed thromboprophylaxis with tailored intensity approach for children hospitalized with COVID‐19 and MIS‐C favors its inclusion in current standard of care. The role of D‐dimer in directing thromboprophylaxis management deserves further evaluation.

Inpatient primary prophylaxis of cancer-associated thromboembolism (CAT)

Cancer-associated thrombosis (CAT) increases morbidity and mortality in oncology patients. The risk of CAT is increased with hospitalization for acute medical illness. The goal of this review will be to examine the available evidence for (1) risk assessment and (2) primary thromboprophylaxis, (3) international published guideline recommendations, and (4) future directions to manage oncology patients admitted for an acute medical illness. A review was performed for each subject to gather information on the available evidence and recommendations available for oncology patients hospitalized for an acute medical illness. Risk assessments for thrombosis are primarily developed and validated in the general population. There is not a risk assessment that has specifically been developed and validated in oncology patients hospitalized for an acute medical illness. Most evidence for thromboprophylaxis of oncology patients is from sub-group analysis of larger randomized-controlled trials in the general population. Evidence is conflicting and suggests an individualized approach evaluating the risk-benefit of thromboprophylaxis. The strength of recommendations of international guidelines is limited because of the available evidence. Guidelines usually recommend utilizing and/or offering thromboprophylaxis to oncology patients hospitalized for an acute medical illness barring contraindications. Future evidence needs to improve risk assessments and knowledge of the appropriate agent, dose, and duration of thromboprophylaxis if indicated. Evidence for risk assessments and primary prophylaxis for oncology patients hospitalized for acute medical illness appears limited, with many research opportunities available to improve understanding on management of this patient population.

Prevention of venous thromboembolism in ambulatory patients with active cancer: Results from ACT4CAT study.

e18677 Background: Venous ThromboEmbolism (VTE), might be a challenge with a lot of negative consequences for patients with active cancer. VTE affects ongoing anticancer treatment, worsening morbidity and mortality, increases economic burden and escalates psychological distress. Incidence of VTE in patients with cancer reported 20%. Current guidelines recommend pharmacologic prophylaxis in ambulatory cancer patients with Khorana score ≥2. Methods: ACT4CAT is a prospective observational phase IV study conducted by HeSMO Greece, aiming to record the clinical practice of VTE prophylaxis in active cancer patients. Ambulatory patients who received thromboprophylaxis enrolled after signing informed consent. Study was approved by bioethics committee. Results: 691 patients from 19 oncology departments received thromboprophylaxis in 1st line 57.6%, 2nd line 14.8%, adjuvant 9.0% and neoadjuvant 7.5%. Age ≥65 found 55%, BMI≥30 17.5% and males 63%. Tumor types: gastrointestinal 45.4%, lung 25.8%, urological 11.6%, gynecological 6.0%, breast 4.2% and others 7.0%. High-Risk for Thrombosis Agents (HRTAs) received 87.2%, specifically: platinum agents (56.3%), antimetabolites (54.2%) and immunotherapy (12.1%). 54,5% of the anticancer agents had potential drug-drug interaction (DDI) with anticoagulation treatment. Thromboprophylaxis duration lasted 5.3±3.5 months. Main agents were: tinzaparin 89.6%, fondaparinux 6.0%, bemiparin 2.2%, enoxaparin 1.6%, apixaban 0.3% and rivaroxaban 0.3%. Intermediate thromboprophylaxis dose received 68% of patients, lower in adjuvant setting (45.2%), with a preference in metastatic cases (OR: 1.5 95% CI: 1.02-2.3, p = 0.026). 14 thrombotic events reported (efficacy: 98.0%, 95%CI: 96.6-98.8%) and 12 grade 1 bleeding (1.7%, 95%CI: 1.0-3.0%). Conclusions: Prevention of VTE in ambulatory patients with active cancer found effective and safe. Apart from the Khorana score, specific patient characteristics, metastasis, HRTAs and DDIs seemed that affect clinical decision for thromboprophylaxis mainly with LMWHs and often on intermediate dose regardless the clinical setting. Oncologists appeared informed that CAT is not negligible risk. Clinical trial information: NCT03909399. [Table: see text]

Thromboprophylaxis in surgically treated colorectal cancer patients with tinzaparin: Intermediate results from the Onco-CAST trial.

e15611 Background: The incidence of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) after colorectal surgery is approximately 29% and 1.6% respectively. The incidence of asymptomatic postoperative DVT in colorectal cancer (CRC) patients has been reported as high as 20%, even under thromboprophylaxis. Thus, thromboprophylaxis after surgical treatment for CRC is crucial. Latest guidelines from International Initiative on Thrombosis and Cancer (ITAC 2019) recommend use of highest prophylactic dose of Low Molecular Weight Heparin (LMWH). Methods: Onco-CAST is a prospective, phase IV, observational, non-interventional cohort study evaluating a) current management approach for CRC surgical prophylaxis and b) efficacy and safety of tinzaparin at 8.000 Anti-Xa IU, once daily (OD), for at least one month post hospital discharge. Patients enrolled after signing informed consent. Onco-CAST was conducted by the Hellenic Society of Coloproctology. Results: Results from 175 CRC patients from 9 Onco Surgical Clinics are reported. Participation completed 79% of patients at report time: 66% males, 67±12 years, BMI: 27.4±5.5. Histology: adenocarcinomas NOS 81%, mucinous adenocarcinomas 9%, small cell neuroendocrine carcinomas 2%, and others. High grade differentiation indicated: 26% and 5% metastatic. 32% treated with right hemicolectomy, 20% with low anterior resection, 12% with sigmoid colectomy, 9% with abdominal-perineal resection, 9% with left hemicolectomy and other methods. 67% treated open and 33% laparoscopic while the median number of lymph nodes dissected for left and right hemicolectomy was 32.5 (Q1-Q3:26-38) and 24 (Q1-Q3: 14.5-32), p = 0.0253. Factors related to thrombosis risk are presented in table, notably, 95% of patients accumulated ≥3 risk factors. Median thromboprophylaxis duration with tinzaparin 8.000 Anti-Xa IU, OD, was: 37 days (1st-3rd quartile: 33-45 days). Three thrombotic events occurred (efficacy 98.3%, 95% CI: 95.1-99.4%), one DVT+PE, one DVT and one due to Central Venous Catheter (CVC). Eight patients experienced bleeding events (4.6%, 95%CI: 2.3-8.8%), 3 minor, 3 major and 2 CNMB, 2 had a possible relation to thromboprophylaxis (1.1%, 95%CI: 0.3-4.1%). Conclusions: Thromboprophylaxis in Surgically Treated Colorectal Cancer Patients with Tinzaparin intermediate dose seems safe and efficient approach.[Table: see text]

Thromboprophylaxis in lung cancer patients with tinzaparin: Results from the investigation on cancer &amp; lung thromboprophylaxis—The iCaLTstudy.

e13531 Background: It is known that malignancies exaggerate the risk of thrombosis up to 20%, while for Lung Cancer (LC) is articulated up to 14%. Likewise, thrombosis amplifies the LC progression, thrombosis-associated lung cancer (TALC). The pathophysiology promoting LCAT &amp; TALC is multifactorial depending on the characteristics of LC, specific anti-cancer modalities, patient features, and biomarkers such as tissue factor, neutrophil extracellular traps released in response to cancer, cancer procoagulant, and cytokines. Low-molecular-weight heparins are used in prophylaxis and treatment for high-burden for thrombosis (HTB) patients, allowing specialists to focus on the cancer disease. Methods: iCaLT is a prospective observational study conducted in Thoracic Diseases General Hospital Sotiria (Athens, Greece) assessing the role of thromboprophylaxis with tinzaparin 10.000 Anti-Xa IU, OD with the systemic anti-cancer therapy (SACT). LC patients with active disease that are currently under treatment are enrolled after signing informed consent and monitored up to six months or until anticoagulation terminates. Results: Results from 106 patients reported, 29 (27%) are still ongoing: 79% were males. Histological results involve: adenocarcinomas 54%, squamous 25%, small cell 15%and others. LC patients received SACT: 55%, 23%, 10%, 6% in 1st, 2nd, 3rdand 4th line. HTB patients with active LC related to 4 factors: disease, treatment, biomarker and patient features are presented in table. On average patients accumulated 3.7±1.1risk factors, 91% of patients accumulated ≥3 risk factors. Median thromboprophylaxis duration was: 4.8 months (1st-3rd quartile: 2.8-6.0 months). One patient experienced thrombotic event in lower extremes and consequently pulmonary embolism (efficacy 99.1%, 95%CI: 94.6-99.8%), five patients experienced minor bleeding adverse events (haemoptysis) (4.7%, 95%CI: 2.0-10.6%), and two patients allergic reactions. Patients with haemoptysis had lower age (60 vs. 67, p=0.1357). Conclusions: Thromboprophylaxis with tinzaparin intermediate dose in high thrombotic burden patients with active lung cancer is effective and safe. Further research is needed.[Table: see text]

Association of perioperative thromboprophylaxis on revision rate due to infection and aseptic loosening in primary total hip arthroplasty - new evidence from the Nordic Arthroplasty Registry Association (NARA).

Background and purposeResults regarding the impact of anticoagulants on revision rate are conflicting. We examined the association between the use of low molecular weight heparin (LMWH) or non-vitamin K oral anticoagulants (NOACs) as thromboprophylaxis after primary total hip arthroplasty (THA) and the revision rate due to infection, aseptic loosening, and all causes.Patients and methodsWe conducted a cohort study (n = 53,605) based on prospectively collected data from the national hip arthroplasty registries from Denmark and Norway. The outcome was time to revision due to infection, aseptic loosening, and all causes, studied separately. Kaplan– Meier (KM) survival analysis and a Cox proportional hazard model was used to estimate implant survival and cause-specific hazard ratios (HRs) with 95% confidence intervals (CI) adjusting for age, sex, Charlson Comorbidity Index, fixation type, start, and duration of thromboprophylaxis, and preoperative use of Vitamin K antagonists, NOAC, aspirin, and platelet inhibitors as confounders.ResultsWe included 40,451 patients in the LMWH group and 13,154 patients in the NOAC group. Regarding revision due to infection, the 1-year and 5-year KM survival was 99% in both the LMWH group and in the NOAC group. During the entire follow-up period, the adjusted HR for revision due to infection was 0.9 (CI 0.7–1.1), 1.6 (CI 1.3–2.1) for aseptic loosening, and 1.2 (CI 1.1–1.4) for all-cause revision for the NOAC compared with the LMWH group. The absolute differences in revision rates between the groups varied from 0.2% to 1%.InterpretationCompared with LMWH, NOACs were associated with a slightly lower revision rate due to infection, but higher revisions rates due to aseptic loosening and all-cause revision. The absolute differences between groups are small and most likely not clinically relevant. In addition, the observed associations might partly be explained by selection bias and unmeasured confounding, and should be a topic for further research.