Venous thromboembolism (VTE) is a common and potentially life-threatening complication in patients with cancer. Both cancer and its treatments increase the risk of developing VTE. Specific cancer types and individual patient comorbidities increase the risk of developing cancer-associated VTE, and the risk of bleeding is increased with anticoagulation therapies. The aims of this article are to summarize the latest evidence for treating cancer-associated VTE, discuss the practical considerations involved, and share best practices for VTE treatment in patients with cancer. The article pays particular attention to challenging contexts including patients with brain, lung, gastrointestinal, and genitourinary tumors and those with hematological malignancies. Furthermore, the article summarizes specific clinical scenarios that require additional treatment considerations, including extremes of body weight, nausea and gastrointestinal disturbances, compromised renal function, and anemia, and touches upon the relevance of drug-drug interactions. Historically, vitamin K antagonists and low-molecular-weight heparins (LMWHs) have been used as therapy for cancer-associated VTE. The development of direct oral anticoagulants has provided additional treatment options, which, in certain instances, offer advantages over LMWHs. There are numerous factors that need to be considered when treating cancer-associated VTE, and although various treatment guidelines are helpful, they do not reflect each unique scenario that may arise in clinical practice. This article provides a summary of the latest evidence and a practical approach for treating cancer-associated VTE.

Hypercoagulation is one of the most distinct prognostic factors of patients with COVID-19 and has been associated with arterial thrombosis and other venous thrombotic events (VTE). Bleeding complications are far less encountered. The International Society on Thrombosis and Haemostasis (ISTH) guidance advises giving prophylactic low-molecular-weight heparin (LMWH) to prevent these events, although there is evidence that the incidence remains high despite using prophylactic LMWH. We describe three cases of COVID-19 pneumonia that were admitted to our intensive care unit (ICU) and developed acute pulmonary embolisms (APE) despite high dosage prophylactic LMWH. These cases raise concerns about using prophylactic LMWH instead of therapeutic anticoagulation in severe and critically COVID-19 patients.

Major abdominopelvic surgery is an important risk factor for postoperative venous thromboembolism (VTE). VTE is the leading cause of 30-day postoperative mortality in patients with cancer undergoing major abdominopelvic surgery. Randomized controlled trials have shown that extended duration thromboprophylaxis using a low molecular weight heparin or a direct oral anticoagulant significantly decreases the risk of overall VTE (symptomatic events and asymptomatic deep vein thrombosis). Hence, several clinical practice guidelines suggest the use of extended duration thromboprophylaxis for all high-risk patients undergoing major abdominopelvic surgery. Despite these recommendations by clinical practice guidelines, adoption of extended duration thromboprophylaxis in clinical practice remains low and clinical equipoise seems to persist. In this narrative review, we aim is to highlight and summarize the reasons that may explain discrepancy between clinical guideline recommendations and current practice regarding extended duration thromboprophylaxis in this patient population. We also aim to review different personalized approaches based on patients\' individualized risk of VTE that may foster shared decision making and improve patient outcomes by reducing decisional conflict, increasing patient knowledge, and increasing risk perception accuracy.

The recent discovery of blue fluorophores with high quantum yields based on pyridone structures inspired the development of new low-molecular-weight fluorophores with bright emissions at tunable wavelengths, which are highly attractive for various applications. In this study, we propose a rational design strategy for 2-pyridone-based fluorophores with bright emissions at long wavelengths. With a detailed understanding of the positional substitution effects on each carbon atom of the 2-pyridone core, we developed a bright blue fluorophore (λabs =377 nm; λem =433 nm; ϵ=13,200 M-1  cm-1 ; ϕF =88 %) through C3 -aryl and C4 -ester substitutions followed by cyclization. Furthermore, by applying the intramolecular charge transfer (ICT) principle, we invented a bright green fluorophore through C3 - and C4 -diester and C6 -aryl substitutions. The ICT fluorophore based on the pyridone structure shows large molar absorptivity (ϵ=20,100 M-1  cm-1 ), longer emission wavelength (λem =539 nm), high emission quantum yield (ϕF =74 %), and large Stokes shift (Δv=5720 cm-1 ), which are comparable to those of practical fluorescent probes.

BACKGROUND: Risk assessment models (RAMs) are used to select women at increased risk of venous thromboembolism (VTE) during pregnancy and the puerperium for thromboprophylaxis.
OBJECTIVE: To estimate the value of potential future studies that would reduce the decision uncertainty associated with offering thromboprophylaxis according to available RAMs in the following groups: high-risk antepartum women (eg, prior VTE), unselected postpartum women, and postpartum women with risk factors (obesity or cesarean delivery).
METHODS: A decision-analytic model was developed to simulate clinical outcomes, lifetime costs, and quality-adjusted life-years for different thromboprophylaxis strategies, including thromboprophylaxis for all, thromboprophylaxis for none, and RAM-based thromboprophylaxis. The expected value of perfect information analysis was used to determine which factors are associated with high decision uncertainty. The value of future research studies was estimated using expected value of sample information analysis. Costs were assessed from a health and social services perspective.
RESULTS: The expected value of perfect information analysis identified high decision uncertainty for high-risk antepartum women (£21.8 million) and obese postpartum women (£13.4 million), which was largely attributable to uncertainty regarding the effectiveness of thromboprophylaxis in reducing VTE. A randomized controlled trial of thromboprophylaxis compared with none in obese postpartum women is likely to have substantial value (£2.8 million; 300 participants per arm). A trial in women with previous VTE would have higher value but would be less acceptable.
CONCLUSIONS: Future research should focus on estimating the effectiveness of thromboprophylaxis in obese postpartum women with additional risk factors who have not had a previous VTE.

Cancer-associated venous thromboembolism (CAT) guidelines recommend direct oral anticoagulants as alternatives to low-molecular-weight heparin (LMWH) in most patients. This study compared the effectiveness and safety of rivaroxaban versus LMWH for a broad CAT cohort. The cohort study used electronic health data from January 2012 to December 2020 to evaluate patients with active cancer experiencing acute venous thromboembolism (VTE) and treated with rivaroxaban or LMWH. Propensity score-overlap weighted hazard ratios (HRs) and 95% confidence intervals (CIs) for VTE, bleeding-related hospitalization, and all-cause mortality were calculated. In total, 4935 patients were identified (27.9% on rivaroxaban and 72.1% on LMWH). The cancer types included gastrointestinal (29.4%), genitourinary (26.2%), lung (24.0%), breast (19.7%), and hematologic (14.4%). Rivaroxaban was associated with a reduction in recurrent VTE versus LMWH among all patients with cancer (HR = 0.78; 95%CI = 0.61-0.99) at 3 months. No differences in bleeding-related hospitalization or all-cause mortality were observed. Directionally similar results to those at 3 months were observed at 6 months for all outcomes. In conclusion, we observed fewer recurrent VTE cases and no increase in bleeding-related hospitalizations with rivaroxaban versus LMWH at 3 months in this patient cohort with various cancer types.

Peripartum management of women using low-molecular-weight heparin (LMWH) varies widely. Minimum time intervals are required between LMWH injection and neuraxial procedure, and they differ by dose.
The objective of this study was to describe the onset of labor and use of analgesia in women using LMWH and to compare practices between intermediate-dose and low-dose LMWH.
In the Highlow study (NCT01828697), 1110 women were randomized to intermediate-dose or low-dose LMWH and were instructed to discontinue LMWH when labor commenced unplanned or 24 hours prior to planned delivery. The required time interval since last injection to receive a neuraxial procedure was ≥24 hours for intermediate-dose LMWH or ≥12 hours for low-dose LMWH.
In total, 1018 women had an ongoing pregnancy for ≥24 weeks. Onset of labor was spontaneous in 198 of 509 (39%) women on intermediate-dose LMWH and in 246 of 509 (49%) on low-dose LMWH. With unplanned onset, a neuraxial procedure was performed in 37% on intermediate-dose and in 48% on low-dose LMWH (risk difference -11%, 95% CI -20% to -2%). Based on time interval, 61% on intermediate-dose and 82% on low-dose LMWH were eligible for a neuraxial procedure. With planned onset, 68% on intermediate-dose and 66% on low-dose LMWH received a neuraxial procedure, whereas 81% and 93%, respectively, were eligible for a neuraxial procedure (risk difference -13%, 95% CI -18% to -8%).
With spontaneous onset of labor, neuraxial procedures were performed less often in women using intermediate-dose LMWH. Irrespective of onset, fewer women on intermediate-dose LMWH than those on low-dose LMWH were eligible for neuraxial procedures based on required time intervals since the last LMWH injection.

The short-term asthma outcome of irritant-induced asthma (IIA) is poorer than that of low-molecular-weight (LMW) sensitizer-induced occupational asthma (OA).
To evaluate the long-term asthma outcome of IIA and LMW-induced OA and to determine which baseline features are associated with a poor long-term outcome.
This follow-up questionnaire study assessed 43 patients diagnosed with IIA and 43 patients with LMW-induced OA at the Finnish Institute of Occupational Health in 2004-2018. The baseline results were analyzed to detect features associated with uncontrolled asthma (Asthma Control Test [ACT] score of ≤19, or ≥2 exacerbations or ≥1 serious exacerbation within 1 year) at follow-up.
The median interval since OA diagnosis was 6.3 years (interquartile range [IQR]: 4.4-11.3 years). Uncontrolled asthma was more frequent with IIA than with LMW-induced OA (58% vs 40%, adjusted odds ratio [OR]: 3.60, 95% confidence interval [CI]: 1.20-10.81). Poor symptom control was the main factor for this difference (median [IQR] ACT score of 18 [15-22] vs 21 [18-23], P = .036, respectively). Among all participants, older age (OR: 1.08 per year, 95% CI: 1.02-1.15), a fractional exhaled nitric oxide (FeNO) value <20 ppb (OR: 5.08, 95% CI: 1.45-17.80), and uncontrolled asthma at baseline (OR: 3.94, 95% CI: 1.31-11.88) were associated with uncontrolled asthma at follow-up.
Long-term asthma control of IIA appears to be inferior to that of LMW-induced OA. Older age, a low FeNO value, and uncontrolled asthma at baseline might indicate a worse long-term outcome among those with IIA and LMW-induced OA.

UNASSIGNED: Diagnosing heparin-induced thrombocytopenia (HIT) at the bedside remains challenging, exposing a significant number of patients at risk of delayed diagnosis or overtreatment. We hypothesized that machine-learning algorithms could be utilized to develop a more accurate and user-friendly diagnostic tool that integrates diverse clinical and laboratory information and accounts for complex interactions.
UNASSIGNED: We conducted a prospective cohort study including 1393 patients with suspected HIT between 2018 and 2021 from 10 study centers. Detailed clinical information and laboratory data were collected, and various immunoassays were conducted. The washed platelet heparin-induced platelet activation assay (HIPA) served as the reference standard.
UNASSIGNED: HIPA diagnosed HIT in 119 patients (prevalence 8.5%). The feature selection process in the training dataset (75% of patients) yielded the following predictor variables: (1) immunoassay test result, (2) platelet nadir, (3) unfractionated heparin use, (4) CRP, (5) timing of thrombocytopenia, and (6) other causes of thrombocytopenia. The best performing models were a support vector machine in case of the chemiluminescent immunoassay (CLIA) and the ELISA, as well as a gradient boosting machine in particle-gel immunoassay (PaGIA). In the validation dataset (25% of patients), the AUROC of all models was 0.99 (95% CI: 0.97, 1.00). Compared to the currently recommended diagnostic algorithm (4Ts score, immunoassay), the numbers of false-negative patients were reduced from 12 to 6 (-50.0%; ELISA), 9 to 3 (-66.7%, PaGIA) and 14 to 5 (-64.3%; CLIA). The numbers of false-positive individuals were reduced from 87 to 61 (-29.8%; ELISA), 200 to 63 (-68.5%; PaGIA) and increased from 50 to 63 (+29.0%) for the CLIA.
UNASSIGNED: Our user-friendly machine-learning algorithm for the diagnosis of HIT (https://toradi-hit.org) was substantially more accurate than the currently recommended diagnostic algorithm. It has the potential to reduce delayed diagnosis and overtreatment in clinical practice. Future studies shall validate this model in wider settings.
UNASSIGNED: Swiss National Science Foundation (SNSF), and International Society on Thrombosis and Haemostasis (ISTH).

BACKGROUND: The optimal timing to initiate venous thromboembolism (VTE) prophylaxis in patients with a traumatic brain injury (TBI) is still unknown. We designed a study to determine the effect that timing of initiation of VTE prophylaxis has on VTE rates in TBI patients.
METHODS: Patient records were obtained from 32 level 1 and 2 trauma centers in the Michigan Trauma Quality Improvement Program from 2008 to 2018. Overall, 5589 patients with a TBI were included and split into cohorts based on VTE prophylaxis initiation time. Outcomes included rate of VTE, mortality, and serious in-hospital complications.
RESULTS: There were nine patients (1.3%) in the <24 hour group with a VTE as compared to 36 (2.6%) in the 24-48 hour group, 51 (4.1%) in the 48-72 hour group, and 181 (8.1%) in the >72 hour group (P < .001). The adjusted odds of VTE were significantly greater in patients initiated within 48-72 hours (AOR 2.861, 95% CI 1.271-6.439) and >72 hours (AOR 3.963, 95% CI 1.824-8.612) compared to <24 hours. Patients that received VTE prophylaxis within 24 hours had similar rates of serious in-hospital complication as patients initiated within 24-48 hours (AOR .956, 95% CI .637-1.434) and 48-72 hour (AOR 1.132, 95% CI .757-1.692) but less than the >72 hour group (AOR 1.662, 95% CI 1.154-2.393) groups.
CONCLUSIONS: Patients initiated on VTE prophylaxis within 48 hours of presentation had lower incidence of VTE without a significant increase in serious complications.