Essentials
We performed a pooled analysis of 926 patients with cancer‐associated incidental pulmonary embolism (IPE).
Vitamin K antagonists (VKA) are associated with a higher risk of major ...hemorrhage.
Recurrence risk is comparable after subsegmental and more proximally localized IPE.
Our results support low molecular weight heparins over VKA and similar management of subsegmental IPE.
Summary
Background
Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on computed tomography scanning not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer‐associated IPE is scarce. We aimed to provide the best available evidence on IPE management.
Methods
Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major hemorrhage, and mortality during 6‐month follow‐up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization, and management were performed.
Results
In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6‐month risks of recurrent VTE, major hemorrhage and mortality were 5.8% (95% confidence interval CI 3.7–8.3%), 4.7% (95% CI 3.0–6.8%), and 37% (95% CI 28–47%). VTE recurrence risk was comparable under low molecular weight heparins (LMWH) and vitamin K antagonists (VKAs) (6.2% vs. 6.4%; hazard ratio HR 0.9; 95% CI 0.3–3.1), while 12% in untreated patients (HR 2.6; 95% CI 0.91–7.3). Risk of major hemorrhage was higher under VKAs than under LMWH (13% vs. 3.9%; HR 3.9; 95% CI 1.6–10). VTE recurrence risk was comparable in patients with an subsegmental IPE and those with a more proximally localized IPE (HR 1.1; 95% CI 0.50–2.4).
Conclusion
These results support the current recommendation to anticoagulate cancer‐associated IPE with LMWH and argue against different management of subsegmental IPE.
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FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background Our aim was to construct a diagnostic model for ruling out chronic thromboembolic pulmonary hypertension (CTEPH) in symptomatic patients after acute pulmonary embolism (PE) that ...is based on simple, non-invasive tests. Methods Plasma levels of various CTEPH associated biomarkers and conventional ECG criteria for right ventricular pressure overload were assessed in 82 consecutive patients with confirmed CTEPH and 160 consecutive patients with a history of PE who were suspected to have CTEPH, but in whom this disease was ruled out. Results ECG criteria of right ventricular hypertrophy were detected more frequently in patients with CTEPH (77%) than in the patients without CTEPH (11%, Odds ratio 26, 95% confidence interval CI 13–53). Also, clotting factor FVIII activity and the levels of N-terminal-pro-brain-type natriuretic peptide (NT-pro-BNP), Growth Differentiation Factor-15, C-reactive protein and urate, but not D-dimer level, were higher in patients with CTEPH. A diagnostic model including ECG criteria and NT-pro-BNP levels had a sensitivity of 94% (95% CI 86-98%) and a specificity of 65% (95% CI 56-72%). The area under the receiver-operator-characteristic curve was 0.80 (95% CI 0.74-0.85) for the diagnosis of CTEPH. Even with high disease prevalences of up to 10%, the negative predictive value of this model proved to be very high (99%, 95% CI 97-100%). Conclusions Ruling out CTEPH in patients after acute PE seems to be safe without additional diagnostic testing in absence of ECG criteria indicative of right ventricular hypertrophy and a normal NT-pro-BNP level.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Essentials
Evidence for the simplified Wells rule in ruling out acute pulmonary embolism (PE) is scarce.
This was a post‐hoc analysis on data from 6 studies comprising 7268 patients with suspected ...PE.
The simplified Wells rule combined with age‐adjusted D‐dimer testing may safely rule out PE.
Given its ease of use, the simplified Wells rule is to be preferred over the original Wells rule.
Summary
Background
The Wells score and D‐dimer testing can safely rule out pulmonary embolism (PE). A simplification of the Wells score has been proposed to improve clinical applicability, but evidence on its performance is scarce.
Objectives
To compare the performances of the original and simplified Wells scores alone and in combination with age‐adjusted D‐dimer testing.
Methods
Individual patient data from 7268 patients with suspected PE enrolled in six management studies were used to evaluate the discriminatory performances of the original and simplified Wells scores. The efficiency and failure rate of the dichotomized original and simplified scores combined with age‐adjusted D‐dimer testing were compared by use of a one‐stage random effects meta‐analysis. Efficiency was defined as the proportion of patients in whom PE could be considered to be excluded on the basis of a ‘PE unlikely’ Wells score and a negative age‐adjusted D‐dimer test result. Failure rate was defined as the proportion of patients with symptomatic venous thromboembolism during a 3‐month follow‐up.
Results
The discriminatory performances of the original and simplified Wells scores were comparable (c‐statistic 0.73 95% confidence interval (CI) 0.72–0.75 versus 0.72 95% CI 0.70–0.73). When combined with age‐adjusted D‐dimer testing, the original and simplified Wells rules had comparable efficiency (3% 95% CI 25–42% versus 30% 95% CI 21–40%) and failure rates (0.9% 95% CI 0.6–1.5% versus 0.8% 95% CI 0.5–1.3%).
Conclusion
The original and simplified Wells rules combined with age‐adjusted D‐dimer testing have similar performances in ruling out PE. Given its ease of use in clinical practice, the simplified Wells rule is to be preferred.
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FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Essentials
Low‐molecular‐weight heparin (LMWH) injections for venous thromboembolism (VTE) may be burdensome.
Patients with active cancer and confirmed VTE were included to evaluate LMWH ...continuation.
The cumulative incidence of discontinuation was 21% after a median period of 90 days.
One out of five patients discontinued LMWH injections because of side effects.
Summary
Background
Current guidelines recommend low‐molecular‐weight heparin (LMWH) monotherapy for 3–6 months as the first‐line treatment for cancer‐associated venous thromboembolism (VTE). However, although daily administration of LMWH injections over a course of several months may be burdensome, the number of patients who stop treatment because of LMWH side‐effects is unknown.
Objectives
To evaluate the continuation rate and complications of daily LMWH injections in patients with cancer‐associated VTE.
Methods
Consecutive patients with active cancer and objectively confirmed symptomatic proximal deep vein thrombosis and/or pulmonary embolism, treated at three Dutch hospitals and one Spanish hospital, were included to evaluate continuation LMWH therapy during LMWH treatment. Patients were excluded when they received other anticoagulants, were lost to follow‐up, or experienced a venous catheter‐associated thrombosis.
Results
A total of 372 patients were analyzed during LMWH treatment for a maximum of 180 days. The cumulative incidence of discontinuation was 21% (95% confidence interval CI 17–25) after a median period of 90 days (interquartile range 60–120 days). Only female sex was found to be significantly associated with premature LMWH discontinuation (odds ratio 1.6; 95% CI 1.03–2.5). Thirty patients (8.1%) developed recurrent VTE, 30 patients (8.3%) suffered a major bleed, and 106 patients (28%) died.
Conclusion
Our study reveals that one of five patients with cancer‐associated VTE stopped LMWH injections because of side‐effects. This finding provides relevant background information for current clinical trials investigating the efficacy and safety of direct oral anticoagulants as compared with LMWH.
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FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Diagnosing upper extremity deep vein thrombosis (UEDVT) can be challenging. Compression ultrasonography is often inconclusive because of overlying anatomic structures that hamper compressing veins. ...Contrast venography is invasive and has a risk of contrast allergy. Magnetic Resonance Direct Thrombus Imaging (MRDTI) and Three Dimensional Turbo Spin-echo Spectral Attenuated Inversion Recovery (3D TSE-SPAIR) are both non-contrast-enhanced Magnetic Resonance Imaging (MRI) sequences that can visualize a thrombus directly by the visualization of methemoglobin, which is formed in a fresh blood clot. MRDTI has been proven to be accurate in diagnosing deep venous thrombosis (DVT) of the leg. The primary aim of this pilot study was to test the feasibility of diagnosing UEDVT with these MRI techniques. MRDTI and 3D TSE-SPAIR were performed in 3 pilot patients who were already diagnosed with UEDVT by ultrasonography or contrast venography. In all patients, UEDVT diagnosis could be confirmed by MRDTI and 3D TSE-SPAIR in all vein segments. In conclusion, this study showed that non-contrast MRDTI and 3D TSE-SPAIR sequences may be feasible tests to diagnose UEDVT. However diagnostic accuracy and management studies have to be performed before these techniques can be routinely used in clinical practice.
•Diagnosing upper extremity deep vein thrombosis (UEDVT) can be challenging.•Magnetic Resonance Direct Thrombus Imaging (MRDTI) can visualize a thrombus directly.•MRDTI can be a feasible test to diagnose UEDVT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To improve the quality and accuracy of the patient‐reported outcome measures that assess health‐related quality of life (HRQoL), guidelines have been developed to standardize the development and ...validation process. Considering the increasing importance of HRQoL questionnaires in research, we set out to review the literature and evaluate whether existing questionnaires developed for deep vein thrombosis (DVT) and pulmonary embolism (PE) fulfill state‐of‐the‐art requirements. The literature search was conducted in March 2019 and updated in September 2020. Seven databases were searched. No time limit was set for the search to include all available questionnaires. The inclusion criteria were original publications describing the development of disease‐specific HRQoL questionnaires specific to DVT or PE in adults and available in English. The questionnaires were assessed to determine whether they fulfill the requirements in the latest guidelines. A total of 3826 references were identified. After the exclusion process, 15 papers were reviewed in full, of which 7 were included. Four questionnaires were developed for chronic venous disease, two were specific to DVT, and one was specific to PE. Most questionnaires we found in this review, fulfilled some but none fulfilled all recommendations in existing guidelines. Because the development of current available HRQoL questionnaires specific to DVT or PE do not fulfil all recommendations of existing guidelines, there is room for improvements within this field. Such improvements could likely enhance the quality associated with the use of these end points in clinical trials and practice.
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FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Patients with Cushing syndrome (CS) are at increased risk of venous thromboembolism (VTE).
The aim was to evaluate the current management of new cases of CS with a focus on VTE and ...thromboprophylaxis.
A survey was conducted within those that report in the electronic reporting tool (e-REC) of the European Registries for Rare Endocrine Conditions (EuRRECa) and the involved main thematic groups (MTG's) of the European Reference Networks for Rare Endocrine Disorders (Endo-ERN) on new patients with CS from January 2021 to July 2022.
Of 222 patients (mean age 44 years, 165 females), 141 patients had Cushing disease (64%), 69 adrenal CS (31%), and 12 patients with ectopic CS (5.4%). The mean follow-up period post-CS diagnosis was 15 months (range 3-30). Cortisol-lowering medications were initiated in 38% of patients. One hundred fifty-four patients (69%) received thromboprophylaxis (including patients on chronic anticoagulant treatment), of which low-molecular-weight heparins were used in 96% of cases. VTE was reported in six patients (2.7%), of which one was fatal: two long before CS diagnosis, two between diagnosis and surgery, and two postoperatively. Three patients were using thromboprophylaxis at time of the VTE diagnosis. The incidence rate of VTE in patients after Cushing syndrome diagnosis in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years.
Thirty percent of patients with CS did not receive preoperative thromboprophylaxis during their active disease stage, and half of the VTE cases even occurred during this stage despite thromboprophylaxis. Prospective trials to establish the optimal thromboprophylaxis strategy in CS patients are highly needed.
The incidence rate of venous thromboembolism in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Notably, this survey showed that there is great heterogeneity regarding time of initiation and duration of thromboprophylaxis in expert centers throughout Europe.
Recent studies have shown that patients with pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant chemo(radio)therapy followed by surgery have an improved outcome compared to patients ...treated with upfront surgery. Hence, patients with PDAC are more and more frequently treated with chemotherapy in the neoadjuvant setting. PDAC patients are at a high risk of developing venous thromboembolism (VTE), which is associated with decreased survival rates. As patients with PDAC were historically offered immediate surgical resection, data on VTE incidence and associated preoperative risk factors are scarce. Current guidelines recommend primary prophylactic anticoagulation in selected groups of patients with advanced PDAC. However, recommendations for patients with (borderline) resectable PDAC treated with chemotherapy in the neoadjuvant setting are lacking. Nevertheless, the prevention of complications is crucial to maintain the best possible condition for surgery. This narrative review summarizes current literature on VTE incidence, associated risk factors, risk assessment tools, and primary thromboprophylaxis in PDAC patients treated with neoadjuvant chemo(radio)therapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
ObjectivePatients with cancer are at increased bleeding risk, and anticoagulants increase this risk even more. Yet, validated bleeding risk models for prediction of bleeding risk in patients with ...cancer are lacking. The aim of this study is to predict bleeding risk in anticoagulated patients with cancer.MethodsWe performed a study using the routine healthcare database of the Julius General Practitioners’ Network. Five bleeding risk models were selected for external validation. Patients with a new cancer episode during anticoagulant treatment or those initiating anticoagulation during active cancer were included. The outcome was the composite of major bleeding and clinically relevant non-major (CRNM) bleeding. Next, we internally validated an updated bleeding risk model accounting for the competing risk of death.ResultsThe validation cohort consisted of 1304 patients with cancer, mean age 74.0±10.9 years, 52.2% males. In total 215 (16.5%) patients developed a first major or CRNM bleeding during a mean follow-up of 1.5 years (incidence rate; 11.0 per 100 person-years (95% CI 9.6 to 12.5)). The c-statistics of all selected bleeding risk models were low, around 0.56. Internal validation of an updated model accounting for death as competing risk showed a slightly improved c-statistic of 0.61 (95% CI 0.54 to 0.70). On updating, only age and a history of bleeding appeared to contribute to the prediction of bleeding risk.ConclusionsExisting bleeding risk models cannot accurately differentiate bleeding risk between patients. Future studies may use our updated model as a starting point for further development of bleeding risk models in patients with cancer.
Pancreatic cancer is associated with a high risk of venous thromboembolism (VTE). However, comprehensive data on incidence, timing and relevant determinants of VTE in this particular population are ...scarce. Current study assesses incidence, timing and predictors of VTE in pancreatic cancer through different phases of disease.
All pancreatic cancer patients treated in our tertiary referral center between 2013 through 2017 were studied. Occurrence of VTE was evaluated from diagnosis through end of follow-up or death. Relevant determinants of VTE were identified in logistic regression models. Hazard ratios were calculated to evaluate impact of VTE on overall survival.
In total, 361 patients were followed for a median period of 43 months; 64 were diagnosed with VTE (18%). Most were tumor related thrombosis (59%), incidental (75%) and occurred after anti-cancer treatment had been stopped (80%), only 1.6% occurred during remission phase. Stage IV pancreatic cancer was a predictor for VTE (hazard ratio (HR) 2.46, 95% confidence interval (CI) 0.9–6.8). Biliary drainage (HR 0.52, 95%CI 0.28–0.98) and tumor resection (HR 0.45, 95%CI 0.45–1.83) were protective factors. VTE was not associated with worse survival (HR 1.3; 95% CI 0.97–1.74).
VTE in pancreatic cancer is disease-stage dependent, with 80% occurring in advanced phases of disease when patients no longer receive active treatment. We speculate that this is the main reason for the absence of a survival effect of VTE in our cohort. These practice-based findings should be taken into account when considering wide-spread introduction of primary thromboprophylaxis in patients with pancreatic cancer.
‘What is known on this topic’•Pancreatic cancer is among the most prothrombotic malignancies•There are ongoing discussions on the introduction of prophylactic anticoagulation in cancer patients
‘What does this paper add’•A detailed overview of different types of VTE in all stages of pancreatic cancer•Tumor location, age and stage are predictors for development of VTE•80% of all VTE occurs in the advanced disease phase. It is therefore debatable whether prophylactic anticoagulation is beneficial for this patient population
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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