ABSTRACT

Management of cancer-associated thrombosis (CAT) is usually performed employing low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs). Low-intensity DOACs are the mainstay for extended duration therapy for VTE in non-oncologic patients. The aim of our study was to evaluate the efficacy and the safety of low doses of apixaban or rivaroxaban as secondary prophylaxis in patients affected by hematological malignancies with follow-up > 12 months. We report an observational, retrospective, single-center study that evaluated consecutive patients referred to our center between January 2016 and January 2023. The DOACs were administered at full dose during the acute phase of VTE and then at low dose for the extended phase. We included 154 patients: 53 patients affected by hematological malignancies compared to 101 non-neoplastic patients. During full-dose treatment, no thrombotic recurrences were observed in the two groups. During low-dose therapy, 2 (1.9%) thrombotic events (tAE) were observed in the control group. During full-dose treatment, the rate of bleeding events (bAE) was 9/154 (5.8%): 6/53 (11%) in hematological patients and 3/101 (2.9%) in non-hematological patients (p = 0.0003). During low-dose therapy, 4/154 (2.6%) bAE were observed: 3/53 (5.5%) in the hematologic group and 1 (1%) in the control group (p = 0.07). We found encouraging data on the safety and efficacy of low doses of DOACs as secondary prophylaxis in the onco-hematologic setting; no thrombotic complications were observed, and the incidence of hemorrhagic events was low.

PMID:37479891 | DOI:10.1007/s00277-023-05369-1

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PubMed articles on: Cancer & VTE/PE

Neutrophil extracellular trap formation is an independent risk factor for occult cancer in patients presenting with VTE

J Thromb Haemost. 2023 Jul 19:S1538-7836(23)00565-2. doi: 10.1016/j.jtha.2023.07.007. Online ahead of print.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE), particularly unprovoked VTE, is associated with occult cancer. Current guidelines recommend limited cancer screening in patients presenting with unprovoked VTE. Only half of the underlying cancer cases are detected by cancer screening, and the optimal screening regimen remains controversial. Neutrophil extracellular traps (NETs) are implicated in cancer-associated thrombosis and elevated biomarkers of NET formation are associated with poor prognosis.

OBJECTIVES AND METHODS: This prospective cohort study investigated the association between blood biomarkers associated with NETs and neutrophil activation (circulating nucleosomal citrullinated histone H3 [H3Cit-DNA], cell-free DNA, and neutrophil elastase) and cancer during a one-year follow-up.

RESULTS AND CONCLUSIONS: Four-hundred-sixty VTE patients were included. Two hundred and twenty-one (48%) had isolated deep vein thrombosis, and 220 (48%) of all VTE cases were unprovoked. Cancer was diagnosed in 29 (7.0%) VTE patients during the follow-up period, and 43 patients had a known active cancer. After adjustment for age and unprovoked VTE, the hazard ratio of cancer during follow-up per 500 ng/ml increase of H3Cit-DNA was 1.79 [95% CI 1.03-3.10] suggesting that H3Cit-DNA is potentially a useful diagnostic marker for cancer in patients with VTE. Furthermore, patients with cancer-associated VTE (known active cancer or cancer diagnosed during follow-up) had higher levels of H3Cit-DNA compared to cancer-free patients with VTE after adjustment for age, hemoglobin, gender, chronic obstructive pulmonary disease, prior cancer and start of anticoagulant treatment (odds ratio 2.06 per 500 ng/ml increase of H3Cit-DNA [95% CI 1.35-3.13]), indicating that elevated NET formation is a hallmark of cancer-associated VTE.

PMID:37479035 | DOI:10.1016/j.jtha.2023.07.007

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Venous thromboembolism and breast cancer

Bull Cancer. 2023 Jul 18:S0007-4551(23)00296-5. doi: 10.1016/j.bulcan.2023.06.001. Online ahead of print.

ABSTRACT

Breast cancer is the most common cancer in women. Patients with breast cancer have a 4-fold increased risk of venous thromboembolism (VTE) compared to age- and sex-matched controls without cancer. VTE remains the second leading cause of death in cancer patients and an independent risk factor for mortality. In women with breast cancer, the main risk factors for developing VTE are increasing age, obesity, disease stage, central catheter placement and cancer treatments, including surgery, chemotherapy, hormonotherapy and cyclin-dependent kinase 4/6 inhibitors. In women receiving tamoxifen, the risk of VTE is particularly increased within the first 6 months after initiation of hormonotherapy, although some evidence suggests that this risk may persist through the first 2 years of treatment. The risk of VTE appears to be lower in patients receiving aromatase inhibitors. In breast cancer patients receiving cyclin-dependent kinase 4/6 inhibitors, the rate of VTE is approximately 6%. Current clinical practice guidelines for the treatment and prevention of VTE in patients with cancer suggest that thromboprophylaxis should not be used routinely in ambulatory cancer patients receiving chemotherapy or hormonotherapy. The risk-benefit ratio of thromboprophylaxis should be assessed on a case-by-case basis and be the subject of multidisciplinary discussion.

PMID:37474353 | DOI:10.1016/j.bulcan.2023.06.001

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PubMed articles on: Cancer & VTE/PE

Risk of thromboembolic events in patients with metastatic solid tumors treated with PARP inhibitors: A systematic review and meta-analysis of phase 3 randomized controlled trials

Cancer Treat Rev. 2023 Jul 17;119:102601. doi: 10.1016/j.ctrv.2023.102601. Online ahead of print.

ABSTRACT

BACKGROUND AND SCOPE: Poly(ADP-ribose) polymerase inhibitors (PARPi) have revolutionized cancer treatment in recent years. These drugs present a favorable safety profile, even though the potential risk of thromboembolic events (TEs) during their use has not been addressed yet. In addition, PARPi have been involved in an active scientific debate regarding non-oncologic indications, particularly during the Coronavirus Disease 2019 pandemic, including potential anti-thromboembolic effect.

METHODS: To clarify whether patients treated with PARPi for metastatic solid tumors are either at increased or decreased risk of TEs, we conducted a systematic review of the literature and meta-analysis, including all phase 3 randomized controlled trials (RCTs) which investigated PARPi in this setting. Search was conducted through Medline, EMBASE, Pubmed, SCOPUS and Google Scholar in February 2023, including the proceedings of the principal oncology meetings of the last 10 years, with no time restriction. For each included study, frequencies of TEs in experimental and control arm were collected.

RESULTS: Our search identified 2,369 reports, of which 20 were lastly selected. A total of 4,946 patients were included, across 12 different RCTs. The meta-analysis did not demonstrate either an increased or a reduced risk in TEs in patients treated with PARPi for metastatic disease (OR 1.50, range: 1.00-2.24; 95% CI; P = 0.050), with low heterogeneity and low publication bias.

CONCLUSION: Although our research did not confirm either increased or decreased risk of TEs for PARPi use, no safety alerts emerged. Thromboembolic risk assessment models should always be integrated in daily clinical routine, to identify high-risk patients.

PMID:37473517 | DOI:10.1016/j.ctrv.2023.102601

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PubMed articles on: Cancer & VTE/PE

Clinical Presentation and Outcomes of Patients With Cancer-Associated Isolated Distal Deep Vein Thrombosis

J Clin Oncol. 2023 Jul 20:JCO2300429. doi: 10.1200/JCO.23.00429. Online ahead of print.

ABSTRACT

PURPOSE: Patients with isolated distal deep vein thrombosis (DVT) have lower rates of adverse outcomes (death, venous thromboembolism [VTE] recurrence or major bleeding) than those with proximal DVT. It is uncertain if such findings are also observed in patients with cancer.

METHODS: Using data from the international Registro Informatizado de la Enfermedad TromboEmbolica venosa registry, we compared the risks of adverse outcomes at 90 days (adjusted odds ratio [aOR]; 95% CI) and 1 year (adjusted hazard ratio [aHR; 95% CI]) in 886 patients with cancer-associated distal DVT versus 5,196 patients with cancer-associated proximal DVT and 5,974 patients with non-cancer-associated distal DVT.

RESULTS: More than 90% of patients in each group were treated with anticoagulants for at least 90 days. At 90 days, the adjusted risks of death, VTE recurrence, or major bleeding were lower in patients with non-cancer-associated distal DVT than in patients with cancer-associated distal DVT (reference): aOR = 0.16 (0.11-0.22), aOR = 0.34 (0.22-0.54), and aOR = 0.47 (0.27-0.80), respectively. The results were similar at 1-year follow-up: aHR = 0.12 (0.09-0.15), aHR = 0.39 (0.28-0.55), and aHR = 0.51 (0.32-0.82), respectively. Risks of death, VTE recurrence, and major bleeding were not statistically different between patients with cancer-associated proximal versus distal DVT, both at 90 days: aOR = 1.11 (0.91-1.36), aOR = 1.10 (0.76-1.62), and aOR = 1.18 (0.76-1.83), respectively, and 1 year: aHR = 1.01 (0.89-1.15), aHR = 1.02 (0.76-1.35), and aHR = 1.10 (0.76-1.61), respectively. However, more patients with cancer-associated proximal DVT, compared with cancer-associated distal DVT, developed fatal pulmonary embolism (PE) during follow-up: The risk difference was 0.40% (95% CI, 0.23 to 0.58).

CONCLUSION: Cancer-associated distal DVT has serious and relatively comparable outcomes compared with cancer-associated proximal DVT. The lower risk of fatal PE from cancer-associated distal DVT needs further investigation.

PMID:37471683 | DOI:10.1200/JCO.23.00429

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PubMed articles on: Cancer & VTE/PE

Comment on: Silent Pulmonary Thromboembolism in Patients Undergoing Craniotomy for Brain Tumor

Turk Neurosurg. 2023;33(4):711. doi: 10.5137/1019-5149.JTN.44181-23.0.

NO ABSTRACT

PMID:37470514 | DOI:10.5137/1019-5149.JTN.44181-23.0

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PubMed articles on: Cancer & VTE/PE

Inferior Vena Cava Filters: Adherence to Clinical Practice Guidelines Recommendations, Retrieval Rates, and Filter Complications in a Tertiary Hospital

Angiology. 2023 Jul 20:33197231190184. doi: 10.1177/00033197231190184. Online ahead of print.

ABSTRACT

The present study evaluated the adherence to guideline recommendations regarding the indication for inferior vena cava filter (IVCF) placement, retrieval rates, complications, thrombotic recurrences, and mortality. Patients in whom an IVCF was placed between 2015 and 2020 in a tertiary hospital were retrospectively included. We considered absolute indication of IVCF placement if all the guidelines evaluated agreed on the indication, relative indication if only some guidelines recommended it and without indication if none of the evaluated guidelines recommended it. From the 185 patients included; 47% had an absolute indication, 15% a relative indication, and 38% had no indication. Filter-associated complications and non-removal rates were 12.4% and 41%, respectively. Venous thromboembolism recurrence rate was 17.8%, being filter-associated complications (24.2 vs 9.8%, P = .02) and thrombosis of the inferior cava or iliac veins (12.1 vs 2.6%, P = .03) more frequent in this group. The mortality rate was 40%, with higher mortality risk in patients with co-existing cancer. Previous major bleeding, filter-associated complications, and mortality were associated with a major risk of non-removal. In conclusion, the adherence to guidelines regarding the indication of IVCF placement is still low and IVCF complications are not negligible. This fact is of special concern in the elderly, comorbid, and cancer patients.

PMID:37470426 | DOI:10.1177/00033197231190184

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PubMed articles on: Cancer & VTE/PE

Glomerular hyperfiltration is an independent predictor of postoperative outcomes: A NSQIP multi-specialty surgical cohort analysis

Nephrology (Carlton). 2023 Jul 19. doi: 10.1111/nep.14221. Online ahead of print.

ABSTRACT

AIM: While high estimated glomerular filtration rate (eGFR) has been associated with increased overall mortality, its effect on postoperative outcomes is relatively understudied. We sought to investigate the association between high eGFR and 30-day postoperative outcomes using a multi-specialty surgical cohort.

METHODS: Using the National Surgical Quality Improvement Program database, we selected adult for whom eGFR could be calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration equation. Based on sex-specific distributions of eGFR stratified by age quintiles, we classified patients into low (<5th95th percentile). The primary outcome was a composite of any 30-day major adverse outcomes, including: death, reoperation, cardiac arrest, myocardial infarction and stroke. Secondary outcomes included 30-day infectious complications, venous thromboembolism (VTE), bleeding requiring transfusion, prolonged length of stay and unplanned readmission. After matching for demographic differences, comorbidity burden and operative characteristics, logistic regression models were used to evaluate the association between extremes of eGFR and the outcomes of interest.

RESULTS: Of 1 668 447 patients, 84 115 (5.07%) had a high eGFR. High eGFR was not associated with major adverse outcomes (odds ratio [OR] 1.00 [95% confidence interval (CI): 0.97, 1.03]); however, it was associated with reoperation (OR 1.04 [95% CI: 1.00,1.08]), infectious complications (OR 1.14 [95% CI: 1.11, 1.16]), VTE (OR 1.15 [95% CI: 1.09, 1.22]) and prolonged length of stay (OR 1.19 [95% CI: 1.16, 1.21]).

CONCLUSION: Our findings support an association between high eGFR and adverse 30-day postoperative outcomes.

PMID:37468129 | DOI:10.1111/nep.14221

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PubMed articles on: Cancer & VTE/PE

A sensitive tissue factor activity assay determined by an optimized thrombin generation method

PLoS One. 2023 Jul 19;18(7):e0288918. doi: 10.1371/journal.pone.0288918. eCollection 2023.

ABSTRACT

BACKGROUND: Tissue factor (TF) is the principal activator of the coagulation system, but an increased concentration in the blood in cancer and inflammatory diseases has been suggested to play a role increasing the risk of venous thromboembolism. However, measurement of the TF concentration is difficult, and quantitation of activity is the most valid estimation. The objective of this study was to establish a sensitive method to measure TF activity based on thrombin generation.

METHODS: The assay is based on thrombin generation (TG) measured on the Calibrated Automated Thrombogram (CAT). Various low concentrations of TF were prepared from reagents containing 1 pM TF and 4 μM phospholipid (PPL), and no TF and 4 μM PPL, and a calibration curve was produced from Lagtime vs TF concentration. TF in blood samples was measured after isolation and resuspension of extracellular vesicles (EVs) in a standard plasma from which EVs had been removed. The same standard plasma was used for the calibrators.

RESULTS: Contact activation of the coagulation system was avoided using CTI plasma samples in Monovette tubes. EVs contain procoagulant phospholipids but addition of PPL only reduced lagtime slightly at very low concentrations of TF resulting in overestimation to a lesser extent at 10 fM but no interference at 30 fM or higher. Addition of EVs to the TG analysis induced a small unspecific TF-independent activity (i.e., an activity not inhibited by antibodies against TF) which also may result in a smaller error in estimation of TF activity at very low levels but the effect was negligible at higher concentrations. It was possible to measure TF activity in healthy controls which was found to be 1-6 fM (EVs were concentrated, i.e. solubilized in a lower volume than the original volume plasma). Coefficient of variation (CV) was below 20% at the low level, and below 10% at a level around 100 fM TF. However, the step with isolation of EVs have a higher inherent CV.

CONCLUSION: A sensitive and rather precise one-stage TG-based method to measure TF activity has been established.

PMID:37467256 | PMC:PMC10355404 | DOI:10.1371/journal.pone.0288918

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PubMed articles on: Cancer & VTE/PE

Does the Use of Negative Pressure Wound Therapy and Postoperative Drains Impact the Development of Surgical Site Infections?: A PARITY Trial Secondary Analysis

J Bone Joint Surg Am. 2023 Jul 19;105(Suppl 1):34-40. doi: 10.2106/JBJS.22.01185. Epub 2023 Jul 19.