ABSTRACT

OBJECTIVES: To determine the associated thromboembolism risk with adding immune checkpoint inhibitors (ICI) to platinum combination chemotherapy compared with platinum combination chemotherapy alone in patients with advanced non-small cell lung cancer.

MATERIALS AND METHODS: This study identified 75,807 patients with advanced non-small cell lung cancer from the Japanese Diagnosis Procedure Combination database who started platinum combination chemotherapy between July 2010 and March 2021. The incidence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and all-cause mortality within 6 months after commencing platinum combination chemotherapy was compared between patients receiving chemotherapy with ICI (ICI group, n = 7,177) and without ICI (non-ICI group, n = 37,903). Survival time analysis was performed using the overlap weighting method with propensity scores to adjust for background factors. The subdistribution hazard ratio for developing thromboembolism was calculated using the Fine-Gray model with death as a competing risk. The hazard ratio for all-cause mortality was also calculated using the Cox proportional hazards model.

RESULTS: Overall, VTE and ATE occurred in 761 (1.0%) and 389 (0.51%) patients, respectively; mortality was 11.7%. Propensity score overlap weighting demonstrated that the subdistribution hazard ratio (95% confidence interval) for VTE and ATE in the ICI group was 1.27 (1.01-1.60) and 0.96 (0.67-1.36), respectively, compared with the non-ICI group. The mortality hazard ratio in the ICI group was 0.68 (0.62-0.74).

CONCLUSION: The addition of ICI to platinum combination therapy was associated with a higher risk of VTE compared with platinum combination therapy alone, while the risk of ATE might be comparable.

PMID:37540262 | DOI:10.1007/s00262-023-03508-1

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PubMed articles on: Cancer & VTE/PE

Low-Molecular-Weight Heparin Versus Warfarin in Adult Cancer Patients as a Precision Medicine for Thrombosis: A Systematic Review and Meta-Analysis

Cureus. 2023 Jul 1;15(7):e41268. doi: 10.7759/cureus.41268. eCollection 2023 Jul.

ABSTRACT

Venous thromboembolism (VTE) is a condition often seen in patients diagnosed with cancer and is recognized as a predictor of poor outcomes in these patients. The probability of VTE recurring is generally higher in people with cancer than in those without; hence, addressing this issue is essential when making healthcare decisions. Therefore, our systematic review was primarily designed to compare low-weight- molecular heparin (LMWH) to warfarin in reducing recurrent VTE among cancer patients. However, other outcomes were also evaluated, such as mortality and bleeding events observed more in cancer patients. The selection of relevant articles was carried out using a database search and a manual search, which involved reviewing reference lists of articles eligible for inclusion in the current review. The methodological quality of each included study was then assessed using Cochrane's risk of bias tool in the Review Manager software (RevMan 5.4.1). Additionally, pooled results were examined using the Review Manager software and presented as forest plots. Our search of electronic databases elicited a total of 2163 articles, of which only six were deemed eligible for inclusion and analysis. Data pooled from the six studies demonstrated the effectiveness of LMWH in minimizing the reoccurrence of VTE over warfarin [risk ratio (RR): 0.67; 95% CI: 0.47 - 0.95; p = 0.03]. However, LMWH had a similar effect statistically as warfarin on the major bleeding events (RR: 1.05; 95% CI: 0.62 - 1.77; p = 0.85), minor bleeding events (RR: 0.80; 95% CI: 0.54 - 1.20; p = 0.28), and all-cause mortality (RR: 1.00; 95% CI: 0.88 - 1.13; p = 0.99). While LMWH demonstrated its effectiveness in minimizing the incidence of VTE recurrence over warfarin in cancer patients, it had no statistical difference in terms of mortality or bleeding events when compared to warfarin. Based on our findings, we recommend that LMWH continues to be used as a first-line treatment regimen to mitigate recurrent VTE in cancer patients.

PMID:37533609 | PMC:PMC10390756 | DOI:10.7759/cureus.41268

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PubMed articles on: Cancer & VTE/PE

Thrombophilia Gene Mutations Predict Venous Thromboembolism in Ambulatory Cancer Patients Receiving Chemotherapy

J Thromb Haemost. 2023 Aug 1:S1538-7836(23)00580-9. doi: 10.1016/j.jtha.2023.07.017. Online ahead of print.

ABSTRACT

BACKGROUND: Inherited thrombophilia and cancer both independently increase the risk of venous thromboembolism (VTE). However, whether the increased VTE risk associated with inherited thrombophilia exists in cancer patients is less clear.

OBJECTIVES: Our objective was to determine the influence of inherited thrombophilia on VTE and bleeding risk in moderate-high risk ambulatory cancer patients receiving chemotherapy.

METHODS: We conducted a post-hoc analysis using blood samples from patients enrolled in the AVERT trial to determine if previously recognized thrombophilia gene mutations (Prothrombin FII G20210A, Factor XI, Fibrinogen Gamma, Serpin Family A Member 10, Factor V K858R, Factor XIII, Factor V Leiden (FVL), and ABO blood) were associated with VTE or bleeding during the 7-months after starting chemotherapy. Logistic regression was used comparing heterozygous and homozygous mutations (combined) to wild type. VTE rates, bleeding rates and risk differences for mutations stratified by prophylactic anticoagulation use were calculated.

RESULTS: Of the 447 patients, there were 39 VTE and 39 bleeding events. The odds of VTE were significantly increased with FVL mutation and non-O blood type [OR: 5.2 (95%CI:1.9-14.7) and 2.7 (95%CI:1.2-6.1), respectively]. The use of anticoagulation prophylaxis resulted in complete protection in FVL patients whereas those not receiving anticoagulation had a VTE rate of 119 per 100 patient-years. Lower VTE rates were also observed in non-O blood type patients taking prophylactic anticoagulation. No other thrombophilia genes tested were significantly associated with VTE or bleeding.

CONCLUSIONS: Our results indicate FVL mutation and ABO blood type may be important VTE predictors in cancer patients starting chemotherapy.

PMID:37536569 | DOI:10.1016/j.jtha.2023.07.017

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PubMed articles on: Cancer & VTE/PE

Illustrated State-of-the-Art Capsules of the ISTH 2023 Congress

Res Pract Thromb Haemost. 2023 Jun 21;7(4):100193. doi: 10.1016/j.rpth.2023.100193. eCollection 2023 May.

ABSTRACT

This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) took place in person in Montréal, Canada, from June 24-28, 2023. The conference, held annually, highlighted cutting-edge advances in basic, translational, population and clinical sciences relevant to the Society. As for all ISTH congresses, we offered a special, congress-specific scientific theme; this year, the special theme was immunothrombosis. Certainly, over the last few years, COVID-19 infection and its related thrombotic and other complications have renewed interest in the concepts of thromboinflammation and immunothrombosis; namely, the relationship between inflammation, infection and clotting. Other main scientific themes of the Congress included Arterial Thromboembolism, Coagulation and Natural Anticoagulants, Diagnostics and Omics, Fibrinolysis and Proteolysis, Hemophilia and Rare Bleeding Disorders, Hemostatic System in Cancer, Inflammation and Immunity, Pediatrics, Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies, Platelets and Megakaryocytes, Vascular Biology, Venous Thromboembolism and Women's Health. Among other sessions, the program included 28 State-of-the-Art (SOA) sessions with a total of 84 talks given by internationally recognized leaders in the field. SOA speakers were invited to prepare brief illustrated reviews of their talks that were peer reviewed and are included in this article. These illustrated capsules highlight the major scientific advances with potential to impact clinical practice. Readers are invited to take advantage of the excellent educational resource provided by these illustrated capsules. They are also encouraged to use the image in social media to draw attention to the high quality and impact of the science presented at the Congress.

PMID:37538494 | PMC:PMC10394567 | DOI:10.1016/j.rpth.2023.100193

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PubMed articles on: Cancer & VTE/PE

Direct oral anticoagulants versus aspirin for primary thromboprophylaxis in patients with multiple myeloma undergoing outpatient therapy: A systematic review and updated meta-analysis

Br J Haematol. 2023 Aug 2. doi: 10.1111/bjh.19017. Online ahead of print.

ABSTRACT

Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased for those undergoing anti-myeloma therapy. Current guidelines suggest low-dose direct oral anticoagulants (DOACs) as an alternative to aspirin for primary thromboprophylaxis in this population, but data comparing these two therapies are limited. We performed a systematic review and meta-analysis to compare DOACs with aspirin for primary thromboprophylaxis in individuals undergoing outpatient anti-myeloma therapy. Studies were selected when comparing DOACs versus aspirin for thrombotic and haemorrhagic outcomes. We included 10 randomised controlled trials and observational studies comprising 1026 patients with MM who received primary thromboprophylaxis with DOACs (n = 337) or aspirin (n = 689). DOAC thromboprophylaxis was associated with a significantly lower incidence of VTE compared with aspirin (OR 0.33; 95% CI 0.16-0.68; p < 0.001). Major, clinically relevant non-major and minor bleeding event rates did not differ significantly between groups. Overall, our meta-analysis suggests that DOACs may be a preferable option to aspirin for the prevention of MM-related thrombosis. However, these results should be interpreted in the context of heterogeneous baseline population characteristics and potential bias from including observational studies. Further research is needed to evaluate the optimal thromboprophylaxis strategy, particularly in high-risk individuals.

PMID:37533165 | DOI:10.1111/bjh.19017

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PubMed articles on: Cancer & VTE/PE

Genetic insights into resting heart rate and its role in cardiovascular disease

Nat Commun. 2023 Aug 2;14(1):4646. doi: 10.1038/s41467-023-39521-2.