Cancer-Associated Thrombosis: An Overview of Mechanisms, Risk Factors, and Treatment

Razak, Norbaini Binti Abdol; Jones, G; Bhandari, Mayank; Berndt, Michael C.; Metharom, Pat

doi:10.3390/cancers10100380

Cited by 445 publications

(393 citation statements)

References 159 publications

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“…VTE is the second cause of mortality in patients with gynecologic cancer, and it has been reported that the risk of DVT and the incidence of PE were estimated at 17-40% and 1-26% in women undergoing gynecologic surgery [9,32].…”

Section: Discussionmentioning

confidence: 99%

Predictive Factors of Deep Vein Thrombosis in Gynecologic Cancer Survivors with Lower Extremity Edema: A Single-Center and Retrospective Study

Kim

Park

et al. 2020

Healthcare

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This study was conducted to examine predictive factors of deep vein thrombosis (DVT) in gynecologic cancer survivors with lower extremity edema (LEE). In the current single-center, retrospective study, there was a total of 315 eligible patients, including 80 patients with DVT and 235 without DVT. They were therefore divided into two groups: the DVT group (n = 80) and the non-DVT group (n = 235). Then, baseline and clinical characteristics of the patients were compared between the two groups. In our study, distant organ metastasis, advanced stage, lymphadectomy, and amount of intraoperative blood loss had a positive predictive value for the occurrence of DVT in gynecologic cancer survivors presenting LEE. In conclusion, our results indicate that it is necessary to consider the possibility of LEE arising from DVT in gynecologic cancer survivors with advanced-stage cancer, distant organ metastasis, lymphadectomy, and intraoperative blood loss over 1500 mL.

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Section: Discussionmentioning

confidence: 99%

Predictive Factors of Deep Vein Thrombosis in Gynecologic Cancer Survivors with Lower Extremity Edema: A Single-Center and Retrospective Study

Kim

Park

et al. 2020

Healthcare

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“…The correlation between cancer and venous thromboembolism (VTE) was first reported in 1865 by Armand Trousseau [15]. In general, active cancer is considered to increase the risk of PTE by 4-7 times [16,17].…”

Section: Discussionmentioning

confidence: 99%

“…PDW is accepted as a more specific marker of platelet activation because it does not increase in response to platelet swelling. There are some studies in the literature regarding the relationship of PDW with PTE [15,26]. Sevuk et al reported that PDW values were higher in patients who developed acute PTE after DVT than those who did not [27].…”

Section: Discussionmentioning

confidence: 99%

Does the Platelet Index Have a Guiding Role in the Association of Cancer and Pulmonary Thromboembolism?

Öcal¹,

Öcal²

2020

Multidiscip Cancer Investig

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Introduction: The diagnostic value of the D-dimer test varies with variable platelet numbers and functions in patients suffering from cancer and concomitant pulmonary thromboembolism (PTE). This requires easy and reliable evaluation tests. In this study, we aimed to investigate the hypothesis that platelet functions may be more guiding in the prediction and diagnosis of PTE rather than the number of platelets in cancer pa- tients. Methods: The clinical, laboratory and radiological findings of all patients diagnosed with PTE were retrieved, retrospectively. Comparisons were performed between “can- cer-free” and “cancer” patients. The patients were also evaluated according to their active and remission status. Results: The data of 232 patients with PTE were reviewed. 172 patients were cancer- free and 60 were diagnosed with cancer. The mean values of D-dimer, mean platelet volume (MPV) and platelet distribution width (PDW) were found to be significantly higher in patients with cancer (P=0.015, P=0.026, and P=0.023; respectively). On the other hand, mean platelet counts were significantly higher in patients without cancer (P=0.05). It was also observed that the mean values of D-dimer, Troponin-I, MPV, and PDW were found to be significantly higher in patients with active cancer (P=0.05, P=0.044, P=0.05, and P=0.042; respectively). However, the mean platelet counts were significantly higher in patients with cancer who were in remission (P=0.05). Conclusions: The morphological characteristics of the platelets are more determinant than the number of platelets in cancer patients with PTE. Platelet indexes such as MPV and PDW may be useful in the prediction, diagnosis, and follow-up of PTE in patients with cancer.

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“…Pancreatic cancer is also associated with thrombotic complications [3]. The elevated risk is attributed to the high metastatic rate and the ability of pancreatic cancer cells to activate platelets and the coagulation cascade [4]. The current standard of care for PDAC includes gemcitabine as a single agent or in combination with nab-paclitaxel.…”

Section: Introductionmentioning

confidence: 99%

Antiplatelet Drug Ticagrelor Enhances Chemotherapeutic Efficacy by Targeting the Novel P2Y12-AKT Pathway in Pancreatic Cancer Cells

Elaskalani

Domenichini

Razak

et al. 2020

Cancers

Self Cite

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Background: Extensive research has reported that extracellular ADP in the tumour microenvironment can stimulate platelets through interaction with the platelet receptor P2Y12. In turn, activated platelets release biological factors supporting cancer progression. Experimental data suggest that the tumour microenvironment components, of which platelets are integral, can promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Thus, overcoming chemoresistance requires combining multiple inhibitors that simultaneously target intrinsic pathways in cancer cells and extrinsic factors related to the tumour microenvironment. We aimed to determine whether ticagrelor, an inhibitor of the ADP–P2Y12 axis and a well-known antiplatelet drug, could be a therapeutic option for PDAC. Methods: We investigated a functional P2Y12 receptor and its downstream signalling in a panel of PDAC cell lines and non-cancer pancreatic cells termed hTERT-HPNE. We tested the synergistic effect of ticagrelor, a P2Y12 inhibitor, in combination with chemotherapeutic drugs (gemcitabine, paclitaxel and cisplatin), in vitro and in vivo. Results: Knockdown studies revealed that P2Y12 contributed to epidermal growth factor receptor (EGFR) activation and the expression of SLUG and ZEB1, which are transcriptional factors implicated in metastasis and chemoresistance. Studies using genetic and pharmacological inhibitors showed that the P2Y12–EGFR crosstalk enhanced cancer cell proliferation. Inhibition of P2Y12 signalling significantly reduced EGF-dependent AKT activation and promoted the anticancer activity of anti-EGFR treatment. Importantly, ticagrelor significantly decreased the proliferative capacity of cancer but not normal pancreatic cells. In vitro, synergism was observed when ticagrelor was combined with several chemodrugs. In vivo, a combination of ticagrelor with gemcitabine significantly reduced tumour growth, whereas gemcitabine or ticagrelor alone had a minimal effect. Conclusions: These findings uncover a novel effect and mechanism of action of the antiplatelet drug ticagrelor in PDAC cells and suggest a multi-functional role for ADP-P2Y12 signalling in the tumour microenvironment.

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Cancer-Associated Thrombosis: An Overview of Mechanisms, Risk Factors, and Treatment

Cited by 445 publications

References 159 publications

Predictive Factors of Deep Vein Thrombosis in Gynecologic Cancer Survivors with Lower Extremity Edema: A Single-Center and Retrospective Study

Predictive Factors of Deep Vein Thrombosis in Gynecologic Cancer Survivors with Lower Extremity Edema: A Single-Center and Retrospective Study

Does the Platelet Index Have a Guiding Role in the Association of Cancer and Pulmonary Thromboembolism?

Antiplatelet Drug Ticagrelor Enhances Chemotherapeutic Efficacy by Targeting the Novel P2Y12-AKT Pathway in Pancreatic Cancer Cells

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