Variant alleles in factor V, prothrombin, plasminogen activator inhibitor-1, methylenetetrahydrofolate reductase and risk of thromboembolism in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab

Falvella, Felicia Stefania; Cremolini, Chiara; Miceli, Rosalba; Nichetti, Federico; Cheli, Stefania; Antoniotti, Carlotta; Infante, Gabriele; Martinetti, Antonia; Marmorino, Federica; Sottotetti, Elisa; Berenato, Rosa; Caporale, Marta; Colombo, Alfredo; Braud, Filippo de; Bartolomeo, Maria Di; Clementi, Emilio; Loupakis, Fotios; Pietrantonio, Filippo

doi:10.1038/tpj.2016.22

Cited by 11 publications

(12 citation statements)

References 38 publications

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“…70 VTE was the outcome in 81 studies, 114,[117][118][119][120][121][122][123] ATE in 4 studies, 34,62,69,109 and a combination of ATE and VTE in 15 studies. 37,38,44,49,65,71,89,[93][94][95]102,103,111,115,116 The patents received thromboprophylaxis in 10 studies, 30,33,41,50,67,78,87,106,119,121 some patients received thromboprophylaxis in 19 studies, 3,44,59,61,66,73,81,85,86,90-92,99,101,104,108 111,113,115 and no thromboprophylaxis was used in 25 studies. 14,35,36,[38][39][40]42,43,46,…”

Section: Resultsmentioning

confidence: 99%

“…37,38,44,49,65,71,89,[93][94][95]102,103,111,115,116 The patents received thromboprophylaxis in 10 studies, 30,33,41,50,67,78,87,106,119,121 some patients received thromboprophylaxis in 19 studies, 3,44,59,61,66,73,81,85,86,90-92,99,101,104,108 111,113,115 and no thromboprophylaxis was used in 25 studies. 14,35,36,[38][39][40]42,43,46,47,51,52,56,70,74,75,77,83,87 Thromboprophylaxis was not reported in 46 studies. 7,2627-29,31,32,34,37,45 48,49,53-55,57,58,60,63-65,68,69,71,72,76,79,80,82,84,89,93-97,100,102,103 107,110,112,116,120,122,123 Of the included studies, 34 studies were rated good, …”

Section: Resultsmentioning

confidence: 99%

“…33,48 Nine studies reported no association between a higher median platelet count in the thrombosis group and the nonthrombosis group. 38,41,45,50,54,62,71,119,123 Filippova et al investigated ovarian cancer patients undergoing splenectomy and measured platelet count from 0 to 15 days postoperative. 41 The median platelet count did not differ between the DVT group and the non-DVT group, but the group who developed DVT had a significantly higher number of days with thrombocytosis than the group who did not develop DVT (8 days [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] vs. 6 days [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16], p ¼ 0.049).…”

Section: Platelet Count and Thrombosismentioning

confidence: 99%

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Platelet Parameters as Biomarkers for Thrombosis Risk in Cancer: A Systematic Review and Meta-analysis

Malte

Højbjerg

Larsen

2023

Semin Thromb Hemost

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Cancer-associated thrombosis (CAT) is a major cause of both morbidity and mortality in cancer patients. Platelet count has been investigated as a predictor of CAT in various settings while knowledge on platelet activation parameters is sparse. This report provides a systematic review and meta-analysis on available literature on associations between platelet count and/or function and arterial and venous thrombosis in adult cancer patients. The review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. PubMed and Embase were searched up to March 2022. The National Heart, Lung, and Blood Institute's tools were used for quality assessment. In total, 100 studies were included which investigated the association between CAT and platelet count (n = 90), platelet indices (n = 19), and platelet function/activation markers (n = 13) in patients with solid cancers (n = 61), hematological cancers (n = 17), or mixed cancer types (n = 22). Eighty-one studies had venous thrombosis as their outcome measure, while 4 had arterial thrombosis and 15 studies had both. We found significantly elevated odds ratio of 1.50 (95% confidence interval: 1.19–1.88) for thrombosis with higher platelet counts. We saw a tendency toward an association between markers of platelet activation in forms of mean platelet volume and soluble P selectin and both arterial and venous thrombosis. Only one study investigated dynamic platelet function using flow cytometry. In conclusion, platelet count is associated with CAT across different cancer types and settings. Platelet function or activation marker analysis may be valuable in assisting thrombosis risk assessment in cancer patients but is sparsely investigated so far.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Platelet Count and Thrombosismentioning

confidence: 99%

See 1 more Smart Citation

Platelet Parameters as Biomarkers for Thrombosis Risk in Cancer: A Systematic Review and Meta-analysis

Malte

Højbjerg

Larsen

2023

Semin Thromb Hemost

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“…The clinical course of the present case suggests that bevacizumab accelerate the growth of a pre-existing thrombus to form a massive thrombus. Single nucleotide polymorphisms (SNPs) related to hereditary thrombophilia have been investigated as risk factors for thromboembolism in cancer patients ( 10 ). Further studies would be useful for clarifying risk factors for thromboembolism in lung cancer patients for whom chemotherapy with bevacizumab is planned.…”

Section: Discussionmentioning

confidence: 99%

Bevacizumab-induced Aortic Arterial Thrombosis

et al. 2018

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A 65-year-old man was diagnosed with advanced non-small, non-squamous lung cancer. He was treated with chemotherapy containing bevacizumab as well as cisplatin and pemetrexed. After 2 courses of treatment, computed tomography revealed that his abdominal aortic artery was almost occluded by a thrombus; however, he had no ischemic symptoms. Heparin infusion and warfarin reduced the size of the arterial thrombus and the patient was subsequently treated with chemotherapy without bevacizumab. No thrombotic events occurred during the subsequent treatment. We later noticed a small organized abdominal arterial clot and calcification on a computed tomography scan taken before bevacizumab treatment. Atherosclerotic changes should be evaluated before the administration of bevacizumab.

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“…Platelets release significant amounts of factors from a-granules such as a2-macroglobulin, plasminogen activator, plasminogen, and plasminogen-activator inhibitor type-1 that help with fibrinolysis, clot dissolution, inflammation resolution, and wound repair (113)(114)(115)(116)(117). They also release tissue remodeling enzymes involved in wound repair that include matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-9, MT1-MMP, MMP-14), tissue inhibitor of metalloproteinases (TIMPs; TIMP-1, TIMP-2 and TIMP-4), as well as a disintegrin and metalloproteinases (ADAMs; ADAM-10, ADAM-17, ADAMTS-13) (118,119).…”

Section: Platelets In Wound Resolutionmentioning

confidence: 99%

The Provocative Roles of Platelets in Liver Disease and Cancer

et al. 2021

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Both platelets and the liver play important roles in the processes of coagulation and innate immunity. Platelet responses at the site of an injury are rapid; their immediate activation and structural changes minimize the loss of blood. The majority of coagulation proteins are produced by the liver—a multifunctional organ that also plays a critical role in many processes: removal of toxins and metabolism of fats, proteins, carbohydrates, and drugs. Chronic inflammation, trauma, or other causes of irreversible damage to the liver can dysregulate these pathways leading to organ and systemic abnormalities. In some cases, platelet-to-lymphocyte ratios can also be a predictor of disease outcome. An example is cirrhosis, which increases the risk of bleeding and prothrombotic events followed by activation of platelets. Along with a triggered coagulation cascade, the platelets increase the risk of pro-thrombotic events and contribute to cancer progression and metastasis. This progression and the resulting tissue destruction is physiologically comparable to a persistent, chronic wound. Various cancers, including colorectal cancer, have been associated with increased thrombocytosis, platelet activation, platelet-storage granule release, and thrombosis; anti-platelet agents can reduce cancer risk and progression. However, in cancer patients with pre-existing liver disease who are undergoing chemotherapy, the risk of thrombotic events becomes challenging to manage due to their inherent risk for bleeding. Chemotherapy, also known to induce damage to the liver, further increases the frequency of thrombotic events. Depending on individual patient risks, these factors acting together can disrupt the fragile balance between pro- and anti-coagulant processes, heightening liver thrombogenesis, and possibly providing a niche for circulating tumor cells to adhere to—thus promoting both liver metastasis and cancer-cell survival following treatment (that is, with minimal residual disease in the liver).

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Variant alleles in factor V, prothrombin, plasminogen activator inhibitor-1, methylenetetrahydrofolate reductase and risk of thromboembolism in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab

Cited by 11 publications

References 38 publications

Platelet Parameters as Biomarkers for Thrombosis Risk in Cancer: A Systematic Review and Meta-analysis

Platelet Parameters as Biomarkers for Thrombosis Risk in Cancer: A Systematic Review and Meta-analysis

Bevacizumab-induced Aortic Arterial Thrombosis

The Provocative Roles of Platelets in Liver Disease and Cancer

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