Thrombin generation, thrombin-antithrombin complex, and prothrombin fragment F1+2 as biomarkers for hypercoagulability in cancer patients

Lundbech, Mikkel; Krag, Andreas Engel; Christensen, Thomas; Hvas, Anne‐Mette

doi:10.1016/j.thromres.2019.12.018

Cited by 48 publications

(62 citation statements)

References 39 publications

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“…Patients with cancer have a 5-fold higher risk of venous thromboembolism than those without malignancy (135)(136)(137). The mechanism of cancer-associated hypercoagulability is still unclear and is not always detectable with PPP-TG (138,139). Several types of cancer cell lines, including pancreat, leukemia and breast origins, express TF, and these cells can induce coagulation in CAT assays (6,7,140).…”

Section: Influence Of Cancer Cells On Tgmentioning

confidence: 99%

“…[135][136][137] The mechanism of cancerassociated hypercoagulability is still unclear and is not always detectable with PPP-TG. 138,139 Several types of cancer cell lines, including pancreatic, leukaemia and breast origins, express TF, and these cells can induce coagulation in CAT assays. 6,7,140 Moreover, cancer cell-induced TG is inhibited by anti-TF antibodies, suggesting a role for in vivo TF-positive cancer cells in thrombogenesis, 6,7,140 although the expression of TF on cancer cells and its effect on TG varies between different cancer types.…”

Section: Influence Of Cancer Cells On Tgmentioning

confidence: 99%

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Added Value of Blood Cells in Thrombin Generation Testing

et al. 2021

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The capacity of blood to form thrombin is a critical determinant of coagulability. Plasma thrombin generation (TG), a test that probes the capacity of plasma to form thrombin, has improved our knowledge of the coagulation system and shows promising utility in coagulation management. Although plasma TG gives comprehensive insights in the function of pro- and anticoagulation drivers, it does not measure the role of blood cells in TG. In this literature review, we discuss currently available continuous TG tests that can reflect the involvement of blood cells in coagulation, in particular the fluorogenic assays that allow continuous measurement in platelet rich plasma and whole blood. We also provide an overview about the influence of blood cells on blood coagulation, with emphasis on the direct influence of blood cells on TG. Platelets accelerate the initiation and velocity of thrombin generation by phosphatidylserine exposure, granule content release and surface receptor interaction with coagulation proteins. Erythrocytes are also major providers of phosphatidylserine and erythrocyte membranes trigger contact activation. Furthermore, leukocytes and cancer cells may be important players in cell-mediated coagulation, because under certain conditions, they express tissue factor, release procoagulant components and can induce platelet activation. We argue that testing TG in the presence of blood cells may be useful to distinguish blood cells-related coagulation disorders. However, it should also be noted that these blood cells-dependent TG assays are not clinically validated. Further standardization and validation studies are needed to explore their clinical usefulness.

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Section: Influence Of Cancer Cells On Tgmentioning

confidence: 99%

Section: Influence Of Cancer Cells On Tgmentioning

confidence: 99%

Added Value of Blood Cells in Thrombin Generation Testing

et al. 2021

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“…Previous reports of breast cancer showed that thrombin increased invasive activity through the thrombin receptor and that inhibition of protease activated receptor-1 (PAR-1) expression reduced invasive potential [3,4]. Thus, the effects of thrombin may account for the observation that thrombin-pretreated melanoma cells markedly enhance pulmonary metastasis in vivo [1]. In contrast, uPAR, a main brinolytic factor of cancer cells, forms a complex with urokinase-type plasminogen activator (uPA) and converts plasminogen into plasmin.…”

Section: Introductionmentioning

confidence: 99%

“…TF is a coagulation factor that activates the extrinsic coagulation cascade, thereby leading to the generation of thrombin and brin. Thrombin stimulates tumor cell adhesion to platelets, endothelial cells, extracellular matrix proteins, as well as tumor cell mitogenesis [1,2]. Previous reports of breast cancer showed that thrombin increased invasive activity through the thrombin receptor and that inhibition of protease activated receptor-1 (PAR-1) expression reduced invasive potential [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Significance of Coagulation and Fibrinolysis Markers for Benign and Malignant Soft Tissue Tumors

Nakamura

Hagi

Okamoto

et al. 2020

Preprint

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Background: The intimate relationship between coagulation and fibrinolysis in malignant tumors is a well-known phenomena, with the malignant phenotype enhancing coagulation and fibrinolysis. We hypothesized that soft tissue sarcoma (STS) affects the expression of coagulation and fibrinolysis markers, which could be used to distinguish STS from benign soft tissue tumors. We analyzed the correlations between plasma levels of D-dimer (DD), plasmin-α2 plasmin inhibitor complex (PIC), soluble fibrin (SF), and thrombin-antithrombin III complex (TAT) in benign soft tissue tumors and STS to elucidate whether these markers can be used to predict STS.Methods: Plasma DD, PIC, SF and TAT levels in primary soft tissue tumors (benign, 67, STS 68) were measured before biopsy or treatment. The marker levels were analyzed and compared to various clinicopathological parameters.Results: In malignancy (STS), the average DD, PIC and SF levels were significantly higher than in benign tumors. Multivariate logistic analysis of continuous variables indicated that only PIC exhibited a significant difference (OR: 24.5, 95%CI: 3.55-170, p=0.0012). Receiver operating characteristic curve analysis produced area under the curve values for DD: 0.691, PIC: 0.784, SF: 0.734 and TAT: 0.588. Youden’s index was used to establish thresholds of 0.37 (DD), 0.80 (PIC), 0.90 (SF) and 0.82 (TAT). Threshold values for PIC and SF indicated high specificity (0.881, 0.791) and high positive predictive value (0.818, 0.745), respectively The highest accuracy value among the markers was observed for PIC (0.704). Significant differences in multivariate analysis of binary variables were demonstrated by categorizing low and high groups based on their threshold, PIC (≥0.80) (OR: 3.36, 95%CI: 1.19-9.43, p=0.0212) and SF (≥0.90) (OR: 2.63, 95%CI: 1.04-6.66, p=0.0404) . Conclusions: Of the coagulation and fibrinolysis markers studied, increased PIC levels were related to STS and over 0.80 PIC was the most suitable for the prediction of STS, which, along with other diagnostic tools, represents a helpful subsidiary tool for the prediction of STS.

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Markers of hypercoagulability in children with newly diagnosed acute lymphoblastic leukemia

Carmona

Kizilocak

Marquez-Casas

et al. 2021

Pediatric Blood & Cancer

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Background: Venous thromboembolism (VTE) is a known complication for children with acute lymphoblastic leukemia (ALL). The aim of this study was to identify laboratory biomarkers that predict which children with ALL are at risk for VTE during induction chemotherapy. Materials and methods: Newly diagnosed ALL patients admitted to Children's HospitalLos Angeles with a central venous catheter (CVC) were eligible to participate. Participants' blood samples (complete blood count [CBC], quantitative D-dimer, prothrombin fragment 1.2 [PTF 1.2], and thrombin-antithrombin complexes [TAT]) were collected at day 0 (baseline/prior to induction), day 7 (±2 days), day 14 (±2 days), day 21 (±2 days), and day 28 (±2 days) of induction chemotherapy or until participants presented with a symptomatic VTE.Results: Seventy-five participants aged 1-21 years were enrolled and included in the final analysis. Twenty-six (35%) of the 75 participants were diagnosed with a CVCassociated VTE (22 asymptomatic and four symptomatic). There was a statistically significant difference between VTE and non-VTE participants for D-dimer (odds ratio [

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Thrombin generation, thrombin-antithrombin complex, and prothrombin fragment F1+2 as biomarkers for hypercoagulability in cancer patients

Cited by 48 publications

References 39 publications

Added Value of Blood Cells in Thrombin Generation Testing

Added Value of Blood Cells in Thrombin Generation Testing

Significance of Coagulation and Fibrinolysis Markers for Benign and Malignant Soft Tissue Tumors

Markers of hypercoagulability in children with newly diagnosed acute lymphoblastic leukemia

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