Antithrombin, an Important Inhibitor in Blood Clots

Zhu, Ying; Cong, Qingwei; Liu, Yue; Wan, Chunling; Yu, Tao; He, Guang; He, Li; Cai, Lei; Chou, Kuo‐Chen

doi:10.2174/1568026616666150923152745

Cited by 7 publications

(8 citation statements)

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“…Antithrombotic system includes many important components, of which AT is the major anticoagulant in plasma of human body [ 18 ]. However, TFPI-1 plays more important roles than AT and other anticoagulants involved in the inhibition of extrinsic pathway of blood coagulation, which is the initiating pathway of blood coagulation [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Tissue Factor Pathway Inhibitor-1 Is a Valuable Marker for the Prediction of Deep Venous Thrombosis and Tumor Metastasis in Patients with Lung Cancer

Fei

Wang

Yuan

et al. 2017

BioMed Research International

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Activation of blood coagulation contributes to cancer progression. Tissue factor pathway inhibitor-1 (TFPI-1) is the main inhibitor of extrinsic coagulation pathway. The aim of this study is to assess the predicting significance of TFPI-1 for thrombotic complication and metastasis in lung cancer patients. Total of 188 non-small cell lung cancer (NSCLC) patients were included in this study. Plasma TFPI-1, D-dimer (D-D), antithrombin (AT), Fibrinogen (Fbg), and coagulating factor VIII activity (FVIII:C) were measured. In NSCLC patients, significantly decreased TFPI-1 and AT and increased D-D, Fbg, and FVIII:C levels were observed, and there was a significant correlation between TFPI-1 and other hemostatic parameters (P < 0.001, resp.). NSCLC patients with deep venous thrombosis (DVT) or metastasis had significantly lower TFPI-1 levels than those without DVT or metastasis (P < 0.01, resp.). Multivariate regression revealed that TFPI-1 acted as a predictor for DVT or tumor metastasis in NSCLC patients [OR: 4.15 or 3.28, P < 0.05, resp.]. The area under ROC curve of TFPI-1 was 0.905 (95% CI, 0.842~0.967) or 0.828 (95% CI, 0.742~0.915) for predicting DVT or metastasis (P < 0.001, resp.). The optimal point of TFPI-1 was 57.7 or 54.3 ng/mL for predicting DVT or metastasis, respectively. Combination of TFPI-1 and D-D measurements can improve the predicting power for DVT or metastasis in NSCLC patients. Our findings suggested that TFPI-1 was a valuable predictor of DVT and tumor metastasis in NSCLC patients.

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Section: Discussionmentioning

confidence: 99%

Tissue Factor Pathway Inhibitor-1 Is a Valuable Marker for the Prediction of Deep Venous Thrombosis and Tumor Metastasis in Patients with Lung Cancer

Fei

Wang

Yuan

et al. 2017

BioMed Research International

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“…Antithrombin (AT) is a major coagulation inhibitor mainly synthesized in the liver [1]. This 58-kDa glycoprotein is a serine protease inhibitor that binds and inactivates thrombin and other coagulation factors, including factors IX, X, XI, and XII [2–4].…”

Section: Introductionmentioning

confidence: 99%

Randomized Comparison Study of Novel Recombinant Human Antithrombin Gamma and Plasma-Derived Antithrombin in Healthy Volunteers

Furuie¹,

Kanda

2019

Clin Drug Investig

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Background and ObjectiveThis paper describes two studies, which aimed to compare the safety and plasma antithrombin activity of recombinant human antithrombin gamma (rhAT-gamma) with plasma-derived antithrombin (pAT) 60 IU/kg, and to establish bioequivalence by adjusting the rhAT-gamma dose to that at which plasma antithrombin activity equaled that for pAT 60 IU/kg, based on results of the first study.MethodsHealthy adult men aged 20–45 years received once-daily doses of rhAT-gamma or pAT intravenously for 3 days (first study: 60 IU/kg of each; second study: 72 IU/kg of rhAT-gamma and 60 IU/kg of pAT). Maximum plasma antithrombin activity after three doses (Cmax,day3) and area under the plasma antithrombin activity-time curve after the third dose (AUC48–t) were analyzed. Safety was also assessed.ResultsIn the first study, we compared AUCs to 121 h (when the lower limit of quantification was first observed). Mean Cmax,day3 was 1.67 IU/mL in the rhAT-gamma group and 1.77 IU/mL in the pAT group; mean AUC48–121 was 58.44 and 71.94 IU·h/mL, respectively. Thus, we set the dose of rhAT-gamma in the second study to 72 IU/kg. As a result, ratios of Cmax,day3 and AUC48–t in the rhAT-gamma vs. the pAT group were 105.7% (90% confidence interval 100.3, 111.3) and 100.5% (90% confidence interval 91.5, 110.4), respectively. Adverse events were more frequent in the rhAT-gamma group.ConclusionsAs 90% confidence intervals for Cmax,day3 and AUC48–t ratios for rhAT-gamma:pAT were within the acceptability range for bioequivalence, rhAT-gamma (72 IU/kg) and pAT (60 IU/kg) are considered bioequivalent.Electronic supplementary materialThe online version of this article (10.1007/s40261-019-00847-9) contains supplementary material, which is available to authorized users.

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“…Among them, AT‐III and HC‐II have been extensively studied. Both AT‐III and HC‐II function as serine protease inhibitors, exerting anticoagulant effects by obstructing the active sites of coagulation factors [110,111] …”

Section: Anticoagulant Mechanisms Of Sulfated Polysaccharidesmentioning

confidence: 99%

Sulfated Polysaccharides with Anticoagulant Potential: A Review Focusing on Structure‐Activity Relationship and Action Mechanism

Chen,

Zhang,

Liu

et al. 2024

Chemistry & Biodiversity

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Thromboembolism is the culprit of cardiovascular diseases, leading to the highest global mortality rate. Anticoagulation emerges as the primary approach for managing thrombotic conditions. Notably, sulfated polysaccharides exhibit favorable anticoagulant efficacy with reduced side effects. This review focuses on the structure‐anticoagulant activity relationship of sulfated polysaccharides and the underlying action mechanisms. It is concluded that chlorosulfonicacid‐pyridine method serves as the preferred technique to synthesize sulfated polysaccharides. The anticoagulant activity of sulfated polysaccharides is linked to the substitution site of sulfate groups, degree of substitution, molecular weight, main side chain structure, and glycosidic bond conformation. Moreover, sulfated polysaccharides exert anticoagulant activity via various pathways, including the inhibition of blood coagulation factors, activation of antithrombin III and heparin cofactor II, antiplatelet aggregation, and promotion of the fibrinolytic system.

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Antithrombin, an Important Inhibitor in Blood Clots

Cited by 7 publications

References 0 publications

Tissue Factor Pathway Inhibitor-1 Is a Valuable Marker for the Prediction of Deep Venous Thrombosis and Tumor Metastasis in Patients with Lung Cancer

Tissue Factor Pathway Inhibitor-1 Is a Valuable Marker for the Prediction of Deep Venous Thrombosis and Tumor Metastasis in Patients with Lung Cancer

Randomized Comparison Study of Novel Recombinant Human Antithrombin Gamma and Plasma-Derived Antithrombin in Healthy Volunteers

Sulfated Polysaccharides with Anticoagulant Potential: A Review Focusing on Structure‐Activity Relationship and Action Mechanism

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