The Role of Cytokines in Induction of Macrophage Procoagulant Activity
Gary A. Levy, Edward H. Cole in Procoagulant Activity in Health and Disease, 2019
In addition to its ability to bind heparin and thereby amplify its anticoagulant properties, antithrombin apparently downregulates TF activity by blocking factor VII binding sites in the absence of heparin.119 Conversely, TF suppresses the anticoagulant activity of the heparin-antithrombin complex in a purified system,120 but little is known concerning those interactions at cell surfaces. Neutrophils are predominant in early DTH lesions, and neutrophil elastase has been linked to proteolysis occurring in inflammatory thrombotic reactions. Interestingly, antithrombin is rendered nonfunctional as an inhibitor of clotting enzymes as a result of a heparin-dependent cleavage by neutrophil elastase.121 Thus, neutrophil sequestration and activation by chemotactic cytokines may contribute to the initial phases of the prothrombotic response. The procoagulant potential of Mo/Mac is therefore not only affected by the type of cells infiltrating an inflammatory lesion and by the levels and sequence of cytokines or other signals inducing a positive response, but may be finely regulated by cells and cytokines influencing anticoagulant (antithrombin) production and mast cell degranulation.
Critical Care and Anaesthesia
Tjun Tang, Elizabeth O'Riordan, Stewart Walsh in Cracking the Intercollegiate General Surgery FRCS Viva, 2020
What are the natural anticoagulant mechanisms?Antithrombin inhibits thrombin, factor Xa and other activated clotting factors.Protein C pathway degrades and inactivates factors Va and VIIIa, thereby blocking thrombin generation.Tissue factor pathway inhibitor inactivates Xa and VIIa.Plasmin causes fibrinolysis by degrading fibrin into fibrin degradation products. It also inactivates Va and VIIIa and disrupts platelet function. Plasminogen activators tPA and uPA activate plasminogen to produce plasmin. Vascular endothelium produces prostacyclin (prostaglandin I2); it is a potent vasodilator that inhibits platelet activation.
Anticoagulants
Kate McCombe, Lara Wijayasiri, Paul Hatton, David Bogod in The Primary FRCA Structured Oral Examination Study Guide 2, 2017
What types of heparin do you know?Naturally occurring heparinA highly sulphated glycosaminoglycan carbohydrate weighing between 3000 and 50 000 Daltons.It is produced by basophils and mast cells.Unfractionated heparin (UFH)Synthetic agent weighing between 5000 and 25 000 Daltons.It binds to and potentiates the action of antithrombin III 1000-fold.Activated antithrombin III inhibits thrombin and other serine proteases that promote blood clotting.
Ameliorative effect of flavonoid-rich extracts from Gongronema latifolium against diabetic cardiomyopathy via serpin A3 and socs3-a in streptozocin treated rats
Published in Biomarkers, 2022
Babatunji Emmanuel Oyinloye, Basiru Olaitan Ajiboye, Oluwafolakemi Johnson, Olutunmise Victoria Owolabi, Jerius Nkwuda Ejeje, Bartholomew I. C. Brai, Olaposi Idowu Omotuyi
The SERPINC1 gene encodes antithrombin (previously known as antithrombin III), which is a type of serine protease inhibitor (serpin). Serpins control several types of chemical reactions by blocking the activity of certain proteins. Antithrombin is found in the bloodstream and is important for controlling blood clotting (Song et al. 2020). While one part of antithrombin binds to thrombin and other clotting proteins, another part of the protein binds to a substance called heparin (Gindele et al. 2021). Antithrombin changes its shape when it binds to heparin. This change in shape allows antithrombin to inactivate clotting proteins at a much faster rate. Over secretion of this protein leads to serpin polymerisation, which does not only reduce the amount of active inhibitor but also leads to accumulation of the polymers, causing cell death and organ failure (Ingwersen 2020).
The antithrombosis effect of dehydroandrographolide succinate: in vitro and in vivo studies
Published in Pharmaceutical Biology, 2022
Bowen Yin, Shuhua Zhang, Yuxi Huang, Yuanzhu Long, Yiguo Chen, Shiyun Zhao, Aiqun Zhou, Minghua Cao, Xiaoming Yin, Daya Luo
In both the in vitro and in vivo experiments, AT-III activity increased by approximately 30–45%, suggesting that DAS effectively prevented the cascade reaction of the intrinsic and extrinsic pathways by enhancing AT-III activity. These results support previous research suggesting that andrographolide derivatives inhibit thrombin-induced platelet aggregation (Thisoda et al. 2006). Based on these findings, we indicated its exact antithrombin mechanism. This enables DAS to consolidate its anticoagulant effect by preventing secondary hemostasis through the inhibition of platelet aggregation. However, this enhancement is limited. On the one hand, antithrombin is responsible for inhibiting 60–70% of thrombin in vivo, and it mainly acts on FII, FIX, FX, FXI, and FXII. On the other hand, with increasing doses, the total amount of partially activated coagulation factors will gradually exceed the inhibitory capacity of AT-III. Therefore, with the increase in AT-III activity, coagulation factors with enhanced activity are still detected with an increasing dose, but the inhibitory effect of AT-III on FII effectively prevented the increase in the prothrombin complex and further inhibited thrombin-induced platelet aggregation. This process directly weakened the effect of secondary hemostasis on reinforcing platelet aggregation, and thus the final effect of DAS on secondary hemostasis was still attributed to the inhibition of platelet aggregation.
First Report of an α Chain Variant [Hb Coombe Park (HBA2: c.382A>G)] from India, Coinherited with a Novel SERPINC1 Gene Mutation: A Double Whammy?
Published in Hemoglobin, 2022
Sona B. Nair, Arundhati S. Athalye, Madhavi Panphalia, Firuza R. Parikh
Hereditary antithrombin (AT) deficiency, an important physiological inhibitor of blood coagulation proteases such as thrombin and factor Xa, are associated with high risk of a pro-thrombotic tendency is caused by mutations/variants in the SERPINC1 gene [4]. It is an autosomal disorder with a dominant inheritance pattern and affects about 1/2000 to 1/3000 individuals [5]. Antithrombin deficiency can be classified as a type I (quantitative) and type II (qualitative or functional) deficiency [6]. To date, several mutations have been reported in the SERPINC1 gene affecting the AT structure and function [7]. Antithrombin deficiency is mainly due to heterozygous mutations, as homozygous mutations are very rare and incompatible with life, though there have been reports of few homozygous cases [5].