Thrombin-Antithrombin III Complexes and Antithrombin III in Amniotic Fluid

Uszyński, M; Kiełkowski, Andrzej; Uszyński, Waldemar; Żekanowska, Ewa

doi:10.1159/000291813

Cited by 7 publications

(6 citation statements)

References 13 publications

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“…Our finding that the median amniotic fluid TAT III complexes concentration increases from the mid-trimester to term is consistent with the report of Koh et al[89] that examined the changes in amniotic fluid TAT III complexes concentration in the second trimester and during the first stage of labor, and documented an increase in TAT III complexes concentration in the first stage of labor as compared to mid-trimester[89]. Uszynski et al[67] examined TAT III complexes concentration in amniotic fluid at term, and concluded that they increased during labor[67]. The amniotic fluid TAT III complexes concentration documented in the latter study[67] during the first stage of labor (54.2 ± 26.4ng/ml) are in agreement with the concentrations we have found.…”

Section: Commentssupporting

confidence: 92%

“…[67,89]. Our finding that the median amniotic fluid TAT III complexes concentration increases from the mid-trimester to term is consistent with the report of Koh et al[89] that examined the changes in amniotic fluid TAT III complexes concentration in the second trimester and during the first stage of labor, and documented an increase in TAT III complexes concentration in the first stage of labor as compared to mid-trimester[89].…”

Section: Commentssupporting

confidence: 90%

“…Uszynski et al[67] examined TAT III complexes concentration in amniotic fluid at term, and concluded that they increased during labor[67]. The amniotic fluid TAT III complexes concentration documented in the latter study[67] during the first stage of labor (54.2 ± 26.4ng/ml) are in agreement with the concentrations we have found.…”

Section: Commentssupporting

confidence: 89%

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Changes in amniotic fluid concentration of thrombin–antithrombin III complexes in patients with preterm labor: Evidence of an increased thrombin generation

Erez¹,

Romer²,

Vaisbuch³

et al. 2009

The Journal of Maternal-Fetal & Neonatal Medicine

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Objective Preterm labor is associated with excessive maternal thrombin generation as evidenced by increased circulating thrombin–antithrombin (TAT) III complexes concentration. In addition to its hemostatic functions, thrombin has uterotonic properties that may participate in the mechanism leading to preterm birth in cases of intrauterine bleeding. Thrombin also has a proinflammatory role, and inflammation is associated with increased thrombin generation. The aim of this study was to determine whether intra-amniotic infection/inflammation (IAI) is associated with increased amniotic fluid (AF) thrombin generation in women with preterm and term deliveries. Study design This cross-sectional study included the following groups: 1) mid-trimester (n=74); 2) term not in labor (n=39); 3) term in labor (n=25); 4) term in labor with IAI (n=22); 5) spontaneous preterm labor (PTL) who delivered at term (n=62); 6) PTL without IAI who delivered preterm (n=59); 7) PTL with IAI (n=71). The AF TAT III complexes concentration was measured by ELISA. Non-parametric statistics were used for analysis. Results 1) TAT III complexes were identified in all AF samples; 2) patients with PTL who delivered preterm, with and without IAI, had a significantly higher median AF TAT III complexes concentration than those with an episode of PTL who delivered at term (p<0.001, p=0.03, respectively); 3) among patients with preterm labor without IAI, elevated AF TAT III complexes concentration were independently associated with a shorter amniocentesis-to-delivery interval (hazard ratio- 1.5, 95%CI, 1.07–2.1); 4) among patients at term, those with IAI had a higher median AF TAT III complexes concentration than those without IAI, whether in labor or not in labor (p=0.02); 5) there was no significant difference between the median AF TAT III complexes concentration of patients at term with and without labor; and 6) patients who had a mid-trimester amniocentesis had a lower median AF TAT III complexes concentration than that of patients at term not in labor (p<0.001). Conclusions We present herein a distinct difference in the pattern of intra-amniotic thrombin generation between term and preterm parturition. Preterm labor leading to preterm delivery is associated with an increased intra-amniotic thrombin generation, regardless of the presence of IAI. In contrast, term delivery is associated with an increased intra-amniotic thrombin generation only in patients with IAI.

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Section: Commentssupporting

confidence: 92%

Section: Commentssupporting

confidence: 90%

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Changes in amniotic fluid concentration of thrombin–antithrombin III complexes in patients with preterm labor: Evidence of an increased thrombin generation

Erez¹,

Romer²,

Vaisbuch³

et al. 2009

The Journal of Maternal-Fetal & Neonatal Medicine

View full text Add to dashboard Cite

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“…Thrombin is activated by estrogen (35) and its levels in the amniotic fluid increase toward the end of gestation in humans (36). Thrombin-like activity has also been detected in the rat pituitary gland (37,38) and in several other endocrine tissues (39).…”

Section: Discussionmentioning

confidence: 99%

Proteolysis of Human Prolactin: Resistance to Cathepsin D and Formation of a Nonangiostatic, C-Terminal 16K Fragment by Thrombin

Khurana¹

1999

Endocrinology

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The N-terminal 16K fragments of rat and human PRLs possess angiostatic activity. 16K PRL has also been detected in vivo in both humans and rats. Based on an in vitro study, cathepsin D, an acid protease, has been implicated in the generation of rat 16K PRL. However, the proteolytic cleavage of human PRL has not been demonstrated. Our objective was to identify an enzyme that is capable of forming an angiostatic human 16K PRL. To confirm the angiostatic action of rat 16K PRL, the fragment was generated by incubating 23K PRL with rat mammary microsomal fraction at pH 3.2. Upon incubation with human umbilical vein endothelial cells (HUVEC), rat 16K PRL, but not 23K PRL, inhibited basal-and basic fibroblast growth factor-stimulated cell proliferation. Intact rat and human PRLs were then incubated with cathepsin D or acidified microsomal pellets of MCF-7 human breast cancer cells. Analysis by SDS-PAGE showed cleavage of rat, but not human, PRL. Next, hormones were incubated with thrombin at pH 7.4. As shown by SDS-PAGE, digestion of both human and rat PRL by thrombin resulted in the formation of 16K fragments. PRL contained within human amniotic fluid was also cleaved by thrombin. Enzyme specificity was supported by prevention of cleavage by the thrombin inhibitor hirudin. When tested with HUVEC, the human 16K PRL was devoid of angiostatic activity. The activity of this fragment in the Nb2 lymphoma bioassay was 10-to 15-fold lower than that of 23K PRL. Mass spectrometry revealed that the fragment has a mass of 16,878.30 Ϯ 15.8 Daltons. Subsequent N-terminal sequencing showed that the thrombin cleavage occurred between amino acid residues 53 (Lys) and 54 (Ala), resulting in the formation of a C-terminal, not an N-terminal, 16K fragment. We conclude that, unlike rat PRL, human PRL is resistant to cleavage by cathepsin D. Thrombin at a physiological pH can generate a C-terminal 16K fragment of human PRL that is not angiostatic and retains little mitogenic activity. We suggest that the precise nature of endogenous 16K PRL fragments that are present in human tissues and body fluids should be carefully examined. (Endocrinology 140: [4127][4128][4129][4130][4131][4132] 1999) H UMAN PRL is a single 23-kDa polypeptide hormone composed of four antiparallel ␣-helices with three intrachain disulfide loops between residues 4 -11, 58 -174, and 191-199 (1). Although the position of the disulfide bonds is homologous between PRLs from different species, their primary amino acid sequences may vary considerably. PRL can undergo several posttranslational modifications (2), including cleavage (3, 4), glycosylation (5, 6), and phosphorylation (7, 8) that have been implicated in its functional diversity. However, the N-terminal 16K fragment of PRL is the only well characterized isoform with a unique biological activity as an antiangiogenic agent (9 -11).Angiogenesis, or formation of new blood vessels, is an integral part of tumorigenesis and metastasis and often results from a shift in the balance between angiogenic and angiosta...

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“…Levels of antithrombin III remain stable during pregnancy [13,15,21,31], whereas heparin cofactor II and α 1 antitrypsin levels are increased during normal pregnancy [15,32]. Little is known about the effect of pregnancy on levels of TF pathway inhibitor, but lower levels during labour have been reported when compared with non-pregnant controls [33]. Protein C, TM (thrombomodulin), protein S, C4b binding protein and APC (activated protein C) inhibitor are all components of the protein C system.…”

Section: Inhibitors Of Blood Coagulationmentioning

confidence: 99%

Haemostasis in normal pregnancy: a balancing act?

Holmes

Wallace

2005

Biochemical Society Transactions

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Pregnancy is a risk factor for venous thrombosis and the incidence of venous thromboembolism during normal pregnancy is 6-fold higher during pregnancy than in the general female population of child-bearing age. This incidence is, however, remarkably low given the increases in markers of haemostatic activation observed during normal pregnancy. During normal healthy pregnancy there are substantial changes in the haemostatic system, many of which are procoagulant and supposed to be in preparation for the haemostatic challenge of delivery. Normal haemostasis requires a balance between coagulation and fibrinolysis to maintain the integrity of the vasculature, and complex physiological changes are evident during pregnancy which appear to ensure a constant coagulation/fibrinolysis balance. This balance is maintained, at least partly, by an increase in fibrinolytic activity, but decreases in other factors such as factor XI and monocyte tissue factor expression may also serve to counterbalance procoagulant changes.

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Thrombin-Antithrombin III Complexes and Antithrombin III in Amniotic Fluid

Cited by 7 publications

References 13 publications

Changes in amniotic fluid concentration of thrombin–antithrombin III complexes in patients with preterm labor: Evidence of an increased thrombin generation

Changes in amniotic fluid concentration of thrombin–antithrombin III complexes in patients with preterm labor: Evidence of an increased thrombin generation

Proteolysis of Human Prolactin: Resistance to Cathepsin D and Formation of a Nonangiostatic, C-Terminal 16K Fragment by Thrombin

Haemostasis in normal pregnancy: a balancing act?

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