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  • Georg Thieme Verlag KG  (3)
  • 1985-1989  (3)
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  • Georg Thieme Verlag KG  (3)
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  • 1985-1989  (3)
Year
  • 1
    Online Resource
    Online Resource
    Georg Thieme Verlag KG ; 1986
    In:  Thrombosis and Haemostasis Vol. 55, No. 03 ( 1986), p. 342-346
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 55, No. 03 ( 1986), p. 342-346
    Abstract: Standard heparin and a LMWH, CY222 do not cross the placenta nor alter fetal coagulation when injected into the pregnant ewe. We found that another LMWH, Pharmuka-10169 (PK-10169) alters fetal coagulation without crossing the placenta in the pregnant sheep. To characterize this anticoagulant we measured the in vitro and in vivo effects of 125I-PK-10169 in maternal and fetal plasmas following administration of PK-10169 to the mother or fetus. The fetal anticoagulant activity was not neutralizable by protamine sulphate and was attributable to the inhibition of thrombin but not factor Xa. In vitro, the fetal anticoagulant activity had properties similar to dermatan sulphate : both catalyzed the inhibition of thrombin but not factor Xa by sheep plasma; and neither was neutralizable by protamine sulphate. These effects were due to the enhanced neutralization of thrombin by heparin cofactor II. We conclude that PK-10169 does not cross the placenta, but does induce the release of an endogenous dermatan sulphate-like substance which alters fetal coagulation.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 1986
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  • 2
    Online Resource
    Online Resource
    Georg Thieme Verlag KG ; 1989
    In:  Thrombosis and Haemostasis Vol. 62, No. 04 ( 1989), p. 1074-1077
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 62, No. 04 ( 1989), p. 1074-1077
    Abstract: Antithrombin III (ATIII) is the main inhibitor of thrombin in adult plasma; α2-macroglobulin (α2M) and heparin cofactor II (HCII) are of lesser importance. The relative contributions of these inhibitors to the inactivation of thrombin may differ during the neonatal period and infancy, when plasma concentrations of α2M are about twice as high as those of ATIII. We therefore compared the relative importance of these anti-proteases for the inhibition of 125I-thrombin in defibrinated pooled adult and neonatal plasma. Observations were also made in pooled plasma of 6 months old infants. 125I-thrombin-inhibitor complexes were quantitated after SDS-PAGE and autoradiography by scanning densitometry. Thrombin (2.5 NIH U/ml) was inhibited more slowly in neonatal than in adult plasma. However, both plasmas inhibited 88% of the added thrombin by 5 minutes. α2M inhibited consistently a larger fraction of thrombin in neonatal than in adult plasma. Consequently, the ratio of thrombin bound to ATIII over thrombin bound to α2M was significantly lower in neonatal ( 〈 2.5) than in adult plasma ( 〉 4.5; p 〈 0.0001). In infant plasma, this ratio was 〈 2.0. Upon addition of therapeutic amounts of heparin (0.4 U/ml), differences between the contributions of ATIII and α2M to the inhibition of thrombin were no longer apparent, as over 90% of complexed thrombin was bound to ATIII in heparinized plasmas of all age groups. We conclude that α2M is an important progressive inhibitor of thrombin in young infants. This finding may explain why healthy newborns rarely suffer from thrombosis, despite their low plasma ATIII levels.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 1989
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    Georg Thieme Verlag KG ; 1988
    In:  Thrombosis and Haemostasis Vol. 60, No. 02 ( 1988), p. 289-292
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 60, No. 02 ( 1988), p. 289-292
    Abstract: The relative deficiency of antithrombin III (AT III) in neonatal plasma results in lower recovery of heparin in some assay systems. It is uncertain whether low AT III levels also limit the antithrombotic effects of heparin in this age group. We therefore compared the antithrombotic properties of heparin in mature pigs and newborn piglets, whose coagulation and inhibitor system closely resembles that of the human neonate. Animals were pretreated with saline, 10 or 25 U/kg heparin (n ≥16 per age group and dose). Following an injection of 100 U/kg thrombin, systemic 125I-fibrinogen consumption and local 125I-fibrinogen incorporation into jugular venous stasis thrombi were measured. Significantly more 125I-fibrinogen was consumed in piglets than in pigs systemically (p 〈 0.0001), as well as within the occluded vein segment (p = 0.0112), largely because heparin was less effective in piglets than in pigs. This neonatal resistance to heparin could not be explained by lower heparin levels in the newborn animals. However, pretreatment with AT III concentrate significantly improved the antithrombotic properties of heparin in this age group (p 〈 0.0001). We conclude that physiologically low AT III levels reduce the efficacy of heparin in neutralizing thrombin activity in newborn piglets. We speculate that AT III deficiency may also limit the antithrombotic properties of heparin in newborn infants with thrombotic disease.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 1988
    Location Call Number Limitation Availability
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