Biochemical and Functional Study of Antithrombin III in Newborn Infants

McDonald, Marilyn M.; Hathaway, William E.; Reeve, E. B.; Leonard, B. D.

doi:10.1055/s-0038-1657125

Cited by 28 publications

(14 citation statements)

References 6 publications

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“…Levels of AT-111 increase with increasing gestational age and postnatal age in healthy infants achieving values in the lower adult range as early as at 1 wk of age (3,16). AT-111 from both premature and full term cord blood has been isolated and is identical to AT-I11 from adults with respect to a variety of functional and immunologic properties thus excluding the possibility of a fetal form of AT-111 (16,21). This study confirms those reports; however, we observed a dysfunctional AT-111 molecule later in the postnatal period in a select population of sick premature infants.…”

Section: Discussionmentioning

confidence: 99%

Dysfunctional Antithrombin III in Sick Premature Infants

et al. 1985

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ABSTRAm. Antithrombin 111, a major inhibitor of activated coagulation factors has low immunologic levels in the human infant. The objective of this study was to deermine if the antithrombin 111 molecule is fully functional in sick premature infants. The populations studied included: adult controls (n = 20), full term healthy infants (n = 18), sick premature infants on day 1 (n = 16) and at >7 days of age (n = lo), and infants with disseminated intravascular coagulation (n = 11). This was diagnosed in the presence of prolonged screening tests, decreased levels of fibrinogen, and platelets along with elevated fibrin degradation products. Plasma antithrombin 111 levels were measured biologically (chromogenic substrate S2238) and immunologically (radialimmunodiffusion), and expressed as a percent of adult pooled plasma. Crossed immunoelectrophoresis were performed in the presence and absence of heparin. The antithrombin 111 biologic/immunologic ratios for adults, healthy full term infants, and sick premature infants on day 1 of life were all near unity. In contrast sick premature infants beyond the 1st wk of life and infants with disseminated intravascular coagulation had lower biologic activity compared to immunologic (B/I = 0.77 f 0.28, 0.78 f 0.17, p < 0.01), respectively. In all groups, the antithrombin 111 molecule was normal on crossed immunoelectrophoresis except for one infant with disseminated intravascular coagulation. Sick premature infants may acquire a dysfunctional antithrombin 111 molecule in the postnatal period. (Pediatr Res 19: 237-239, 1985) Abbreviations AT-111, antithrombin 111 RDS, respiratory distress syndrome BPD, bronchopulmonary dysplasia DIC, disseminated intravascular coagulation CIE, cross-immunoelectrophoresis APTT, activated partial thromboplastin time PT, prothrombin time TcT, thrombin clotting time EACA, €-amino caproic acid Normal hemostasis depends on a delicate balance between the procoagulant and fibrinolytic systems and their respective inhibitors. AT-111, the major inhibitor for the coagulation system

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Section: Discussionmentioning

confidence: 99%

Dysfunctional Antithrombin III in Sick Premature Infants

et al. 1985

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“…12,28 This study, which employed chromogenic microanalytic techniques, has confirmed previous reports of a significant reduction (35-45%) in the levels of antithrombin III, plasminogen, 2,4,7,15,31 and protein C 7,13 in neonates compared with adults; no such differences were noted in the levels of alpha2-antiplasmin. Recent evidence has also shown that fetal and adult antithrombin possess the same molecular weight, charge, and electrophoretic migration pattern, 16,30 and therefore newborns display a quantitative and not qualitative deficiency of antithrombin. The low neonatal levels of the hemostatic inhibitors, antithrombin III, and protein C, but not alpha2-antiplasmin, are in the range defined for thromboembolic disorders.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] The data, which represent the reference values for Saudi neonates, are compared in Table 2 with similar data from other ethnic populations.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Although this subject has interested many researchers in the last two decades, the numerous data available for healthy newborn infants are inconsistent and difficult to obtain and interpret. This is due to such factors as variable methods of blood collection and assay procedures, variable gestational age, birth weight and vitamin K status, wide ranges of clotting factor proteins, and small number of observations, which make it difficult to define true normal values or to draw valid comparisons between these data.…”

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confidence: 99%

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Coagulation Parameters in Maternal and Cord Blood at Delivery

et al. 1990

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A wide range of hemostatic variables were studied in 300 maternal/neonatal pairs at the time of delivery and also in 375 healthy nonpregnant women who served as controls. There was significant prolongation of the prothrombin time, partial thromboplastin time, and reptilase time in neonatal (cord) blood compared to maternal blood. The plasma levels of fibrinogen, antithrombin III, protein C, plasminogen, factor VIII coagulant and ristocetin cofactor activities, factor X, and platelet counts were significantly lower in neonatal than maternal plasma. In contrast, the thrombin time, alpha2-antiplasmin, and serum fibrin degradation products showed comparable values for both mothers and neonates. von Willebrand factor antigen showed a more significant elevation in mothers than neonates; however, the ratio of von Willebrand factor antigen/factor VIII coagulant was similar in both (1.56 and 1.57, respectively). There was a significant correlation only between factor VIII coagulant levels in mothers and their babies (r = 0.69; P < 0.05) but not for the other hemostatic variables studied. The differences between our results and those reported in smaller published studies are discussed.

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“…The formation of complexes of procoagulant proteins with AT is accelerated 1000-fold by heparin (12). Newborn infants have been shown to have approximately 50% adult plasma concentration of a functionally normal AT (6,13). Heparin resistance, or failure to achieve a plasma anti-Xa activity commensurate with therapeutic heparin infusion rate, is commonly found in infants and ascribed to low neonatal levels of AT (14 -16).…”

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confidence: 99%

Development of Coagulation Regulatory Proteins in the Fetal and Neonatal Lamb

Manco‐Johnson

2002

Pediatric Research

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To investigate the development of coagulation regulatory proteins-protein C (PC), protein S (PS), and antithrombin (AT)-in relationship to the procoagulant protein factor X (FX), a chronically catheterized fetal ovine model was used. Infusion and sampling catheters were placed into pregnant ewes and their fetuses and maintained from mid-gestation. From a total of 110 fetuses, 17 lambs, and 63 ewes that were studied on one to 15 occasions, 212 fetal, 88 neonatal, and 157 maternal samples were obtained. Liver tissue was obtained from 31 fetuses and 15 ewes. Plasma levels of all proteins studied were higher in the ewe than in the fetus (p Ͻ 0.0001). Plasma levels of FX, PC, and PS achieved neonatal levels by mid-gestation with mild but significant decreases during mid-and late gestation. Fetal and early neonatal plasma concentrations of these vitamin K-dependent proteins fit a model with both quadratic (p Ͻ 0.01) and linear (p Ͻ 0.01) components. The discrepant levels in mRNA relative to plasma concentration were consistent with regulatory control beyond the level of transcription. In contrast, a simple linear increase in plasma protein levels was determined for the vitamin K-independent coagulation regulatory protein, AT (p for quadratic component Ͼ 0.05). This study suggests that fetal regulation of coagulation proteins follows characteristic patterns relative to the vitamin K dependence of the protein rather than its role as a procoagulant versus regulatory protein. The hemostatic systems of the fetus and neonate differ from that of the adult. Plasma concentrations of coagulation proteins mature at different rates during in utero and postnatal development (1-3). In particular, vitamin K-dependent factors, prothrombin, PC, PS, and factors VII, IX, and X, as well as contact factors XI, XII, prekallikrein, and high-molecular-weight kininogen, are present in very low concentrations in the fetus and do not achieve normal adult levels until later infancy to adolescence (2-7). Clinically, the well neonate has a functionally intact hemostatic system. However, the stressed infant demonstrates an increased predisposition to thrombosis, both induced and spontaneous (8). The increased rate of thrombosis in neonates is generally attributed to physiologically low levels of coagulation regulatory proteins, particularly PC, PS, and AT.PC is a vitamin K-dependent serine protease that serves a critical role in the regulation of coagulation. Activated PC, with its cofactor PS, inactivates activated procoagulant factors V and VIII (9). Infants with severe genetic deficiencies of either PC or PS manifest spontaneous thrombosis in utero or within hours of birth (10, 11). Our previous work showed that the mean concentration of PC in the extremely preterm infant is 0.20 U/mL, as compared with 1.00 U/mL in healthy adults (6, 7). An increased risk of catheter-related and spontaneous thrombosis was demonstrated in preterm infants with plasma concentrations of PC Ͻ0.10 U/mL (7).AT is an essential regulatory protein that functions through i...

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Biochemical and Functional Study of Antithrombin III in Newborn Infants

Cited by 28 publications

References 6 publications

Dysfunctional Antithrombin III in Sick Premature Infants

Dysfunctional Antithrombin III in Sick Premature Infants

Coagulation Parameters in Maternal and Cord Blood at Delivery

Development of Coagulation Regulatory Proteins in the Fetal and Neonatal Lamb

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