Immunologic Studies of Antithrombin III Heparin Cofactor in the Newborn

1978 ◽  
Vol 39 (03) ◽  
pp. 624-630 ◽  
Author(s):  
W E Hathaway ◽  
L L Neumann ◽  
C A Borden ◽  
L J Jacobson

SummarySerial quantitative immunoelectrophoretic (IE) measurements of antithrombin III heparin cofactor (AT III) were made in groups of well and sick newborn infants classified by gestational age. Collection methods (venous vs. capillary) did not influence the results; serum IE measurements were comparable to AT III activity by a clotting method. AT III is gestational age-dependent, increasing from 28.7% of normal adult values at 28-32 weeks to 50.9% at 37-40 weeks, and shows a gradual increase to term infant levels (57.4%) by 3-4 weeks of age. Infants with the respiratory distress syndrome (RDS) show lower levels of AT III in the 33-36 week group, 22% vs. 44% and in the 37-40 week group, 33.6% vs. 50.9%, than prematures without RDS. Infants of 28-32 week gestational age had only slight differences, RDS = 24%, non-RDS = 28.7%. The lowest levels of AT III were seen in patients with RDS complicated by disseminated intravascular coagulation and those with necrotizing enterocolitis. Crossed IE on representative infants displayed a consistent pattern which was identical to adult controls except for appropriate decreases in the amplitude of the peaks. The thrombotic complications seen in the sick preterm infant may be related to the low levels of AT III.

Author(s):  
S Braude ◽  
J Arias ◽  
R D Hughes ◽  
J Canalese ◽  
A E S Gimson ◽  
...  

The antithrombin III (ATIII) levels in 17 patients with fulminant hepatic failure due to viral hepatitis or paracetamol overdose were found to be 25.8%±SD 12.80 of normal on admission. The levels did not correlate with eventual survival or death and remained essentially unchanged for up to 7 days.In an attempt to assess the role of the low levels of AT III during the course of hepatic failure and in relation to treatment by charcoal haemoperfusion we have infused patients with commercially purified ATIII. Preliminary measurements of ATIII (chromogenic substrate method) were made and ATIII infused to achieve a plasma concentration of 50 to 70%. Infusion was by an initial bolus of 1500-2000 units followed by up to 500 units every 6 hours. To date 3 patients in Grade IV hepatic coma have been treated, one died 1 day after admission and the other two survived. In the latter the return of the prothrombin time to normal was similar to that in patients without the addition of ATIII. In one of the survivors the platelet count did not fall, suggesting ATIII may have had a protective effect on platelet consumption. There was also an indication, that there was a more uniform and better response to heparin anticoagulation during haemoperfusion than found previously without ATIII infusion.Further patients will be treated to evaluate whether AT III substitution can reduce the consumptive coagulopathy and platelet destruction which occurs in the course of fulminant hepatic failure.


1982 ◽  
Vol 47 (01) ◽  
pp. 056-058 ◽  
Author(s):  
M M McDonald ◽  
W E Hathaway ◽  
E B Reeve ◽  
B D Leonard

SummaryAntithrombin III (AT-III) was isolated by heparin affinity chromatography from adult venous and newborn term and preterm umbilical cord blood. The purified proteins were compared by SDS-PAGE, rocket immuno-electrophoresis, protein concentration by microbiuret relative to optical density at 280 nm, heparin cofactor specific activity, progressive neutralization of thrombin and factor Xa at 37°C and pH related antithrombin kinetics. The structural evaluations revealed a fetal AT-III of molecular weight, charge and electrophoretic migration indistinguishable from adult AT-III. The functional studies showed that, on an equimolar basis, the rates of thrombin and Xa interactions with fetal AT-III were as rapid as those with adult AT-III. The catalytic rates of various concentrations of heparin were also equal. The newborn infant, therefore, displays a quantitative but not qualitative deficiency of AT-III.


Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 33-39 ◽  
Author(s):  
D Menache ◽  
JP O'Malley ◽  
JB Schorr ◽  
B Wagner ◽  
C Williams ◽  
...  

Antithrombin III (Human) (AT III) was administered to 18 patients with documented hereditary AT III deficiency. In eight patients with no ongoing clinical symptoms of thrombosis, the percent increase per unit AT III infused per kilogram of body weight ranged from 1.56% to 2.74%, and the half-life from 43.3 to 77.0 hours. No significant difference was noted between patients receiving and those not receiving coumarin therapy. In clinically ill patients, the in vivo recovery was significantly lower and ranged from 0.64% to 1.90% increase per unit AT III infused/kg. Efficacy of AT III was evaluated in 13 patients for the prevention or treatment of thrombosis. AT III was efficacious as assessed by the absence of thrombotic complications after surgery and/or parturition, and the nonextension and nonrecurrence of thrombosis in patients exhibiting an acute thrombotic episode. No side effects were noted. Follow-up studies indicated no hepatitis B seroconversion and no alanine aminotransferase elevations in patients who were not transfused with other blood products.


Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 33-39 ◽  
Author(s):  
D Menache ◽  
JP O'Malley ◽  
JB Schorr ◽  
B Wagner ◽  
C Williams ◽  
...  

Abstract Antithrombin III (Human) (AT III) was administered to 18 patients with documented hereditary AT III deficiency. In eight patients with no ongoing clinical symptoms of thrombosis, the percent increase per unit AT III infused per kilogram of body weight ranged from 1.56% to 2.74%, and the half-life from 43.3 to 77.0 hours. No significant difference was noted between patients receiving and those not receiving coumarin therapy. In clinically ill patients, the in vivo recovery was significantly lower and ranged from 0.64% to 1.90% increase per unit AT III infused/kg. Efficacy of AT III was evaluated in 13 patients for the prevention or treatment of thrombosis. AT III was efficacious as assessed by the absence of thrombotic complications after surgery and/or parturition, and the nonextension and nonrecurrence of thrombosis in patients exhibiting an acute thrombotic episode. No side effects were noted. Follow-up studies indicated no hepatitis B seroconversion and no alanine aminotransferase elevations in patients who were not transfused with other blood products.


1984 ◽  
Vol 52 (01) ◽  
pp. 042-044 ◽  
Author(s):  
Dona M Lynch ◽  
Linda K Leff ◽  
Stephen E Howe

SummaryThree antithrombin-III assays (Sigma functional plasma, von Kaulla functional serum, and Calbiochem-Behring radial immunodiffusion) are compared using preoperative serum and plasma from 48 patients admitted for cardiovascular or other major vascular surgery. Medical records were reviewed for evidence of thrombotic complications. Eight patients (17%) in this selected population had clinical evidence of postoperative thrombotic complications. The sensitivity and specificity for each AT-III assay were calculated, and the positive and negative predictive values in this population were determined. Sigma’s plasma AT-III had the highest positive predictive value (67%) and negative predictive value (100%). The functional serum and RID assays had significantly lower positive predictive values (23% and 38% respectively) and negative predictive values of 86%. Using the Two Sample t-Test to evaluate differences in AT- III values between the two patient groups, i.e., those who experienced thrombotic complications and those who did not, only the functional plasma AT-III method was statistically significant at a 95% confidence interval.


2018 ◽  
Vol 35 (3-4) ◽  
pp. 78-83
Author(s):  
Rachma F. Boedjang

The subjects of the study consisted of 164 sick newborn infants (97 boys and 67 girls) who had no signs or symptoms of infections. The intravenous fluid drip (at scalp vein or saphenous vein) was put on soon after taking blood culture. Removal of venous catheters was indicated when the patients condition. No longer needed their use or there was sign of local infection. This study showed that the lower the birth weight or the gestational age, the higher the incidence of infection. The most prominent nosocomial infection in this study was phlebitis (16.5%) followed by infiltration (14.6%), and bacteremia (7 ,9%). The predominant microorganism was E. coli (59.7%). The overall incidence of nosocomial infection was 44.5% and the mortality was 24.7%.


PEDIATRICS ◽  
1975 ◽  
Vol 56 (3) ◽  
pp. 374-379
Author(s):  
Boyd W. Goetzman ◽  
Robert C. Stadalnik ◽  
Hugo G. Bogren ◽  
Willard J. Blankenship ◽  
Richard M. Ikeda ◽  
...  

Catheterization of the aorta via the umbilical artery provides a convenient route for monitoring arterial blood pressure, for obtaining blood specimens for measurement of blood gas tensions and chemistries, and for the infusion of fluids and pharmacologic preparations in sick newborn infants. Use of this technique may be accompanied by a number of complications of which thrombotic phenomena are the most common. Twenty-three of 98 (24%) newborn infants undergoing umbilical artery catheterization were found to have thrombotic complications determined by aortography. No correlation was present between the duration of time that the umbilical artery catheters were in place and the occurrence of thrombotic complications. From paired aortographic or aortographic and autopsy studies in 24 patients, it was concluded that if a thrombotic complication did not occur early, none was likely to occur subsequently. One patient was considered to have died as a direct result of a thrombotic complication. Aortography is a safe, simple, and reliable technique for the early detection of thrombotic complications of umbilical artery catheters. Umbilical artery catheterization is not without risk and careful selection of patients for this procedure is indicated.


PEDIATRICS ◽  
1972 ◽  
Vol 50 (3) ◽  
pp. 483-485
Author(s):  
Eleni Damoulaki-Sfakianaki ◽  
Alex Robertson ◽  
Leandro Cordero

It has been known that the development of skin creases on the sole of the foot occurs in late intrauterine life and that after birth this is a helpful clinical sign to determine gestational age. Until 36 weeks of gestation there are only one or two transverse skin creases on the anterior part of the sole. The posterior two-thirds of the sole are smooth. By 37 to 38 weeks of gestation more creases have appeared and in the full-term infant there is a complex series of criss-crossed creases covering the entire sole. Since no racial differences in the presence or absence of this sign have ever been published a study was designed to compare the development of skin creases on the sole of the foot between Caucasian and Negro newborn infants.


1993 ◽  
Vol 69 (05) ◽  
pp. 418-421 ◽  
Author(s):  
Barbara Schmidt ◽  
Patsy Vegh ◽  
Marilyn Johnston ◽  
Maureen Andrew ◽  
Jeffrey Weitz

SummaryBackground: Disseminated intravascular coagulation (DIC) is usually diagnosed in sick infants who have prolonged clotting times, depletion of platelets and coagulation factors, and elevated levels of fibrin derivatives. However, the diagnostic accuracy of abnormal coagulation profiles in neonates at risk of DIC has been uncertain. Since DIC is characterized by activation of both the coagulation and fibrinolytic systems, the objective of this study was to determine whether coagulation screening tests correctly identify infants with biochemical evidence of increased thrombin and plasmin generation.Methods: Non-surgical patients in a tertiary care nursery who were sick enough to require an indwelling arterial catheter for monitoring purposes, were enrolled in a prospective cohort study. Blood samples for thrombin/antithrombin III (TAT) complexes and the plasmin-derived fibrinopeptide Bβ1-42 were drawn 36 to 72 h after birth from a free-flowing arterial line. Platelet counts, D-Dimer levels, plasma fibrinogen concentrations and prothrombin times, expressed as International Normalized Ratios or INR, were measured at the same time.Results: One hundred patients were studied. Fifty-seven infants had elevated levels of TAT (≥4 μg/l) and Bβ1-42 (≥4 nmol/l). The sensitivities of platelets <150 × 109/l, D-Dimer >500 ng/ml, fibrinogen <1.5 g/l, and INR >1.5 were 39%, 30%, 12%, and 11%, respectively. Corresponding specificities were 88%, 91%, 98%, and 95%.Conclusions: Abnormal coagulation screens in sick newborn infants strongly support a diagnosis of DIC. However, normal screens do not exclude activation of the coagulation and fibrinolytic systems.


Author(s):  
R Egbring ◽  
H G Klingemann ◽  
N Heimburger ◽  
H E Karges ◽  
J Beule ◽  
...  

In patients with acute severe hepatic failure the synthesis of clotting factors and inhibitors is considerably diminished. The decrease of clotting factors may be enhanced by liberation of thromboplastic substances from liver cell debris, leading to thrombus formation in the sinusoids and to further cell damage. At the low levels of clotting factors and inhibitors signs of disseminated intravascular coagulation as well as hyperfibrinolysis have been demonstrated. Treatment with heparin to prevent coagulation is insufficient at low levels of antithrombin III (AT III). Therefore, Vogel und Fritsche 1979 suggested the substitution of AT III in these cases.We now report about 3 patients who were admitted to the clinic together with severe signs of liver damage after oral uptake of CCl4 On the day of admission several clotting factors plasminogen and alpha2-antiplasmin were significantly diminished; AT III levels between 25-45% of the norm were found. (Diss. Eckhardt-Klaßnitz). Therefore we started treatment with AT III concentrate from Behringwerke (1000-2000 I.U. daily for 3 to 14 days) and fresh frozen plasma (total volume of 2 1 within the first 3 days).AT III was simultaneously determined by clotting test, a chromogenic substrate test, and immunologically. Hemodialysis was necessary in 2 patients. Unter treatment with AT III and fresh frozen plasma no bleeding tendency occured Though two of the patients showed severe intoxication on admission all could be dismissed with only slight histological signs of liver alterations. Treatment with AT III concentrates, therefore, seems of value in patients with acute yellow liver dystrophy.


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