Histidine-Rich Glycoprotein and in Term and Preterm Newborns James J. Corrigan, Jr,
Levels
MD, Monette A. Jeter, PhD
\s=b\ The newborn's fibrinolytic system is not the same as that in the adult. Hypoplasminogenemia with normal (adult) levels of \g=a\2-plasmin inhibitor and plasmino-
gen activator inhibitor are characteristic of the newborn's lytic system. This combination suggests that the newborn may have an impaired lytic system that may
explain, in part, the thrombotic events that are frequently observed. Histidine-rich glycoprotein (HRG), another fibrinolytic inhibitor, retards fibrinolysis by interfering with plasminogen's binding to fibrin. Levels of HRG have been reported to be reduced in term newborns. This finding has not been studied recently and to our knowledge, there are no reports of HRG
levels in premature infants. The purpose of this study was to measure the plasma levels of HRG and plasminogen in three groups of patients: normal adults (n 48), normal term newborns (n=43), and normal premature newborns (n 18). The protein levels were determined by electroimmunoassay. Cross-immunoelectrophoresis was also performed for HRG. Cord blood was employed for obtaining new\x=req-\ born citrated plasma. The newborns had significantly lower plasminogen and HRG levels when compared with those of the adults. Also, the HRG levels of the premature newborns were lower than those of the term newborns. In conclusion, the newborns had lower levels of HRG than adults, with premature newborns having the lowest levels. This may allow for more plasminogen to be available for fibrin binding even though newborns have =
=
hypoplasminogenemia. (AJDC. 1990;144:825-828)
IT istidine-rich glycoprotein (HRG) is a
Plasminogen Plasma
plasma a2-glycoprotein discov¬ biologic function is
ered in 1972 whose
Accepted for publication November 3,1989. From the Department of Pediatrics and the Children's Research Center, University of Arizona Health Sciences Center, Tucson. Reprint requests to Department of Pediatrics, University of Arizona Health Sciences Center, Tucson, AZ 85724 (Dr Corrigan).
unclear. However, recent studies sug¬ gest that HRG is an inhibitor in the fibrinolytic mechanism by acting to in¬ terfere with plasminogen binding to fi¬ brin." Under normal physiologic condi¬ tions, about 50% of the plasminogen circulates as a reversible complex with HRG thereby reducing the effective plasminogen concentration and thus producing an antifibrinolytic effect. ' Reports by Heimburger et al5 in 1972 and Morgan et al6 in 1978 indicated that the neonatal serum concentration of HRG was about 20% to 30% of that of the adult. To our knowledge, there are no reports on HRG levels in premature newborns or on comparisons between plasminogen and HRG concentrations in the newborn. It is known that the fibrinolytic system ofthe newborn is not the same as that of the older child or adult.7 The plasminogen level is re¬ duced, whereas the naturally occurring inhibitors (a2-antiplasmin and plasmino¬ gen activator inhibitor) are at levels re¬ ported for adult plasma.8"11 This com¬ bination (hypoplasminogenemia with normal inhibitor levels) has been used to explain, in part, the thrombotic tenden¬ cy in the newborn. Decreased HRG lev¬ els, however, would be an advantage for the newborn and could help counterbal¬ ance the hypofibrinolytic state. In this study, we measured HRG and plasminogen concentration in plasma samples from normal term and preterm newborns. The newborns' levels for both proteins were significantly lower than the levels for adults. The preterm newborn showed the lowest levels. However, the data suggest that propor¬ tionately more plasminogen is available in the newborn than in the adult for
fibrinolysis. PATIENTS AND METHODS Blood samples were obtained by venipuncture from 48 adults and from cord blood of 43
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Michigan User on 06/11/2015
normal term newborns and 18 normal pre¬ term newborns (^37 weeks' gestational
age). Nine volumes of whole blood were anticoagulated with 1 vol of 0.1 mol/L of sodium citrate. The samples were centrifuged for 20 minutes at 1500
Levels
MD, Monette A. Jeter, PhD
\s=b\ The newborn's fibrinolytic system is not the same as that in the adult. Hypoplasminogenemia with normal (adult) levels of \g=a\2-plasmin inhibitor and plasmino-
gen activator inhibitor are characteristic of the newborn's lytic system. This combination suggests that the newborn may have an impaired lytic system that may
explain, in part, the thrombotic events that are frequently observed. Histidine-rich glycoprotein (HRG), another fibrinolytic inhibitor, retards fibrinolysis by interfering with plasminogen's binding to fibrin. Levels of HRG have been reported to be reduced in term newborns. This finding has not been studied recently and to our knowledge, there are no reports of HRG
levels in premature infants. The purpose of this study was to measure the plasma levels of HRG and plasminogen in three groups of patients: normal adults (n 48), normal term newborns (n=43), and normal premature newborns (n 18). The protein levels were determined by electroimmunoassay. Cross-immunoelectrophoresis was also performed for HRG. Cord blood was employed for obtaining new\x=req-\ born citrated plasma. The newborns had significantly lower plasminogen and HRG levels when compared with those of the adults. Also, the HRG levels of the premature newborns were lower than those of the term newborns. In conclusion, the newborns had lower levels of HRG than adults, with premature newborns having the lowest levels. This may allow for more plasminogen to be available for fibrin binding even though newborns have =
=
hypoplasminogenemia. (AJDC. 1990;144:825-828)
IT istidine-rich glycoprotein (HRG) is a
Plasminogen Plasma
plasma a2-glycoprotein discov¬ biologic function is
ered in 1972 whose
Accepted for publication November 3,1989. From the Department of Pediatrics and the Children's Research Center, University of Arizona Health Sciences Center, Tucson. Reprint requests to Department of Pediatrics, University of Arizona Health Sciences Center, Tucson, AZ 85724 (Dr Corrigan).
unclear. However, recent studies sug¬ gest that HRG is an inhibitor in the fibrinolytic mechanism by acting to in¬ terfere with plasminogen binding to fi¬ brin." Under normal physiologic condi¬ tions, about 50% of the plasminogen circulates as a reversible complex with HRG thereby reducing the effective plasminogen concentration and thus producing an antifibrinolytic effect. ' Reports by Heimburger et al5 in 1972 and Morgan et al6 in 1978 indicated that the neonatal serum concentration of HRG was about 20% to 30% of that of the adult. To our knowledge, there are no reports on HRG levels in premature newborns or on comparisons between plasminogen and HRG concentrations in the newborn. It is known that the fibrinolytic system ofthe newborn is not the same as that of the older child or adult.7 The plasminogen level is re¬ duced, whereas the naturally occurring inhibitors (a2-antiplasmin and plasmino¬ gen activator inhibitor) are at levels re¬ ported for adult plasma.8"11 This com¬ bination (hypoplasminogenemia with normal inhibitor levels) has been used to explain, in part, the thrombotic tenden¬ cy in the newborn. Decreased HRG lev¬ els, however, would be an advantage for the newborn and could help counterbal¬ ance the hypofibrinolytic state. In this study, we measured HRG and plasminogen concentration in plasma samples from normal term and preterm newborns. The newborns' levels for both proteins were significantly lower than the levels for adults. The preterm newborn showed the lowest levels. However, the data suggest that propor¬ tionately more plasminogen is available in the newborn than in the adult for
fibrinolysis. PATIENTS AND METHODS Blood samples were obtained by venipuncture from 48 adults and from cord blood of 43
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Michigan User on 06/11/2015
normal term newborns and 18 normal pre¬ term newborns (^37 weeks' gestational
age). Nine volumes of whole blood were anticoagulated with 1 vol of 0.1 mol/L of sodium citrate. The samples were centrifuged for 20 minutes at 1500
