Thromboembolic Disease and Antithrombotic Therapy in Newborns

Andrew, Maureen; Monagle, Paul; deVeber, Gabrielle; Chan, Anthony

doi:10.1182/asheducation-2001.1.358

Cited by 98 publications

(94 citation statements)

References 172 publications

(172 reference statements)

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“…Previous population- 35,36 and hospital-based 13,22,24 estimates range from 18 to 93 per 100 000 live births. These figures underestimate the true prevalence of PAS, given that they do not include infants and children who present outside the newborn period.…”

Section: Prevalencementioning

confidence: 99%

Perinatal Stroke in Children With Motor Impairment: A Population-Based Study

et al. 2004

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ABSTRACT. Objective. Risk factors for perinatal arterial stroke (PAS) are poorly understood. Most previous studies lack an appropriate control group and include only infants with symptoms in the newborn period. We set out to determine prenatal and perinatal risk factors for PAS.Methods. In a population-based, case-control study nested within the cohort of 231 582 singleton infants who were born at >36 weeks' gestation in Northern California Kaiser hospitals from 1991 to 1998, we searched electronically for children with motor impairment and reviewed their medical records to identify diagnoses of PAS. Control subjects were randomly selected from the study population. A medical record abstractor reviewed delivery records without knowledge of case status.Results. The prevalence of PAS with motor impairment was 17/100 000 live births. Of 38 cases, 26 (68%) presented after 3 months of age with hemiparesis or seizures. All 12 newborns with acute stroke symptoms had seizures. A delayed presentation was more common in children with moderate to severe motor impairment than among infants with only mild motor abnormalities (24 of 31 vs 2 of 7). Prepartum risk factors significantly associated with PAS in multivariate analysis were preeclampsia (odds ratio [OR]: 3.6; 95% confidence interval [CI]: 1.1-11.4) and intrauterine growth restriction (OR: 5.3; 95% CI: 1.5-18.6). Newborns with PAS were also at higher risk of delivery complications, such as emergency cesarean section (OR: 6.8; 95% CI: 2.7-16.6), 5-minute Apgar <7 (OR: 23.6; 95% CI: 4.1-237), and resuscitation at birth (OR: 4.5; 95% CI: 1.6 -12.3).Conclusions. Preeclampsia and intrauterine growth restriction (IUGR) may be independent risk factors for perinatal stroke resulting in motor impairment. Large multicenter studies that include all children with perinatal stroke are needed to determine further the risk factors and outcome of perinatal stroke. Pediatrics 2004;114:612-619; perinatal stroke, epidemiology, neonate, infarction, cerebral palsy.

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Section: Prevalencementioning

confidence: 99%

Perinatal Stroke in Children With Motor Impairment: A Population-Based Study

et al. 2004

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“…Neonatal arterial ischemic stroke is most frequently caused by large vessel infarcts involving the carotid circulation in more than 2/3 of cases (Andrew et al 2001). In many of these infants, either perinatal complications or cardiac disease can be identifi ed (Golomb et al 2001).…”

Section: Incidencementioning

confidence: 99%

Thrombosis in the critically ill neonate: incidence, diagnosis, and management

Nold¹

2008

VHRM

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Among children, newborn infants are most vulnerable to development of thrombosis and serious thromboembolic complications. Amongst newborns, those neonates who are critically ill, both term and preterm, are at greatest risk for developing symptomatic thromboembolic disease. The most important risk factors are infl ammation, DIC, impaired liver function, fl uctuations in cardiac output, and congenital heart disease, as well as exogenous risk factors such as central venous or arterial catheters. In most clinically symptomatic infants, diagnosis is made by ultrasound, venography, or CT or MRI angiograms. However, clinically asymptomatic vessel thrombosis is sometimes picked up by screening investigations or during routine imaging for other indications. Acute management of thrombosis and thromboembolism comprises a variety of approaches, including simple observation, treatment with unfractionated or low molecular weight heparin, as well as more aggressive interventions such as thrombolytic therapy or catheter-directed revascularization. Long-term follow-up is dependent on the underlying diagnosis. In the majority of infants, stabilization of the patients' general condition and hemodynamics, which allows removal of indwelling catheters, renders long-term anticoagulation superfl uous. Nevertheless, in certain types of congenital heart disease or inherited thrombophilia, long-term prophylaxis may be warranted. This review article focuses on pathophysiology, diagnosis, and acute and long-term management of thrombosis in critically ill term and preterm neonates.

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“…The human preterm and term neonates show an increased predisposition to thrombosis compared with the older infant and child (8). The increased incidence of thrombosis in the neonatal period has been ascribed to lower plasma concentrations of coagulation regulatory proteins secondary to physiologic immaturity.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

mentioning

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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Thromboembolic Disease and Antithrombotic Therapy in Newborns

Cited by 98 publications

References 172 publications

Perinatal Stroke in Children With Motor Impairment: A Population-Based Study

Perinatal Stroke in Children With Motor Impairment: A Population-Based Study

Thrombosis in the critically ill neonate: incidence, diagnosis, and management

Development of Coagulation Regulatory Proteins in the Fetal and Neonatal Lamb

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