Abstract
The first weeks of life have the highest rate of thrombotic complications in the pediatric age, and thromboembolism mainly affects sick newborns. It is well known that despite low levels of procoagulant factors in the first months of life, newborns show a perfect hemostasis; this is probably due to the balancing effect of the low levels of physiological inhibitors (protein C, protein S, and antithrombin).
Some other pathophysiological insights are available to favor the knowledge of the process that pathological situations may lead newborns to experience thromboembolic complications. In the recent years, genetic prothrombotic conditions have been widely studied but their role in determining thrombosis in the neonates is still under debate. Moreover, in the sick newborn, especially preterm, several acquired perinatal and iatrogenic conditions might result in a disturbance between coagulation and fibrinolysis, leading to thrombus formation. The use of central lines, cardiac diseases and polycythemia, renal diseases such as congenital nephrotic syndrome and neonatal hemolytic uremic syndrome, peripartum asphyxia, infants of diabetic mothers, dehydration, septicemia, necrotizing enterocolitis, acute respiratory distress syndrome, and extracorporeal membrane oxygenation lead to elevated thrombin generation and subsequent thrombus formation.
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Abbreviations
- ACA:
-
Anticardiolipin antibodies
- AIS:
-
Arterial ischemic stroke
- APA:
-
Antiphospholipid antibodies
- APLS:
-
Antiphospholipid syndrome
- ArT:
-
Arterial thrombosis
- AT:
-
Antithrombin (natural anticoagulant)
- CNS:
-
Central nervous system
- CSVT:
-
Cerebral sinovenous thrombosis
- CVL:
-
Central venous line
- ETP:
-
Endogenous thrombin potential
- FI:
-
Fibrinogen
- FII:
-
Coagulation factor II
- FV:
-
Coagulation factor V
- FVII:
-
Coagulation factor VII
- FVIII:
-
Coagulation factor VIII
- FVL:
-
Factor V Leiden (prothrombotic polymorphism of FV)
- FX:
-
Coagulation factor X
- FXIII:
-
Coagulation factor XIII
- LA:
-
Lupus anticoagulant
- MTHFR:
-
Methylenetetrahydrofolate reductase
- PAP:
-
Plasmin-alpha2-antiplasmin complex
- PC:
-
Protein C (natural anticoagulant)
- PE:
-
Pulmonary embolism
- PLG:
-
Plasminogen
- PRT G20210A:
-
Prothrombotic mutation of factor II G20210A
- PS:
-
Protein S (natural anticoagulant cofactor of PC)
- PVT:
-
Portal vein thrombosis
- RVT:
-
Renal vein thrombosis
- TAT:
-
Thrombin–antithrombin complex
- TE:
-
Thromboembolic events
- TF:
-
Tissue factor
- TFPI:
-
TF pathway inhibitor
- TM:
-
Thrombomodulin
- UAC:
-
Umbilical artery catheter
- UVC:
-
Umbilical vein catheter
- VWF:
-
Von Willebrand factor
References
Adams-Chapman I, Vaucher YE, Bejar RF et al (2002) Maternal floor infarction of the placenta: association with central nervous system injury and adverse neurodevelopmental outcome. J Perinatol 22(3):236–241, Ref Type: Pamphlet
Albisetti M (2003) The fibrinolytic system in children. Semin Thromb Hemost 29:339–348
Andrew M (1995) Developmental hemostasis: relevance to hemostatic problems during childhood. Semin Thromb Hemost 21:341–356
Andrew M (2000) Arterial thromboembolic complication in pediatric patients. In: Andrew M, Monagle PT, Brooker LA (eds) Thromboembolic complications during infancy and childhood. B.C. Decker, Hamilton, pp 165–199
Andrew M, Paes B, Milner R et al (1987) Development of the human coagulation system in the full-term infant. Blood 70:165–172
Andrew M, Paes B, Milner R et al (1988) Development of the human coagulation system in the healthy premature infant. Blood 72:1651–1657
Andrew M, Paes B, Johnston M (1990) Development of the hemostatic system in the neonate and young infant. Am J Pediatr Hematol Oncol 12:95–104
Andrew M, David M, Adams M et al (1994) Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood 83:1251–1257
Andrew M, Monagle PT, Brooker LA (2000) Developmental hemostasis: relevance to thromboembolic complications in pediatric patients. In: Andrew M, Monagle PT, Brooker LA (eds) Thromboembolic complications during infancy and childhood. B.C. Decker, Hamilton/Lewiston
Aronis S, Platokouki H, Photopoulos S et al (1998) Indications of coagulation and/or fibrinolytic system activation in healthy and sick very-low-birth-weight neonates. Biol Neonate 74:337–344
Benavent A, Estelles A, Aznar J et al (1984) Dysfunctional plasminogen in full term newborn – study of active site of plasmin. Thromb Haemost 51:67–70
Benders MJ, Groenendaal F, Uiterwaal CS et al (2007) Maternal and infant characteristics associated with perinatal arterial stroke in the preterm infant. Stroke 38:1759–1765
Berman W Jr, Fripp RR, Yabek SM et al (1991) Great vein and right atrial thrombosis in critically ill infants and children with central venous lines. Chest 99:963–967
Bokenkamp A, von KR, Nowak-Gottl U et al (2000) Neonatal renal venous thrombosis in Germany between 1992 and 1994: epidemiology, treatment and outcome. Eur J Pediatr 159:44–48
Boo NY, Wong NC, Zulkifli SS, Lye MS (1999) Risk factors associated with umbilical vascular catheter-associated thrombosis in newborn infants. J Paediatr Child Health 35:460–465
Burke CJ, Tannenberg AE (1995) Prenatal brain damage and placental infarction – an autopsy study. Dev Med Child Neurol 37:555–562
Chalmers EA (2005) Perinatal stroke – risk factors and management. Br J Haematol 130:333–343
Chalmers EA (2006) Epidemiology of venous thromboembolism in neonates and children. Thromb Res 118:3–12
Clark P (2003) Changes of hemostasis variables during pregnancy. Semin Vasc Med 3:13–24
Cohen RS, Ramachandran P, Kim EH, Glasscock GF (1995) Retrospective analysis of risks associated with an umbilical artery catheter system for continuous monitoring of arterial oxygen tension. J Perinatol 15:195–198
Curry CJ, Bhullar S, Holmes J et al (2007) Risk factors for perinatal arterial stroke: a study of 60 mother-child pairs. Pediatr Neurol 37:99–107
Cvirn G, Gallistl S, Leschnik B, Muntean W (2003) Low tissue factor pathway inhibitor (TFPI) together with low antithrombin allows sufficient thrombin generation in neonates. J Thromb Haemost 1:263–268
de Veber GA, the Canadian Pediatric Ischemic Stroke Study Group (2000) Canadian pediatric ischemic registry: analysis of children with arterial ischemic stroke. (abstract). Ann Neurol 48:514
DeVeber G, Andrew M, Adams C et al (2001) Cerebral sinovenous thrombosis in children. NEngl J Med 345:417–423
El BA, Hussein HA, bou-Elew HH, bdel Kader MS (2004) Study of protein C, protein S, and antithrombin III in hypoxic newborns. Pediatr Crit Care Med 5:163–166
Estan J, Hope P (1997) Unilateral neonatal cerebral infarction in full term infants. Arch Dis Child Fetal Neonatal Ed 76:F88–F93
Feldman JP, Feinstein JA, Lamberti JJ, Perry SB (2005) Angiojet catheter-based thrombectomy in a neonate with postoperative pulmonary embolism. Catheter Cardiovasc Interv 66:442–445
Fitzgerald KC, Williams LS, Garg BP et al (2006) Cerebral sinovenous thrombosis in the neonate. Arch Neurol 63:405–409
Franzoi M, Simioni P, Luni S et al (2002) Effect of delivery modalities on the physiologic inhibition system of coagulation of the neonate. Thromb Res 105:15–18
Fritsch P, Cvirn G, Cimenti C et al (2006) Thrombin generation in factor VIII-depleted neonatal plasma: nearly normal because of physiologically low antithrombin and tissue factor pathway inhibitor. J Thromb Haemost 4:1071–1077
Fukui H, Takase T, Ikari H et al (1979) Factor VIII procoagulant activity, factor VIII related antigen and von Willebrand factor in newborn cord blood. Br J Haematol 42:637–646
Gamillscheg A, Nurnberg JH, exi-Meskishvili V et al (1997) Surgical emergency embolectomy for the treatment of fulminant pulmonary embolism in a preterm infant. J Pediatr Surg 32:1516–1518
Golomb MR (2003) The contribution of prothrombotic disorders to peri- and neonatal ischemic stroke. Semin Thromb Hemost 29:415–424
Golomb MR, MacGregor DL, Domi T et al (2001) Presumed pre- or perinatal arterial ischemic stroke: risk factors and outcomes. Ann Neurol 50:163–168
Gunther G, Junker R, Strater R et al (2000) Symptomatic ischemic stroke in full-term neonates : role of acquired and genetic prothrombotic risk factors. Stroke 31:2437–2441
Heilmann L, von Tempelhoff GF, Pollow K (2003) Antiphospholipid syndrome in obstetrics. Clin Appl Thromb Hemost 9:143–150
Hellstrom-Westas L, Ley D, Berg AC et al (2005) VWF-cleaving protease (ADAMTS13) in premature infants. Acta Paediatr 94:205–210
Israels SJ, Daniels M, McMillan EM (1990) Deficient collagen-induced activation in the newborn platelet. Pediatr Res 27:337–343
John JB, Cron SG, Kung GC, Mott AR (2007) Intracardiac thrombi in pediatric patients: presentation profiles and clinical outcomes. Pediatr Cardiol 28:213–220
Kavakli K, Canciani MT, Mannucci PM (2002) Plasma levels of the von Willebrand factor-cleaving protease in physiological and pathological conditions in children. Pediatr Hematol Oncol 19:467–473
Kenny D, Tsai-Goodman B (2007) Neonatal arterial thrombus mimicking congenital heart disease. Arch Dis Child Fetal Neonatal Ed 92:F59–F61
Knofler R, Hofmann S, Weissbach G et al (1998) Molecular markers of the endothelium, the coagulation and the fibrinolytic systems in healthy newborns. Semin Thromb Hemost 24:453–461
Kosch A, Kuwertz-Broking E, Heller C et al (2004) Renal venous thrombosis in neonates: prothrombotic risk factors and long-term follow-up. Blood 104:1356–1360
Kuhle S, Massicotte P, Chan A, Mitchell L (2004) A case series of 72 neonates with renal vein thrombosis. Data from the 1-800-NO-CLOTS Registry. Thromb Haemost 92:729–733
Kurnik K, Kosch A, Strater R et al (2003) Recurrent thromboembolism in infants and children suffering from symptomatic neonatal arterial stroke: a prospective follow-up study. Stroke 34:2887–2892
Lau KK, Stoffman JM, Williams S et al (2007) Neonatal renal vein thrombosis: review of the English-language literature between 1992 and 2006. Pediatrics 120:e1278–e1284
Manco-Johnson MJ (2005) Development of hemostasis in the fetus. Thromb Res 115(Suppl 1):55–63
Manco-Johnson MJ, Sifontes M, Nuss R (1999) Coagulation abnormalities in neonatal catheter related thrombosis. (Abstract). Thromb Haemost 82(suppl):384
Manco-Johnson MJ, Grabowski EF, Hellgreen M et al (2002) Laboratory testing for thrombophilia in pediatric patients. On behalf of the Subcommittee for Perinatal and Pediatric Thrombosis of the Scientific and Standardization Committee of the International Society of Thrombosis and Haemostasis (ISTH). Thromb Haemost 88:155–156
Marsh D, Wilkerson SA, Cook LN, Pietsch JB (1988) Right atrial thrombus formation screening using two-dimensional echocardiograms in neonates with central venous catheters. Pediatrics 81:284–286
Mercuri E, Cowan F, Gupte G et al (2001) Prothrombotic disorders and abnormal neurodevelopmental outcome in infants with neonatal cerebral infarction. Pediatrics 107:1400–1404
Michelson AD (1998) Platelet function in the newborn. Semin Thromb Hemost 24:507–512
Monagle P, Adams M, Mahoney M et al (2000) Outcome of pediatric thromboembolic disease: a report from the Canadian Childhood Thrombophilia Registry. Pediatr Res 47:763–766
Monagle P, Barnes C, Ignjatovic V et al (2006) Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb Haemost 95:362–372
Morag I, Epelman M, Daneman A et al (2006) Portal vein thrombosis in the neonate: risk factors, course, and outcome. J Pediatr 148:735–739
Moreno-Cabral RJ, Breitweser JA (1983) Pulmonary embolectomy in the neonate. Chest 84:502–504
Muntean W, Leschnik B, Baier K et al (2004) In vivo thrombin generation in neonates. J Thromb Haemost 2:2071–2072
Nowak-Gottl U, von KR, Gobel U (1997a) Neonatal symptomatic thromboembolism in Germany: two year survey. Arch Dis Child Fetal Neonatal Ed 76:F163–F167
Nowak-Gottl U, Debus O, Findeisen M et al (1997b) Lipoprotein (a): its role in childhood thromboembolism. Pediatrics 99:E11
Nowak-Gottl U, Dubbers A, Kececioglu D et al (1997c) Factor V Leiden, protein C, and lipoprotein (a) in catheter-related thrombosis in childhood: a prospective study. J Pediatr 131:608–612
Nowak-Gottl U, Junker R, Hartmeier M et al (1999) Increased lipoprotein(a) is an important risk factor for venous thromboembolism in childhood. Circulation 100:743–748
Nowak-Gottl U, Kosch A, Schlegel N (2003) Neonatal thromboembolism. Semin Thromb Hemost 29:227–234
Perutelli P, Molinari AC (2007) von Willebrand factor, von Willebrand factor-cleaving protease, and shear stress. Cardiovasc Hematol Agents Med Chem 5:305–310
Raju TN, Nelson KB, Ferriero D, Lynch JK (2007) Ischemic perinatal stroke: summary of a workshop sponsored by the National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke. Pediatrics 120:609–616
Redline RW, Wilson-Costello D, Borawski E et al (1998) Placental lesions associated with neurologic impairment and cerebral palsy in very low-birth-weight infants. Arch Pathol Lab Med 122:1091–1098
Revel-Vilk S, Chan A, Bauman M, Massicotte P (2003) Prothrombotic conditions in an unselected cohort of children with venous thromboembolic disease. J Thromb Haemost 1:915–921
Roach ES, Golomb MR, Adams R et al (2008) Management of stroke in infants and children: a scientific statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young. Stroke 39:2644–2691
Ross P Jr, Ehrenkranz R, Kleinman CS, Seashore JH (1989) Thrombus associated with central venous catheters in infants and children. J Pediatr Surg 24:253–256
Sanerkin NG, Edwards P, Jacobs J (1966) Pulmonary thrombo-embolic phenomena in the newborn. J Pathol Bacteriol 91:569–574
Saracco P, Parodi E, Fabris C et al (2009) Management and investigation of neonatal thromboembolic events: genetic and acquired risk factors. Thromb Res 123:805–809
Schmidt B, Andrew M (1995) Neonatal thrombosis: report of a prospective Canadian and international registry. Pediatrics 96:939–943
Schmugge M, Rand ML, Bang KW et al (2003) The relationship of von Willebrand factor binding to activated platelets from healthy neonates and adults. Pediatr Res 54:474–479
Schmugge M, Bang KW, Blanchette VS et al (2007) Platelet activation and von Willebrand factor binding to platelets in newborn infants with central venous lines. Acta Haematol 117:145–148
Shah JK, Mitchell LG, Paes B et al (1992) Thrombin inhibition is impaired in plasma of sick neonates. Pediatr Res 31:391–395
Stein PD, Kayali F, Olson RE (2004) Incidence of venous thromboembolism in infants and children: data from the National Hospital Discharge Survey. J Pediatr 145:563–565
Tripodi A, Ramenghi LA, Chantarangkul V et al (2008) Normal thrombin generation in neonates in spite of prolonged conventional coagulation tests. Haematologica 93(8):1256–1259
Tsai HM, Sarode R, Downes KA (2002) Ultralarge von Willebrand factor multimers and normal ADAMTS13 activity in the umbilical cord blood. Thromb Res 108:121–125
van Ommen CH, Heijboer H, Buller HR et al (2001) Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands. J Pediatr 139:676–681
Williams MD, Chalmers EA, Gibson BE (2002) The investigation and management of neonatal haemostasis and thrombosis. Br J Haematol 119:295–309
Wu YW, March WM, Croen LA et al (2004) Perinatal stroke in children with motor impairment: a population-based study. Pediatrics 114:612–619
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Claudio, M.A., Saracco, P. (2018). The Thrombotic Risk of the Newborn. In: Buonocore, G., Bracci, R., Weindling, M. (eds) Neonatology. Springer, Cham. https://doi.org/10.1007/978-3-319-29489-6_239
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