Neonatal Hemostatic Disorders: Issues and Challenges

Abstract

Neonates form a unique cohort with distinct features associated with the hemostatic system compared with older children and adults. The development of the human hemostatic system begins around 10 weeks in utero and continues to evolve during childhood. This dynamic period termed developmental hemostasis should be taken into consideration when diagnosing a neonate with disorders of bleeding or thrombosis.

Keywords

neonate - hemostasis - bleeding - thrombosis - anticoagulation

^* The authors Santosh S. Hanmod and Rohith Jesudas have contributed equally to this article.

• References

• 1 Saracco P, Bagna R, Gentilomo C , et al; Neonatal Working Group of Registro Italiano Trombosi Infantili (RITI). Clinical Data of Neonatal Systemic Thrombosis. J Pediatr 2016; 171: 60-6.e1
• 2 Soucie JM, Evatt B, Jackson D ; The Hemophilia Surveillance System Project Investigators. Occurrence of hemophilia in the United States. Am J Hematol 1998; 59 (4) 288-294
• 3 Cade JF, Hirsh J, Martin M. Placental barrier to coagulation factors: its relevance to the coagulation defect at birth and to haemorrhage in the newborn. BMJ 1969; 2 (5652) 281-283
• 4 Monagle P, Massicotte P. Developmental haemostasis: secondary haemostasis. Semin Fetal Neonatal Med 2011; 16 (6) 294-300
• 5 Cvirn G, Gallistl S, Leschnik B, Muntean W. Low tissue factor pathway inhibitor (TFPI) together with low antithrombin allows sufficient thrombin generation in neonates. J Thromb Haemost 2003; 1 (2) 263-268
• 6 Mandelbrot L, Guillaumont M, Leclercq M , et al. Placental transfer of vitamin K1 and its implications in fetal hemostasis. Thromb Haemost 1988; 60 (1) 39-43
• 7 Andrew M, Paes B, Milner R , et al. Development of the human coagulation system in the full-term infant. Blood 1987; 70 (1) 165-172
• 8 Weinstein MJ, Blanchard R, Moake JL, Vosburgh E, Moise K. Fetal and neonatal von Willebrand factor (vWF) is unusually large and similar to the vWF in patients with thrombotic thrombocytopenic purpura. Br J Haematol 1989; 72 (1) 68-72
• 9 Jilma-Stohlawetz P, Homoncik M, Jilma B , et al. High levels of reticulated platelets and thrombopoietin characterize fetal thrombopoiesis. Br J Haematol 2001; 112 (2) 466-468
• 10 Corrigan Jr JJ, Sleeth JJ, Jeter M, Lox CD. Newborn's fibrinolytic mechanism: components and plasmin generation. Am J Hematol 1989; 32 (4) 273-278
• 11 Monagle P, Barnes C, Ignjatovic V , et al. Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb Haemost 2006; 95 (2) 362-372
• 12 Coags Uncomplicated. Available at: https://www.coagsuncomplicated.com/Home.aspx . Accessed August 20, 2016
• 13 Stevens SM, Woller SC, Bauer KA , et al. Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. J Thromb Thrombolysis 2016; 41 (1) 154-164
• 14 Klaassen IL, van Ommen CH, Middeldorp S. Manifestations and clinical impact of pediatric inherited thrombophilia. Blood 2015; 125 (7) 1073-1077
• 15 Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian and international registry. Pediatrics 1995; 96 (5 Pt 1): 939-943
• 16 Thornburg CD, Smith PB, Smithwick ML, Cotten CM, Benjamin Jr DK. Association between thrombosis and bloodstream infection in neonates with peripherally inserted catheters. Thromb Res 2008; 122 (6) 782-785
• 17 Thornburg C, Pipe S. Neonatal thromboembolic emergencies. Semin Fetal Neonatal Med 2006; 11 (3) 198-206
• 18 Monagle P, Chan AK, Goldenberg NA , et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 ((2 Suppl):) e737S-801S
• 19 Ergaz Z, Simanovsky N, Rozovsky K , et al. Clinical outcome of umbilical artery catheter-related thrombosis - a cohort study. J Perinatol 2012; 32 (12) 933-940
• 20 Lynch JK, Hirtz DG, DeVeber G, Nelson KB. Report of the National Institute of Neurological Disorders and Stroke workshop on perinatal and childhood stroke. Pediatrics 2002; 109 (1) 116-123
• 21 Kirton A, Shroff M, Pontigon AM, deVeber G. Risk factors and presentations of periventricular venous infarction vs arterial presumed perinatal ischemic stroke. Arch Neurol 2010; 67 (7) 842-848
• 22 Raju TN, Nelson KB, Ferriero D, Lynch JK ; NICHD-NINDS Perinatal Stroke Workshop Participants. 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 2007; 120 (3) 609-616
• 23 Heller C, Heinecke A, Junker R , et al; Childhood Stroke Study Group. Cerebral venous thrombosis in children: a multifactorial origin. Circulation 2003; 108 (11) 1362-1367
• 24 Moharir MD, Shroff M, Pontigon AM , et al. A prospective outcome study of neonatal cerebral sinovenous thrombosis. J Child Neurol 2011; 26 (9) 1137-1144
• 25 Winyard PJ, Bharucha T, De Bruyn R , et al. Perinatal renal venous thrombosis: presenting renal length predicts outcome. Arch Dis Child Fetal Neonatal Ed 2006; 91 (4) F273-F278
• 26 Zigman A, Yazbeck S, Emil S, Nguyen L. Renal vein thrombosis: a 10-year review. J Pediatr Surg 2000; 35 (11) 1540-1542
• 27 Morag I, Epelman M, Daneman A , et al. Portal vein thrombosis in the neonate: risk factors, course, and outcome. J Pediatr 2006; 148 (6) 735-739
• 28 Williams S, Chan AK. Neonatal portal vein thrombosis: diagnosis and management. Semin Fetal Neonatal Med 2011; 16 (6) 329-339
• 29 Morag I, Shah PS, Epelman M, Daneman A, Strauss T, Moore AM. Childhood outcomes of neonates diagnosed with portal vein thrombosis. J Paediatr Child Health 2011; 47 (6) 356-360
• 30 Kim JH, Lee YS, Kim SH, Lee SK, Lim MK, Kim HS. Does umbilical vein catheterization lead to portal venous thrombosis? Prospective US evaluation in 100 neonates. Radiology 2001; 219 (3) 645-650
• 31 Auletta MJ, Headington JT. Purpura fulminans. A cutaneous manifestation of severe protein C deficiency. Arch Dermatol 1988; 124 (9) 1387-1391
• 32 Price VE, Ledingham DL, Krümpel A, Chan AK. Diagnosis and management of neonatal purpura fulminans. Semin Fetal Neonatal Med 2011; 16 (6) 318-322
• 33 Rogenhofer N, Bohlmann MK, Beuter-Winkler P , et al. Prevention, management and extent of adverse pregnancy outcomes in women with hereditary antithrombin deficiency. Ann Hematol 2014; 93 (3) 385-392
• 34 Hirsh J, Anand SS, Halperin JL, Fuster V ; American Heart Association. AHA scientific statement: guide to anticoagulant therapy: heparin: a statement for healthcare professionals from the American Heart Association. Arterioscler Thromb Vasc Biol 2001; 21 (7) E9-E9
• 35 Kulkarni R. Bleeding in the newborn. Pediatr Ann 2001; 30 (9) 548-556
• 36 Kulkarni R, Soucie JM, Lusher J , et al; Haemophilia Treatment Center Network Investigators. Sites of initial bleeding episodes, mode of delivery and age of diagnosis in babies with haemophilia diagnosed before the age of 2 years: a report from the Centers for Disease Control and Prevention's (CDC) Universal Data Collection (UDC) project. Haemophilia 2009; 15 (6) 1281-1290
• 37 White II GC, Rosendaal F, Aledort LM, Lusher JM, Rothschild C, Ingerslev J ; Factor VIII and Factor IX Subcommittee. Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 2001; 85 (3) 560
• 38 Chalmers EA. Neonatal coagulation problems. Arch Dis Child Fetal Neonatal Ed 2004; 89 (6) F475-F478
• 39 Werner EJ, Broxson EH, Tucker EL, Giroux DS, Shults J, Abshire TC. Prevalence of von Willebrand disease in children: a multiethnic study. J Pediatr 1993; 123 (6) 893-898
• 40 Jaffray J, Young G, Ko RH. The bleeding newborn: A review of presentation, diagnosis, and management. Semin Fetal Neonatal Med 2016; 21 (1) 44-49
• 41 Rare Coagulation Disorders Resource Room. Available at: http://www.rarecoagulationdisorders.org/ . Accessed August 20, 2016
• 42 Palla R, Peyvandi F, Shapiro AD. Rare bleeding disorders: diagnosis and treatment. Blood 2015; 125 (13) 2052-2061
• 43 Simon D, Kunicki T, Nugent D. Platelet function defects. Haemophilia 2008; 14 (6) 1240-1249
• 44 Zenciroglu A, Bas AY, Demirel N, Yarali N. Glanzmann thrombasthenia in a neonate. Indian Pediatr 2007; 44 (1) 40-42
• 45 Kenet G, Krümpel A, Nowak-Göttl U. Bleeding issues in neonates, infants and young children. Thromb Res 2009; 123 (Suppl. 02) S35-S37
• 46 Siboni SM, Zanon E, Sottilotta G , et al. Central nervous system bleeding in patients with rare bleeding disorders. Haemophilia 2012; 18 (1) 34-38
• 47 Klinge J, Auberger K, Auerswald G, Brackmann HH, Mauz-Körholz C, Kreuz W. Prevalence and outcome of intracranial haemorrhage in haemophiliacs--a survey of the paediatric group of the German Society of Thrombosis and Haemostasis (GTH). Eur J Pediatr 1999; 158 (Suppl. 03) S162-S165
• 48 Ljung RC. Intracranial haemorrhage in haemophilia A and B. Br J Haematol 2008; 140 (4) 378-384
• 49 Altisent C, Martorell M, Vidal F, Sánchez MA, Parra R. The optimal mode of delivery for the haemophilia carrier expecting an affected infant: further considerations. Haemophilia 2011; 17 (5) 818-819
• 50 Chalmers EA, Williams MD, Richards M , et al; Paediatric Working Party of Ukhcdo. Management of neonates with inherited bleeding disorders--a survey of current UK practice. Haemophilia 2005; 11 (2) 186-187
• 51 Chalmers E, Williams M, Brennand J, Liesner R, Collins P, Richards M ; Paediatric Working Party of United Kingdom Haemophilia Centre Doctors' Organization. Guideline on the management of haemophilia in the fetus and neonate. Br J Haematol 2011; 154 (2) 208-215
• 52 Kulkarni R, Lusher J. Perinatal management of newborns with haemophilia. Br J Haematol 2001; 112 (2) 264-274
• 53 Srivastava A, Brewer AK, Mauser-Bunschoten EP , et al; Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia. Guidelines for the management of hemophilia. Haemophilia 2013; 19 (1) e1-e47
• 54 Curnow J, Pasalic L, Favaloro EJ. Treatment of von Willebrand Disease. Semin Thromb Hemost 2016; 42 (2) 133-146
• 55 Young G, Wicklund B, Neff P, Johnson C, Nugent DJ. Off-label use of rFVIIa in children with excessive bleeding: a consecutive study of 153 off-label uses in 139 children. Pediatr Blood Cancer 2009; 53 (2) 179-183
• 56 Gkiougki E, Mitsiakos G, Chatziioannidis E, Papadakis E, Nikolaidis N. Predicting response to rFVIIa in neonates with intractable bleeding or severe coagulation disturbances. J Pediatr Hematol Oncol 2013; 35 (3) 221-226
• 57 Yilmaz D, Karapinar B, Balkan C, Akisü M, Kavakli K. Single-center experience: use of recombinant factor VIIa for acute life-threatening bleeding in children without congenital hemorrhagic disorder. Pediatr Hematol Oncol 2008; 25 (4) 301-311
• 58 Alten JA, Benner K, Green K, Toole B, Tofil NM, Winkler MK. Pediatric off-label use of recombinant factor VIIa. Pediatrics 2009; 123 (3) 1066-1072
• 59 Madan B, Street AM. What is the optimal mode of delivery for the haemophilia carrier expecting an affected infant-vaginal delivery or caesarean delivery?. Haemophilia 2010; 16 (3) 425-426
• 60 Nazir HF, Al Lawati T, Beshlawi I , et al. Mode of delivery and risk of intracranial haemorrhage in newborns with severe haemophilia A: a multicentre study in Gulf region. Haemophilia 2016; 22 (3) e134-e138
• 61 Davies J, Kadir RA. Mode of delivery and cranial bleeding in newborns with haemophilia: a systematic review and meta-analysis of the literature. Haemophilia 2016; 22 (1) 32-38
• 62 Economou M, Banov L, Ljung R. Perinatal aspects of haemophilia. Eur J Haematol Suppl 2014; 76: 21-25
• 63 Kulkarni R, Lusher JM. Intracranial and extracranial hemorrhages in newborns with hemophilia: a review of the literature. J Pediatr Hematol Oncol 1999; 21 (4) 289-295
• 64 Nowak-Göttl U, Limperger V, Bauer A, Kowalski D, Kenet G. Bleeding issues in neonates and infants - update 2015. Thromb Res 2015; 135 (Suppl. 01) S41-S43
• 65 Kamphuis MM, Paridaans NP, Porcelijn L, Lopriore E, Oepkes D. Incidence and consequences of neonatal alloimmune thrombocytopenia: a systematic review. Pediatrics 2014; 133 (4) 715-721
• 66 McQuilten ZK, Wood EM, Savoia H, Cole S. A review of pathophysiology and current treatment for neonatal alloimmune thrombocytopenia (NAIT) and introducing the Australian NAIT registry. Aust N Z J Obstet Gynaecol 2011; 51 (3) 191-198
• 67 Peterson JA, McFarland JG, Curtis BR, Aster RH. Neonatal alloimmune thrombocytopenia: pathogenesis, diagnosis and management. Br J Haematol 2013; 161 (1) 3-14
• 68 Chakravorty S, Roberts I. How I manage neonatal thrombocytopenia. Br J Haematol 2012; 156 (2) 155-162