Semin Thromb Hemost 2020; 46(02): 147-154
DOI: 10.1055/s-0040-1702203
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Trauma-Induced Coagulopathy in Children

Amelia C. Lucisano
1   Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
,
Christine M. Leeper
1   Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
,
Barbara A. Gaines
2   Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
› Author Affiliations
Further Information

Publication History

Publication Date:
11 March 2020 (online)

Abstract

Trauma-induced coagulopathy (TIC) is well documented in injured children. However, many important features of pediatric hemostasis are still in development in early childhood and may impact TIC. Certain pediatric subgroups are at a higher risk. Traumatic brain injury, which occurs with a higher rate in children, and physical child abuse are known risk factors for TIC that deserve special consideration. Resuscitation of a pediatric trauma patient follows many of the same goals as in the injured adult trauma, although some key aspects of pediatric resuscitation require ongoing investigation. Venous thromboembolism occurs with higher rates in certain high-risk groups of pediatric trauma patients, although overall it is considerably less frequent in children as compared with adults.

 
  • References

  • 1 Andrew M, Paes B, Milner R. , et al. Development of the human coagulation system in the full-term infant. Blood 1987; 70 (01) 165-172
  • 2 Andrew M, Paes B, Milner R. , et al. Development of the human coagulation system in the healthy premature infant. Blood 1988; 72 (05) 1651-1657
  • 3 Andrew M, Schmidt B, Mitchell L, Paes B, Ofosu F. Thrombin generation in newborn plasma is critically dependent on the concentration of prothrombin. Thromb Haemost 1990; 63 (01) 27-30
  • 4 Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood 1992; 80 (08) 1998-2005
  • 5 Attard C, van der Straaten T, Karlaftis V, Monagle P, Ignjatovic V. Developmental hemostasis: age-specific differences in the levels of hemostatic proteins. J Thromb Haemost 2013; 11 (10) 1850-1854
  • 6 Tripodi A, Ramenghi LA, Chantarangkul V. , et al. Normal thrombin generation in neonates in spite of prolonged conventional coagulation tests. Haematologica 2008; 93 (08) 1256-1259
  • 7 Guzzetta NA, Miller BE. Principles of hemostasis in children: models and maturation. Paediatr Anaesth 2011; 21 (01) 3-9
  • 8 Strauss T, Sidlik-Muskatel R, Kenet G. Developmental hemostasis: primary hemostasis and evaluation of platelet function in neonates. Semin Fetal Neonatal Med 2011; 16 (06) 301-304
  • 9 Israels SJ, Rand ML, Michelson AD. Neonatal platelet function. Semin Thromb Hemost 2003; 29 (04) 363-372
  • 10 Corrigan Jr JJ, Sleeth JJ, Jeter M, Lox CD. Newborn's fibrinolytic mechanism: components and plasmin generation. Am J Hematol 1989; 32 (04) 273-278
  • 11 Cap A, Hunt B. Acute traumatic coagulopathy. Curr Opin Crit Care 2014; 20 (06) 638-645
  • 12 Christiaans SC, Duhachek-Stapelman AL, Russell RT, Lisco SJ, Kerby JD, Pittet JF. Coagulopathy after severe pediatric trauma. Shock 2014; 41 (06) 476-490
  • 13 MacLeod JBA, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma 2003; 55 (01) 39-44
  • 14 MacLeod JBA, Winkler AM, McCoy CC, Hillyer CD, Shaz BH. Early trauma induced coagulopathy (ETIC): prevalence across the injury spectrum. Injury 2014; 45 (05) 910-915
  • 15 Gonzalez E, Moore EE, Moore HB, Chapman MP, Silliman CC, Banerjee A. Trauma-induced coagulopathy: an institution's 35 year perspective on practice and research. Scand J Surg 2014; 103 (02) 89-103
  • 16 Sakellaris G, Blevrakis E, Petrakis I. , et al. Acute coagulopathy in children with multiple trauma: a retrospective study. J Emerg Med 2014; 47 (05) 539-545
  • 17 Whittaker B, Christiaans SC, Altice JL. , et al. Early coagulopathy is an independent predictor of mortality in children after severe trauma. Shock 2013; 39 (05) 421-426
  • 18 Vogel AM, Radwan ZA, Cox Jr CS, Cotton BA. ; B VArZcCc. Admission rapid thrombelastography delivers real-time “actionable” data in pediatric trauma. J Pediatr Surg 2013; 48 (06) 1371-1376
  • 19 Choi PM, Vogel AM. Acute coagulopathy in pediatric trauma. Curr Opin Pediatr 2014; 26 (03) 343-349
  • 20 Leeper CM, Kutcher M, Nasr I. , et al. Acute traumatic coagulopathy in a critically injured pediatric population: definition, trend over time, and outcomes. J Trauma Acute Care Surg 2016; 81 (01) 34-41
  • 21 Holmes JF, Goodwin HC, Land C, Kuppermann N. Coagulation testing in pediatric blunt trauma patients. Pediatr Emerg Care 2001; 17 (05) 324-328
  • 22 Patregnani JT, Borgman MA, Maegele M, Wade CE, Blackbourne LH, Spinella PC. Coagulopathy and shock on admission is associated with mortality for children with traumatic injuries at combat support hospitals. Pediatr Crit Care Med 2012; 13 (03) 273-277
  • 23 Hendrickson JE, Shaz BH, Pereira G. , et al. Coagulopathy is prevalent and associated with adverse outcomes in transfused pediatric trauma patients. J Pediatr 2012; 160 (02) 204-209.e3
  • 24 Leeper CM, Gaines BA. Viscoelastic hemostatic assays in the management of the pediatric trauma patient. Semin Pediatr Surg 2017; 26 (01) 8-13
  • 25 Dempfle C-E, Borggrefe M. Point of care coagulation tests in critically ill patients. Semin Thromb Hemost 2008; 34 (05) 445-450
  • 26 Cotton BA, Faz G, Hatch QM. , et al. Rapid thrombelastography delivers real-time results that predict transfusion within 1 hour of admission. J Trauma 2011; 71 (02) 407-414 , discussion 414–417
  • 27 Holcomb JB, Minei KM, Scerbo ML. , et al. Admission rapid thrombelastography can replace conventional coagulation tests in the emergency department: experience with 1974 consecutive trauma patients. Ann Surg 2012; 256 (03) 476-486
  • 28 Leeper CM, Neal MD, McKenna C, Sperry JL, Gaines BA. Abnormalities in fibrinolysis at the time of admission are associated with deep vein thrombosis, mortality, and disability in a pediatric trauma population. J Trauma Acute Care Surg 2017; 82 (01) 27-34
  • 29 Liras IN, Cotton BA, Cardenas JC, Harting MT. Prevalence and impact of admission hyperfibrinolysis in severely injured pediatric trauma patients. Surgery 2015; 158 (03) 812-818
  • 30 Leeper CM, Neal MD, McKenna CJ, Gaines BA. Trending fibrinolytic dysregulation: fibrinolysis shutdown in the days after injury is associated with poor outcome in severely injured children. Ann Surg 2017; 266 (03) 508-515
  • 31 Russell RT, Maizlin II, Vogel AM. Viscoelastic monitoring in pediatric trauma: a survey of pediatric trauma society members. J Surg Res 2017; 214: 216-220
  • 32 Barcelona SL, Thompson AA, Coté CJ. Intraoperative pediatric blood transfusion therapy: a review of common issues. Part II: transfusion therapy, special considerations, and reduction of allogenic blood transfusions. Paediatr Anaesth 2005; 15 (10) 814-830
  • 33 Dehmer JJ, Adamson WT. Massive transfusion and blood product use in the pediatric trauma patient. Semin Pediatr Surg 2010; 19 (04) 286-291
  • 34 Avarello JT, Cantor RM. Pediatric major trauma: an approach to evaluation and management. Emerg Med Clin North Am 2007; 25 (03) 803-836 , x
  • 35 Leeper CM, McKenna C, Gaines BA. Too little too late: hypotension and blood transfusion in the trauma bay are independent predictors of death in injured children. J Trauma Acute Care Surg 2018; 85 (04) 674-678
  • 36 Gunter Jr OL, Au BK, Isbell JM, Mowery NT, Young PP, Cotton BA. Optimizing outcomes in damage control resuscitation: identifying blood product ratios associated with improved survival. J Trauma 2008; 65 (03) 527-534
  • 37 Dente CJ, Shaz BH, Nicholas JM. , et al. Improvements in early mortality and coagulopathy are sustained better in patients with blunt trauma after institution of a massive transfusion protocol in a civilian level I trauma center. J Trauma 2009; 66 (06) 1616-1624
  • 38 Cotton BA, Au BK, Nunez TC, Gunter OL, Robertson AM, Young PP. Predefined massive transfusion protocols are associated with a reduction in organ failure and postinjury complications. J Trauma 2009; 66 (01) 41-48 , discussion 48–49
  • 39 Holcomb JB, Tilley BC, Baraniuk S. , et al; PROPPR Study Group. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA 2015; 313 (05) 471-482
  • 40 Parker RI. Pediatrics . In: Gonzales E, Moore HB, Moore E. , eds. Trauma Induced Coagulopathy. New York, NY: Springer; 2016: 499-515
  • 41 Diab YA, Wong ECC, Luban NLC. Massive transfusion in children and neonates. Br J Haematol 2013; 161 (01) 15-26
  • 42 Shroyer MC, Griffin RL, Mortellaro VE, Russell RT. Massive transfusion in pediatric trauma: analysis of the National Trauma Databank. J Surg Res 2017; 208: 166-172
  • 43 Nosanov L, Inaba K, Okoye O. , et al. The impact of blood product ratios in massively transfused pediatric trauma patients. Am J Surg 2013; 206 (05) 655-660
  • 44 Chidester SJ, Williams N, Wang W, Groner JI. A pediatric massive transfusion protocol. J Trauma Acute Care Surg 2012; 73 (05) 1273-1277
  • 45 Hendrickson JE, Shaz BH, Pereira G. , et al. Implementation of a pediatric trauma massive transfusion protocol: one institution's experience. Transfusion 2012; 52 (06) 1228-1236
  • 46 Butler EK, Mills BM, Arbabi S. , et al. Association of blood component ratios with 24-hour mortality in injured children receiving massive transfusion. Crit Care Med 2019; 47 (07) 975-983
  • 47 Drucker NA, Wang SK, Newton C. Pediatric trauma-related coagulopathy: balanced resuscitation, goal-directed therapy and viscoelastic assays. Semin Pediatr Surg 2019; 28 (01) 61-66
  • 48 ACS TQIP Massive Transfusion In Trauma Guidelines. Available at: https://www.facs.org/-/media/files/quality-programs/trauma/tqip/transfusion_guildelines.ashx?la=en . Accessed July 11, 2019
  • 49 Acker SN, Hall B, Hill L, Partrick DA, Bensard DD. Adult-based massive transfusion protocol activation criteria do not work in children. Eur J Pediatr Surg 2017; 27 (01) 32-35
  • 50 Kamyszek RW, Leraas HJ, Reed C. , et al. Massive transfusion in the pediatric population: a systematic review and summary of best-evidence practice strategies. J Trauma Acute Care Surg 2019; 86 (04) 744-754
  • 51 Yazer MH, Jackson B, Sperry JL, Alarcon L, Triulzi DJ, Murdock AD. Initial safety and feasibility of cold-stored uncrossmatched whole blood transfusion in civilian trauma patients. J Trauma Acute Care Surg 2016; 81 (01) 21-26
  • 52 Leeper CM, Yazer MH, Cladis FP, Saladino R, Triulzi DJ, Gaines BA. Use of uncrossmatched cold-stored whole blood in injured children with hemorrhagic shock. JAMA Pediatr 2018; 172 (05) 491-492
  • 53 Leeper CM, Yazer MH, Cladis FP, Saladino R, Triulzi DJ, Gaines BA. Cold-stored whole blood platelet function is preserved in injured children with hemorrhagic shock. J Trauma Acute Care Surg 2019; 87 (01) 49-53
  • 54 Roberts I, Shakur H, Afolabi A. , et al; CRASH-2 collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet 2011; 377 (9771): 1096-1101 , 1101.e1–1101.e2
  • 55 Eckert MJ, Wertin TM, Tyner SD, Nelson DW, Izenberg S, Martin MJ. Tranexamic acid administration to pediatric trauma patients in a combat setting: the pediatric trauma and tranexamic acid study (PED-TRAX). J Trauma Acute Care Surg 2014; 77 (06) 852-858 , discussion 858
  • 56 Maeda T, Michihata N, Sasabuchi Y. , et al. Safety of tranexamic acid during pediatric trauma: a nationwide database study. Pediatr Crit Care Med 2018; 19 (12) e637-e642
  • 57 Moore HB, Moore EE, Gonzalez E. , et al. Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: the spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy. J Trauma Acute Care Surg 2014; 77 (06) 811-817 , discussion 817
  • 58 Epstein DS, Mitra B, O'Reilly G, Rosenfeld JV, Cameron PA. Acute traumatic coagulopathy in the setting of isolated traumatic brain injury: a systematic review and meta-analysis. Injury 2014; 45 (05) 819-824
  • 59 Kumar MA. Coagulopathy associated with traumatic brain injury. Curr Neurol Neurosci Rep 2013; 13 (11) 391
  • 60 Talving P, Lustenberger T, Lam L. , et al. Coagulopathy after isolated severe traumatic brain injury in children. J Trauma 2011; 71 (05) 1205-1210
  • 61 Maegele M. Coagulopathy after traumatic brain injury: incidence, pathogenesis, and treatment options. Transfusion 2013; 53 (Suppl. 01) 28S-37S
  • 62 Schneier AJ, Shields BJ, Hostetler SG, Xiang H, Smith GA. Incidence of pediatric traumatic brain injury and associated hospital resource utilization in the United States. Pediatrics 2006; 118 (02) 483-492
  • 63 Zhang J, Zhang F, Dong J-F. Coagulopathy induced by traumatic brain injury: systemic manifestation of a localized injury. Blood 2018; 131 (18) 2001-2006
  • 64 Donahue DL, Beck J, Fritz B. , et al. Early platelet dysfunction in a rodent model of blunt traumatic brain injury reflects the acute traumatic coagulopathy found in humans. J Neurotrauma 2014; 31 (04) 404-410
  • 65 Cohen MJ, Brohi K, Ganter MT, Manley GT, Mackersie RC, Pittet JF. Early coagulopathy after traumatic brain injury: the role of hypoperfusion and the protein C pathway. J Trauma 2007; 63 (06) 1254-1261 , discussion 1261–1262
  • 66 McCully SP, Schreiber MA. Traumatic brain injury and its effect on coagulopathy. Semin Thromb Hemost 2013; 39 (08) 896-901
  • 67 Davis PK, Musunuru H, Walsh M. , et al. Platelet dysfunction is an early marker for traumatic brain injury-induced coagulopathy. Neurocrit Care 2013; 18 (02) 201-208
  • 68 Samuels JM, Moore EE, Silliman CC. , et al. Severe traumatic brain injury is associated with a unique coagulopathy phenotype. J Trauma Acute Care Surg 2019; 86 (04) 686-693
  • 69 Chesnut RM, Marshall LF, Klauber MR. , et al. The role of secondary brain injury in determining outcome from severe head injury. J Trauma 1993; 34 (02) 216-222
  • 70 Manley G, Knudson MM, Morabito D, Damron S, Erickson V, Pitts L. Hypotension, hypoxia, and head injury: frequency, duration, and consequences. Arch Surg 2001; 136 (10) 1118-1123
  • 71 Shibahashi K, Sugiyama K, Okura Y, Tomio J, Hoda H, Hamabe Y. Defining hypotension in patients with severe traumatic brain injury. World Neurosurg 2018; 120: e667-e674
  • 72 Brenner M, Stein DM, Hu PF, Aarabi B, Sheth K, Scalea TM. Traditional systolic blood pressure targets underestimate hypotension-induced secondary brain injury. J Trauma Acute Care Surg 2012; 72 (05) 1135-1139
  • 73 Suttipongkaset P, Chaikittisilpa N, Vavilala MS. , et al. Blood pressure thresholds and mortality in pediatric traumatic brain injury. Pediatrics 2018; 142 (02) e20180594
  • 74 Christian CW, Block R. ; Committee on Child Abuse and Neglect; American Academy of Pediatrics. Abusive head trauma in infants and children. Pediatrics 2009; 123 (05) 1409-1411
  • 75 Parks SE, Annest JL, Hill HAKD. Pediatric Abusive Head Trauma: Recommended Definitions for Public Health Surveillance and Research. Available at: https://www.cdc.gov/violenceprevention/pdf/PedHeadTrauma-a.pdf . Accessed March 26, 2019
  • 76 King WJ, MacKay M, Sirnick A. ; Canadian Shaken Baby Study Group. Shaken baby syndrome in Canada: clinical characteristics and outcomes of hospital cases. CMAJ 2003; 168 (02) 155-159
  • 77 Keenan HT, Runyan DK, Marshall SW, Nocera MA, Merten DF, Sinal SH. A population-based study of inflicted traumatic brain injury in young children. JAMA 2003; 290 (05) 621-626
  • 78 Kemp A, Cowley L, Maguire S. Spinal injuries in abusive head trauma: patterns and recommendations. Pediatr Radiol 2014; 44 (Suppl. 04) S604-S612
  • 79 Kemp AM, Stoodley N, Cobley C, Coles L, Kemp KW, Geddes J. Apnoea and brain swelling in non-accidental head injury. Arch Dis Child 2003; 88 (06) 472-476 , discussion 472–476
  • 80 Kemp AM, Joshi AH, Mann M. , et al. What are the clinical and radiological characteristics of spinal injuries from physical abuse: a systematic review. Arch Dis Child 2010; 95 (05) 355-360
  • 81 Shannon P, Becker L. Mechanisms of brain injury in infantile child abuse. Lancet 2001; 358 (9283): 686-687
  • 82 Johnson DL, Boal D, Baule R. Role of apnea in nonaccidental head injury. Pediatr Neurosurg 1995; 23 (06) 305-310
  • 83 Leeper CM, Nasr I, McKenna C, Berger RP, Gaines BA. Elevated admission international normalized ratio strongly predicts mortality in victims of abusive head trauma. J Trauma Acute Care Surg 2016; 80 (05) 711-716
  • 84 Lucisano AC, Leeper CM, Strotmeyer SJ, Gaines BA. Characterization of Trauma Induced Coagulopathy in Pediatric Patients with Severe Abusive Compared to Accidental Head Trauma [abstract]. Presented at: Annual Meeting of the American Association for the Surgery of Trauma;0 September 18–20, 2019; Houston, TX:
  • 85 Raffini L, Huang Y-S, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007. Pediatrics 2009; 124 (04) 1001-1008
  • 86 Leeper CM, Vissa M, Cooper JD, Malec LM, Gaines BA. Venous thromboembolism in pediatric trauma patients: ten-year experience and long-term follow-up in a tertiary care center. Pediatr Blood Cancer 2017; 64 (08) e26415
  • 87 Landisch RM, Hanson SJ, Punzalan RC, Braun K, Cassidy LD, Gourlay DM. Efficacy of surveillance ultrasound for venous thromboembolism diagnosis in critically ill children after trauma. J Pediatr Surg 2018; 53 (11) 2195-2201
  • 88 Hanson SJ, Punzalan RC, Greenup RA, Liu H, Sato TT, Havens PL. Incidence and risk factors for venous thromboembolism in critically ill children after trauma. J Trauma 2010; 68 (01) 52-56
  • 89 Hanson SJ, Punzalan RC, Arca MJ. , et al. Effectiveness of clinical guidelines for deep vein thrombosis prophylaxis in reducing the incidence of venous thromboembolism in critically ill children after trauma. J Trauma Acute Care Surg 2012; 72 (05) 1292-1297
  • 90 Landisch RM, Hanson SJ, Cassidy LD, Braun K, Punzalan RC, Gourlay DM. Evaluation of guidelines for injured children at high risk for venous thromboembolism: a prospective observational study. J Trauma Acute Care Surg 2017; 82 (05) 836-844
  • 91 Chima RS, Hanson SJ. Venous thromboembolism in critical illness and trauma: pediatric perspectives. Front Pediatr 2017; 5: 47
  • 92 Van Arendonk KJ, Schneider EB, Haider AH, Colombani PM, Stewart FD, Haut ER. Venous thromboembolism after trauma: when do children become adults?. JAMA Surg 2013; 148 (12) 1123-1130
  • 93 Thompson AJ, McSwain SD, Webb SA, Stroud MA, Streck CJ. Venous thromboembolism prophylaxis in the pediatric trauma population. J Pediatr Surg 2013; 48 (06) 1413-1421
  • 94 Mahajerin A, Petty JK, Hanson SJ. , et al. Prophylaxis against venous thromboembolism in pediatric trauma: a practice management guideline from the Eastern Association for the Surgery of Trauma and the Pediatric Trauma Society. J Trauma Acute Care Surg 2017; 82 (03) 627-636