Skip to main content

Advertisement

SpringerLink
Log in

Platelet Dysfunction is an Early Marker for Traumatic Brain Injury-Induced Coagulopathy

  • Original Article
  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

Background

The goal of this study is to determine the presence of platelet dysfunction in patients with traumatic brain injury (TBI). The mechanisms underlying the coagulopathy associated with TBI remain elusive. The question of platelet dysfunction in TBI is unclear.

Methods

This was a prospective observational study conducted at Memorial Hospital of South Bend, IN, and Denver Health Medical Center, CO. A total of 50 patients sustaining TBI, and not under treatment with anticoagulants or platelet inhibitors, were analyzed utilizing modified thromboelastography (TEG) with platelet mapping (TEG/PM), along with standard coagulation tests.

Results

Compared to normal controls, patients with severe TBI had a significantly increased percentage of platelet ADP and arachidonic acid (AA) receptor inhibition. Furthermore, the percentage of ADP inhibition distinguished between survivors and non-survivors in patients with TBI (Mann–Whitney test, P = 0.035). ADP inhibition correlates strongly with severity of TBI (Mann–Whitney test, P = 0.014), while AA inhibition did not.

Conclusion

These data indicate that early platelet dysfunction is prevalent after severe TBI, can be measured in a point-of-care setting using TEG/PM, and correlates with mortality. The mechanism responsible for this platelet dysfunction and associated implications for TBI management remains to be defined.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Stein SC, Smith DH. Coagulopathy in traumatic brain injury. Neurocrit Care. 2004;1:479–88.

    Article  PubMed  Google Scholar 

  2. Laroche M, Kutcher ME, Huang MC, Cohen MJ, Manley GT. Coagulopathy after traumatic brain injury. Neurosurgery. 2012;70:1334–45.

    Article  PubMed  Google Scholar 

  3. Kashuk JL, Moore EE, Sawyer M, et al. Postinjury coagulopathy management: goal directed resuscitation via POC thromboelastography. Ann Surg. 2010;251:604–14.

    Article  PubMed  Google Scholar 

  4. Oertel M, Kelly DF, McArthur D, et al. Progressive hemorrhage after head trauma: predictors and consequences of the evolving injury. J Neurosurg. 2002;96(1):109–16.

    Article  PubMed  Google Scholar 

  5. Lustenberger T, Talving P, Kobayashi L, et al. Time course of coagulopathy in isolated severe traumatic brain injury. Injury. 2010;41(9):924–8.

    Article  PubMed  Google Scholar 

  6. Talving P, Benfield R, Hadjizacharia P. INaba K, Chan LS, Demetriades D. Coagulopathy in severe traumatic brain injury: a prospective study. J Trauma. 2009;66(1):55–61.

    Article  PubMed  Google Scholar 

  7. Wafaisade A, Lefering R, Tjardes T, et al. Acute coagulopathy in isolated traumatic brain injury. Neurocrit Care. 2012;12(2):211–9.

    Article  Google Scholar 

  8. Carrick MM, Tyroch AH, Youens CA, Handley T. Subsequent development of thrombocytopenia and coagulopathy in moderate and severe head injury: support for serial laboratory examination. J Trauma. 2005;58(4):725–9.

    Article  PubMed  Google Scholar 

  9. Vavilala MS, Dunbar PJ, Rivara FP, Lam AM. Coagulopathy predicts poor outcome following head injury in children less than 16 years of age. J Neurosurg Anesthesiol. 2001;13(1):13–8.

    Article  PubMed  CAS  Google Scholar 

  10. Stein SC, Young GS, Talucci RC, Greenbaum BH, Ross SE. Delayed brain injury after head trauma: significance of coagulopathy. Neurosurgery. 1992;30(2):160–5.

    Article  PubMed  CAS  Google Scholar 

  11. Stein SC, Spettell C, Young G, Ross SE. Delayed and progressive brain injury in closed head trauma: radiological demonstration. Neurosurgery. 1993;32(1):25–30.

    Article  PubMed  CAS  Google Scholar 

  12. Nekludov M, Bellander BM, Blomback M, Wallen HN. Platelet dysfunction in patients with severe traumatic brain injury. J Neurotrauma. 2007;24(11):1699–706.

    Article  PubMed  Google Scholar 

  13. Schnuriger B, Inaba K, Abdelsayed GA, et al. The impact of platelets on the progression of traumatic intracranial hemorrhage. J Trauma. 2010;68(4):881–5.

    Article  PubMed  Google Scholar 

  14. Akins PT, Guppy KH, Sahrakar K, Hawk MW. Slippery platelet syndromes in subdural hematoma. Neurocrit Care. 2010;12(3):375–81.

    Article  PubMed  Google Scholar 

  15. Ciavarella D, Reed RL, Counts RB, Heimbach DM, Carrico CJ. Clotting factor levels and risk of diffuse microvascular bleeding in the massively transfused patient. Brit J Haematol. 1987;67:365–8.

    Article  CAS  Google Scholar 

  16. Carroll RC, Craft RM, Langdon RL, et al. Early evaluation of acute traumatic coagulopathy by thromboelastography. Transl Res. 2009;154:34–9.

    Article  PubMed  Google Scholar 

  17. Wohlauer MV, Moore EE, Thomas S, et al. Early platelet dysfunction: an unrecognized role in the acute coagulopathy of trauma. J Am Coll Surg. 2012;214(5):739–46.

    Article  PubMed  Google Scholar 

  18. Windelov NA, Welling KL, Ostrowski SR, Johansson PI. The prognostic value of thromboelastography in identifying neurosurgical patients with worse prognosis. Blood Coagul Fibrinolysis. 2011;22:416–9.

    Article  PubMed  Google Scholar 

  19. Schöchl H, Solomon C, Traintinger S, et al. Thromboelastometric (ROTEM) findings in patients suffering from isolated severe traumatic brain injury. Neurotrauma. 2011;10:2033–41.

    Article  Google Scholar 

  20. Solomon C, Traintinger S, Ziegler B, et al. Platelet function following trauma: a Multiple Electrode Aggregometry study. Thromb Haemost. 2011;106:1–9.

    Article  Google Scholar 

  21. Enriquez LJ, Shore-Lesserson L. Point-of-care coagulation testing and transfusion algorithms. Br J Anaesth. 2009;103:i14–22.

    Article  PubMed  Google Scholar 

  22. Naidech AM, Jovanovic B, Liebling S, et al. Reduced platelet activity is associated with early clot growth and worse 3-month outcome after intracerbral hemorrhage. Stroke. 2009;40:2398–401.

    Article  PubMed  Google Scholar 

  23. Gonzalez E, Pieracci FM, Moore EE, et al. Coagulation abnormalities in the trauma patient: the role of point-of-care thromboelastography. Semin Thromb Hemost. 2010;36:723–37.

    Article  PubMed  Google Scholar 

  24. Cap AP, Spinella PC. Severity of head injury is associated with increased risk of coagulopathy in combat casualities. J Trauma. 2011;71(1):S78–81.

    Article  PubMed  Google Scholar 

  25. Piek J, Chesnut RM, Marshall LF et al. Extracranial complications of severe head injury. J Neurosurg. 1992;77(6):901–7

    Google Scholar 

  26. Baker SP, O’Neill BB, Haddon W, et al. The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma. 1974;14:187–96.

    Article  PubMed  CAS  Google Scholar 

  27. Boschen L, Wiinberg B, Kjelgaard-Hansen M, Steinbruchel DA, Johansson PI. Evaluation of the TEG platelet mapping assay in blood donors. Thromb J. 2007;5:3.

    Article  Google Scholar 

  28. Chen L, Bracey AW, Radovancevic R, et al. Clopidogrel and bleeding in patients undergoing elective coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2004;128:425–31.

    Article  PubMed  Google Scholar 

  29. Saggar V, Mittal RS, Vyas MC. Hemostatic abnormalities in patients with closed head injuries and their role in predicting early mortality. J Neurotrauma. 2009;26(10):1665–8.

    Article  PubMed  Google Scholar 

  30. Van der Sande JJ, Emeis JJ, Lindeman J. Intravascular coagulation: a common phenomenon in minor experimental head injury. J Neurosurg. 1981;54(1):21–5.

    Article  PubMed  Google Scholar 

  31. Kaufman HH, Hui KS, Mattson JC, et al. Clinicopathological correlations of disseminated intravascular coagulation in patients with head injury. Neurosurgery. 1984;15(1):34–42.

    Article  PubMed  CAS  Google Scholar 

  32. Cortez SC, McIntosh TK, Noble LJ. Experimental fluid percussion brain injury: vascular disruption and neuronal and glial alterations. Brain Res. 1989;482(2):271–82.

    Article  PubMed  CAS  Google Scholar 

  33. Dietrich WD, Alonoso O, Halley M. Early microvascular and neuronal consequences of traumatic brain injury: a light and electron microscopic study in rats. J Neurotrauma. 1994;11(3):289–301.

    Article  PubMed  CAS  Google Scholar 

  34. Maeda T, Katayama Y, Kawamata T, Aoyama N, Mori T. Hemodynamic depression and microthrombosis in the peripheral areas of cortical contusion in the rat: role of platelet activating factor. Acta Neurochir Suppl. 1997;70:102–5.

    PubMed  CAS  Google Scholar 

  35. Scherer RU, Spangenber P. Procoagulant activity in patients with isolated severe head trauma. Crit Care Med. 1988;26(1):149–56.

    Article  Google Scholar 

  36. 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(6):1254–61.

    Article  PubMed  CAS  Google Scholar 

  37. Creutzfeldt CJ, Becker KJ, Longstreth WT Jr, Tirschwell DL, Weinstein JR. Platlet dysfunction in intraparenchymal hemorrhage. Stroke. 2009;40:e645.

    Article  PubMed  Google Scholar 

  38. Ziai WC, Torbey MT, Kickler TS, Oh S, Bhardwaj A, Wityk RJ. Platelet count and function in spontaneous intracerebral hemorrhage. J Strok Cerebrovasc Dis. 2003;12(4):201–6.

    Article  Google Scholar 

  39. Pareti FI, Capitanio A, Mannucci L, Ponticelli C, Mannucci PM. Acquired dysfunction due to the circulation of “exhausted” platelets. Am J Med. 1980;69:235–40.

    Article  PubMed  CAS  Google Scholar 

  40. Jacoby RC, Owings JT, Holmes J, Battistella FD, Gosselin RC, Paglieroni TG. Platelet activation and function after trauma. J Trauma. 2001;51:639–47.

    Article  PubMed  CAS  Google Scholar 

  41. Gando S, Nanzaki S, Kemmotsu O. Coagulofibrinolytic changes after isolated head injury are not different from those in trauma patients without head injury. J Trauma. 1999;46:1070–7.

    Article  PubMed  CAS  Google Scholar 

  42. Kashuk JL, Moore EE, Sawyer M, et al. Primary fibrinolysis is integral in the pathogenesis of the acute coagulopathy of trauma. Ann Surg. 2010;252:434–42.

    PubMed  Google Scholar 

  43. Bartal C, Yitzak A. The role of thromboelastography and recombinant factor VIIa in trauma. Curr Opin Anaesthesiol. 2009;22:281–8.

    Article  PubMed  Google Scholar 

  44. Morgenstern LB, Hemphill C, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage. Stroke. 2010;41:2108–29.

    Article  PubMed  Google Scholar 

  45. Spinella PC, Wade CE, Blackbourne LH et al. The association of blood component use ratios with the survival of massively transfused trauma patients with and without severe brain injury. J Trauma. 2011;71(2 Suppl 3):S343–52.

    Google Scholar 

  46. Holcomb JB, Wade CE, Michalek JE, et al. Increased plasma and platelet to red blood cell ratios improves outcomes in 466 massively transfused civilian trauma patients. Ann Surg. 2008;248:447–58.

    PubMed  Google Scholar 

  47. Inaba K, Branco B, Rhee P, et al. Impact of plasma transfusion in trauma patients who do not require massive transfusion. J Am Coll Surg. 2010;210:957–65.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Ed Evans CCP and Eric Guerra CCP for performing Thromboelastography, Dr. Fang Liu and Anton Crepinsek for their statistical analyses and Abby Lowe, Madhura Sundararajan, Sarah Noveroske, Dr. Hanuma Chitta for their efforts in data acquisition and manuscript edits.

Disclosure

Dr. Walsh received consulting fees from CSL Behring.

Author information

Authors and Affiliations

  1. W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, 46556, USA

    Patrick K. Davis, Harsha Musunuru, Mark Walsh, Robert Cassady, Victoria A. Ploplis & Francis J. Castellino

  2. Memorial Hospital of South Bend, Emergency Trauma Center, South Bend, IN, 46601, USA

    Mark Walsh, Robert Cassady, Robert Yount, Andrew Losiniecki, Janet Howard & Scott G. Thomas

  3. Indiana University School of Medicine – South Bend, South Bend, IN, 46617, USA

    Mark Walsh

  4. Deparment of Surgery, University of Colorado, Denver, CO, 80045, USA

    Ernest E. Moore

  5. Department of Surgery, Denver Health Medical Center, Denver, CO, 8020, USA

    Max V. Wohlauer

Authors
  1. Patrick K. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Harsha Musunuru
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark Walsh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert Cassady
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert Yount
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrew Losiniecki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ernest E. Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Max V. Wohlauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Janet Howard
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Victoria A. Ploplis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Francis J. Castellino
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Scott G. Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark Walsh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Davis, P.K., Musunuru, H., Walsh, M. et al. Platelet Dysfunction is an Early Marker for Traumatic Brain Injury-Induced Coagulopathy. Neurocrit Care 18, 201–208 (2013). https://doi.org/10.1007/s12028-012-9745-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12028-012-9745-6

Keywords

Search

Navigation