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World Journal of Emergency Surgery

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Open Access 01-12-2015 | Research article

Evaluation of clotting factor activities early after severe multiple trauma and their correlation with coagulation tests and clinical data

Authors: Manuel Burggraf, Arzu Payas, Max Daniel Kauther, Carsten Schoeneberg, Sven Lendemans

Published in: World Journal of Emergency Surgery | Issue 1/2015

Abstract

Introduction

Traumatic injuries are amongst the leading causes of death worldwide, frequently as a result of uncontrolled hemorrhage. Critical deficiencies in clotting factors have been noted in trauma-induced coagulopathy. However, the exact underlying conditions that result in devastating coagulopathies remain unclear. The purpose of this study was to elucidate these underlying deficiencies.

Methods

Blood samples were drawn from 45 severely injured trauma patients on their arrival at the resuscitation room, and the activities of all soluble clotting factors and routine coagulation tests were assessed. The Mann–Whitney-U-test was used to assess differences in coagulation activity between the patients and healthy controls. Furthermore, Spearman’s rank correlation was used to analyze the blood work.

Results

After severe trauma the levels of serum fibrinogen and calcium were significantly reduced. Furthermore, traumatized patients had a significantly increased International Normalized Ratio (INR) compared to healthy controls. The median activities of all clotting factors were reduced after severe multiple trauma, with the exception of factor VIII, which was increased. Statistically significant differences were observed for factors II (80 vs. 122 %, P < 0.0001), V (76 vs. 123 %, P < 0.0001), VII (90 vs. 114 %, P = 0.002), VIII (200 vs. 108 %, P < 0.0001), and X (86 vs. 122 %, P < 0.0001). Spearman’s correlation indicated a significant negative correlation between INR on arrival with fibrinogen and levels of factors II, V, and VII, whereas Partial Thromboplastin Time was significantly negatively correlated with factor VIII (all P < 0.0001).

Conclusions

These findings suggest a general but rather moderate impairment of clotting factor activities following severe multiple trauma. In the concept of a calculated coagulation therapy, this could demand for the use of factor concentrates with higher ratios of clotting factors. Finally, the physiological importance of strongly elevated factor VIII activity remains unclear, but a possible interference with ex vivo measurements of Partial Thromboplastin Time has to be considered.

Herbert HK, Hyder AA, Butchart A, Norton R. Global health: injuries and violence. Infect Dis Clin North Am. 2011;25(3):653–68. doi:10.1016/j.idc.2011.06.004.CrossRefPubMed

Sauaia A, Moore FA, Moore EE, Moser KS, Brennan R, Read RA, et al. Epidemiology of trauma deaths: a reassessment. J Trauma. 1995;38(2):185–93.CrossRefPubMed

Hoyt DB. A clinical review of bleeding dilemmas in trauma. Semin Hematol. 2004;41(1 Suppl 1):40–3.CrossRefPubMed

Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003;54(6):1127–30. doi:10.1097/01.TA.0000069184.82147.06.CrossRefPubMed

MacLeod JB, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma. 2003;55(1):39–44. doi:10.1097/01.TA.0000075338.21177.EF.CrossRefPubMed

Rugeri L, Levrat A, David JS, Delecroix E, Floccard B, Gros A, et al. Diagnosis of early coagulation abnormalities in trauma patients by rotation thrombelastography. J Thromb Haemost. 2007;5(2):289–95. doi:10.1111/j.1538-7836.2007.02319.x.CrossRefPubMed

Maegele M, Lefering R, Yucel N, Tjardes T, Rixen D, Paffrath T, et al. Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients. Injury. 2007;38(3):298–304. doi:10.1016/j.injury.2006.10.003.CrossRefPubMed

Gonzalez EA, Moore FA, Holcomb JB, Miller CC, Kozar RA, Todd SR, et al. Fresh frozen plasma should be given earlier to patients requiring massive transfusion. J Trauma. 2007;62(1):112–9. doi:10.1097/01.ta.0000250497.08101.8b.CrossRefPubMed

Gruen RL, Jurkovich GJ, McIntyre LK, Foy HM, Maier RV. Patterns of errors contributing to trauma mortality: lessons learned from 2,594 deaths. Ann Surg. 2006;244(3):371–80. doi:10.1097/01.sla.0000234655.83517.56.PubMedCentralPubMed

10.

Brohi K, Cohen MJ, Ganter MT, Matthay MA, Mackersie RC, Pittet JF. Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway? Ann Surg. 2007;245(5):812–8. doi:10.1097/01.sla.0000256862.79374.31.PubMedCentralCrossRefPubMed

11.

Brohi K, Cohen MJ, Ganter MT, Schultz MJ, Levi M, Mackersie RC, et al. Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis. J Trauma. 2008;64(5):1211–7. doi:10.1097/TA.0b013e318169cd3c.CrossRefPubMed

12.

Wolberg AS, Meng ZH, Monroe 3rd DM, Hoffman M. A systematic evaluation of the effect of temperature on coagulation enzyme activity and platelet function. J Trauma. 2004;56(6):1221–8.CrossRefPubMed

13.

Martini WZ, Pusateri AE, Uscilowicz JM, Delgado AV, Holcomb JB. Independent contributions of hypothermia and acidosis to coagulopathy in swine. J Trauma. 2005;58(5):1002–9.CrossRefPubMed

14.

Engstrom M, Schott U, Romner B, Reinstrup P. Acidosis impairs the coagulation: A thromboelastographic study. J Trauma. 2006;61(3):624–8. doi:10.1097/01.ta.0000226739.30655.75.CrossRefPubMed

15.

Lucas CE, Ledgerwood AM, Mammen EF. Altered coagulation protein content after albumin resuscitation. Ann Surg. 1982;196(2):198–202.PubMedCentralCrossRefPubMed

16.

Martin DJ, Lucas CE, Ledgerwood AM, Hoschner J, McGonigal MD, Grabow D. Fresh frozen plasma supplement to massive red blood cell transfusion. Ann Surg. 1985;202(4):505–11.PubMedCentralCrossRefPubMed

17.

Ciavarella D, Reed RL, Counts RB, Baron L, Pavlin E, Heimbach DM, et al. Clotting factor levels and the risk of diffuse microvascular bleeding in the massively transfused patient. Br J Haematol. 1987;67(3):365–8.CrossRefPubMed

18.

Harrigan C, Lucas CE, Ledgerwood AM. The effect of hemorrhagic shock on the clotting cascade in injured patients. J Trauma. 1989;29(10):1416–21.CrossRefPubMed

19.

Rizoli SB, Scarpelini S, Callum J, Nascimento B, Mann KG, Pinto R, et al. Clotting factor deficiency in early trauma-associated coagulopathy. J Trauma. 2011;71(5 Suppl 1):S427–34. doi:10.1097/TA.0b013e318232e5ab.PubMedCentralCrossRefPubMed

20.

Cohen MJ, Kutcher M, Redick B, Nelson M, Call M, Knudson MM, et al. Clinical and mechanistic drivers of acute traumatic coagulopathy. J Trauma Acute Care Surg. 2013;75(1 Suppl 1):S40–7. doi:10.1097/TA.0b013e31828fa43d.PubMedCentralCrossRefPubMed

21.

Woodhams B, Girardot O, Blanco MJ, Colesse G, Gourmelin Y. Stability of coagulation proteins in frozen plasma. Blood Coagul Fibrinolysis. 2001;12(4):229–36.CrossRefPubMed

22.

Minei JP, Schmicker RH, Kerby JD, Stiell IG, Schreiber MA, Bulger E, et al. Severe traumatic injury: regional variation in incidence and outcome. Ann Surg. 2010;252(1):149–57. doi:10.1097/SLA.0b013e3181df0401.PubMedCentralCrossRefPubMed

23.

Zurcher M, Sulzer I, Barizzi G, Lammle B, Alberio L. Stability of coagulation assays performed in plasma from citrated whole blood transported at ambient temperature. Thromb Haemost. 2008;99(2):416–26. doi:10.1160/TH07-07-0448.PubMed

24.

Vivien B, Langeron O, Morell E, Devilliers C, Carli PA, Coriat P, et al. Early hypocalcemia in severe trauma. Crit Care Med. 2005;33(9):1946–52.CrossRefPubMed

25.

Hiippala ST, Myllyla GJ, Vahtera EM. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth Analg. 1995;81(2):360–5.PubMed

26.

Schlimp CJ, Voelckel W, Inaba K, Maegele M, Ponschab M, Schochl H. Estimation of plasma fibrinogen levels based on hemoglobin, base excess and Injury Severity Score upon emergency room admission. Crit Care. 2013;17(4):R137. doi:10.1186/cc12816.PubMedCentralCrossRefPubMed

27.

Jansen JO, Scarpelini S, Pinto R, Tien HC, Callum J, Rizoli SB. Hypoperfusion in severely injured trauma patients is associated with reduced coagulation factor activity. J Trauma. 2011;71(5 Suppl 1):S435–40. doi:10.1097/TA.0b013e318232e5cb.CrossRefPubMed

28.

Begbie M, Notley C, Tinlin S, Sawyer L, Lillicrap D. The Factor VIII acute phase response requires the participation of NFkappaB and C/EBP. Thromb Haemost. 2000;84(2):216–22.PubMed

29.

Hollestelle MJ, Thinnes T, Crain K, Stiko A, Kruijt JK, van Berkel TJ, et al. Tissue distribution of factor VIII gene expression in vivo--a closer look. Thromb Haemost. 2001;86(3):855–61.PubMed

30.

Jacquemin M, Neyrinck A, Hermanns MI, Lavend'homme R, Rega F, Saint-Remy JM, et al. FVIII production by human lung microvascular endothelial cells. Blood. 2006;108(2):515–7. doi:10.1182/blood-2005-11-4571.CrossRefPubMed

31.

Brohi K, Cohen MJ, Davenport RA. Acute coagulopathy of trauma: mechanism, identification and effect. Curr Opin Crit Care. 2007;13(6):680–5. doi:10.1097/MCC.0b013e3282f1e78f.CrossRefPubMed

32.

Theusinger OM, Spahn DR, Ganter MT. Transfusion in trauma: why and how should we change our current practice? Curr Opin Anaesthesiol. 2009;22(2):305–12. doi:10.1097/ACO.0b013e3283212c7c.CrossRefPubMed

33.

Kheirabadi BS, Crissey JM, Deguzman R, Holcomb JB. In vivo bleeding time and in vitro thrombelastography measurements are better indicators of dilutional hypothermic coagulopathy than prothrombin time. J Trauma. 2007;62(6):1352–9. doi:10.1097/TA.0b013e318047b805.CrossRefPubMed

34.

Martini WZ, Cortez DS, Dubick MA, Park MS, Holcomb JB. Thrombelastography is better than PT, aPTT, and activated clotting time in detecting clinically relevant clotting abnormalities after hypothermia, hemorrhagic shock and resuscitation in pigs. J Trauma. 2008;65(3):535–43. doi:10.1097/TA.0b013e31818379a6.CrossRefPubMed

Title: Evaluation of clotting factor activities early after severe multiple trauma and their correlation with coagulation tests and clinical data
Authors: Manuel Burggraf
Arzu Payas
Max Daniel Kauther
Carsten Schoeneberg
Sven Lendemans
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: World Journal of Emergency Surgery / Issue 1/2015
Electronic ISSN: 1749-7922
DOI: https://doi.org/10.1186/s13017-015-0038-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Evaluation of clotting factor activities early after severe multiple trauma and their correlation with coagulation tests and clinical data

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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