Effect of temperature on thromboelastography and implications for clinical use in newborns undergoing therapeutic hypothermia

Katie R Forman, Edward Wong, Meanavy Gallagher, Robert McCarter, Naomi L C Luban, An N Massaro, Katie R Forman, Edward Wong, Meanavy Gallagher, Robert McCarter, Naomi L C Luban, An N Massaro

Abstract

Background: Encephalopathic neonates undergoing therapeutic hypothermia have increased risk for coagulopathy secondary to perinatal asphyxia and effects of cooling on the coagulation enzyme cascade. Thromboelastography (TEG) allows for a comprehensive assessment of coagulation that can be regulated for temperature. TEG has not been previously evaluated in newborns undergoing hypothermia treatment.

Methods: Encephalopathic neonates treated with systemic hypothermia were enrolled in this prospective observational study. Daily blood specimens were collected for standard coagulation tests and platelet counts during hypothermia and after rewarming. Concurrent TEG assays were performed at 33.5 and 37.0 °C for comparison.

Results: A total of 48 paired TEGs from 24 subjects were performed. Forty percent of the subjects were males, the mean (± SD) birth weight was 3.2 ± 0.7 kg, and the mean gestational age was 38.4 ± 1.4 wk. TEG results differed significantly between assays performed at 37.0 vs. 33.5 °C, indicating more impaired coagulation at 33.5 °C. TEG parameters clot kinetics, angle, maximum amplitude (MA), and coagulation index were significantly associated with clinical bleeding (P < 0.05). These remained significant (except for MA) after controlling for transfusion therapy.

Conclusion: TEG results are affected by temperature, consistent with the known association of hypothermia with coagulopathy. Several TEG parameters are predictive of clinical bleeding in newborns undergoing hypothermia. Selected cutpoints to predict bleeding risk are temperature dependent.

Figures

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Representative example of thromboelastograph with measured parameters depicted schematically.
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Effect of temperature on TEG parameters. The gray bars represent 37°C while the white bars represent 33.5°C. All bars represent mean ± 95% confidence interval. Significant differences by paired T-tests are shown with asterisks (*p

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Receiver operating curves for K, α,…

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Receiver operating curves for K, α, MA and CI. The diagonal line represents an…

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Receiver operating curves for K, α, MA and CI. The diagonal line represents an Area under the curve (AUC) of 0.5, indicating a non-informative test. Panel A: K performed at 33.5°C. AUC = 0.7377, Cutpoint = 3.4 min, Sensitivity = 62.5% and Specfificity = 90.9%. Panel B: K performed at 37°C. AUC = 0.7876, Cutpoint = 2.6 min, Sensitivity = 76.9%, Specificity = 81.8%. Panel C: α performed at 33.5°C. AUC = 07377, Cutpoint = 52.3 degrees, Sensitivity = 66.7% and Specfificity = 88.4%. Panel D: α performed at 37°C. AUC = 0.7955, Cutpoint = 57.6 degrees, Sensitivity = 76.9%, Specificity = 81.8%. Panel E: MA performed at 33.5°C. AUC = 0.8172, Cutpoint = 56.1 mm, Sensitivity = 70.83% and Specfificity = 81.82. Panel F: MA performed at 37°C. AUC = 0.8217, Cutpoint = 58.1 mm, Sensitivity = 88.46%, Specificity = 61.18%. Panel G: CI performed at 33.5°C. AUC = 0.7173, Cutpoint = −4.6, Sensitivity = 70.83% and Specfificity = 76.19%. Panel H: CI performed at 37°C. AUC = 0.6476, Cutpoint = −3.3, Sensitivity = 68%, Specificity = 66.67%.
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Receiver operating curves for K, α, MA and CI. The diagonal line represents an Area under the curve (AUC) of 0.5, indicating a non-informative test. Panel A: K performed at 33.5°C. AUC = 0.7377, Cutpoint = 3.4 min, Sensitivity = 62.5% and Specfificity = 90.9%. Panel B: K performed at 37°C. AUC = 0.7876, Cutpoint = 2.6 min, Sensitivity = 76.9%, Specificity = 81.8%. Panel C: α performed at 33.5°C. AUC = 07377, Cutpoint = 52.3 degrees, Sensitivity = 66.7% and Specfificity = 88.4%. Panel D: α performed at 37°C. AUC = 0.7955, Cutpoint = 57.6 degrees, Sensitivity = 76.9%, Specificity = 81.8%. Panel E: MA performed at 33.5°C. AUC = 0.8172, Cutpoint = 56.1 mm, Sensitivity = 70.83% and Specfificity = 81.82. Panel F: MA performed at 37°C. AUC = 0.8217, Cutpoint = 58.1 mm, Sensitivity = 88.46%, Specificity = 61.18%. Panel G: CI performed at 33.5°C. AUC = 0.7173, Cutpoint = −4.6, Sensitivity = 70.83% and Specfificity = 76.19%. Panel H: CI performed at 37°C. AUC = 0.6476, Cutpoint = −3.3, Sensitivity = 68%, Specificity = 66.67%.

References

    1. Bauman ME, Cheung PY, Massicotte MP. Hemostasis and platelet dysfunction in asphyxiated neonates. J Pediatr. 2011;158:e35–e39.
    1. Suzuki S, Morishita S. Hypercoagulability and DIC in high-risk infants. Semin Thromb Hemost. 1998;24:463–466.
    1. Shah P, Riphagen S, Beyene J, Perlman M. Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2004;89:F152–F155.
    1. Sarkar S, Barks JD, Bhagat I, Donn SM. Effects of therapeutic hypothermia on multiorgan dysfunction in asphyxiated newborns: whole-body cooling versus selective head cooling. J Perinatol. 2009;29:558–563.
    1. Castle V, Andrew M, Kelton J, Giron D, Johnston M, Carter C. Frequency and mechanism of neonatal thrombocytopenia. J Pediatr. 1986;108:749–755.
    1. Roberts IA, Murray NA. Thrombocytopenia in the newborn. Curr Opin Pediatr. 2003;15:17–23.
    1. Michelson AD, Barnard MR, Khuri SF, Rohrer MJ, MacGregor H, Valeri CR. The effects of aspirin and hypothermia on platelet function in vivo. Br J Haematol. 1999;104:64–68.
    1. Reed RL, 2nd, Johnson TD, Hudson JD, Fischer RP. The disparity between hypothermic coagulopathy and clotting studies. J Trauma. 1992;33:465–470.
    1. Reed RL, 2nd, Bracey AW, Jr, Hudson JD, Miller TA, Fischer RP. Hypothermia and blood coagulation: dissociation between enzyme activity and clotting factor levels. Circ Shock. 1990;32:141–152.
    1. Rohrer MJ, Natale AM. Effect of hypothermia on the coagulation cascade. Crit Care Med. 1992;20:1402–1405.
    1. Straub A, Breuer M, Wendel HP, Peter K, Dietz K, Ziemer G. Critical temperature ranges of hypothermia-induced platelet activation: possible implications for cooling patients in cardiac surgery. Thromb Haemost. 2007;97:608–616.
    1. Wolberg AS, Meng ZH, Monroe DM, 3rd, Hoffman M. A systematic evaluation of the effect of temperature on coagulation enzyme activity and platelet function. J Trauma. 2004;56:1221–1228.
    1. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013;1:CD003311.
    1. Shankaran S. Therapeutic hypothermia for neonatal encephalopathy. Curr Treat Options Neurol. 2012;14:608–619.
    1. Shankaran S, Pappas A, McDonald SA, et al. Childhood outcomes after hypothermia for neonatal encephalopathy. N Engl J Med. 2012;366:2085–2092.
    1. Shankaran S, Laptook AR, Tyson JE, et al. Evolution of encephalopathy during whole body hypothermia for neonatal hypoxic-ischemic encephalopathy. J Pediatr. 2012;160:567–572. e563.
    1. Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353:1574–1584.
    1. Azzopardi D, Brocklehurst P, Edwards D, et al. The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: a randomised controlled trial. BMC Pediatr. 2008;8:17.
    1. Gunn AJ, Wyatt JS, Whitelaw A, et al. Therapeutic hypothermia changes the prognostic value of clinical evaluation of neonatal encephalopathy. J Pediatr. 2008;152:55–58. 58 e51.
    1. Wyatt JS, Gluckman PD, Liu PY, et al. Determinants of outcomes after head cooling for neonatal encephalopathy. Pediatrics. 2007;119:912–921.
    1. Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005;365:663–670.
    1. Eicher DJ, Wagner CL, Katikaneni LP, et al. Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. Pediatr Neurol. 2005;32:11–17.
    1. Edwards RM, Naik-Mathuria BJ, Gay AN, Olutoye OO, Teruya J. Parameters of thromboelastography in healthy newborns. Am J Clin Pathol. 2008;130:99–102.
    1. Luddington RJ. Thrombelastography/thromboelastometry. Clin Lab Haematol. 2005;27:81–90.
    1. Scarpelini S, Rhind SG, Nascimento B, et al. Normal range values for thromboelastography in healthy adult volunteers. Braz J Med Biol Res. 2009;42:1210–1217.
    1. Nair SC, Dargaud Y, Chitlur M, Srivastava A. Tests of global haemostasis and their applications in bleeding disorders. Haemophilia 16 Suppl 5. 2010:85–92.
    1. Mitchell LG, Goldenberg NA, Male C, et al. Definition of clinical efficacy and safety outcomes for clinical trials in deep venous thrombosis and pulmonary embolism in children. J Thromb Haemost. 2011;9:1856–1858.
    1. Haizinger B, Gombotz H, Rehak P, Geiselseder G, Mair R. Activated thrombelastogram in neonates and infants with complex congenital heart disease in comparison with healthy children. Br J Anaesth. 2006;97:545–552.
    1. Moganasundram S, Hunt BJ, Sykes K, et al. The relationship among thromboelastography, hemostatic variables, and bleeding after cardiopulmonary bypass surgery in children. Anesth Analg. 2010;110:995–1002.
    1. Alexander DC, Butt WW, Best JD, Donath SM, Monagle PT, Shekerdemian LS. Correlation of thromboelastography with standard tests of anticoagulation in paediatric patients receiving extracorporeal life support. Thromb Res. 2010;125:387–392.
    1. Kang Y, Borland LM, Picone J, Martin LK. Intraoperative coagulation changes in children undergoing liver transplantation. Anesthesiology. 1989;71:44–47.
    1. Goobie SM, Soriano SG, Zurakowski D, McGowan FX, Rockoff MA. Hemostatic changes in pediatric neurosurgical patients as evaluated by thrombelastograph. Anesth Analg. 2001;93:887–892.
    1. Chan KL, Summerhayes RG, Ignjatovic V, Horton SB, Monagle PT. Reference values for kaolin-activated thromboelastography in healthy children. Anesth Analg. 2007;105:1610–1613. table of contents.
    1. Christensen RD, Sheffield MJ, Lambert DK, Baer VL. Effect of therapeutic hypothermia in neonates with hypoxic-ischemic encephalopathy on platelet function. Neonatology. 2012;101:91–94.
    1. Fraser CD, Jr, Jaquiss RD, Rosenthal DN, et al. Prospective trial of a pediatric ventricular assist device: Supplimentary Material - Protocol - Appendix H: Anticoagulation and platelet inhibition protocol. N Engl J Med. 2012;367
    1. Shinya H, Matsuo N, Takeyama N, Tanaka T. Hyperammonemia inhibits platelet aggregation in rats. Thrombosis Research. 1996;81:195–201.
    1. Gibson JB, Berry GT. Pathophysiology of metabolic disease of the live. In: Polin RA, Fox WW, Abman SH, editors. Fetal and Neonatal Physiology. Philadelphia: Pa:W.B. Saunders Co; 2004. pp. 1211–1218.

Source: PubMed

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