Establishing Thromboelastography with Platelet-Function Analyzer Reference Ranges and Other Measures in Healthy Term Pregnant Women

Abstract

Objective The diagnosis of coagulopathy cannot always be performed at point of care. Thromboelastography (TEG) and the platelet-function analyzer (PFA-100), have emerged as reliable means for coagulation analysis. However, their reliable utility in pregnancy remains to be determined. We sought to establish reference values with concomitant determination of other known coagulation measures in nonlaboring gravidae in an effort to report the mean and variance of multiple testing modalities.

Study Design Fifty-nine term, nonlaboring, pregnant women without comorbidities were enrolled, either at presentation for scheduled delivery or at presentation to triage for a non–labor-related indication. TEG, PFA-100, and complete coagulation measures of the overall hemostatic function (including prothrombin time, activated partial thromboplastin time, fibrinogen, protein C, protein S, von Willebrand factor antigen, ristocetin cofactor activity, and ADAMTS-13) were performed. Prior investigations of TEG and PFA-100 parameters in normal gravidae were reviewed, and pooled means and standard deviations (as a measure of variance) were calculated.

Results TEG and PFA-100 parameters were significantly different among pregnant gravidae compared with nonpregnant reference ranges, and varied in association with other measures of the coagulation system. Our results and the pooled results reflect a hypercoagulable state.

Conclusion Our data suggest that TEG values are significantly different in term, nonlaboring, healthy gravidae compared with nonpregnant reference values. Pooled means and standard deviations shown here may be considered for reference.

Keywords

thromboelastography - platelet-function analyzer - pregnancy - reference values

• References

• 1 Stirling Y, Woolf L, North WR, Seghatchian MJ, Meade TW. Haemostasis in normal pregnancy. Thromb Haemost 1984; 52 (2) 176-182
• 2 Cerneca F, Ricci G, Simeone R, Malisano M, Alberico S, Guaschino S. Coagulation and fibrinolysis changes in normal pregnancy. Increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive fibrinolysis. Eur J Obstet Gynecol Reprod Biol 1997; 73 (1) 31-36
• 3 Choi JW, Pai SH. Tissue plasminogen activator levels change with plasma fibrinogen concentrations during pregnancy. Ann Hematol 2002; 81 (11) 611-615
• 4 Uchikova EH, Ledjev II. Changes in haemostasis during normal pregnancy. Eur J Obstet Gynecol Reprod Biol 2005; 119 (2) 185-188
• 5 Bellart J, Gilabert R, Fontcuberta J, Carreras E, Miralles RM, Cabero L. Coagulation and fibrinolytic parameters in normal pregnancy and in pregnancy complicated by intrauterine growth retardation. Am J Perinatol 1998; 15 (2) 81-85
• 6 Stammers AH, Bruda NL, Gonano C, Hartmann T. Point-of-care coagulation monitoring: applications of the thromboelastography. Anaesthesia 1998; 53 (Suppl. 02) 58-59
• 7 Cammerer U, Dietrich W, Rampf T, Braun SL, Richter JA. The predictive value of modified computerized thromboelastography and platelet function analysis for postoperative blood loss in routine cardiac surgery. Anesth Analg 2003; 96 (1) 51-57
• 8 Chitlur M, Sorensen B, Rivard GE , et al. Standardization of thromboelastography: a report from the TEG-ROTEM working group. Haemophilia 2011; 17 (3) 532-537
• 9 Vincelot A, Nathan N, Collet D, Mehaddi Y, Grandchamp P, Julia A. Platelet function during pregnancy: an evaluation using the PFA-100 analyser. Br J Anaesth 2001; 87 (6) 890-893
• 10 American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 95: anemia in pregnancy. Obstet Gynecol 2008; 112 (1) 201-207
• 11 Committee on Practice Bulletins--Obstetrics. Practice Bulletin No. 137: Gestational diabetes mellitus. Obstet Gynecol 2013; 122 (2 Pt 1) 406-416
• 12 American College of Obstetricians and Gynecologists. ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists Number 76, October 2006: postpartum hemorrhage. Obstet Gynecol 2006; 108 (4) 1039-1048
• 13 American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Obstet Gynecol 2002; 99 (1) 159-167
• 14 American College of Obstetricians and Gynecologists. Task Force on Hypertension in Pregnancy. Washington, DC: American College of Obstetricians and Gynecologists; 2013: 1-100
• 15 Sharma SK, Philip J, Wiley J. Thromboelastographic changes in healthy parturients and postpartum women. Anesth Analg 1997; 85 (1) 94-98
• 16 Davies JR, Fernando R, Hallworth SP. Hemostatic function in healthy pregnant and preeclamptic women: an assessment using the platelet function analyzer (PFA-100) and thromboelastograph. Anesth Analg 2007; 104 (2) 416-420
• 17 Polak F, Kolnikova I, Lips M, Parizek A, Blaha J, Stritesky M. New recommendations for thromboelastography reference ranges for pregnant women. Thromb Res 2011; 128 (4) e14-e17
• 18 Macafee B, Campbell JP, Ashpole K , et al. Reference ranges for thromboelastography (TEG(®) ) and traditional coagulation tests in term parturients undergoing caesarean section under spinal anaesthesia. Anaesthesia 2012; 67 (7) 741-747
• 19 Della Rocca G, Dogareschi T, Cecconet T , et al. Coagulation assessment in normal pregnancy: thrombelastography with citrated non activated samples. Minerva Anestesiol 2012; 78 (12) 1357-1364
• 20 Karlsson O, Sporrong T, Hillarp A, Jeppsson A, Hellgren M. Prospective longitudinal study of thromboelastography and standard hemostatic laboratory tests in healthy women during normal pregnancy. Anesth Analg 2012; 115 (4) 890-898
• 21 Fassoulaki A, Staikou C. The impact of spinal anaesthesia for caesarean delivery on coagulation assessed by thromboelastography. Int J Obstet Anesth 2013; 22 (1) 42-46
• 22 Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol 2009; 114 (6) 1326-1331
• 23 Sánchez-Luceros A, Farías CE, Amaral MM , et al. von Willebrand factor-cleaving protease (ADAMTS13) activity in normal non-pregnant women, pregnant and post-delivery women. Thromb Haemost 2004; 92 (6) 1320-1326
• 24 Zhang D, Xiao J, Huang H , et al. Von Willebrand factor antigen and ADAMTS13 activity assay in pregnant women and severe preeclamptic patients. J Huazhong Univ Sci Technolog Med Sci 2010; 30 (6) 777-780
• 25 Molvarec A, Rigó Jr J, Bõze T , et al. Increased plasma von Willebrand factor antigen levels but normal von Willebrand factor cleaving protease (ADAMTS13) activity in preeclampsia. Thromb Haemost 2009; 101 (2) 305-311
• 26 Mahieu B, Jacobs N, Mahieu S , et al. Haemostatic changes and acquired activated protein C resistance in normal pregnancy. Blood Coagul Fibrinolysis 2007; 18 (7) 685-688
• 27 Sharma JB, Malhotra M. Successful management of uterine incision hemorrhage in caesarean section with topical oxidized regenerated cellulose (Surgicel Nu Knit): a case report. Arch Gynecol Obstet 2006; 274 (2) 115
• 28 Wallaschofski H, Donné M, Eigenthaler M , et al. PRL as a novel potent cofactor for platelet aggregation. J Clin Endocrinol Metab 2001; 86 (12) 5912-5919
• 29 Wallaschofski H, Kobsar A, Sokolova O, Eigenthaler M, Lohmann T. Co-activation of platelets by prolactin or leptin—pathophysiological findings and clinical implications. Horm Metab Res 2004; 36 (1) 1-6
• 30 Roeloffzen WW, Kluin-Nelemans HC, Mulder AB, Veeger NJ, Bosman L, de Wolf JT. In normal controls, both age and gender affect coagulability as measured by thrombelastography. Anesth Analg 2010; 110 (4) 987-994
• 31 Böck M, De Haan J, Beck KH , et al. Standardization of the PFA-100(R) platelet function test in 105 mmol/l buffered citrate: effect of gender, smoking, and oral contraceptives. Br J Haematol 1999; 106 (4) 898-904
• 32 Chitlur M, Lusher J. Standardization of thromboelastography: values and challenges. Semin Thromb Hemost 2010; 36 (7) 707-711
• 33 Hill JS, Devenie G, Powell M. Point-of-care testing of coagulation and fibrinolytic status during postpartum haemorrhage: developing a thrombelastography®-guided transfusion algorithm. Anaesth Intensive Care 2012; 40 (6) 1007-1015