Thromboelastographic Assessment of Fibrinolytic Activity in Postpartum Hemorrhage: A Retrospective Single-Center Observational Study

Abstract

BACKGROUND: Postpartum hemorrhage is a leading cause of maternal mortality. Antifibrinolytic therapy has the potential to influence outcomes in postpartum hemorrhage, but the incidence of elevated fibrinolytic activity in postpartum hemorrhage is unknown. METHODS: We retrospectively reviewed thromboelastography (TEG) results obtained for postpartum hemorrhage from 118 deliveries at The University of Chicago. TEG results were obtained as part of our postpartum hemorrhage protocol when blood loss exceeded 500 mL after vaginal delivery or 1000 mL after cesarean delivery. Our primary outcome was the incidence of elevated fibrinolytic activity, which we predefined as clot lysis ≥3% at 30 minutes (Ly30) on kaolin TEG. Platelet-mediated clot retraction can also lead to an elevated Ly30 on kaolin TEG. Therefore, to distinguish between fibrinolysis and clot retraction, we evaluated clot lysis using functional fibrinogen TEG, which contains a platelet inhibitor. We considered a kaolin TEG Ly30 ≥3% in conjunction with a nonzero functional fibrinogen TEG Ly30 suggestive of elevated fibrinolytic activity. We also recorded quantitative blood loss, primary etiology of hemorrhage, standard laboratory measurements of coagulation, and demographic and obstetric characteristics of the study population. RESULTS: The median kaolin TEG Ly30 was 0.2% (interquartile range: 0%–0.8%). Fifteen of 118 women (12.7%; 95% confidence interval, 7.9%–19.9%) had kaolin TEG Ly30 values ≥3%. Of 15 patients with elevated Ly30 values, functional fibrinogen TEG Ly30 was available for 13, of which none demonstrated detectable clot lysis. CONCLUSIONS: Our observation that none of the patients in our sample with kaolin TEG Ly30 values ≥3% had a nonzero functional fibrinogen TEG Ly30 value suggests that the observed elevations in kaolin TEG Ly30 may have been secondary to platelet-mediated clot retraction as opposed to fibrinolysis. Platelet-mediated clot retraction should be distinguished from fibrinolysis when assayed using viscoelastic techniques in postpartum hemorrhage. Further research is necessary to determine the optimal methods to assess fibrinolytic activity in postpartum hemorrhage.

Viscoelastometric Testing to Assess Hemostasis of COVID-19: A Systematic Review

“…Fibrinolysis is monitored at a specific time x minutes after MA was reached for TEG (LY(x) parameter), and by maximal lysis ML (reduction in clot firmness after MCF in relation to MCF) or lysis of the clot at a given time x minutes after CT was reached (LI(x)) parameter for ROTEM and ClotPro. The diminution in clot maximum amplitude was thought to be due to both fibrinolysis and potentially platelet-mediated clot retraction [4][5][6]93]. However, as no change in clot mechanical strength after the maximum was reached was reported in many studies in COVID-19 patients, platelet-mediated clot retraction does not seem to play a significant role here.…”

“…Values in italics and in brackets are the reference values; we have indicated our reference ranges* for information purposes. Comorbidities: 1 Overweight and obesity, associated with high blood pressure, diabetes and cardiovascular risk factors; 2 High blood pressure, diabetes and some additional comorbidities; 3 Overweight and obesity, with some additional comorbidities; 4 Overweight and obesity; 5 Overweight and obesity, associated with high blood pressure, diabetes, pulmonary disease and cardiovascular risk factors; 6 Overweight and obesity, associated with high blood pressure; 7 Overweight and obesity, associated with cardiovascular risk factors, pulmonary disease and kidney disease; 8 Overweight and obesity, associated with diabetes, cardiovascular risk factors, pulmonary disease and kidney disease; 9 Overweight and obesity, associated with high blood pressure, diabetes, kidney disease and cardiovascular risk factors; 10 Overweight and obesity, associated with high blood pressure, diabetes, pulmonary disease, kidney disease and cardiovascular risk factors; 11 The number of COVID-19 patients with at least one VET performed in each article ranged from 1 [26,38,65] to 64 [58]. Mean or median adult COVID-19 patients ages ranged from 39 [65] to 84 years [68].…”

“…Second, four studies [32,38,39,50] out of five showed an increase in α angle in EXTEM or in TEM-tPA, whereas the last reported a normal or even a decrease one [37]. 1 No difference between D0 and D10 (p > 0.05); 2 Normalization between D0 and D10 (p < 0.05); 3 Higher MCF in ICU patients than in IMW ones (p < 0.05); 4 Higher A(x) in ICU patients than in IMW ones (p < 0.05); 5 Lower ML in patients with TE (p < 0.05); 6 Longer CT in patients with TE (p < 0.05); 7 Higher clot amplitude in COVID-19 patients upon admission (p < 0.0001); 8 Higher MCF in COVID-19 patients upon admission (p < 0.0001); 9 Higher clot amplitude in COVID-19 patients upon admission (p < 0.05); 10 Higher MCF in COVID-19 patients upon admission (p < 0.05); 11 Shorter CFT in COVID-19 patients (p < 0.001); 12 Higher MCF in COVID-19 patients (p < 0.05); 13 Higher MCF with low dose of LMWH (p < 0.001); 14 Higher A(x) in patients with TE (p < 0.05); 15 Higher MCF in patients with TE (p < 0.05); 16 Shorter CFT in patients with TE (p < 0.05). Results from the APTEM assay were only reported by one case report [26] and were consistent with the absence of hyperfibrinolysis (data not shown).…”

“…In contrast to conventional clotting tests, viscoelastic tests (VETs) monitor changes of viscoelastic properties of a forming and evolving clot from whole blood, before and beyond the clotting point; they are often referred to as a global hemostasis test, although some aspects of hemostasis are not explored [1][2][3]. Coagulation occurs in the presence of platelets and red blood cells, and fibrinolysis can translate into a decrease in clot mechanical strength after its maximum has been reached, but clot retraction seems to play a role here as well [4][5][6]. VETs are based on the mechanical properties of the clot, like mechanical strength, and are influenced by its composition in platelets, fibrin, red blood cells, and factor XIII [7][8][9].…”

Viscoelastic Hemostatic Assays for Postpartum Hemorrhage

“…The use of TEG and ROTEM in the identification of hypocoagulopathy and guiding BCT/HAT in PPH is rising in popularity. Only recently have TEG and ROTEM been increasingly studied within the context of PPH [2,3,21,25,[52][53][54][55]58,59,[74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92]. BCT/HAT can be tailored to this patient population's specific needs using TEG or ROTEM parameters.…”