1. Introduction

Obstetric hemorrhage still represents a significant risk for maternal morbidity and mortality, especially in clinical settings where hemostatic alterations coincide with underlying obstetric pathologies, including but not limited to major blood loss, placenta accreta/percreta, antiplatelet therapy, and patients with inherited coagulopathies [1]. Managing major bleeding events requires clinicians to immediately interpret the patient’s coagulation tests and effectively adjust the patient’s coagulation profile, thereby preventing further deterioration and promoting optimal health outcomes [2]. The application of viscoelastic goal-directed therapy (GDT) has proven to be highly effective in managing patients with obstetric hemorrhage. The appropriate use of the technology, proficient interpretation, and subsequent transfusion planning have decreased mortality, perioperative morbidity, total transfusion, and waste of blood products [3, 4]. The reaction time (R-Time), clot dynamics, angle, and maximum amplitude [R, K, α, MA] provide the most valuable information about the blood coagulation profile, enzymatic activity, clot kinetics, and mechanical features [5, 6]. The test can generate clot parameters within 10–20 min. This feature enables the rapid development of a tailored transfusion strategy for the patient. It improves the blood product approach throughout the patient’s clinical evolution in the ever-changing OR scene [7–9].

To effectively distinguish between healthy hemostatic states and altered ones using thromboelastography (TEG)-generated targets, one must establish reference intervals carefully, tailored to specific demographics. Doing so ensures accurate discrimination while minimizing the risk of misinterpretation or inappropriate responses [10].

It is well documented that pregnant women have an increased tendency toward hypercoagulability, characterized by increased activity of their coagulation factors, platelets, and fibrinogen levels [11]; moreover, they feature decreased endogenous anticoagulants and an increase in antifibrinolytic profile because of increments in PAI-2 [12]. However, we have not adequately characterized the parameters of patients in their third trimester until now.

Our center is a tertiary-level hospital providing gynecological, obstetrical, and neonatal medical services in seven Northern Mexican states. In 2021, the hospital attended 14,833 live births, 633 (3.89%) postpartum hemorrhage cases, and 68 (0.7%) massive bleeding events (defined as loss of > 50% blood volume). Since 2014, every hemorrhage case has received multidisciplinary care from rapid response teams, which has improved patient survival rates, decreased morbidity outcomes, and reduced the necessity for intensive therapy and hospitalization.

The management philosophy for these patients emphasizes GDT, along with prompt and well-informed clinical decisions intended to anticipate, control, and follow up on patients who experience obstetric hemorrhage. At our center, patients experiencing significant bleeding because of obstetric hemorrhage undergo transfusion GDT for optimal management. The established targets guiding this approach include the following: hemoglobin concentration: A target range of 70–80 g per liter (g/L) is maintained with red blood cells [13, 14]. Coagulation parameters: prothrombin time (PT) to achieve a time < 16 s or an international normalized ratio (INR) value below 1.5 with fresh frozen plasma (FFP) 10 mL/Ikg [9, 13]. Fibrinogen replacement therapy is utilized based on readiness, either by human fibrinogen concentrate or cryoprecipitate. The target fibrinogen level concentration of ≥ 2 g/L is aimed for during the acute phase of hemorrhage [15]. Target platelet count: During the acute process, levels between 50,000 and 75,000 platelets/μL with platelet apheresis [16].

Furthermore, our center employs TEG (TEG 5000 Thrombelastograph; Haemonetics, Braintree, MA, USA) conducted by trained personnel operating the equipment, validating specimens, and interpreting curve parameters within the operating theater. This resource allows rapid and reliable coagulation assessment and decision-making abilities during active bleeding [13]. The optimization target for TEG in clinical management is a R-Time of less than 8 min; the intervention strategy is the administration of FFP at a dose of 10 mL/kg [17]. The MA goal is greater than 60 mm, and the therapeutic approach is first line with the supplemental administration of fibrinogen and adjunctive therapy of platelet apheresis. The corrective measures for an α-Angle above 59° are fibrinogen supplementation and platelet Apheresis based on clinical assessment [13]. A TEG schematic utility framework for evaluating each stage of the coagulation cascade, complemented by additional information on therapeutic transfusion goals, is illustrated in Figure 1.

Although our country has access to the technology, we have noticed that the principal TEG algorithms employed among our patient population primarily utilize reference intervals obtained from nonlocal sources. Beyond evaluating reference ranges, our study also explores distinct coagulation traits unique to local obstetric patients compared to their counterparts in other global regions. Our ultimate objective is to facilitate data-driven decision-making tailored to the requirements of our specialized population.

2. Methods

2.1. Patient Selection

The research study received approval from the Instituto Mexicano del Seguro Social, Hospital, Unidad Médica de Alta Especialidad Hospital de Ginecología y Obstetricia, No. 23 Bioethics and Research Committee [F-2021-1905-030]. The study was performed according to the Helsinki Declaration’s ethical principles and the nation’s standards. We utilized the Equator Network’s suggested guidelines for observational study design, specifically the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist [18]. For further details, please refer to Supporting Information 1.

The third-trimester patients included in the study were aged 18 and 38 years, recently admitted to labor, or scheduled for elective c-section. Exclusion criteria included patients with an active SARS-CoV-2 infection or those with a positive PCR test within 3 months of the previous evaluation; pregnant women with urinary tract infections, chorioamnionitis, preterm labor, multiple pregnancies, or fetal growth problems were also excluded. Pregnancy disorders such as preeclampsia, Lupus, antiphospholipid syndrome, concurrent antiplatelet therapy, signs of hepatic abnormalities, and patients with congenital or acquired coagulation disorders were also excluded. The research recruited 375 patient profiles who presented for delivery or cesarean section; however, only 280 patients met the established inclusion criteria, thus qualifying them for further analysis. Thirty-five women were excluded because they had a urinary tract infection recently. Twenty-one women were dealing with preeclampsia or other blood pressure problems that made them ineligible. Seventeen couldn’t participate as they were on antiplatelet medication. Fourteen women had multiple pregnancies. Fetal development issues ruled out three expectant mothers. Five cases were eliminated for other reasons. The consort flow diagram is included in Figure 2.

3. Results

The analysis included the clinical records and samples from those 280 patients in their third trimester who were either admitted to labor or underwent elective c-sections. These patients had a median age of 26 (IQR 22–31) and experienced at least two previous pregnancies (IQR 1–3). The demographic profiles, blood tests, and coagulation results obtained from the samples are presented in Table 1.

The viscoelastic analysis provided several essential parameters for the patient’s blood coagulation profile. Enzymatic activity was evaluated using the R-Time (R), which ranged between 1 and 7 min. Clot kinetics (K) were faster than the average adult, with a reference interval of 1–2  min. The rate of clot formation, measured as the angle (α), fell within the lower critical values, below 59 degrees of aperture. Typically, this value becomes apparent 5–8 min after clot initiation. The MA reference interval ranges from 60 to 86 mm. Clot lysis at 30 and 60 min exhibited similar values in healthy adults: 0%–6% and 0%–8%, respectively. Other important TEG parameters include curve amplitude at 30 min (A30) and amplitude at 60 min (A60); these figures closely align with the reference values derived from MA. Clot elastic strength (G) measurements in the patient’s samples went from 8 to 32 dyn/cm². The remaining reference intervals for the TEG parameters can be found in Table 2.

4. Discussion

This research provides significant evidence on the coagulation profile and reference values for pregnant women in their third trimester from the northeastern region of Mexico.

Interestingly, our study reveals differences between pregnant women in Mexico and those from other regions [17, 19–26]. In comparison with similar publications in terms of population and methodologies within the field, the R-Times (R) of our samples were significantly shorter than the published data (δ = −1.21, p < 0.001), even when compared to reports not utilizing citrate—Figure 3. Cloth kinetics (K) displayed minimal discrepancies with half of the published figures (the United States: Antony et al.; the United Kingdom: Shreeve et al.; ITA: Della Rocca et al.; The Czech Republic: Polak et al.; the United Kingdom.: Davies et al.). However, when categorized regionally, our patients presented shorter values compared to Europe (δ = −0.46, p < 0.001) or North America (δ = −1.17, p < 0.001)—Figure 4. Angle measurements (α) did not show differences in the same studies where cloth kinetics (K) did not. Nevertheless, our regional angle parameters differed from Europe’s (δ = 0.64, p < 0.001) while being similar to North America’s (δ = −0.22, p = 0.062) values—Figure 5. The MA of the curve in our samples exceeded most published data, apart from the MacAfee et al. (the United Kingdom.) report (δ = 0.05, p = 0.7584). Only the MA values from Fassoulaki et al. (Greece) were considerably larger than our regional amplitudes (δ = −1.57, p < 0.001). Our samples showed greater curve amplitude when compared to the European region (δ = 0.37, p = 0.001) and North America (δ = 0.75, p = 0.001) —Figure 6. At 30 min, cloth lysis varied regionally, displaying higher values than North American counterparts (δ = 0.42, p = 0.0048); however, there were no differences against all available data (δ = 0.1, p = 0.7219)—Figure 7.

Specifically, our patients demonstrated shorter R-Times, faster clotting kinetics, higher angle values, and clot amplitude compared to previously published data. These findings emphasize the importance of establishing distinct reference values for pregnant women in Mexico. As a result, we need to reassess transfusion thresholds for the use of plasma, platelets, and fibrinogen in third-trimester patients across our country or patients with Mexican backgrounds.

The changes observed with TEG mainly describe the intrinsic coagulation pathway behavior. The following areas summarize the coagulation changes in our sample: (1) increased enzymatic activity, (2) more significant platelet response, and (3) increased fibrinogen polymerization rate.

Increased enzymatic activity along the intrinsic pathway may explain the shorter R-Times observed in our patients. Variance in enzymatic activity between different populations has been reported by Cheung, Chay, and Ma who describe the diminished activity of coagulation factors II, V, VII, IX, and X among Chinese patients compared to Caucasian samples [27]. Moreover, Lutsey et al. sampled Caucasian, Hispanic, Chinese, and African-American ethnic groups and found significant differences in Factor VIII, Factor X, and thrombin activity in African-Americans [28]. Roberts et al. also found differences among the ethnic groups analyzed, with higher peak thrombin formation in African Caribbean groups [29]. The relevance of these changes in the coagulation profiles has led to new therapeutic discussions and redesign of antithrombotic therapy in Asiatic populations [30].

Platelet activity is a more intricate phenomenon that involves genetic, metabolic, and environmental factors. Under typical biological conditions, various platelet subsets have distinct aggregation rates, collagen reactivity, and biochemistry [31–33]. Nevertheless, ethnic differences in the aggregation pattern caused by the GPIIIa Pl^A1/A2 polymorphism increased the cardiovascular risk in White South African samples when contrasted against Indian or African subjects [34]. Herrera-Galeano et al. found that changes in the platelet endothelial aggregation receptor-1 are associated with variations in cell contact reactivity; the caucasian subjects showed increased aggregation and reduced response to aspirin [35]. Moreover, Garofano et al. found 480 differentially expressed platelet-associated genes among African-American and Caucasian individuals; however, they did not assess platelet function or the impact of genomic variation [36]. The platelet genetic polymorphisms translate into platelet function variations and influence interrelationships with other blood cells. For example, Allen et al. observed that activated platelets, their association with monocytes, and their pro-thrombotic and inflammatory properties are increased in healthy African-American individuals [37].

Fibrinogen bioavailability is an essential factor in thrombus formation, and the plasma concentrations modify its interaction with thrombin, platelets, membrane, and clot stabilization by Factor XIII [38]. The plasmatic levels have been reported to contrast between ethnic groups. The MESA study found greater fibrinogen levels in Black American and Hispanic samples [28]. Jeong et al. found that East Asians had lower plasma fibrinogen levels and lower MA of the TEG than Caucasian patients [39]. Genetic polymorphism in the subunit chains may influence the synthesis rate, polymerization, or crosslinking by FXIII. Standeven et al. reported that Aα Thr312Ala polymorphism increased fibrin diameter by facilitating FXIII’s enzyme activity [40]. Other conditions, like the β fibrinogen gene polymorphism, are frequent in the Japanese population and have been associated with the risk of stroke [41]. Canseco et al. studied Mexican patients and found that β fibrinogen 455 G/A and −148 C/T polymorphisms increased plasma fibrinogen levels.

Our findings showed increased coagulation dynamics and MA, representing increased enzymatic, fibrinogen, and platelet activity. However, the biological factors determining these changes in our sample should be an area of interest for future research.

5. Conclusion

In the sampled third-trimester obstetric patients from the Northern region of Mexico, reference values were estimated with high precision. These patients displayed heightened coagulation activity, characterized by shorter clot R-Times, quicker clot dynamics, larger angle values, overall greater curve amplitudes, and no significant differences in enzymatic lysis activity compared to samples from other geographic regions.

Disclosure

The funders had no role in the study design, data collection, analysis, interpretation, writing of the report, or decision to submit the paper for publication.

Conflicts of Interest

The authors declare no conflicts of interest.

Funding

This study was supported by internal funding from Instituto Mexicano del Seguro Social, and no external financial or material supports were provided.

Supporting Information

The sequential explanation of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist has been appended as supporting information for additional guidance. We provide this document to give an overview of how we make our research adhere to the guidelines set forth by the STROBE initiative, aiming to enhance the transparency and quality of reporting in observational studies.