Severe haemorrhage remains the leading cause of maternal mortality worldwide. International guidelines recommend the use of viscoelastic testing to guide post‐partum haemorrhage (PPH) treatment [1]. Unlike traditional assays, viscoelastic testing uses whole blood and provides real‐time clotting data, enabling faster decisions. Viscoelastic testing results correlate with fibrinogen levels and help predict PPH progression and outcomes [2, 3]. Previous studies used older devices like ROTEM® (Werfen, Barcelona, Spain) or TEG® (Haemonetics Corporation, Boston, MA, USA) but not the newer ClotPro® (Haemonetics Corporation). This shares key features with ROTEM yet may yield different results; thus, ClotPro‐specific reference ranges are needed [2, 3, 4]. This study aimed to establish corresponding reference ranges in parturients using the ClotPro device.
We report data from a prospective observational study conducted between May 2023 and January 2024 at the University Hospital Brno, Czech Republic. Ethical approval was granted by the Ethics Committee of University Hospital Brno and all women studied provided informed consent. The study group comprised healthy women admitted to the hospital for labour at physiological term (≥ 38 weeks gestation), aged 18–45 y with a pre‐pregnancy BMI of 18.5–30.0 kg.m‐2 and who had blood samples collected before onset of labour. The study blood sample was collected in a coagulation tube (S‐Monovette® Citrate 9NC/3.0 ml; Sarstedt AG, Nümbrecht, Germany), inverted gently several times, immediately transported and analysed within 2 h with the ClotPro device by a trained anaesthetist. Three basic viscoelastic tests to evaluate the extrinsic (EX‐test) and intrinsic (IN‐test) coagulation pathways, as well as fibrinogen function (FIB‐test), were performed. Reference ranges for ClotPro parameters were determined according to International Federation of Clinical Chemistry and Laboratory Medicine guidelines by calculation of percentiles 2.5 and 97.5 [5]. A 90%CI for both the lower and upper limits was calculated according to 5000 bootstrap resamples with replacement from the original dataset. We compared our ClotPro reference ranges for this population with those established using the ROTEM device, as well as with the manufacturer‐provided ClotPro reference ranges.
A total of 130 participants were analysed; 19 were admitted for caesarean section and 111 for spontaneous labour; mean (SD) age was 31 (4.4) y and pre‐pregnancy BMI 23.5 (3.32) kg.m‐2. Table 1 shows the reference ranges of ClotPro parameters for the EX‐test, IN‐test and FIB‐test in the study population. The following reference ranges are considered clinically relevant in routine practice: EX‐test clotting time (39–67 s); amplitude at 5 min (39–59 mm); maximum clot firmness (57–70 mm); maximum lysis (1–9%). IN‐test clotting time (121–172 s); FIB‐test amplitude at 5 min (15–29 mm); and maximum clot firmness (19–35 mm). Table 1 includes a comparison with the general reference ranges from the manufacturer for ClotPro and the peri‐partum reference ranges for ROTEM.
Table 1.
Comparison of reference ranges.
| Parameter | ClotPro® for parturient population | ClotPro® manufacturer | ROTEM® [6] | |
|---|---|---|---|---|
| Lower limit (CI*) | Upper limit (CI*) | Reference range | Reference range | |
| EX‐test | EXTEM | |||
| Clotting time; s | 39 (37–41) | 67 (63–69) | 38–65 | 31–63 |
| Clot formation time; s | 33 (30–35) | 102 (80–130) | 42–93 | 41–120 |
| A5; mm | 39 (35–43) | 59 (58–60) | 39–58 | ‐ |
| A10; mm | 49 (45–53) | 66 (65–66) | 47–64 | 48–74 |
| A20; mm | 55 (52–59) | 69 (69–69) | 52–67 | 47–78 |
| Maximum clot firmness; mm | 57 (53–60) | 70 (69–72) | 53–68 | 42–78 |
| Maximum lysis; % | 1 (1–1) | 9 (8–10) | 2–12 | 0–41 |
| IN‐test | INTEM | |||
|---|---|---|---|---|
| Clotting time; s | 121 (114–128) | 172 (166–180) | 139–187 | 109–225 |
| Clot formation time; s | 37 (37–42) | 100 (80–118) | 52–139 | 40–103 |
| A5; mm | 36 (34–41) | 58 (55–59) | 32–53 | ‐ |
| A10; mm | 45 (44–50) | 65 (63–65) | 41–61 | 55–72 |
| A20; mm | 52 (50–55) | 68 (67–69) | 48–65 | 62–77 |
| Maximum clot firmness; mm | 53 (51–56) | 69 (67–69) | 49–65 | 63–78 |
| Maximum lysis; % | 2 (1–2) | 11 (10–12) | 1–11 | 0–15 |
| FIB‐test | FIBTEM | |||
|---|---|---|---|---|
| Clotting time; s | 36 (35–38) | 74 (67–77) | 55–87 | 31–79 |
| A5; mm | 15 (14–15) | 29 (26–30) | 6–21 | ‐ |
| A10; mm | 16 (16–17) | 31 (28–32) | 7–23 | 12–38 |
| A20; mm | 18 (17–19) | 32 (29–34) | 8–25 | 13–40 |
| Maximum clot firmness; mm | 19 (17–21) | 35 (32–37) | 9–27 | 13–45 |
90% Confidence limits based on bootstrap resampling.
EX‐test and EXTEM, extrinsic pathway specific test; IN‐test and INTEM, intrinsic pathway specific test; FIB‐test and FIBTEM, fibrinogen‐specific test; A5, A10, A20, amplitude at 5, 10 and 20 min, respectively.
We established ClotPro reference values by analysing physiological parameters in women admitted for labour or elective caesarean delivery in cases of uncomplicated pregnancies. Compared with the manufacturer‐provided reference values, the ClotPro ranges established in our study differed in clotting time for the IN‐test and FIB‐test; clot formation time for the EX‐test and IN‐test; and amplitude values for the EX‐test and IN‐test. The most significant difference was seen in the fibrinogen‐specific test, the lower limit of which was as much as twice the manufacturer‐provided value, thereby suggesting a substantial shift in the threshold for fibrinogen supplementation. Compared with the peri‐partum ROTEM values established by de Lange et al. [6], our ClotPro reference ranges in labouring women differed across all parameters, particularly in the fibrinogen‐specific test, in agreement with previous studies [2, 4, 6]. Consequently, the reference ranges for parturients cannot be used interchangeably between the ClotPro and ROTEM devices.
The study has several limitations. First, the group consisted of slightly different subgroups, namely labouring and non‐labouring women before caesarean delivery. Second, the blood sampling timing was not strictly standardised. However, both limitations have not been found to have clinically significant effects [6, 7].
The ClotPro reference ranges established in our study address an important knowledge gap regarding its use in parturients. They may serve as a basis for developing a PPH management algorithm, similar to how the ROTEM reference ranges established by de Lange et al. have been applied, as they reflect the physiological changes in coagulation among parturients [6]. Currently, an updated version of the ClotPro device, named MultiClot® and compatible with the original system, has been developed recently and is currently undergoing the registration process. Its new assays will be fully compatible with ClotPro and are expected to be registered and released in 2025.
Acknowledgements
The study was registered at ClinicalTrials.gov (NCT05935137). The authors would like to thank Katerina Vanickova, Radka Stepanova, Martin Janku, Veronika Koci, Jana Cernanova, Lucie Cuperova and the staff of the Department of Obstetrics and Gynaecology and the staff of the Emergency Department, University Hospital Brno for their collaboration and support throughout the study. The publication was written with the support of the Specific University Research provided by the Ministry of Education, Youth and Sports, Czech Republic. The project was supported by the Ministry of Health, Czech Republic—conceptual development of research organisation. In the past 5 years, KV and RG have received honoraria for lecturing from CSL Behring. KV has received honoraria for lecturing from A.M.I., s.r.o. No other competing interests declared. Open access publishing facilitated by Masarykova univerzita, as part of the Wiley ‐ CzechELib agreement.
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