Early viscoelastometric point-of-care testing during postpartum haemorrhage

Early viscoelastometric point-of-care testing during postpartum haemorrhage

Ramler PI, Gillissen A, Henriquez DDCA, Caram-Deelder C, Markovski AA, et al. Acta Obstetricia et Gynecologica Scandinavica. 2021;100(9), 1656-1664. doi: 10.1111/aogs.14172.

• This prospective cohort study evaluated FIBTEM A5 as a potential early point-of-care parameter to predict progression to severe postpartum haemorrhage, and compared its predictive value with that of the conventional Clauss fibrinogen assay
• In standard clinical care, FIBTEM 5 may be a poor predictor of bleeding progression at onset of postpartum haemorrhage
• However, FIBTEM 5 may be a useful point-of-care test for women with ongoing haemorrhage >1500 ml of blood loss

Globally, postpartum haemorrhage is the principal cause of maternal mortality (Kassebaum et al., 2013; Brace et al., 2004; Zwart et al., 2008; Callaghan et al., 2008), with research indicating that in blood samples taken during postpartum haemorrhage, fibrinogen concentration of ≤2 g/L correlates with bleeding severity (Charbit et al., 2007; Cortet et al., 2012; de Lloyd et al., 2011; Gillissen et al., 2018). Current coagulation detection methods take at least one hour to produce results, and are therefore not useful predictors of bleeding progression and cannot be relied upon to guide timely haemostatic intervention during the acute phase of postpartum haemorrhage (Toulon et al. 2009; Solomon et al., 2012).

In this multicentre prospective cohort study, FIBTEM A5 (rotational thromboelastometry [ROTEM^®, Tem International GmbH, Munich, Germany] fibrin-based assay amplitude of clot firmness at five minutes) was explored as a potential point-of-care diagnostic to predict progression to severe postpartum haemorrhage (SPPH). Previous studies have shown that FIBTEM A5 results correspond positively with fibrinogen concentrations from plasma obtained during pregnancy and postpartum blood loss, and unlike common coagulation tests such as the Clauss fibrinogen assay, FIBTEM A5 results can be available in just 10–15 minutes (Huissoud et al., 2009a; Huissoud et al., 2009b). 

Based on earlier research conducted by Collins et al. (2014) which indicated it could predict postpartum haemorrhage progression, the researchers sought to explore whether FIBTEM A5 could be used in standard care, as a predictive diagnostic during postpartum haemorrhage onset to differentiate between women who progress to severe haemorrhage and those who do not. This study also compared FIBTEM A5’s value as a predictive diagnostic to the Clauss fibrinogen assay.

What did the researchers do?

A total of 391 women were included in the study, which was part of a larger study, Towards better prognostic and diagnostic strategies for Major Obstetric Haemorrhage (TeMpOH-2). Study participants were recruited from three hospitals in the Netherlands, all being aged ≥18 (median age, 32, range 28–35) and pregnant with gestational age of ≥24 weeks. They were monitored for postpartum haemorrhage, defined as ≥1000 ml blood loss within 24 hours of childbirth, and followed until discharge.

Consecutive blood samples were taken to measure blood loss, and total blood loss was measured once bleeding stopped. At least one blood sample between 800–1500 ml of blood loss was to be taken from each participant prior to fibrinogen concentrate and blood component administration, to measure full blood count, fibrinogen using the Clauss method (Stang et al., 2013), and FIBTEM A5 using a ROTEM^® Delta device (Tem International GmbH). In line with Dutch and English guidelines, in cases where women had multiple samples taken in this range the first sample >1000 ml was analysed. Excluded from the analysis were women with a known coagulation disorder or who had used anticoagulants. In addition, maternal and obstetric features were collected.

SPPH was defined as per Table 1.

Table 1. Severe postpartum haemorrhage definition.

Table 2 outlines the methods used to investigate the study’s aims.

Table 2. The aims and analytical methods employed in the study. FIBTEM A5, rotational thromboelastometry fibrin-based assay amplitude of clot firmness at five minutes.

A subgroup analysis of predictive value of FIBTEM A5 and fibrinogen was conducted for women whose blood samples were taken between 1000–1500 ml of blood loss, which aligns with Dutch and English guidelines for coagulation testing when blood loss is >1000 ml. STATA statistical software was utilised for all analyses.

What were the findings?

SPPH occurred in 72 women (18%), with median (interquartile ranges, IQR) total blood loss being 1400 ml (1100–2000). Sixty-six (17%) women had >2000 ml of total blood loss, and in 13 (3%) of women, ≥4 packed red blood cells were transfused.

There was moderate correlation (r_s = 0.53) between FIBTEM A5 values and concentration of fibrinogen.

For blood loss between 800–1500 ml, the AUC was 0.58 (95% CI, 0.50–0.65) for progression to SPPH for fibrinogen, and 0.53 (95% CI, 0.46–0.61) for FIBTEM A5 (Figure 1).

Figure 1. Fibrinogen and FIBTEM A5 ROC curves for progression to severe postpartum haemorrhage within the range of 800–1500 ml blood loss following birth. FIBTEM A5, rotational thromboelastometry fibrin-based assay amplitude of clot firmness at five minutes; ROC, receiver operating characteristics.

Outcomes for fibrinogen indicated an AUC for progression to:

• total blood loss >2000 ml of 0.55 (95% CI, 0.47–0.62)
• ≥4 packed red blood cells of 0.63 (95% CI, 0.44–0.81)
• any invasive intervention of 0.59 (95% CI, 0.42–0.75)

Outcomes for FIBTEM A5 indicated an AUC for progression to:

• total blood loss >2000 ml of 0.50 (95% CI, 0.42–0.58)
• ≥4 packed red blood cells of 0.51 (95% CI, 0.33–0.70)
• any invasive intervention of 0.53 (95% CI, 0.38–0.68)

For measurements between 800–1500 ml of blood loss, fibrinogen concentration ≤2 g/L had a positive predictive value to indicate SPPH of 50% (95% CI, 25–75), while the predictive value of FIBTEM A5 ≤12 mm was just 22.5% (95% CI, 14–33)

Results from the subgroup analysis (n=306), in which samples were taken between 1000–1500 ml of blood loss, revealed that AUC values for progression to the severe level of blood loss correlated with the measurements taken between 800–1500 ml blood loss (0.57; 95% CI, 0.49–0.65 for fibrinogen, and 0.55; 95% CI, 0.47–0.64 for FIBTEM A5). 

What were the main conclusions?

When used as part of standard care, FIBTEM A5 is not considered a reliable test to predict progression of bleeding at postpartum haemorrhage onset, particularly in women with total blood loss <1500 ml. However, it may be a useful diagnostic to help guide clinical decision making in women with >1500 ml blood loss or at high risk of coagulopathy. The researchers highlight the need for further investigation before FIBTEM A5 forms part of standard care for postpartum haemorrhage, due to its high cost and only moderate correlation between FIBTEM A5 values and concentration of fibrinogen.

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