There are a multitude of causes of bleeding during pregnancy. Coagulopathy may occur alongside haemorrhage due to dilution and / or consumption of clotting factors. Rotational thromboelastometry (ROTEM) testing can provide rapid ‘point of care’ assessment of coagulation, and this may be used to guide treatment during obstetric haemorrhage. At Liverpool Women’s Hospital, we routinely use ROTEM values to guide treatment of coagulopathy in major haemorrhage.
Pregnancy is a hypercoaguable state, which confers some protection against haemorrhage at the time of delivery and in the immediate post partum period. In general pro-coagulant levels increase and anti-coagulant levels decrease. The role of fibrinogen is particularly important in providing this protection with fibrinogen levels being greatly elevated by term.
Previously published references ranges2 for ROTEM during pregnancy have been derived from pregnant women in the third trimester, and are hypercoaguable compared to non-pregnant individuals. However, massive haemorrhage may also occur at much earlier gestations. In the first trimester, rupture of ectopic pregnancy, termination of pregnancy or miscarriage can result in life threatening bleeding. During the second trimester conditions such as placenta praevia, preecplamsia and placental abruption are associated with a significant risk of caesarean section and haemorrhage.
In order to be able to appropriately interpret ROTEM results at earlier gestations of pregnancy, we wished to determine, for the first time ever, reference ranges for pregnant women during the first and second trimesters.
The aim was to determine normal ranges for ROTEM parameters, for women in the first, second and third trimesters of pregnancy.
Ethical approval was granted by a regional ethics committee. Pregnant women were recruited into three groups according to trimester of pregnancy, plus a control group of age matched non-pregnant women.
Women with known coagulopathies, conditions associated with coagulopathy or taking medications affecting coagulation were excluded.
Following informed consent, citrated blood was sampled for ROTEM® testing with EXTEM® and FIBTEM ®reagents, Clauss fibrinogen and full blood count.
ROTEM parameters recorded were;
EXTEM®: Clotting time (CT), Clot amplitude at five minutes post CT (A5), Maximum clot firmness (MCF)
FIBTEM®: A5 and MCF.
Results from the four groups were compared using ANOVA and Dunn’s multiple comparison testing to determine whether the groups were significantly different.
Median, 2.5 and 97.5 percentiles were calculated for each parameter for each group.
316 women were recruited. One patient was excluded due to an inadequate sample. These were grouped as first (T1, n=99), second (T2, n=60), third (T3, n=80) trimester and control (C, n=75)
Whilst there was no significant difference in FIBTEM values between control and first trimester groups, by the second trimester a significant increase was seen.
Both FIBTEM A5 and MCF values were statistically different compared with controls (p<0.0001).
A further increase occurred between second and third trimesters (p<0.05) FIBTEM A5 18(7-31) and MCF 23(8-49).
Plasma fibrinogen levels also increased from non-pregnant levels with each stage of pregnancy. This mirrored the changes seen in FIBTEM values.
EXTEM® A5 and MCF were significantly increased in pregnancy versus the non-pregnant group, with the major increase being from the second trimester onwards (first trimester A5 median (2.5-97.5th centile) 44mm (30-54), third trimester A5 49mm (31-63), p<0.0001).
EXTEM® CT was reduced in pregnancy from the first trimester and did not significantly differ from then on (control 56s (49-65), first trimester 51s (47-56)).
ROTEM® provides rapid assessment of maternal coagulation status. In this study, we have demonstrated significant differences in normal ROTEM values between trimesters. This has implications for using ROTEM values to guide treatment in women who haemorrhage during the first and second trimesters. The observed changes in FIBTEM A5 and MCF paralleled changes in plasma fibrinogen, consistent with previous studies.3
At Liverpool Women’s Hospital we use a ROTEM® guided major haemorrhage pathway for treatment of coagulopathy, in particular fibrinogen replacement is guided by FIBTEM values. This is currently based upon term reference ranges, but the information provided by this study will allow us to tailor treatment further in women who suffer major haemorrhage in the early stages of pregnancy.
Based upon our results, we suggest that FIBTEM values in the first trimester can be compared to non-pregnant normal ranges. For women who bleed during the second trimester, a separate reference range may be useful. This will enable optimal goal directed therapy for major haemorrhage throughout pregnancy, potentially reducing the risk of thromboembolic complications.
1 Simon L, Santi TM, Sacquin P, Hamza J. Pre-anaesthetic assessment of coagulation abnormalities in obstetric patients: usefulness, timing and clinical implications. British Journal of Anaesthesia. 1997 Jun;78(6):678–83.
2. Armstrong S, Fernando R, Ashpole K, Simons R, Columb M. Assessment of coagulation in the obstetric population using ROTEM. International Journal of Obstetric Anesthesia. Elsevier Ltd; 2011 Oct 1;20(4):293–8.
3. Huissoud C, Carrabin N, Audibert F, et al. Bedside assessment of fibrinogen level in postpartum haemorrhage by thrombelastometry. Br J Obstet Gynaecol 2009 May 14;116(8):1097–102.