Postpartum haemorrhage (PPH) is a bleeding complication that accounts for approximately one in four maternal deaths, making it the most common cause of maternal death worldwide (Kassebaum et al., 2014). The incidence rate in developed countries has increased in recent years, related primarily to an increase in the use of oxytocin for progressing labour (Belghiti et al., 2011). PPH is usually the result of uterine atony, but may be due to uterine rupture, abnormal placentation, placental abruption, genital tract trauma and coagulation defects (Abdul-Kadir et al., 2014). Comorbidities such as foetal death can also impact on PPH severity.
During pregnancy, several haemostatic changes induce a prothrombotic state, with an increase in fibrinogen and procoagulation factors, and a decrease in anticoagulants (O'Riordan & Higgins, 2003; Brenner, 2004). This implies an inherent importance for hypercoagulability in women giving birth, supported further by the fact that both primary and secondary coagulopathies are risk factors for PPH (Cortet et al., 2012).
Fibrinogen levels increase during pregnancy by about 2 g/L overall, to an average of 5 g/L at nine months (Simon et al., 1997; Huissoud et al., 2009). As with other traumas involving major blood loss, fibrinogen is one of the first coagulants to drastically decrease in PPH (Chauleur et al., 2008; de Lloyd et al., 2011). Indeed, this loss may be due to both dilutional and consumptive coagulopathies such as DIC and hyperfibrinolysis (Roberts et al., 2018).
In the last decade, studies have been documenting the correlation between fibrinogen levels and PPH severity and the role for fibrinogen as a diagnostic indicator. In an early study, a fibrinogen level of less than 2 g/L, measured at the point of uterotonic treatment, was found to be 100% predictive of severe PPH. The same study showed that each 1 g/L decrease in fibrinogen leads to an approximately 2.6-fold increase in risk for severe PPH (Charbit et al., 2007). This finding was reiterated in the 2012 Cortet study, in which fibrinogen levels were correlated to the severity of PPH in women who took part in the PITHAGORE6 trial (Deneux-Tharax et al., 2010; Cortet et al., 2012). Women with PPH who did not progress to severe PPH had a mean fibrinogen level of 4.2 g/L versus the 3.4 g/L measured in those who experienced severe PPH (p<0.001). Fibrinogen level was associated to PPH severity independently of other factors with an odds ratio of 1.9 for fibrinogen levels of 2–3 g/L, and 11.99 for fibrinogen <2 g/L.
In a more recent prospective study of 809 patients who underwent vaginal deliveries, the difference in predelivery fibrinogen levels for PPH and severe PPH was slightly less but still significant (4.67 g/L and 4.22 g/L, respectively; p=0.004; where incidence rates were 12% and 3.5%) (Niepraschk-von Dollen et al., 2016).
Other risk factors for the progression of PPH to severe PPH include increasing age and obstetric comorbidities such as foetal death, myomas and placenta previa. Only fibrinogen levels are modifiable in a clinical setting and therefore fibrinogen monitoring should be standardised for patients who present additional non–modifiable risk factors (Guasch & Gilsanz, 2016).
Fibrinogen levels are easily modifiable in practice. Fibrinogen monitoring should therefore be standard practice for patients that present comorbidities.
Whilst further investigation is required to understand fully whether low fibrinogen levels are causative in the onset of PPH, there is strong evidence that fibrinogen levels serve as an early diagnostic marker for PPH severity. Given that fibrinogen is critical for clot formation in coagulation, PPH patients are often treated with fibrinogen replacement therapies. This will be discussed more extensively in the treatment section.
Abnormal fibrinogen function is common in most patients of cirrhosis, chronic active liver disease and hepatic failure. End stage liver disease (ESLD) can negatively impact on fibrinogen synthesis and metabolism. ESLD patients tend to have normal to high levels of plasma fibrinogen; however, there are scenarios where ESLD patients present either high levels of fibrinogen degradation products indicating hyperfibrinolysis or acquired hypofibrinogenaemia with fibrinogen levels of less than 0.8–1.0 g/L (Saner & Kirchner, 2016).
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