was the sole independent predictive factor for
poor outcome. 4 A plasma fibrinogen level under
a 2g/l threshold showed a predictive value for
progression toward severe bleeding of 100%
(CI 95% 79–100). This level was higher than the
‘historical’ threshold of <1g/l, which indicated
in the general population the need to initiate
replacement therapy, or the 1.5g/dl threshold
identified by Grottke et al in an experimental
animal setting. 9 This higher threshold could be
explained by a higher than normal plasma
fibrinogen level during pregnancy and the
post-partum period. 10 An analysis by Cortet et al
of 738 women with PPH clearly confirmed the
importance of fibrinogen levels. 11 The mean
plasma fibrinogen concentration at diagnosis
was 4.2g/l (SD= 1.2g/l) among patients without
worsening, and 3.4g/l (SD=0.9g/l; p<0.001) in the
group developing severe PPH. The plasma
fibrinogen level was again associated with PPH
severity, independently of other factors, with
an adjusted odds ratio of 1.90 (1.16–3.09) for
fibrinogen levels between 2 and 3g/l, and 11.99
(2.56–56.06) for fibrinogen levels <2g/l. de Lloyd
et al identified fibrinogen <1.5g as a marker of
severity in patients admitted to the ICU. 12 Gayat
et al identified fibrinogen decrease as a major
component of a score to predict the need for
invasive procedures. 13 Moreover, a plasma
fibrinogen level has been implicated as an
independent factor of intrauterine balloon. 14
With a high level of evidence, an early fibrinogen
decrease and a FIBTEM 5 minutes amplitude
were identified as a predictor of morbidity. 15–17
Correcting plasma fibrinogen levels
Two serases are able to digest fibrinogen:
thrombin (inhibitor: antithrombin) and plasmin
(inhibitor: antiplasmin) and there are several
ways to supplement its decrease. 18,19 Tranexamic
16
HHE 2018 | hospitalhealthcare.com
acid is an antifibrinolytic drug blocking the
ternary (tissue plasmin activator–plasminogen–
fibrin) complex link. After a first positive
high-dose trial, 20 use of tranexamic acid became
more popular due to the results of a large
international placebo-controlled, randomised
controlled trial (RCT) – the WOMAN trial – which
demonstrated a reduction in mortality due
to bleeding. However in the WOMAN trial,
mortality rate was as high as 2.3% because
recruitment was mostly conducted in developing
countries and neither mortality nor hysterectomy
rate were reduced in the treatment group. 21
As an antifibrinolytic drug, tranexamic acid
inhibits plasmin peak and fibrinolysis with
no influence on fibrinogen. 5 Hence, fibrinogen
supplementation is a specific part of the
treatment of coagulopathy.
To supplement fibrinogen plasma
concentration, three blood products (plasma,
cryoprecipitate or fibrinogen concentrates) are
available. 18,22 Due to their concentration ratios,
the volumes needed to increase plasma levels by
1g are 2400ml, 400ml and 100ml, for fresh frozen
plasma, cryoprecipitate and fibrinogen
concentrate, respectively. 22
Fibrinogen supplementation in PPH
The role of fibrinogen supplementation
in the management of PPH has been studied. 23–27
Efficacy of fibrinogen concentrate
supplementation in PPH is demonstrated in case
reports in various clinical settings. Ahmed et al
retrospectively compared two periods of
fibrinogen replacement using cryoprecipitate
(n=14) or fibrinogen concentrate (n=20) in 77 cases
of massive obstetric haemorrhages out of 21,614
deliveries. Clinicians used a mean dose of 2.21 ±
0.35 pools of cryoprecipitate or 4 ± 0.8g
fibrinogen concentrates. The mean estimated