Pregnancy and post-partum
anaemia, need for transfusion and
invasive procedures, and maternal
morbi-mortality: Hb drop compared with
the reference level, percentage of patients
developing anaemia (Hb < 8g/dl),
requirement for PRBC transfusion or any
other blood products, requirement of
intrauterine balloon tamponade and/or
invasive procedure (arterial ligature, or
embolisation, or hysterectomy), and
calculated blood loss.
Regarding the population selection,
evidence has shown that fibrinogen
supplementation may be more efficient in
patients with hypofibrinogenemia. The
study population may therefore be better
selected among patients with quite severe
PPH at risk of developing coagulopathy.
The criteria of selection was to enrol
patients at the beginning of prostaglandin
(sulprostone; Nalador ® ) administration,
which is a time-validated second step of
uterotonic treatment in the algorithm of
the French PPH management guidelines
(30 French guidelines). Prostaglandins
are advocated after no more than 30
minutes of ongoing PPH and oxytocin
failure. This inclusion criterion has been
used previously. 4 Randomisation
stratification by centres should protect
against the bias of variable team
reactivity times in taking the decision
for oxytocin–prostaglandin switch.
Thromboelastometric identification of
coagulopathic patients was not chosen in
the FIDEL protocol because most of the
centres are not equipped to perform this.
18
Which fibrinogen concentrate dose
to stop bleeding?
The fibrinogen dose administered
depends on the severity of haemorrhage
as well as on the initial plasma level.
Grottke demonstrated that a single dose
of 2g and a target level of 1.5g/l was able
to avoid death in an experimental design
of liver injury in pigs. 9 In cases of severe
acute obstetrical haemorrhage, larger
doses of fibrinogen concentrate (4–8g)
might be necessary. In a study by Kikuchi
et al, 1g fibrinogen concentrate increased
the plasma fibrinogen level to
approximately 400mg/l only. 24 Makino et
al obtained a similar increase of 32mg/
dl/g fibrinogen concentrate administered,
which was not sufficient to properly
correct severe hypofibrinogenemia in
deep coagulopathic atonic patients. 25 The
FIDEL trial aims to determine the more
efficient place of a 3g dose of fibrinogen
concentrate infusion, likely by
administering it earlier in coagulopathic
hospitalpharmacyeurope.com
patients before PPH becomes life-
threatening. This dose was selected on the
basis of an anticipated amount of blood loss
and corresponding fibrinogen loss at the
time of prostaglandin administration.
Because the main objective of the study is to
assess the benefit associated with an early
administration of fibrinogen as a
therapeutic strategy, the 3g dose required
in the protocol is lower than the 4–8g dose
recommended in the Summary of Product
Characteristics to treat the most severe
PPH. Additional open-label administrations
of fibrinogen concentrate will be allowed in
both groups, as a rescue therapy, if the
severity of the clinical situation requires it,
and as per investigator discretion.
Conclus