TY - JOUR
T1 - Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage
T2 - randomized controlled trial
AU - Wikkelsø, A J
AU - Edwards, H M
AU - Afshari, A
AU - Stensballe, J
AU - Langhoff-Roos, J
AU - Albrechtsen, C
AU - Ekelund, Kim
AU - Hanke, G
AU - Secher, E L
AU - Sharif, H F
AU - Pedersen, Lars Møller
AU - Troelstrup, Ane
AU - Lauenborg, Jeannet
AU - Mitchell, A.U.
AU - Fuhrmann, Lone
AU - Svare, J
AU - Madsen, M G
AU - Bødker, B
AU - Møller, A M
AU - FIB-PPH trial group
N1 - © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: [email protected].
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Background In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. Methods In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre-1, RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre-1, transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. Results Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre-1. The intervention group received a mean dose of 26 mg kg-1 fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre-1 (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. Conclusions We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. Clinical trial registration ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.
AB - Background In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. Methods In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre-1, RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre-1, transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. Results Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre-1. The intervention group received a mean dose of 26 mg kg-1 fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre-1 (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. Conclusions We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. Clinical trial registration ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.
KW - Double-Blind Method
KW - Erythrocyte Transfusion
KW - Female
KW - Fibrinogen
KW - Hemostasis
KW - Humans
KW - Postpartum Hemorrhage
KW - Pregnancy
KW - Treatment Outcome
U2 - 10.1093/bja/aeu444
DO - 10.1093/bja/aeu444
M3 - Journal article
C2 - 25586727
SN - 0007-0912
VL - 114
SP - 623
EP - 633
JO - British Journal of Anaesthesia
JF - British Journal of Anaesthesia
IS - 4
ER -