Recombinant coagulation factor VIIa
In refractory cases of PPH, medical interventions aimed at addressing coagulopathy may be considered. Among these options is recombinant activated factor VIIa (known as eptacog alfa in some countries).[36]Muñoz M, Stensballe J, Ducloy-Bouthors AS, et al. Patient blood management in obstetrics: prevention and treatment of postpartum haemorrhage. A NATA consensus statement. Blood Transfus. 2019 Mar;17(2):112-36.
https://www.bloodtransfusion.it/bt/article/view/243
http://www.ncbi.nlm.nih.gov/pubmed/30865585?tool=bestpractice.com
It is approved in Europe for the treatment of severe PPH when uterotonics are insufficient to achieve haemostasis. However, it is not approved in the US for this indication, although it is sometimes used off-label.[146]Murakami M, Kobayashi T, Kubo T, et al. Experience with recombinant activated factor VII for severe post-partum hemorrhage in Japan, investigated by Perinatology Committee, Japan Society of Obstetrics and Gynecology. J Obstet Gynaecol Res. 2015 Aug;41(8):1161-8.
https://obgyn.onlinelibrary.wiley.com/doi/10.1111/jog.12712
http://www.ncbi.nlm.nih.gov/pubmed/26013425?tool=bestpractice.com
[147]Phillips LE, McLintock C, Pollock W, et al. Recombinant activated factor VII in obstetric hemorrhage: experiences from the Australian and New Zealand Haemostasis Registry. Anesth Analg. 2009 Dec;109(6):1908-15.
https://journals.lww.com/anesthesia-analgesia/fulltext/2009/12000/recombinant_activated_factor_vii_in_obstetric.29.aspx
http://www.ncbi.nlm.nih.gov/pubmed/19923520?tool=bestpractice.com
While some studies have suggested a potential decrease in the overall need for blood product transfusion during acute haemorrhage with factor VIIa, a significant survival advantage has not been conclusively established.[141]Pacheco LD, Saade GR, Hankins GDV. Medical management of postpartum hemorrhage: an update. Semin Perinatol. 2019 Feb;43(1):22-6.
http://www.ncbi.nlm.nih.gov/pubmed/30503399?tool=bestpractice.com
The use of factor VIIa is limited by the heightened risk of thrombosis. Further research is needed to establish its safety profile and efficacy specifically for treating PPH. Nonetheless, in rare circumstances where immediate access to blood bank resources is constrained, it holds potential as an adjunct to massive transfusion protocols for prompt correction of coagulopathy, but must not delay, or be considered a substitute for, a life-saving procedure such as embolisation or surgery.[4]Royal College of Obstetricians and Gynaecologists. Prevention and management of postpartum haemorrhage: green-top guideline no. 52. BJOG. 2017 Apr;124(5):e106-49.
https://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.14178
http://www.ncbi.nlm.nih.gov/pubmed/27981719?tool=bestpractice.com
Careful consideration of risks and benefits is essential and a lower dose can help minimise the risk of thrombosis.[3]Committee on Practice Bulletins-Obstetrics. Practice bulletin no. 183: postpartum hemorrhage. Obstet Gynecol. 2017 Oct;130(4):e168-86.
http://www.ncbi.nlm.nih.gov/pubmed/28937571?tool=bestpractice.com
[107]Pacheco LD, Saade GR, Costantine MM, et al. An update on the use of massive transfusion protocols in obstetrics. Am J Obstet Gynecol. 2016 Mar;214(3):340-4.
http://www.ncbi.nlm.nih.gov/pubmed/26348379?tool=bestpractice.com
[141]Pacheco LD, Saade GR, Hankins GDV. Medical management of postpartum hemorrhage: an update. Semin Perinatol. 2019 Feb;43(1):22-6.
http://www.ncbi.nlm.nih.gov/pubmed/30503399?tool=bestpractice.com
[148]Lavigne-Lissalde G, Aya AG, Mercier FJ, et al. Recombinant human FVIIa for reducing the need for invasive second-line therapies in severe refractory postpartum hemorrhage: a multicenter, randomized, open controlled trial. J Thromb Haemost. 2015 Apr;13(4):520-9.
https://www.jthjournal.org/article/S1538-7836(22)08387-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25594352?tool=bestpractice.com
[149]Ghadimi K, Welsby IJ. Pro: factor concentrates are essential for hemostasis in complex cardiac surgery. J Cardiothorac Vasc Anesth. 2018 Feb;32(1):558-64.
http://www.ncbi.nlm.nih.gov/pubmed/29217233?tool=bestpractice.com
Fibrinogen concentrates
Early activation of fibrinolysis during haemorrhage leads to a decline in serum fibrinogen levels, which serves as an early indicator of severe PPH. Replacing or augmenting fibrinogen levels is crucial for clot formation, and it has been established as an independent predictor of mortality in patients with major trauma.[150]McQuilten ZK, Bailey M, Cameron PA, et al. Fibrinogen concentration and use of fibrinogen supplementation with cryoprecipitate in patients with critical bleeding receiving massive transfusion: a bi-national cohort study. Br J Haematol. 2017 Oct;179(1):131-41.
http://www.ncbi.nlm.nih.gov/pubmed/28653339?tool=bestpractice.com
Maintaining fibrinogen levels above 2 g/L (200 mg/dL) is typically recommended, and cryoprecipitate has traditionally been used for fibrinogen replacement. However, cryoprecipitate has limitations, including the need for thawing before use and the potential for viral transmission.[151]Franchini M, Lippi G. Fibrinogen replacement therapy: a critical review of the literature. Blood Transfus. 2012 Jan;10(1):23-7.
https://www.bloodtransfusion.it/public/pre2018archives/2012/BloodTransfus2012_Vol10_Issue_1_023-027_015-11.pdf
http://www.ncbi.nlm.nih.gov/pubmed/22153684?tool=bestpractice.com
Fibrinogen concentrates undergo viral inactivation during the manufacturing process, resulting in an improved safety profile, and are available for immediate use at room temperature. Limited studies on the use of fibrinogen concentrates in PPH have shown a decreased need for blood product transfusion and subsequent volume overload without adverse effects.[152]Matsunaga S, Takai Y, Nakamura E, et al. The clinical efficacy of fibrinogen concentrate in massive obstetric haemorrhage with hypofibrinogenaemia. Sci Rep. 2017 Apr 24;7:46749.
https://www.nature.com/articles/srep46749
http://www.ncbi.nlm.nih.gov/pubmed/28436465?tool=bestpractice.com
Nonetheless, further research is necessary to explore the use of fibrinogen concentrates in managing PPH.
Prothrombin complex concentrates
Prothrombin complex concentrates consist of clotting factors II, VII, IX, and X, as well as proteins C and S, all of which are dependent on vitamin K. They are available in different preparations, with some including three of the factors and others all four.[141]Pacheco LD, Saade GR, Hankins GDV. Medical management of postpartum hemorrhage: an update. Semin Perinatol. 2019 Feb;43(1):22-6.
http://www.ncbi.nlm.nih.gov/pubmed/30503399?tool=bestpractice.com
Prothrombin complex concentrates are currently approved only for reversing warfarin-induced bleeding, but there are limited data on their off-label use for replenishing clotting factors in severe haemorrhage. Typically, the dose used is lower to minimise the risk of thrombosis.[153]Guyatt GH, Akl EA, Crowther M, et al. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141(2 suppl):7S-47S.
https://journal.chestnet.org/article/S0012-3692(12)60114-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/22315257?tool=bestpractice.com
[154]Younis M, Ray-Zack M, Haddad NN, et al. Prothrombin complex concentrate reversal of coagulopathy in emergency general surgery patients. World J Surg. 2018 Aug;42(8):2383-91.
http://www.ncbi.nlm.nih.gov/pubmed/29392436?tool=bestpractice.com
This off-label use may be beneficial in the management of obstetric haemorrhage, particularly for patients with severe liver dysfunction or acquired factor deficiencies.[118]Kogutt BK, Vaught AJ. Postpartum hemorrhage: Blood product management and massive transfusion. Semin Perinatol. 2019 Feb;43(1):44-50.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015778
http://www.ncbi.nlm.nih.gov/pubmed/30527516?tool=bestpractice.com
However, further research is necessary to establish the safety profile and determine the optimal dosing before prothrombin complex concentrates can be routinely used in the treatment of refractory PPH.[3]Committee on Practice Bulletins-Obstetrics. Practice bulletin no. 183: postpartum hemorrhage. Obstet Gynecol. 2017 Oct;130(4):e168-86.
http://www.ncbi.nlm.nih.gov/pubmed/28937571?tool=bestpractice.com
[4]Royal College of Obstetricians and Gynaecologists. Prevention and management of postpartum haemorrhage: green-top guideline no. 52. BJOG. 2017 Apr;124(5):e106-49.
https://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.14178
http://www.ncbi.nlm.nih.gov/pubmed/27981719?tool=bestpractice.com
[36]Muñoz M, Stensballe J, Ducloy-Bouthors AS, et al. Patient blood management in obstetrics: prevention and treatment of postpartum haemorrhage. A NATA consensus statement. Blood Transfus. 2019 Mar;17(2):112-36.
https://www.bloodtransfusion.it/bt/article/view/243
http://www.ncbi.nlm.nih.gov/pubmed/30865585?tool=bestpractice.com