Semin Thromb Hemost 2008; 34(1): 104-112
DOI: 10.1055/s-2008-1066022
© Thieme Medical Publishers

A Critical Review on the Use of Recombinant Factor VIIa in Life-Threatening Obstetric Postpartum Hemorrhage

Massimo Franchini1 , Massimo Franchi2 , Valentino Bergamini2 , Gian Luca Salvagno3 , Martina Montagnana3 , Giuseppe Lippi3
  • 1Servizio di Immunoematologia e Trasfusione - Centro Emofilia, Azienda Ospedaliera di Verona, Verona; Italy
  • 2Dipartimento Materno Infantile e di Biologia-Genetica, Sezione di Ginecologia e Ostetricia, Università di Verona, Verona; Italy
  • 3Istituto di Chimica e Microscopia Clinica, Dipartimento di Scienze Biomediche e Morfologiche, Università di Verona, Verona; Italy
Further Information

Publication History

Publication Date:
07 April 2008 (online)

ABSTRACT

The objective of this review was to evaluate and summarize the current literature on the unlicensed use of the novel agent recombinant activated factor VII (rFVIIa) in the management of major postpartum hemorrhage. After a systematic electronic search without temporal limits on MEDLINE, EMBASE, OVID and SCOPUS, the bibliographic references of all retrieved studies and reviews were additionally assessed for further reports of clinical trials. Unpublished works were also identified by searching abstracts from the most eminent conferences on this topic. In total, there were 31 studies that fulfilled our inclusion criteria. These studies incorporated 118 cases of massive postpartum hemorrhage treated with rFVIIa. The median age of the patients was 31.4 years, and cesarean section appeared to increase the risk of postpartum hemorrhage. At a median dose of 71.6 μg/kg, rFVIIa was reported to be effective in stopping or reducing bleeding in nearly 90% of the reported cases. Based on the evidence from the literature, we give some recommendations on the use of rFVIIa in massive postpartum hemorrhage. Nevertheless, although these reports suggest the potential role of rFVIIa in treating massive postpartum hemorrhage refractory to standard therapy, we advise particular caution in interpreting these results, as they are derived from few and uncontrolled studies. Further evidence is needed using well-designed clinical trials to better assess the optimal dose, the effectiveness, and the safety of rFVIIa in such critical bleeding conditions.

REFERENCES

  • 1 Bonnar J. Massive obstetric haemorrhage.  Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;  14 1-18
  • 2 Jansen A J, van Rhenen D J, Steegers E A, Duvekot J J. Postpartum hemorrhage and transfusion of blood and blood components.  Obstet Gynecol Surv. 2005;  60 663-671
  • 3 Khan K S, Wojdyla D, Say L, Gulmezoglu A M, Van Look P F. WHO analysis of causes of maternal death: a systematic review.  Lancet. 2006;  367 1066-1074
  • 4 CEMACH .The Confidential Enquiries into Maternal Deaths in the United Kingdom. Available at: http://www.cemach.org.uk. Accessed December 27, 2007
  • 5 ACOG . Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists number 76, October 2006: postpartum hemorrhage.  Obstet Gynecol. 2006;  108 1039-1047
  • 6 Burtelow M, Riley E, Druzin M, Fontaine M, Viele M, Goodnough L T. How we treat: management of life-threatening primary postpartum hemorrhage with a standardized massive transfusion protocol.  Transfusion. 2007;  47 1564-1572
  • 7 Sobieszczyk S, Breborowicz G. Management recommendations for postpartum hemorrhage.  Arch Perinat Med. 2004;  10 1-4
  • 8 Mousa H A, Alfirevic Z. Treatment of primary postpartum haemorrhage.  Cochrane Syst Database Rev. 2003;  , CD003249
  • 9 Allam M S, B-Lynch C. The B-Lynch and other uterine compression suture techniques.  Int J Gynaecol Obstet. 2005;  89 236-241
  • 10 Ghezzi F, Cromi A, Uccella S, Raio L, Bolis P, Surbek D. The Hayman technique: a simple method to treat postpartum hemorrhage.  BJOG. 2007;  114 362-365
  • 11 Bouwmeester F W, Bolte A C, van Geijn H P. Pharmacological and surgical therapy for primary postpartum hemorrhage.  Curr Pharm Des. 2005;  11 759-773
  • 12 Nègrier C, Lienhart A. Overall experience with Novoseven® .  Blood Coagul Fibrinolysis. 2000;  11(suppl 1) 19-24
  • 13 Hedner U, Erhardtsen E. Potential role for rFVIIa in transfusion medicine.  Transfusion. 2002;  42 114-124
  • 14 Franchini M, Zaffanello M, Veneri D. Recombinant factor VIIa. An update on its clinical use.  Thromb Haemost. 2005;  93 1027-1035
  • 15 Ghorashian S, Hunt B J. “Off-license” use of recombinant activated factor VII.  Blood Rev. 2004;  18 245-259
  • 16 Franchini M, Lippi G, Franchi M. The use of recombinant activated factor VII in obstetric and gynaecological haemorrhage.  BJOG. 2007;  114 8-15
  • 17 Lisman T, De Groot P G. Mechanism of action of recombinant factor VIIa.  J Thromb Haemost. 2003;  1 1138-1139
  • 18 Moscardo F, Perez F, de la Rubia J et al.. Successful treatment of severe intra-abdominal bleeding associated with disseminated intravascular coagulation using recombinant activated factor VII.  Br J Haematol. 2001;  114 174-176
  • 19 Brueckner S, Sedemund-Adib B, Malik E et al.. Treatment of a post partum bleeding complication with recombinant factor VIIa [abstract].  Blood. 2001;  98 80b
  • 20 Breborowicz G H, Sobieszczyk S, Szymankiewicz M. Efficacy of recombinant activated factor VII (rFVIIa,NovoSeven®) in prenatal medicine.  Arch Perinat Med. 2002;  8 21-27
  • 21 Sobieszczyk S, Breborowicz G H, Markwitz W, Mallinger S, Adamski D, Kruszynski Z. Effect of recombinant activated factor VII (RFVIIA; NovoSeven) in a patient in haemorrhagic shock after obstetrical hysterectomy.  Ginekol Pol. 2002;  73 230-233
  • 22 Zupancic Salek S, Sokolic V, Viskovic T, Sanjug J, Simic M, Kastelan M. Successful use of recombinant factor VIIa for massive bleeding after caesarean section due to HELLP syndrome.  Acta Haematol. 2002;  108 162-163
  • 23 Sokolic V, Bukovic D, Fures R et al.. Recombinant factor VIIa (rFVIIa) is effective at massive bleeding after cesarean section - a case report.  Coll Antropol. 2002;  26(Suppl) 155-157
  • 24 Bouwmeester F W, Jonkhoff A R, Verheijen R HM, van Geijn H P. Successful treatment of life-threatening postpartum hemorrhage with recombinant activated factor VII.  Obstet Gynecol. 2003;  101 1174-1176
  • 25 Kretzschmar M, Zahm D M, Remmler K, Pfeiffer L, Victor L, Schirmeister W. Pathophysiological and therapeutic aspects of amniotic fluid embolism (anaphylactoid syndrome of pregnancy): case report with lethal outcome and overview.  Anaesthesist. 2003;  52 419-426
  • 26 Dart B W, Cockerham W T, Torres C, Kipikasa J H, Maxwell R A. A novel use of recombinant factor VIIa in HELLP syndrome associated with spontaneous hepatic rupture and abdominal compartment syndrome.  J Trauma. 2004;  57 171-174
  • 27 Boehlen F, Morales M A, Fontana P, Ricou B, Irion O, de Moerloose P. Prolonged treatment of massive postpartum haemorrhage with recombinant factor VIIa: case report and review of the literature.  BJOG. 2004;  111 284-287
  • 28 Segal S, Shemesh I Y, Blumental R et al.. Treatment of obstetric hemorrhage with recombinant factor VIIa (rFVIIa).  Arch Gynecol Obstet. 2003;  268 266-267
  • 29 Segal S, Shemesh I Y, Blumental R et al.. The use of recombinant factor VIIa in severe postpartum hemorrhage.  Acta Obstet Gynecol Scand. 2004;  83 771-772
  • 30 Merchant S M, Mathew P, Vanderjagt T J, Howdieshell T R, Crookston K P. Recombinant factor VIIa in management of spontaneous subcapsular liver hematoma associated with pregnancy.  Obstet Gynecol. 2004;  103 1055-1058
  • 31 Lim Y, Loo C C, Chia V, Fun W. Recombinant factor VIIa after amniotic fluid embolism and disseminated intravascular coagulopathy.  Int J Gynaecol Obstet. 2004;  87 178-179
  • 32 Price G, Kaplan J, Skowronski G. Use of recombinant factor VIIa to treat life-threatening non-surgical bleeding in a post-partum patient.  Br J Anaesth. 2004;  93 298-300
  • 33 Gidiri M, Noble W, Rafique Z, Patil K, Lindow S W. Caesarean section for placenta praevia complicated by postpartum haemorrhage managed successfully with recombinant activated human coagulation Factor VIIa.  J Obstet Gynaecol. 2004;  24 925-926
  • 34 Ahonen J, Jokela R. Recombinant factor VIIa for life-threatening post-partum haemorrhage.  Br J Anaesth. 2005;  94 592-595
  • 35 Holub Z, Feyereisl J, Kabelik L, Rittstein T. Successful treatment of severe post-partum bleeding after caesarean section using recombinant activated factor VII.  Ceska Gynekol. 2005;  70 144-148
  • 36 Shamsi T S, Hossain N, Soomro N et al.. Use of recombinant factor VIIa for massive postpartum haemorrhage: case series and review of literature.  J Pak Med Assoc. 2005;  55 512-515
  • 37 Tanchev S, Platikanov V, Karadimov D. Administration of recombinant factor VIIa for the management of massive bleeding due to uterine atonia in the post-placental period.  Acta Obstet Gynecol Scand. 2005;  84 402-403
  • 38 Hollnberger H, Gruber E, Seelbach G B. Major post-partum hemorrhage and treatment with recombinant factor VIIa.  Anesth Analg. 2005;  101 1886-1887
  • 39 Nowacka E, Krawczynska W R, Teliga C J et al.. Recombinant factor VIIa for severe bleeding during cesarean section for quadruplet pregnancy. Case report.  Anest Inten Teap. 2005;  37 259-262
  • 40 Verre M, Bossio F, Mammone A, Piccirillo M, Tancioni F, Varano M. Use of recombinant activated factor VII in a case of severe postpartum haemorrhage.  Minerva Ginecol. 2006;  58 81-84
  • 41 Palomino M A, Chaparro M J, de Elvira M J, Curiel E B. Recombinant activated factor VII in the management of massive obstetric bleeding.  Blood Coagul Fibrinolysis. 2006;  17 226-227
  • 42 Heilmann L, Wild C, Hojnacki B, Pollow K. Successful treatment of life-threatening bleeding after cesarean section with recombinant activated factor VII.  Clin Appl Thromb Hemost. 2006;  12 227-279
  • 43 Pepas L P, Arif-Adib M, Kadir R A. Factor VIIa in puerperal hemorrhage with disseminated intravascular coagulation.  Obstet Gynecol. 2006;  108 757-761
  • 44 Sobieszczyk S, Breborowicz G, Platicanov V, Tanchev S, Kessler C M. Recombinant factor VIIa in the management of postpartum bleeds: an audit of clinical use.  Acta Obstet Gynecol Scand. 2006;  85 1239-1247
  • 45 Prosper S C, Goudge C S, Lupo V R. Recombinant factor VIIa to successfully manage disseminated intravascular coagulation from amniotic fluid embolism.  Obstet Gynecol. 2007;  109 524-525
  • 46 Haynes J, Laffan M, Plaat F. Use of recombinant activated factor VII in massive obstetric hemorrhage.  Int J Obstet Anesth. 2007;  16 40-49
  • 47 Jirapinyo M, Manonai J, Herabutya Y, Chuncharunee S. Effectiveness of recombinant activated factor VII (rFVII a) for controlling intractable postpartum bleeding: report of two cases and literature review.  J Med Assoc Thai. 2007;  90 977-981
  • 48 Ahonen J, Jokela R, Korttila K. An open non-randomized study of recombinant activated factor VII in major postpartum hemorrhage.  Acta Anaesthesiol Scand. 2007;  51 929-936
  • 49 Selo-Ojeme D O, Okonofua F E. Risk factors for primary postpartum haemorrhage. A case control study.  Arch Gynecol Obstet. 1997;  259 179-187
  • 50 Chichakli L O, Atrash H K, Mackay A P, Musani A S, Berg B J. Pregnancy-related mortality in the United Stats due to hemorrhage: 1979-1992.  Obstet Gynecol. 1999;  94 721-725
  • 51 Karalapillai D, Popham P. Recombinant factor VIIa in massive postpartum hemorrhage.  Int J Obstet Anesth. 2007;  16 29-34
  • 52 Ministero della Salute .Raccomandazione n°6 - Raccomandazione per la prevenzione della morte materna correlata al travaglio e/o parto. Available at: http://www.ministerosalute.it. Accessed December 27, 2007
  • 53 Vincent J L, Rossaint R, Riou B, Ozier Y, Zideman D, Spahn D R. Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding - a European perspective.  Crit Care. 2006;  10 1-12
  • 54 Clark A D, Gordon W C, Walker I D, Tait R C. ‘Last-ditch’ use of recombinant factor VIIa in patients with massive haemorrhage is ineffective.  Vox Sang. 2004;  86 120-124
  • 55 O'Connell K A, Wood J J, Wise R P, Lozier J N, Braun M M. Thromboembolic adverse events after use of recombinant human coagulation factor VIIa.  JAMA. 2006;  295 293-298
  • 56 Lynn M, Jeroukhimov I, Klein Y, Martinowitz U. Updates in the management of severe coagulopathy in trauma patients.  Intensive Care Med. 2002;  28 S241-S247
  • 57 Laffan M, O'Connell N M, Perry D J, Hodgson A J, O'Shaughnessy D, Smith O. Analysis and results of the recombinant factor VIIa extended-use registry.  Blood Coagul Fibrinolysis. 2003;  14(Suppl 1) S35-S38
  • 58 Erhardtsen E. Ongoing NovoSeven trials.  Intensive Care Med. 2002;  28 S248-S255
  • 59 Novo Nordisk Limited .NovoSeven summary of product characteristics. Version no. 3; N7/IBEC/015/3. Baagsvaerd, Denmark; Novo Nordisk
  • 60 Franchini M, Manzato F, Salvagno G L, Lippi G. The potential role of recombinant factor VII activated for the treatment of severe bleeding associated with disseminated intravascular coagulation: a systematic review.  Blood Coagul Fibrinolysis. 2007;  18 589-593
  • 61 Winter C, Macfarlane A, Deneux-Tharaux C et al.. Variations in policies for management of the third stage of labour and the immediate management of postpartum haemorrhage in Europe.  BJOG. 2007;  114 845-854

Massimo FranchiniM.D. 

Servizio di Immunoematologia e Trasfusione - Centro Emofilia, Ospedale Policlinico

Piazzale L. Scuro, 10 - 37134 Verona, Italy

Email: massimo.franchini@azosp.vr.it

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