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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
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Publication History

Publication Date:
07 April 2008 (online)

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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 Unpublished works were also identified by searching abstracts from the most eminent conferences on this topic.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.

KEYWORDS

Postpartum hemorrhage - obstetrics - gynecology - bleeding - rFVIIa

REFERENCES

  • 1 Bonnar J. Massive obstetric haemorrhage.  Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;  14 1-18
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 4 CEMACH .The Confidential Enquiries into Maternal Deaths in the United Kingdom. Available at: http://www.cemach.org.uk. Accessed December 27, 2007
    Google Scholar
  • 5 ACOG . Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists number 76, October 2006: postpartum hemorrhage.  Obstet Gynecol. 2006;  108 1039-1047
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 7 Sobieszczyk S, Breborowicz G. Management recommendations for postpartum hemorrhage.  Arch Perinat Med. 2004;  10 1-4
    PubMedGoogle Scholar
  • 8 Mousa H A, Alfirevic Z. Treatment of primary postpartum haemorrhage.  Cochrane Syst Database Rev. 2003;  , CD003249
    PubMedGoogle Scholar
  • 9 Allam M S, B-Lynch C. The B-Lynch and other uterine compression suture techniques.  Int J Gynaecol Obstet. 2005;  89 236-241
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 12 Nègrier C, Lienhart A. Overall experience with Novoseven® .  Blood Coagul Fibrinolysis. 2000;  11(suppl 1) 19-24
    PubMedGoogle Scholar
  • 13 Hedner U, Erhardtsen E. Potential role for rFVIIa in transfusion medicine.  Transfusion. 2002;  42 114-124
    CrossrefPubMedGoogle Scholar
  • 14 Franchini M, Zaffanello M, Veneri D. Recombinant factor VIIa. An update on its clinical use.  Thromb Haemost. 2005;  93 1027-1035
    PubMedGoogle Scholar
  • 15 Ghorashian S, Hunt B J. “Off-license” use of recombinant activated factor VII.  Blood Rev. 2004;  18 245-259
    CrossrefPubMedGoogle Scholar
  • 16 Franchini M, Lippi G, Franchi M. The use of recombinant activated factor VII in obstetric and gynaecological haemorrhage.  BJOG. 2007;  114 8-15
    PubMedGoogle Scholar
  • 17 Lisman T, De Groot P G. Mechanism of action of recombinant factor VIIa.  J Thromb Haemost. 2003;  1 1138-1139
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 34 Ahonen J, Jokela R. Recombinant factor VIIa for life-threatening post-partum haemorrhage.  Br J Anaesth. 2005;  94 592-595
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 38 Hollnberger H, Gruber E, Seelbach G B. Major post-partum hemorrhage and treatment with recombinant factor VIIa.  Anesth Analg. 2005;  101 1886-1887
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 51 Karalapillai D, Popham P. Recombinant factor VIIa in massive postpartum hemorrhage.  Int J Obstet Anesth. 2007;  16 29-34
    CrossrefPubMedGoogle Scholar
  • 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
    Google Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 58 Erhardtsen E. Ongoing NovoSeven trials.  Intensive Care Med. 2002;  28 S248-S255
    CrossrefPubMedGoogle Scholar
  • 59 Novo Nordisk Limited .NovoSeven summary of product characteristics. Version no. 3; N7/IBEC/015/3. Baagsvaerd, Denmark; Novo Nordisk
    Google Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar

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