Fibrinogn and postpartum hemorrhage - Association or causality?
Keywords:
Postpartum hemorrhage, Fibrinogen, Causality, Association, Shock hemorrhagic
Abstract
Postpartum hemorrhage (PPH) is the leading cause of maternal death worldwide, accounting for one in four maternal deaths. Despite efforts in public health policy, the incidence of massive PPH has increased in recent years even in first world countries. In Colombia, PPH is the second leading cause of maternal death. Multiple observational studies have provided evidence about the association between the concentration levels of fibrinogen in blood plasma and the severity of PPH, proposing the systematic use of fibrinogen concentrates as a prophylactic or therapeutic measure in patients with obstetric hemorrhage. However, the statistical relationship demonstrated in such studies should not necessarily be interpreted as a cause-effect relationship. Traditionally, we have used the criteria postulated by Sir Arthur Bradford Hill to establish a causal relationship. Therefore, the most pragmatic way to evaluate a possible causal relationship is through a randomized placebo-controlled experiment. Experiments of this kind available to date have methodological deficiencies or have been criticized for internal validity. As a result, the statistical relationship (association) between low levels of fibrinogen and PPH cannot be certainly interpreted as a cause-effect relationship and the use of fibrinogen concentrates may only be justified in the context of new clinical trials.
References
1. Hogan MC, Foreman KJ, Naghavi M, Ahn SY, Wang M, Makela SM, et al. Maternal mortality for 181 countries, 1980-2008: a systematic analysis of progress towards Millennium Development Goal 5. Lancet. 2010;375:1609-23.
2. Vélez-Álvarez GA, Agudelo-Jaramillo B, Gómez-Dávila JG, Zuleta-Tobón JJ. Código rojo: guía para el manejo de la hemorragia obstétrica. Rev Colomb Obstet Ginecol. 2009;60:34-48.
3. Lennox C, Marr L. Scottish confidential audit of severe maternal morbidity, 9th annual report (data from 2011). Healthcare Improvement Scotland; 2013.
4. Kramer MS, Berg C, Abenhaim H, Dahhou M, Rouleau J, Mehrabadi A, et al. Incidence, risk factors, and temporal trends in severe postpartum hemorrhage. Am J Obstet Gynecol. 2013;209, 449.e1-e7.
5. Lutomski JE, Byrne BM, Devane D, Greene RA. Increasing trends in atonic postpartum haemorrhage in Ireland: an 11-year population-based cohort study. BJOG. 2012;119:306-14.
6. Say L, Chou D, Gemmill A, Tuncalp Ö, Moller A-B, Daniels J, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2:e323-33.
7. Ronsmans C, Graham WJ. Maternal mortality: who, when, where, and why. Lancet. 2006;368:1189-200.
8. Rojas-Suarez J, Paternina-Caicedo AJ, Miranda J, Mendoza R, Dueñas-Castel C, Bourjeily G. Comparison of severity-of-illness scores in critically ill obstetric patients: a 6-year retrospective cohort. Crit Care Med. 2014;42:1047-54.
9. Vélez-Álvarez GA, Gómez-Dávila JG, Zuleta-Tobón JJ. Analysing maternal deaths caused by haemorrhage in the department of Antioquia, Colombia from 2004 to 2005. Rev Colomb Obstet Ginecol. 2006;57:147-55.
10. Gómez-Dávila JG, Osorio-Castaño JH, Vélez-Álvarez GA, Zuleta-Tobón JJ, Londoño-Cardona JG, Velásquez-Penagos JA, et al. Guía de práctica clínica para la prevención y el manejo de la hemorragia posparto y complicaciones del choque hemorrágico. Rev Colomb Obstet Ginecol. 2013;64:425-52.
11. García A, Navarro JR, Eslava-Schmalbach J. Encuesta sobre código rojo en cinco instituciones de salud de Bogotá. Rev Colomb Anestesiol. 2010;38:51-65.
12. García Velásquez V,González Agudelo M, Cardona Ospina A, Ardila Castellanos R. Association between fibrinogen levels and the severity of postpartum haemorrhage. Colomb J Anesthesiol. 2015;43:136-41.
13. Butwick AJ. Postpartum hemorrhage and low fibrinogen levels: the past, present and future. Int J Obstet Anesth. 2013;22:87-91.
14. Uchikova EH, Ledjev II. Changes in haemostasis during normal pregnancy. Eur J Obstet Gynecol Reprod Biol. 2005;119:185-8.
15. Hahn L, Korsan-Bengtsen K. The coagulation system during caerean section. Coagulation, fibrinolysis and hormonal levels in peripheral and uterine venous blood during caesarean section. Acta Obstet Gynecol Scand. 1975;54:49-55.
16. Charbit B, Mandelbrot L, Samain E, Baron G, Haddaoui B, Keita H, et al. The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage. J Thromb Haemost. 2007;5:266-73.
17. Guimicheva B, Czuprynska J, Arya R. The prevention of pregnancy-related venous thromboembolism. Br J Haematol. 2015;168:163-74.
18. Roberts I. Post partum haemorrhage and the WOMAN trial. Rev Colomb Anestesiol. 2010;38:314-7.
19. Shakur H, Elbourne D, Gülmezoglu M, Alfirevic Z, Ronsmans C, Allen E, et al. The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials. 2010;11:40.
20. Bolliger D, Szlam F, Molinaro RJ, Rahe-Meyer N, Levy JH, Tanaka KA. Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model. Br J Anaesth. 2009;102:793-9.
21. Levy JH, Szlam F, Tanaka KA, Sniecienski RM. Fibrinogen and hemostasis: a primary hemostatic target for the management of acquired bleeding. Anesth Analg. 2012;114:261-74.
22. Fenger-Eriksen C, Ingerslev J, Sørensen B. Fibrinogen concentrate - a potential universal hemostatic agent. Expert Opin Biol Ther. 2009;9:1325-33.
23. Huissoud C, Carrabin N, Audibert F, Levrat A, Massignon D, Berland M, et al. Bedside assessment of fibrinogen level in postpartum haemorrhage by thrombelastometry. BJOG. 2009;116:1097-102.
24. de Lloyd L, Bovington R, Kaye A, Collis RE, Rayment R, Sanders J, et al. Standard haemostatic tests following major obstetric haemorrhage. Int J Obstet Anesth. 2011;20:135-41.
25. Gayat E, Resche-Rigon M, Morel O, Rossignol M, Mantz J, Nicolas-Robin A, et al. Predictive factors of advanced interventional procedures in a multicentre severe postpartum haemorrhage study. Intensive Care Med. 2011;37:1816-25.
26. Cortet M, Deneux-Tharaux C, Dupont C, Colin C, Rudigoz R-C, Bouvier-Colle M-H, et al. Association between fibrinogen level and severity of postpartum haemorrhage secondary analysis of a prospective trial. Br J Anaesth. 2012;108:984-9.
27. Poujade O, Zappa M, Letendre I, Ceccaldi PF, Vilgrain V. Luton D. Predictive factors for failure of pelvic arterial embolization for postpartum hemorrhage. Int J Gynaecol Obstet. 2012;117:119-23.
28. Shibata Y, Shigemi D, Ito M, Terada K, Nakanishi K, Kato M, et al. Association between fibrinogen levels and severity of postpartum hemorrhage in singleton vaginal deliveries at a Japanese perinatal center. J Nippon Med Sch. 2014;81:94-6.
29. Levy JH, Welsby I, Goodnough LT. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy. Transfusion. 2014;54:1389-405.
30. Guasch E, Alsina E, Díez J, Ruiz R, Gilsanz F. Hemorragia obstétrica: estudio observacional sobre 21.726 partos en 28 meses. Rev Esp Anestesiol Reanim. 2009;56:139-46.
31. Doyle BC. Association does not prove causality. Emerg Med J. 2006;23:490.
32. Rosenberg EI, Bass PF, Davidson RA. Arriving at correct conclusions: the importance of association, causality, and clinical significance. South Med J. 2012;105:161-6.
33. Hill AB. The environment and disease: association or causation? Proc R Soc Med. 1965;58:295-300.
34. Marshall T. Bradford-Hill Criteria provide the way ahead for controversial theory. Int J Surg. 2005;3:287-8.
35. Wikkelsø A, Lunde J, Johansen M, Stensballe J, Wetterslev J, Møller AM, et al. Fibrinogen concentrate in bleeding patients. Cochrane Database Syst Rev. 2013;8:CD008864.
36. Wikkelsoe AJ, Afshari A, Stensballe J, Langhoff-Roos J, Albrechtsen C, Ekelund K, et al. The FIB-PPH trial: fibrinogen concentrate as initial treatment for postpartum haemorrhage: study protocol for a randomised controlled trial. Trials. 2012;13:110.
37. Wikkelsø AJ, Edwards HM, Afshari A, Stensballe J, Langhoff-Roos J, Albrechtsen C, et al. Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial. Br J Anaesth. 2015;114:623-33.
38. Ickx B, Samama CM. Fibrinogen concentrates for post-partum haemorrhage? Do not miss the most relevant population! Br J Anaesth. 2015;114:548-50.
39. De La Peña Silva AJ, Pérez Delgado R, Yepes Barreto I, De La Peña Martínez M. ¿Es útil la estimación visual en la determinación de la magnitud de la hemorragia perioperatoria?: un estudio de concordancia en anestesiólogos de hospitales de mediana y alta complejidad en Cartagena, Colombia. Rev Colomb Anestesiol. 2014;42:247-54.
40. Rubio-Romero JA, Gaitán-Duarte HG, Rodríguez-Malagón N. Concordancia entre la estimación visual y la medición del volumen recolectado en una bolsa del sangrado intraparto en mujeres con parto normal en Bogotá, Colombia, 2006. Rev Colomb Obstet Ginecol. 2008;59:92-102.
41. Pacagnella RC, Souza JP, Durocher J, Perel P, Blum J, Winikoff B, et al. A systematic review of the relationship between blood loss and clinical signs. PLoS ONE. 2013;8:e57594.
42. Aawar N, Alikhan R, Bruynseels D, Cannings-John R, Collis R, Dick J, et al. Fibrinogen concentrate versus placebo for treatment of postpartum haemorrhage: study protocol for a randomised controlled trial. Trials. 2015;16:169.
2. Vélez-Álvarez GA, Agudelo-Jaramillo B, Gómez-Dávila JG, Zuleta-Tobón JJ. Código rojo: guía para el manejo de la hemorragia obstétrica. Rev Colomb Obstet Ginecol. 2009;60:34-48.
3. Lennox C, Marr L. Scottish confidential audit of severe maternal morbidity, 9th annual report (data from 2011). Healthcare Improvement Scotland; 2013.
4. Kramer MS, Berg C, Abenhaim H, Dahhou M, Rouleau J, Mehrabadi A, et al. Incidence, risk factors, and temporal trends in severe postpartum hemorrhage. Am J Obstet Gynecol. 2013;209, 449.e1-e7.
5. Lutomski JE, Byrne BM, Devane D, Greene RA. Increasing trends in atonic postpartum haemorrhage in Ireland: an 11-year population-based cohort study. BJOG. 2012;119:306-14.
6. Say L, Chou D, Gemmill A, Tuncalp Ö, Moller A-B, Daniels J, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2:e323-33.
7. Ronsmans C, Graham WJ. Maternal mortality: who, when, where, and why. Lancet. 2006;368:1189-200.
8. Rojas-Suarez J, Paternina-Caicedo AJ, Miranda J, Mendoza R, Dueñas-Castel C, Bourjeily G. Comparison of severity-of-illness scores in critically ill obstetric patients: a 6-year retrospective cohort. Crit Care Med. 2014;42:1047-54.
9. Vélez-Álvarez GA, Gómez-Dávila JG, Zuleta-Tobón JJ. Analysing maternal deaths caused by haemorrhage in the department of Antioquia, Colombia from 2004 to 2005. Rev Colomb Obstet Ginecol. 2006;57:147-55.
10. Gómez-Dávila JG, Osorio-Castaño JH, Vélez-Álvarez GA, Zuleta-Tobón JJ, Londoño-Cardona JG, Velásquez-Penagos JA, et al. Guía de práctica clínica para la prevención y el manejo de la hemorragia posparto y complicaciones del choque hemorrágico. Rev Colomb Obstet Ginecol. 2013;64:425-52.
11. García A, Navarro JR, Eslava-Schmalbach J. Encuesta sobre código rojo en cinco instituciones de salud de Bogotá. Rev Colomb Anestesiol. 2010;38:51-65.
12. García Velásquez V,González Agudelo M, Cardona Ospina A, Ardila Castellanos R. Association between fibrinogen levels and the severity of postpartum haemorrhage. Colomb J Anesthesiol. 2015;43:136-41.
13. Butwick AJ. Postpartum hemorrhage and low fibrinogen levels: the past, present and future. Int J Obstet Anesth. 2013;22:87-91.
14. Uchikova EH, Ledjev II. Changes in haemostasis during normal pregnancy. Eur J Obstet Gynecol Reprod Biol. 2005;119:185-8.
15. Hahn L, Korsan-Bengtsen K. The coagulation system during caerean section. Coagulation, fibrinolysis and hormonal levels in peripheral and uterine venous blood during caesarean section. Acta Obstet Gynecol Scand. 1975;54:49-55.
16. Charbit B, Mandelbrot L, Samain E, Baron G, Haddaoui B, Keita H, et al. The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage. J Thromb Haemost. 2007;5:266-73.
17. Guimicheva B, Czuprynska J, Arya R. The prevention of pregnancy-related venous thromboembolism. Br J Haematol. 2015;168:163-74.
18. Roberts I. Post partum haemorrhage and the WOMAN trial. Rev Colomb Anestesiol. 2010;38:314-7.
19. Shakur H, Elbourne D, Gülmezoglu M, Alfirevic Z, Ronsmans C, Allen E, et al. The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials. 2010;11:40.
20. Bolliger D, Szlam F, Molinaro RJ, Rahe-Meyer N, Levy JH, Tanaka KA. Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model. Br J Anaesth. 2009;102:793-9.
21. Levy JH, Szlam F, Tanaka KA, Sniecienski RM. Fibrinogen and hemostasis: a primary hemostatic target for the management of acquired bleeding. Anesth Analg. 2012;114:261-74.
22. Fenger-Eriksen C, Ingerslev J, Sørensen B. Fibrinogen concentrate - a potential universal hemostatic agent. Expert Opin Biol Ther. 2009;9:1325-33.
23. Huissoud C, Carrabin N, Audibert F, Levrat A, Massignon D, Berland M, et al. Bedside assessment of fibrinogen level in postpartum haemorrhage by thrombelastometry. BJOG. 2009;116:1097-102.
24. de Lloyd L, Bovington R, Kaye A, Collis RE, Rayment R, Sanders J, et al. Standard haemostatic tests following major obstetric haemorrhage. Int J Obstet Anesth. 2011;20:135-41.
25. Gayat E, Resche-Rigon M, Morel O, Rossignol M, Mantz J, Nicolas-Robin A, et al. Predictive factors of advanced interventional procedures in a multicentre severe postpartum haemorrhage study. Intensive Care Med. 2011;37:1816-25.
26. Cortet M, Deneux-Tharaux C, Dupont C, Colin C, Rudigoz R-C, Bouvier-Colle M-H, et al. Association between fibrinogen level and severity of postpartum haemorrhage secondary analysis of a prospective trial. Br J Anaesth. 2012;108:984-9.
27. Poujade O, Zappa M, Letendre I, Ceccaldi PF, Vilgrain V. Luton D. Predictive factors for failure of pelvic arterial embolization for postpartum hemorrhage. Int J Gynaecol Obstet. 2012;117:119-23.
28. Shibata Y, Shigemi D, Ito M, Terada K, Nakanishi K, Kato M, et al. Association between fibrinogen levels and severity of postpartum hemorrhage in singleton vaginal deliveries at a Japanese perinatal center. J Nippon Med Sch. 2014;81:94-6.
29. Levy JH, Welsby I, Goodnough LT. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy. Transfusion. 2014;54:1389-405.
30. Guasch E, Alsina E, Díez J, Ruiz R, Gilsanz F. Hemorragia obstétrica: estudio observacional sobre 21.726 partos en 28 meses. Rev Esp Anestesiol Reanim. 2009;56:139-46.
31. Doyle BC. Association does not prove causality. Emerg Med J. 2006;23:490.
32. Rosenberg EI, Bass PF, Davidson RA. Arriving at correct conclusions: the importance of association, causality, and clinical significance. South Med J. 2012;105:161-6.
33. Hill AB. The environment and disease: association or causation? Proc R Soc Med. 1965;58:295-300.
34. Marshall T. Bradford-Hill Criteria provide the way ahead for controversial theory. Int J Surg. 2005;3:287-8.
35. Wikkelsø A, Lunde J, Johansen M, Stensballe J, Wetterslev J, Møller AM, et al. Fibrinogen concentrate in bleeding patients. Cochrane Database Syst Rev. 2013;8:CD008864.
36. Wikkelsoe AJ, Afshari A, Stensballe J, Langhoff-Roos J, Albrechtsen C, Ekelund K, et al. The FIB-PPH trial: fibrinogen concentrate as initial treatment for postpartum haemorrhage: study protocol for a randomised controlled trial. Trials. 2012;13:110.
37. Wikkelsø AJ, Edwards HM, Afshari A, Stensballe J, Langhoff-Roos J, Albrechtsen C, et al. Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial. Br J Anaesth. 2015;114:623-33.
38. Ickx B, Samama CM. Fibrinogen concentrates for post-partum haemorrhage? Do not miss the most relevant population! Br J Anaesth. 2015;114:548-50.
39. De La Peña Silva AJ, Pérez Delgado R, Yepes Barreto I, De La Peña Martínez M. ¿Es útil la estimación visual en la determinación de la magnitud de la hemorragia perioperatoria?: un estudio de concordancia en anestesiólogos de hospitales de mediana y alta complejidad en Cartagena, Colombia. Rev Colomb Anestesiol. 2014;42:247-54.
40. Rubio-Romero JA, Gaitán-Duarte HG, Rodríguez-Malagón N. Concordancia entre la estimación visual y la medición del volumen recolectado en una bolsa del sangrado intraparto en mujeres con parto normal en Bogotá, Colombia, 2006. Rev Colomb Obstet Ginecol. 2008;59:92-102.
41. Pacagnella RC, Souza JP, Durocher J, Perel P, Blum J, Winikoff B, et al. A systematic review of the relationship between blood loss and clinical signs. PLoS ONE. 2013;8:e57594.
42. Aawar N, Alikhan R, Bruynseels D, Cannings-John R, Collis R, Dick J, et al. Fibrinogen concentrate versus placebo for treatment of postpartum haemorrhage: study protocol for a randomised controlled trial. Trials. 2015;16:169.
How to Cite
1.
Rincón-Valenzuela DA, Bocanegra JC, Guevara J. Fibrinogn and postpartum hemorrhage - Association or causality?. Colomb. J. Anesthesiol. [Internet]. 2017 Apr. 1 [cited 2024 Apr. 18];45(2):136–139. Available from: https://www.revcolanest.com.co/index.php/rca/article/view/273
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2017-04-01
How to Cite
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Rincón-Valenzuela DA, Bocanegra JC, Guevara J. Fibrinogn and postpartum hemorrhage - Association or causality?. Colomb. J. Anesthesiol. [Internet]. 2017 Apr. 1 [cited 2024 Apr. 18];45(2):136–139. Available from: https://www.revcolanest.com.co/index.php/rca/article/view/273
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