Haematological and fibrinolytic status of Nigerian women with post-partum haemorrhage

Ian Roberts, Haleema Shakur, Bukola Fawole, Modupe Kuti, Oladapo Olayemi, Adenike Bello, Olayinka Ogunbode, Taiwo Kotila, Chris O Aimakhu, Tolulase Olutogun, Beverley J Hunt, Sumaya Huque, Ian Roberts, Haleema Shakur, Bukola Fawole, Modupe Kuti, Oladapo Olayemi, Adenike Bello, Olayinka Ogunbode, Taiwo Kotila, Chris O Aimakhu, Tolulase Olutogun, Beverley J Hunt, Sumaya Huque

Abstract

Background: Early treatment with tranexamic acid reduces deaths due to bleeding after post-partum haemorrhage. We report the prevalence of haematological, coagulation and fibrinolytic abnormalities in Nigerian women with postpartum haemorrhage.

Methods: We performed a secondary analysis of the WOMAN trial to assess laboratory data and rotational thromboelastometry (ROTEM) parameters in 167 women with postpartum haemorrhage treated at University College Hospital, Ibadan, Nigeria. We defined hyper-fibrinolysis as EXTEM maximum lysis (ML) > 15% on ROTEM. We defined coagulopathy as EXTEM clot amplitude at 5 min (A5) < 40 mm or prothrombin ratio > 1.5.

Results: Among the study cohort, 53 (40%) women had severe anaemia (haemoglobin< 70 g/L) and 17 (13%) women had severe thrombocytopenia (platelet count < 50 × 109/L). Thirty-five women (23%) had ROTEM evidence of hyper-fibrinolysis. Based on prothrombin ratio criteria, 16 (12%) had coagulopathy. Based on EXTEM A5 criteria, 49 (34%) had coagulopathy.

Conclusion: Our findings suggest that, based on a convenience sample of women from a large teaching hospital in Nigeria, hyper-fibrinolysis may commonly occur in postpartum haemorrhage. Further mechanistic studies are needed to examine hyper-fibrinolysis associated with postpartum haemorrhage. Findings from such studies may optimize treatment approaches for postpartum haemorrhage.

Trial registration: The Woman trial was registered: NCT00872469; ISRCTN76912190 (Registration date: 22/03/2012).

Keywords: Coagulation; Fibrinolysis; Postpartum haemorrhage.

Conflict of interest statement

Ethics approval and consent to participate

Approvals to conduct this study were obtained from the Ethics Committees of London School of Hygiene and Tropical Medicine and the University of Ibadan & University College Hospital Ethics Committee. Regulatory approval was obtained from the Nigerian National Agency for Food and Drug Administration and Control (NAFDAC). The study was undertaken according to ICH-GCP guidelines. The consent procedures is detailed in the WOMAN Trial protocol [22]. Briefly, we obtained written consent from a patient if their physical and mental capacity allowed. If a patient could not give written consent, we obtained proxy consent from a relative or representative. If a proxy was unavailable, then if local regulation allows, we deferred or waived consent. In this situation, we informed the patient about the trial as soon as possible, and obtained written consent to use the data. The London School of Hygiene & Tropical Medicine is the sponsor.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
ROTEM traces with (top) and without (bottom) hyper-fibrinolysis
Fig. 2
Fig. 2
Annotated trace showing ROTEM parameters
Fig. 3
Fig. 3
Scatterplot of the relationship between estimated blood loss and ROTEM ML and A5

References

    1. CRASH-2 trial collaborators. Shakur H, Roberts I, Bautista R, Caballero J, Coats T, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23–32. doi: 10.1016/S0140-6736(10)60835-5.
    1. CRASH-2 collaborators. Roberts I, Shakur H, Afolabi A, Brohi K, Coats T, et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011;377(9771):1096–1101. doi: 10.1016/S0140-6736(11)60278-X.
    1. Roberts I, Prieto-Merino D, Manno D. Mechanism of action of tranexamic acid in bleeding trauma patients: an exploratory analysis of data from the CRASH-2 trial. Crit Care. 2014;18:685. doi: 10.1186/s13054-014-0685-8.
    1. Raza I, Davenport R, Rourke C, Platton S, Manson J, Spoors C, Khan S, De'ath H, Allard S, Hart D, John Pasi K, Hunt BJ, Stanworth S, Maccallum P, Brohi K. The incidence and magnitude of fibrinolytic activation in trauma patients. J Thromb Haemost. 2013;11(2):307–314. doi: 10.1111/jth.12078.
    1. Chapman MP, Moore EE, Moore HB, Gonzalez E, Gamboni F, Chandler JG, Mitra S, Ghasabyan A, Chin TL, Sauaia A, Banerjee A, Silliman CC. Overwhelming tPA release, not PAI-1 degradation, is responsible for hyperfibrinolysis in severely injured trauma patients. J Trauma Acute Care Surg. 2016;80:16–25. doi: 10.1097/TA.0000000000000885.
    1. Cap A, Hunt BJ. The pathogenesis of traumatic coagulopathy. Anaesthesia. 2015;70(Suppl 1):e96–101. doi: 10.1111/anae.12914.
    1. The WOMAN Trial Collaborators Effect of early administration of tranexamic acid on mortality, hysterectomy, other morbidities in women with postpartum haemorrhage (the WOMAN trial): a randomised, placebo-controlled trial. Lancet. 2017;389(10084):2105–2116. doi: 10.1016/S0140-6736(17)30638-4.
    1. Wikkelsø AJ, Edwards HM, Afshari A, Stensballe J, Langhoff-Roos J, Albrechtsen C, Ekelund K, Hanke G, Secher EL, Sharif HF, Pedersen LM, Troelstrup A, Lauenborg J, Mitchell AU, Fuhrmann L, Svare J, Madsen MG, Bødker B, Møller AM, FIB-PPH trial group Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial. Br J Anaesth. 2015;114:623–633. doi: 10.1093/bja/aeu444.
    1. World Health Organization (WHO) The prevalence of Anaemia in women: a tabulation of available information. Geneva: WHO; 1992.
    1. Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003;54:1127–1130. doi: 10.1097/01.TA.0000069184.82147.06.
    1. Hagemo JS, Christiaans SC, Stanworth SJ, et al. Detection of acute traumatic coagulopathy and massive transfusion requirements by means of rotational thromboelastometry: an international prospective validation study. Crit Care. 2015;19(1):97. doi: 10.1186/s13054-015-0823-y.
    1. de Lange NM, van Rheeneen-Flach LE, Lance MD, Mooyman L, et al. Peri-partum reference ranges for ROTEM®thromboelastometry. Br J Anaesth. 2014;112(5):852–859. doi: 10.1093/bja/aet480.
    1. Ronsmans C, Graham WJ. Lancet maternal survival series steering group: maternal mortality: who, when, where, and why. Lancet. 2006;368(9542):1189–1200. doi: 10.1016/S0140-6736(06)69380-X.
    1. Solomon C, Collis R, Collins P. Haemostatic monitoring during postpartum haemorrhage and implications for management. Br J Anaesth. 2012;109(6):851–863. doi: 10.1093/bja/aes361.
    1. Erhabor O, Isaac I, Muhammad A, Abdulrahman Y, Ezimah A, Adias T. Some hemostatis parameters in women with obstetric haemorrhage in Sokoto, Nigeria. Int J Womens Health. 2013;5:285–291. doi: 10.2147/IJWH.S43503.
    1. Mackinnon S, Walker ID, Davidson JF, Walker JJ. Plasma fibrinolysis during and after normal childbirth. Br J Haematol. 1987;65:339–342. doi: 10.1111/j.1365-2141.1987.tb06864.x.
    1. Bremer HA, Brommer EJP, Wallenburg HCS. Effects of labour and delivery on fibrinolysis. Eur J Ob Gynaecol Repro Biol. 1994;55:163–168. doi: 10.1016/0028-2243(94)90032-9.
    1. Ducloy-Bouthors AS, Duhamel A, Kipnis E, Tournoys A, Prado-Dupont A, Elkalioubie A, Jeanpierre E, Debize G, Peynaud-Debayle E, DeProst D, Huissoud C, Rauch A, Susen S. Postpartum haemorrhage related early increase in D-dimers is inhibited by tranexamic acid: haemostasis parameters of a randomized controlled open labelled trial. Br J Anaesth. 2016;116:641–648. doi: 10.1093/bja/aew021.
    1. Okwesili A, Ibrahim K, Nnadi D, Barnabas B, Abdulrahaman Y, Buhari H, Udomah F, Imoru M, Egenti B, Erhabor O. Fibrinogen levels among pregnant women of African descent in Sokoto north western Nigeria. Front Biomed Sci. 2016;1(2):7–11.
    1. Madden E, Lee G, Kotler DP, et al. Association of Antiretroviral Therapy with fibrinogen levels in HIV infection. AIDS. 2008;22(6):707–715. doi: 10.1097/QAD.0b013e3282f560d9.
    1. Olatunbosun O, Abasiattai A, Bassey E, James R, Ibanga G, Morgan A. Prevalence of anaemia among pregnant women at booking in the University of Uyo Teaching Hospital. Uyo: Biomed Research International; 2014.
    1. Nair M, Choudhry MK, Choudhry SS, Kakoty SD, Sarma UC, Webster P, et al. Association between maternal anaemia and pregnancy outcome: a cohort study in Assam, India. BMJ Global Health. 2016;1:e000026. doi: 10.1136/bmjgh-2015-000026.
    1. Butwick A, Walsh E, Kuzniewicz M, Li S, Escobar G. Patterns and predictors of severe postpartum anemia after cesarean section. Transfusion. 2017;57:36–44. doi: 10.1111/trf.13815.
    1. Jones RM, de Lloyd L, Kealaher EJ, Lilley GJ, Precious E, Burckett st Laurent D, Hamlyn V, Collis RE, Collins PW, collaborators Platelet count and transfusion requirements during moderate or severe postpartum haemorrhage. Anaesthesia. 2016;71:648–656. doi: 10.1111/anae.13448.
    1. Collins PW, Lilley G, Bruynseels D, et al. Fibrin-based clot formation as an early and rapid biomarker for progression of postpartum hemorrhage: a prospective study. Blood. 2014;124:1727–1736. doi: 10.1182/blood-2014-04-567891.

Source: PubMed

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