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

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)  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)

Effect of tranexamic acid on coagulation and fibrinolysis in women with postpartum haemorrhage (WOMAN-ETAC): a single-centre, randomised, double-blind, placebo-controlled trial

Background: Postpartum haemorrhage (PPH) is a leading cause of maternal death. The WOMAN trial showed that tranexamic acid (TXA) reduces death due to bleeding in women with PPH. We evaluated the effect of TXA on fibrinolysis and coagulation in a sample of WOMAN trial participants. Methods: : Adult women with a clinical diagnosis of PPH were randomised to receive 1 g TXA or matching placebo in the WOMAN trial. Participants in the WOMAN trial at University College Hospital (Ibadan, Nigeria) also had venous blood taken just before administration of the first dose of trial treatment and again 30 (±15) min after the first dose (the ETAC study).  We aimed to determine the effects of TXA on fibrinolysis (D-dimer and rotational thromboelastometry maximum clot lysis (ML)) and coagulation (international normalized ratio and clot amplitude at 5 min). We compared outcomes in women receiving TXA and placebo using linear regression, adjusting for baseline measurements. Results: : Women (n=167) were randomised to receive TXA (n=83) or matching placebo (n=84). Due to missing data, seven women were excluded from analysis. The mean (SD) D-dimer concentration was 7.1 (7.0) mg/l in TXA-treated women and 9.6 (8.6) mg/l in placebo-treated women (p=0.09). After adjusting for baseline, the D-dimer concentration was 2.16 mg/l lower in TXA-treated women (-2.16, 95% CI -4.31 to 0.00, p=0.05). There was no significant difference in ML between TXA- and placebo-treated women (12.3% (18.4) and 10.7% (12.6), respectively; p=0.52) and no significant difference after adjusting for baseline ML (1.02, 95% CI -3.72 to 5.77, p=0.67).  There were no significant effects of TXA on any other parameters. Conclusion: TXA treatment was associated with reduced D-dimer levels but had no apparent effects on thromboelastometry parameters or coagulation tests. Registration: ISRCTN76912190 (initially registered 10/12/2008, WOMAN-ETAC included on 22/03/2012) and NCT00872469 (initially registered 31/03/2009, WOMAN-ETAC included on 22/03/2012)

Total antioxidant status in sickle cell anemia

Background: The homozygous sickle cell anemia (SCA) has an unstable hemoglobin (HbS). The heme group dissociates easily from globin chain and the iron is released and free within the red cell. In addition, the sickle red cells release cell-free hemoglobin after undergoing intravascular hemolysis. These contribute to increased reactive oxygen species and oxidative stress ensues. Oxidative stress contributes to complications such as acute chest syndrome and pulmonary hypertension both of which are severe manifestations of SCA. Objectives: In this study, we set out to correlate inflammatory markers of disease severity with oxidative stress. Materials and Methods: We compared the total antioxidant status of 61 steady-state SCA patients with 60 HbAA controls. We then investigated associations between the total antioxidant levels and hematological and clinical indices of the patients in order to establish a relationship between markers of oxidative stress and markers of sickle cell severity. Results: We found that that total antioxidants were significantly lower in SCA compared with control levels (50% lower). The total antioxidants levels were inversely proportional to leukocyte and especially neutrophil cell counts which are pro-inflammatory markers. Conclusion: Oxidative stress which leads to secondary complications correlates with pro-inflammatory markers of clinical severity in SCA

WOMAN-ETAC Dataset

The WOMAN trial is an international clinical trial to study the effect of tranexamic acid on death, hysterectomy and other maternal outcomes, in women with PPH.14. The trial tested whether tranexamic acid, a blood clot stabiliser discovered in Japan in the 1950’s, could become an essential tool for fighting excessive bleeding soon after giving birth. This condition, known as postpartum haemorrhage, is the number one cause of maternal death around the world, particularly in low and middle income countries. Dataset contains baseline and follow-up measurements for: D-dimer concentration (mg/L), Maximum lysis (%), Haemoglobin concentration (g/L), International normalized ratio (INR), Prothrombin time (seconds), Activated partial thromboplastin time (seconds), Fibrinogen concentration (g/L), Clotting time (seconds), Amplitude (firmness) at 5 minutes (mm), Amplitude at 10 minutes (mm), Clot lysis at 30 and 60 minutes (%), and Maximum clot firmness (mm). THE DATASET CAN BE DOWNLOADED FROM THE FREEBIRD PLATFORM AT https://ctu-app.lshtm.ac.uk/freebird/