A paper published today in the Journal of Thrombosis and Haemostasis from authors based at Semmelweis University in Hungary and the London School of Hygiene & Tropical Medicine (LSHTM) shows that anaemia can compromise clotting of the blood and may make tranexamic acid (TXA) – a drug used to stop women dying from postpartum haemorrhage – less effective.
This highlights the importance of preventing, detecting and treating anaemia as a way of reducing postpartum haemorrhage and protecting women and children in childbirth.
Dr Nikolett Wohner, one of the lead authors of the study said: “This study was conducted to understand the roles of TXA and red blood cells in the inhibition of fibrinolysis – a normal process that prevents blood clots from growing and becoming problematic. This is crucial, as severe bleeding after childbirth is one of the principal causes of maternal death worldwide.”
“We know that anaemia increases the risk of postpartum haemorrhage and the risk of death should it occur. However, the biological mechanisms through which anaemia increases the risk of postpartum bleeding are yet to be determined in detail,” added Professor Krasimir Kolev, the other lead author of the study.
Postpartum haemorrhage is responsible for about 70,000 maternal deaths every year, almost all of which occur in low- and middle-income countries. When given within three hours of birth, TXA reduces deaths due to bleeding in women by almost one third. Over one-third of pregnant women in the world are anaemic and many are severely anaemic. The Clinical Trials Unit at LSHTM is carrying out the WOMAN-2 trial to see if giving TXA can prevent postpartum haemorrhage in women with moderate and severe anaemia.
How a fibrin clot – a protein produced in response to bleeding – breaks down was quantified by an array of techniques coupled with a robust novel statistical analysis. The researchers’ approaches ranged from simple measurements of the rate at which a small steel ball placed on top of a fibrin clot settles when fibrin strands have been broken down, to sophisticated electron microscopic studies.
Professor Ian Roberts, a further author of the study and one the leads for the WOMAN-2 Trial said: “We found that both red cells and TXA reduced fibrinolysis, but we also conducted further analysis to see if the combined effect of red cells and TXA was greater than the sum of their individual effects. If they interacted in this way, this might mean that TXA would be more effective in women with higher haemoglobin levels.”
The data from this study provide insights into the mechanisms through which anaemia increases the risk of postpartum haemorrhage. By supporting a causal biological effect of anaemia on the risk of postpartum haemorrhage, they emphasise the importance of preventing and treating anaemia in pregnant women.
They also suggest plausible biological mechanisms through which anaemia might modify the effect of TXA on the risk of postpartum bleeding, making it slightly less effective.
The WOMAN-2 Trial will examine this hypothesis in over 15,000 women with moderate and severe anaemia in four countries. The results of this trial are expected in 2024.