Reducing maternal mortality by diagnosing undetected bleeding disorders

As defined by the World Health Organization, Postpartum hemorrhage (PPH) refers to a blood loss of 500 ml or more following childbirth. This condition affects 1 in 20 women with live births, and constitutes the leading direct cause of maternal mortality globally, accounting for almost a third of all deaths. A large number of them could be avoided by timely and appropriate management, made easier by antenatal assessment for PPH risk. «However, up to 30% of PPHs are unexplained, occurring in women deemed low risk», reports Dr. Michelle Lavin, an AXA grantee at Royal College of Surgeons in Ireland (RCSI) (Ireland) According to the hematologist, one major explanation is the current lack of awareness of congenital bleeding disorders (CBDs). «Studies of women with CBD have demonstrated markedly increased PPH rates compared to healthy controls (40% versus 5%). Despite this evidence, and the high population prevalence of CBD (up to 2%), current state-of-the-art clinical obstetric practice does not involve antenatal screening for CBD», she reports. In reaction to this, Dr. Lavin is leading a research project to determine if PPH risk can be assessed using antenatal bleeding assessment tools (BATs). The long-term objective of this project, called 'The PPH Prevent study', is to encourage the adoption of this simple form of screening into routine obstetric care, to ultimately reduce the number of deaths worldwide.

Diagnosing congenital bleeding disorders, such as Von Willebrand disease (VWD), particularly in its milder forms, is a well-recognized challenge. The development of bleeding assessment tools, in the form of questionnaires, has helped meet this challenge. They consist in collecting data regarding both the presence and severity of a variety of symptoms to generate a bleeding score (BS) that reflects the patient’s likelihood of having a CBD. «Reduced Von Willebrand Factor levels, the most common of these disorders, may be found in up to 1% of the population, but the majority of them remain undiagnosed. Although serious bleeding can occur, especially heavy periods, many women do not consider this abnormal and may not get tested with their doctor. The result is that when these women arrive for obstetric care, they are treated as low-risk pregnancies, when really, they are at a high risk of bleeding ». Indeed, «PPH can be effectively treated if detected early», the researcher points out. «But when women are not considered high risk, PPH is less likely to be detected until substantial blood loss has occurred, and it can be too late. For instance, a drug called tranexamic acid has recently been shown to significantly reduce both morbidity and mortality from PPH, but late administration significantly reduces therapeutic efficacy, with a 10% decrease in survival benefit for every 15 minute delay».

Antenatal identification of women at risk for heightened vigilance at time of delivery

One strategy is thus to improve antenatal risk stratification, such that heightened vigilance at time of delivery can be instituted for those identified as high risk. Current PPH risk-assessment tools mostly focus on maternal age and obstetric risks like the number of times the woman has been pregnant, position of the placenta, and complications in the pregnancy. « By looking at bleeding scores, we’re trying to think outside the box about what else could be contributing to risk», Dr. Lavin explains. The hypothesis the project is testing is that an abnormal BS is a crucial additional tool for identifying and classifying women at risk of PPH. To do so, she and her team will follow a cohort of pregnant women during their 1st, 2nd and 3rd trimesters, until delivery, collecting data regarding the relationship between their BAT scores, PPH occurrence and congenital hemostatic disorders. The findings will then be disseminated as widely as possible via submission to peer-reviewed publications, but also through participation in specialized international conferences, notably that of the International Society on Thrombosis and Haemostasis (ISTH). Dr. Michelle Lavin has indeed recently been appointed co-chair of their scientific subcommittee on Von Willebrand Factor.

«In medical research, women’s health and in particular reproductive health, has been a long neglected topic. When it comes to talking about the bleeding women experience, such as heavy periods or bleeding at delivery, taboos still exist and women may be reluctant to discuss these problems. This silence is hiding a major global problem, with over 14 million women a year experiencing a postpartum haemorrhage. We need to consider new approaches to try and tackle this problem».