Each year, worldwide, about 536,000 women die from causes related to pregnancy and childbirth. Almost all (99%) of the deaths are in low and middle income countries.[1] Postpartum haemorrhage is the most common cause of maternal death.[2] Of the 14 million women who have postpartum haemorrhage each year, 1-2% die, with an average interval from onset of bleeding to death of 2 to 4 hours.[2] Haemorrhage is also an important cause of maternal mortality in high income countries, accounting for about 13% of maternal deaths.[3]
Postpartum haemorrhage also contributes to hospital morbidity because patients may require a blood transfusion, which can transmit blood borne viral infections. Approximately 1% of women with spontaneous vaginal deliveries receive a blood transfusion, but the rate increases to about 5% for women with instrumental deliveries or caesarean sections.[4] The risk of infection from transfused blood is higher in countries unable to thoroughly screen the blood used for transfusion.[5] In high income countries, the risk of transfusion transmitted infections is lower, but adverse reactions related to blood transfusion are a common adverse event.[6]
The World Health Organization (WHO) defines postpartum haemorrhage as blood loss of 500 ml or more.[7] The diagnosis is based on a clinical estimate of blood loss. The WHO states that the loss of 500 ml of blood should be considered an alert, after which the health of the woman may be endangered.[7] In many parts of the world, the loss of 500 ml of blood can be a serious threat to health due to the high prevalence of severe anaemia. Severe anaemia is a common consequence of postpartum bleeding and affects about 11% of the 14 million women with postpartum haemorrhage each year.[8]
The main causes of postpartum haemorrhage are uterine atony, trauma to the genital tract during delivery and retained placenta.[9] Risk factors for postpartum haemorrhage include primiparity, prolonged or augmented labour, multiple births, polyhydramnious, anaesthesia, macrosomia, obesity, and placental abruption. Nevertheless, the majority of women with postpartum haemorrhage have low-risk pregnancies.[2] There is evidence from randomised controlled trials that prophylactic oxytocin can reduce the incidence of post partum bleeding (relative risk [RR] for blood loss greater than 500 ml = 0.50, 95% Confidence Interval [CI] 0.43 to 0.59).[10]
The treatment of postpartum haemorrhage may include drugs to increase uterine contractility, volume replacement for blood loss, and various surgical procedures including uterine compression sutures, arterial ligation, selective artery embolisation, intrauterine tamponade and hysterectomy.[11-13] The cumulative incidence of emergency hysterectomy varies between regions but is estimated at between 0.04 and 1.25% for all deliveries.[14]
Systemic anti-fibrinolytic agents are widely used in surgery to prevent clot breakdown (fibrinolysis) to reduce blood loss. A systematic review[15] of randomised controlled trials of anti-fibrinolytic agents in elective surgical patients identified 211 randomised controlled trials including 20,781 randomised participants. The results showed that aprotinin reduced the risk of blood transfusion by a relative 34% (RR 0.66, 95%CI 0.61 to 0.71) and tranexamic acid by a relative 39% (RR 0.61, 95%CI 0.54 to 0.69). In those requiring transfusion, aprotinin reduced the transfused blood volume by 1.1 units (95%CI 0.83 to 1.31) and tranexamic acid by 1.1 units (95%CI 0.64 to 1.59). A pooled analysis showed that anti-fibrinolytic agents reduce the need for re-operation due to bleeding (RR 0.52, 95%CI 0.40 to 0.69) and there was a non-significant reduction in the risk of death (RR 0.90, 95%CI 0.67 to 1.20) in the anti-fibrinolytic treated group. There was no evidence of increased risk of developing thrombotic events.
The 5th Millennium Development Goal is to reduce maternal deaths by 75% by the year 2015.[16] To achieve this goal, a reduction in maternal mortality of at least 5.5% each year is necessary. As haemorrhage accounts for around 25% of maternal deaths, an effective treatment for the management of postpartum haemorrhage could contribute significantly to the goal of reducing maternal mortality. Anti-fibrinolytic agents might reduce the need for hysterectomy, reduce the risk of severe anaemia and avoid the need for blood transfusion.
This systematic review aimed to quantify the effectiveness and safety of anti-fibrinolytic agents in the prevention or treatment of postpartum bleeding.
