Pregnant women can safely receive the mildest treatment

A new study confirms that a low dose of anticoagulant medicine is sufficient to prevent new blood clots in pregnant women who have previously had thrombosis.

Jens Fuglsang, consultant, Department of Gynaecology and Obstetrics, Aarhus University Hospital, Associate Professor and PhD at the Department of Clinical Medicine, Aarhus University. Photo: Aarhus University Hospital

Pregnant women who have previously had a blood clot in the legs or lungs have an increased risk of developing a new blood clot during pregnancy and in the first weeks after childbirth.

The preventive treatment consists of daily injections with anticoagulant medicine. However, pregnant women metabolise the medicine in a different way to non-pregnant women, and as a consequence, it has not been entirely clear how such preventive treatment could best be applied during pregnancy.

Too small a dose of anticoagulant could result in a greater risk of a new blood clot, while a higher dose might cause side effects such as major bleeding during childbirth.

Now a new study, the Highlow study, in which researchers from Aarhus University Hospital and Aarhus University have participated, has made it clear that a low dose of anticoagulant medicine is enough to keep blood clots away.

The new study has been published in The Lancet, one of the world’s leading scientific journals. The study compares two doses of anticoagulant medicine: a low and a medium-sized dose.

In a randomised experiment, the pregnant women received treatment from the first stage of pregnancy until six weeks after childbirth. The study involved 1,110 women in nine different countries. In Denmark, pregnant women at Aarhus University Hospital and Aalborg University Hospital participated.

The Highlow study found that the low dose of anticoagulant medicine that would also be given to non-pregnant women was sufficient to prevent new blood clots. The group of pregnant women who received a large dose of anticoagulant did not experience fewer blood clots. However, the group with the higher dose did not more frequently have greater bleeding, either.

“The study suggests that pregnant women should not be given increased doses of anticoagulant medicine,” says Associate Professor and Consultant Jens Fuglsang PhD of the Department of Gynaecology and Obstetrics, Aarhus University Hospital, and the Department of Clinical Medicine, Aarhus University.

Jens Fuglsang was employed on the project and treated the participating patients at Aarhus University Hospital.

“There can be significant side effects associated with anticoagulant medicine, so the fact that you can make do with a low dose of blood-thinning medication during and after pregnancy is very good news for many pregnant women.”

As a secondary finding, the study suggests that a higher dose of anticoagulant medicine could result in slightly fewer blood clots in the time after childbirth, in relation to both deep and superficial blood clots in the lungs and legs. However, the study was not designed to study the post-natal period with sufficient confidence, as in that case there would have had to be many more pregnant women involved in the study. This finding is therefore more uncertain.

Behind the research results:

Type of study: A nonblinded, randomised, controlled multicentre study

Partners: Hospitals in the Netherlands, France, Ireland, Belgium, Norway, Denmark, Canada, the USA and Russia

External funding: Ministère des Solidarités et de la Santé in France, the Health Research Board in Ireland, GSK/Aspen and Pfizer

Read the scientific article: Bistervels, Ingrid M; van den Akker, Eline S; Benachi, Alexandra et al.: Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study). The Lancet, Published Ahead of Print: 28 October, 2022. DOI: 10.1016/S0140-6736(22)02128-6

Further information:

Associate Professor, PhD and consultant, Jens Fuglsang
Department of Clinical Medicine, Aarhus University and Department of Gynaecology and Obstetrics, Aarhus University Hospital,
Tel.: +45 3071 4690