Von Willebrand Disease and Pregnancy: Efficacy of Preventive Treatment

Why is this study on von Willebrand disease and pregnancy important?

Von Willebrand disease is a common inherited bleeding disorder. Women affected by it have an increased risk of bleeding, particularly during childbirth. This complication, called postpartum hemorrhage (PPH), can be serious. Normally, during pregnancy, the body increases its production of coagulation proteins, von Willebrand factor (VWF) and factor VIII (FVIII), to prepare for childbirth. However, in many women with von Willebrand disease, this natural increase is not enough.

They often require preventive treatment. This treatment involves injecting concentrated clotting factors to achieve safe levels. However, uncertainty persists. Experts do not know the ideal target levels or optimal dosages to effectively protect all patients. Indeed, significant hemorrhages still occur despite this precaution. A new Dutch study has therefore examined the effectiveness of a specific treatment to better understand and, ultimately, improve the management of von Willebrand disease and pregnancy.

The research question and the method used

The researchers wanted to concretely evaluate a preventive treatment. They sought to determine whether the administered doses allowed them to reach the coagulation factor levels recommended by medical guidelines. They also analyzed the frequency of hemorrhages despite this treatment. To do this, the team conducted a retrospective study at a large hospital in the Netherlands.

Specifically, they examined the medical records of 19 women with von Willebrand disease. All had received treatment with VWF/FVIII concentrate (Haemate P) during their delivery between 2008 and 2022. The scientists collected several types of data:

• The type of von Willebrand disease of each patient.
• Their coagulation factor levels before and during treatment.
• The doses of treatment received.
• The occurrence and volume of bleeding after childbirth.

Then, they compared the factor levels measured in these women with the targets set by the Dutch recommendations at the time.

Key results of treatment for von Willebrand disease during pregnancy

The study yielded several important findings that shed light on the challenges of current management.

Treatment goals are met

The first result is positive. The prescribed treatment doses successfully increased VWF and FVIII levels to meet the recommended targets. Immediately after the first injection, the “peak” (highest) levels were compliant. Furthermore, the “trough” (lowest) levels, just before a new injection, remained above the safety threshold for the first critical 72 hours.

Postpartum hemorrhage remains frequent

Despite this biological success, one result is striking. Nearly half of the women in the study still experienced postpartum hemorrhage. In total, 9 out of 19 patients (47%) experienced excessive bleeding. This high figure shows that reaching current targets is not always enough to prevent this complication.

Notable accumulation of factor VIII

Researchers observed another interesting phenomenon. In most women, factor VIII levels were already relatively high just before the start of treatment due to pregnancy-related changes. The administration of the concentrate then caused a further increase, leading to very high levels that persisted over time. Fortunately, no woman developed thrombosis (blood clot), despite these significant levels.

What do these results mean for patients and doctors?

These observations have direct implications for clinical practice. They suggest that the current strategy, while useful, can be improved.

Firstly, the coagulation factor targets recommended in current guidelines may not be high enough. Since hemorrhages occur even when these targets are met, it is possible that patients need even higher levels to be fully protected. This idea is reinforced by the fact that healthy women achieve much higher factor levels during a normal pregnancy.

Secondly, monitoring is essential. The study shows that the bodies of pregnant women eliminate factor VIII much more slowly than those of non-pregnant individuals. This explains its accumulation. Doctors must therefore carefully monitor FVIII levels to avoid excessively high rates over a long period, even if no thrombosis risk materialized here. This could lead to the use of treatments containing less FVIII.

Finally, the pharmacokinetic model developed by the study is a promising tool. In the future, it could help predict each patient’s reaction to treatment and personalize dosages for maximum effectiveness.

Study limitations and future prospects

Every scientific study has limitations, and this one is no exception. The main one is its small size. With only 19 patients, it is difficult to generalize the conclusions to all women with von Willebrand disease, particularly to the different subtypes of the disease.

Furthermore, the retrospective nature of the study means that it depends on the quality of existing data in medical records, which can sometimes be incomplete. For example, the visual estimation of blood loss volume may lack precision.

These studies highlight a crucial need for further research. Prospective studies, which follow patients in real-time, and of a larger scale are necessary. They will confirm these results and answer the key question: would higher coagulation factor targets reduce the risk of hemorrhage?

Conclusion: What to remember

This study provides valuable insight into the management of von Willebrand disease and pregnancy. Here are the four essential points to remember:

1. Goals are met, but bleeding persists. Current treatment successfully increases coagulation factors to recommended levels, but this does not prevent nearly half of patients from experiencing hemorrhage.
2. Factor VIII accumulates. The bodies of pregnant women eliminate it more slowly, leading to very high levels during treatment.
3. Monitoring is crucial. Blood level monitoring is essential to adjust treatment, optimize protection, and avoid excessively high FVIII levels.
4. Research must continue. Current recommendations may not be optimal. New studies are imperative to define the best strategies and improve the safety of mothers and their children.

Additional resources

• Original study publication (DOI)

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