Anticoagulation and cerebral small vessel disease – what really causes intracerebral haemorrhage

Researchers from the University College London and the Inselspital, University Hospital Bern have clarified the role of anticoagulation in intracerebral haemorrhages in two coupled studies. The team of David Werring and David Seiffge succeeded in establishing cerebral small vessel disease as the most probable cause. Prevention of cerebral haemorrhages to focus on detection and treatment of small vessel disease. Re-establishing anticoagulation after intracerebral haemorrhage to protect against ischaemic stroke is now investigated.

Cardiovascular diseases are usually complex and affect multiple organs simultaneously. Treatments for vascular diseases in the brain may therefore have implications for the treatment of cardiac diseases. It is therefore important to understand the respective causes and effects. This study explores the causes of intracerebral haemorrhages and links them to the risk of stroke associated with atrial fibrillation. It suggests a fundamental new assessment of the effects of blood thinning on intracerebral haemorrhages.

About 1,000 patients with intracerebral haemorrhage are treated at stroke units each year in Switzerland. Intracerebral haemorrhages are more often fatal than other forms of strokes, and their incidence has not decreased in the past 30 years. The use of blood thinners was previously considered not only to be a risk factor but potential cause for a intracerebral haemorrhage.

Anticoagulation should not be regarded as primary cause

This publication includes the results of two studies conducted by the team of Prof. Werring. It contrasts the role of blood thinning with that of cerebral small vessel disease (SVD) in intracerebral haemorrhages. A moderate to severe cerebral SVD is shown to be closely associated with the occurrence of cerebral haemorrhages. Dr David Seiffge summarized the results as follows: “Our results show that SVD is a precondition for intracerebral haemorrhages under anticoagulation. The degree of SVD in the brain may be used to predict intracerebral haemorrhages. Without SVD the occurrence of intracerebral haemorrhage is close to zero. Consequently, anticoagulation should no longer be considered a cause of intracerebral haemorrhages.”

Why is this important? Protection against stroke for patients with atrial fibrillation

Blood thinning offers important protection against ischemic stroke in patients with atrial fibrillation. Anticoagulation reduces the risk of ischemic stroke in these cases by two-thirds. In the past, anticoagulation has been discontinued immediately in the event of an intracerebral haemorrhage and patients were left unprotected against the risk of a stroke. The new study results now point to a new path: according to the findings, intracerebral haemorrhages can be prevented etiologically by treating cerebral SVD and protection against stroke can be maintained through an adapted continuation of blood thinning. The exact timing and gradation of the two therapies are the subject of further studies.

A challenging methodological approach: combining two multicentre studies

The publication comprises data originating from two independent studies supervised by Prof. David Werring, UCL.The publication is based on two independent, multicentre observational studies. First, a cross-sectional study was carried out with 1,030 patients with intracerebral haemorrhages. CT and MRI were used to look for markers of SVD in the brain. 1,447 patients with atrial fibrillation and cerebral circulatory disorders were enrolled in a second, prospective study. In this group, the incidence of cerebral haemorrhages and ischaemic stroke was considered in relation to blood thinning.

Using this approach, it was possible to show that SVD is a prerequisite for intracerebral haemorrhage. Patients without such a condition did not have a single brain haemorrhage within the first 2 years in the study, despite being treated with a blood thinner. In contrast, at 1.56% per year, the risk was significantly increased for moderate to severe SVD.

A new way of looking at the situation is needed

The study results suggest that blood thinning alone can no longer be considered a cause of intracerebral haemorrhages. Prof. Marcel Arnold points out: «As a new approach, microangiopathies should be systematically searched for and treated in a targeted manner in order to prevent intracerebral haemorrhages. Suitable specialist outpatient clinics are now available. This would reduce the risk of intracerebral haemorrhages.»

A large, international randomised trial (ENRICH-AF), coordinated in Switzerland by David Seiffge, is currently underway with the aim of aligning anticoagulation and microangiopathy therapies with each other.


  • Prof. David Werring MD, Queen Square Institute of Neurology, University College London
  • PD David Julian Seiffge MD, Senior Attending in Department of Neurology, Inselspital, University Hospital Bern
  • Prof. Marcel Arnold MD, Physician-in-Chief Stroke Center, Inselspital, University Hospital Bern
  • Prof. Urs Fischer MD, Head in-patient Acute Neurology , Inselspital, University Hospital Bern


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Intrazerebrale Haemorrhagie - Hirnblutung: Der blau eingefärbte Bereich bezeichnet den Ausschnitt im MRI, der eine Hirnblutung anzeigt. (Autor: D.J. Seiffge, copyright: Insel Gruppe)

PD Dr. med. David Julian Seiffge, Oberarzt Klinik für Neurologie, Inselspital, Universitätsspital Bern

Prof. Dr. med. Urs Fischer, Leiter Stationäre Akutneurologie, Inselspital, Universitätsspital Bern

Prof. Dr. med Marcel Arnold, Chefarzt Stroke Center, Inselspital, Universitätsspital Bern