Blood clot formation in cerebral cavernous malformations

2022-08-23

Blood coagulation and blood clot formation are relevant for the disease cerebral cavernoma, CCM. Therefore, antithrombotic therapy may be beneficial for cavernoma patients. This is shown in a new study from IGP.

The vascular lesions, or blood-vessel malformations, that appear in a cerebral cavernoma – also known as a cerebral cavernous malformation (CCM) resemble mulberries. They bleed easily, which may cause epileptic attack, neurological problems and stroke. For a long time, antithrombotic therapy was not prescribed for CCM patients because of the risk for hemorrhage, but more recent studies show that such therapy does not promote hemorrhage and could even be beneficial.

To determine the role of blood coagulation and the formation of blood clots (thrombosis) in CCM, the researchers have in the present study examined mice with a mutation that results in blood vessel lesions similar to the ones on humans with CCM. They have also examined brain tissues from CCM patients.

“Our experiments have provided several indications that coagulation is an important factor in CCM. In both mice and humans, we discovered blood clots in the vessel lesions. Several genes that are involved in coagulation were also more active in mice with CCM lesions than in control mice," says Peetra Magnusson, who has led the study.

The researchers could also identify a number of proteins that contribute to the coagulation but also some anticoagulant proteins. These proteins were localised in different areas of the lesions which suggests that some regions are prone to thrombi and other regions are prone to hemorrhage.

The study also showed that the tissues surrounding the lesions with thrombosis were hypoxic.

“Prolonged exposure to hypoxia may lead to neural cell loss and cell death. We think that this might cause the neuropathological conditions such as stroke," says Peetra Magnusson.

The results from the study support the concept that antithrombotic therapy may be beneficial for patients with CCM. An increased understanding of the molecular mechanisms behind the coagulation could give insights regarding suitable antithrombotic pharmaceuticals for CCM patients.

The study has been published in the journal Blood.

More information:
Article in Blood
Peetra Magnusson’s research in Elisabetta Dejana’s group

Microscope image of a brain from a mouse with CCM3 disease showing regions in the brain that lack oxygen (
A brain from a mouse with CCM3 disease showing regions in the brain that lack oxygen (hypoxia, magenta)
due to blood vessels (collagen IV, blue) that are occluded with coagulated blood (fibrin, green). 
Photo: Fabrizio Orsenigo and Maria Globisch

Last modified: 2022-01-26