Regarding Multiple Familial Cavernous Hemangiomas and Anti-inflammatories

[stronghold]

Previously people with angiomas were told to avoid anti inflammatory drugs (celebrox, viox?, ibuprofen) but the latest according to Nature Medicine February 09 is that Cavernomas are directly related to the fact that the endothelial layer of the blood vessels do not return to normal state after inflammation or injury and in response hemorrage or lesion development ocurrs (Dr Awad - taken from www.angiomaalliance.com).  So my question is, was the original assumption about anti inflammatory drugs a result of confusing correlation with causation ie we give someone a anti inflammatory and they have a bleed and we assume it is the anti inflammatory that caused it but the reality is the bleed was already getting ready to happen and by the time we offered the anti inflammatory it was too late and the endothelial layer wasnt/isnt going to respond anyway.  I am not sure how/what the function of statins are other than they lower cholesterol and remove the inner lining of cell residue?  I think.  Can you explain this clearly and simply and provide clarification?
Thank you.

[jp518]

I have a cavernoma and was just told by my neurosurgeon that anti-inflammatories wouldn't cause a bleed, but would make it worse if I had one.  This has been a big concern for me since I have daily headaches (big arachnoid cyst, too) and arthritis in my back.  I'm really interested in hearing the answer to this.  I know that there is a new clinical trial with the statins - was also wondering about the connection.
Judy

[Neuro Forum]

Thanks for using the forum. I am happy to address your questions, and my answer will be based on the information you provided here. Please make sure you recognize that this forum is for educational purposes only, and it does not substitute for a formal office visit with your doctor.

You are correct in stating that recent research has shown that certain inflammatory molecules have been implicated in the processes occurring within a cavernous angioma. However, this does not contradict the recommendation for patients with cavernous angiomas to avoid non-steroidal anti-inflammatory medications (NSAIDs) which include ibuprofen, celebrex, vioxx, and others.

In general, when a bleed occurs, for example, when you sustain a paper cut, your body responds immediately by initiating what is called a coagulation cascade in order to form a clot at the site of bleeding, to stop bleeding. First, platelets go to the area, and release several substances including one particular substance called thromboxane, and other clotting factors are recruited to the area, a clot then a scab eventually forms. This process occurs everywhere in the body to stop a bleed.

NSAIDs like ibuprofen and vioxx inhibit the formation of some of the molecules involved in the clotting cascade, so that when bleeding occurs, the body's normal response to the bleeding is impaired. The most important medication to do this is aspirin, because aspirin inhibits platelets for 7 days (that's why it has to be stopped several days before a procedure). Other NSAIDs like ibuprofen act similarly to aspirin but for a much shorter time, hours.

Because cavernous angiomas exhibit microbleeds spontaneously, if a person is taking an NSAID when a tiny bleed occurs, the body's normal defenses to stop the bleeding are impaired, leading to bleeding for a longer time, increasing the risk of a larger hemorrhage. Therefore, while the anti-inflammatory effect of NSAIDs could potentially help cavernous angiomas (theoretically), the reason they are avoided in patients with cavernous angiomas is because of the risk of bleeding.

Regarding statins, recent research in animal models of one particular genetic type of cavernous angiomas, the CCM2 animal model (a mouse model), has shown that the gene CCM2 functions in endothelium, the cells that make up the blood vessel lining, and absence of CCM2 leads to abnormal blood vessel formation and function. This abnormality was found to be mediated by a specific protein called Rho. Statins disrupt cholesterol synthesis, which in turn reduce the levels of Rho. It is hypothesized that statins will reduce the abnormalities in the endothelium that are mediated by the gene CCM2 acting through the protein Rho.

The hope is that statins will show benefit in patients with cavernous angiomas; however, cautious optimism is advised because animal data does not unfortunately always translate into human benefit. To make matters even more confusing, I will mention in case you come across this in your reading, that there has been other research that in other populations (not in cavernous angioma patients), statins may actually increase risk of bleeding.

The results of the research trial you mention above will hopefully shed light on this.

Thank you for this opportunity to answer your questions, I hope you find the information I have provided useful, good luck.