Magnesium in Vasospasm, Ischemic Stroke, and Long-Term Antithrombotic Therapy

Here are 6,300 articles discussing magnesium (Mg2+) in the treatment or etiology of vasospasm, such as occurs in response to intracranial hemorrhages:

http://scholar.google.com/scholar?q=magnesium+vasospasm&hl=en&lr=

That's not to say there aren't issues with the use of vasodilators, such as Mg2+, following subarachnoid hemorrhages or even ischemic strokes. When vasodilators are used at the same time as thrombolytic drugs, such as tissue plasminogen activator, this can increase the risk of hemorrhage (meaning the risk of a second hemorrhage following the vasoconstriction, or vasospasm, that may follow the first hemorrhage). Here's an interesting article on the use of intravenous Mg2+, administered by paramedics before people with ischemic strokes get to the hospital, as a pre-thrombolytic neuroprotective. It's difficult to get any neuroprotection without thrombolysis, but 20 percent of the people got some benefit (even though 74 percent didn't):

http://stroke.ahajournals.org/cgi/content/full/strokeaha;35/5/e106

Mg2+ is a mild NMDA-receptor antagonist (there's an Mg2+ binding site on the NMDA receptor), too, and that effect decreases calcium influx into neurons following stroke. NMDA-receptor-mediated calcium influx is a major cause of neuronal damage and loss following ischemia. That article, along with the ones on vasospasm, are on Mg2+ as a short-term vasodilator or neuroprotective, but Mg2+ also has the advantage of being more of a selective antithrombotic than both an antithrombotic and anticoagulant. This article shows that Mg2+ doesn't decrease platelet aggregation or increase the bleeding time but is, at high enough concentrations, as strongly antithrombotic as two antithrombotic drugs (drugs that block platelet aggregation induced by the binding of fibrinogen to glycoprotein IIb/IIIa on platelets):

http://circ.ahajournals.org/cgi/content/full/105/16/1970

Here are some articles showing a fairly selective antithrombotic effect (inhibition of platelet-dependent thrombosis), along with less of a hemorrhagic effect (no or minimal effects on platelet aggregation), of Mg2+:

http://www.ncbi.nlm.nih.gov/pubmed/10904104

http://www.ncbi.nlm.nih.gov/pubmed/10925332

Some articles have found that Mg2+ can increase bleeding, but it tends to have less of a hemorrhagic effect than many other substances that influence the coagulation cascade.

That article in Thrombosis Research (http://www.ncbi.nlm.nih.gov/pubmed/10904104) talks about some possible mechanisms for the antithrombotic effects of Mg2+. They reference an article showing that inhibition of calcium influx into platelets could explain the effects of Mg2+, and the authors reference other articles attributing the antithrombotic effects to the inhibition of thromboxane A2 by Mg2+.

There's some really interesting research, a lot of it now, showing that it's possible to produce selective antithrombotic effects with less-pronounced hemorrhagic effects by preventing the action of the complex of tissue factor with factor VIIa (tissue factor binds to factor VIIa, and then that binding complex activates factor X into factor Xa). Here's an example of an article on that: (http://www.ncbi.nlm.nih.gov/pubmed/12714830). What's strange is that inhibition of factor Xa did produce hemorrhagic effects, which would seem to make no sense. But the authors suggested that the inhibitor of the tissue factor/factor VIIa complex had blocked the thrombogenic effects of factor Xa, by preventing the soluble complex of tissue factor and factor VIIa from activating factor X, but had allowed some membrane-associated tissue factor to still have some hemostatic (antihemorrhagic) effects. But why wouldn't that membrane-bound tissue factor be present in the presence of solely the factor Xa inhibitor and also prevent the hemorrhagic effects of the factor Xa inhibitor? I don't think researchers understand the mechanisms well yet, and this is an incredibly complex area of medicine. I don't understand it well. It's very chaotic, and the coagulation is self-sustaining and frequently very poorly regulated by the body. Wow--that last article I cited has been cited 369 times. That's unusual and shows it's had some impact (the whole "impact factor" equation has become popular in rating the supposed importance or "impactfulness" of individual articles).