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36078Re: IMPORTANT INFO: Taking CoQ10 with blood thinners

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  • Imbali (Bettina Schmolla)
    Mar 30, 2009
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      Hi Susan and Carol,

      sorry, I had intended to investigate in this topic much earlier, but then ... ;-) - Nevertheless, it was only postponed, not forgotten! :-)

      First I want to say, I am not an expert, "only" a very interested lay person with two heart kitties who might need "blood thinners" (I dislike this expression, as these drugs don't really thin the blood, they simply prevent the forming of clots in it) one day as well ...

      I did not check the resemblence of CoQ10 and Vitamin K, I "simply believe you" here. ;-) But to me it was especially interesting if Vitamin K (or anything that is structurally related) is really a kind of antidot to *any* kind of "blood thinner" or only to coumarin drugs.

      I like starting my research in Wikipedia, I must confess, and here it looks like Vitamin K is only relevant for treatments with coumarin drugs:

      http://en.wikipedia.org/wiki/Vitamin_k
      Vitamin K is involved in the carboxylation of certain glutamate residues in proteins to form gamma-carboxyglutamate residues (abbreviated Gla-residues).
      [...]
      At this time 14 human proteins with Gla domains have been discovered, and they play key roles in the regulation of three physiological processes:
      * Blood coagulation: (prothrombin (factor II), factors VII, IX, X,
      protein C, protein S and protein Z).
      [...]
      Warfarin and other coumarin drugs block the action of the Vitamin K epoxide reductase. This results in decreased concentrations of Vitamin K and Vitamin K hydroquinone in the tissues, such that the carboxylation reaction catalyzed by the glutamyl carboxylase is inefficient. This results in the production of clotting factors with inadequate Gla. Without Gla on the amino termini of these factors, they no longer bind stably to the blood vessel endothelium and cannot activate clotting to allow formation of a clot during tissue injury.

      http://en.wikipedia.org/wiki/Warfarin
      Warfarin inhibits the vitamin K-dependent synthesis of biologically active forms of the calcium-dependent clotting factors II, VII, IX and X, as well as the regulatory factors protein C, protein S, and protein Z.
      [...]
      The precursors of these factors require carboxylation of their glutamic acid residues to allow the coagulation factors to bind to phospholipid surfaces inside blood vessels, on the vascular endothelium. The enzyme that carries out the carboxylation of glutamic acid is gamma-glutamyl carboxylase. The carboxylation reaction will proceed only if the carboxylase enzyme is able to convert a reduced form of vitamin K (vitamin K hydroquinone) to vitamin K epoxide at the same time. The vitamin K epoxide is in turn recycled back to vitamin K and vitamin K hydroquinone by another enzyme, the vitamin K epoxide reductase (VKOR). Warfarin inhibits epoxide reductase[7] (specifically the VKORC1 subunit[23][24]), thereby diminishing available vitamin K and vitamin K hydroquinone in the tissues, which inhibits the carboxylation activity of the glutamyl carboxylase. When this occurs, the coagulation factors are no longer carboxylated at certain glutamic acid residues, and are incapable of binding to the endothelial surface of blood vessels, and are thus biologically inactive.
      (Wow, I had to re-read this several times to get the feeling that I understand it!)
      As the body's stores of previously-produced active factors degrade (over several days) and are replaced by inactive factors, the anticoagulation effect becomes apparent. The coagulation factors are produced, but have decreased functionality due to undercarboxylation; they are collectively referred to as PIVKAs (proteins induced [by] vitamin K absence/antagonism), and individual coagulation factors as PIVKA-number (e.g. PIVKA-II). The end result of warfarin use, therefore, is to diminish blood clotting in the patient.
      [...]
      The effects of warfarin can be reversed with vitamin K, or, when rapid reversal is needed (such as in case of severe bleeding), with prothrombin complex concentrate—which contains only the factors inhibited by warfarin—or fresh frozen plasma (depending upon the clinical indication) in addition to intravenous vitamin K.

      If I read this I find it even hard to understand how exactly CoQ10 can interfere with coumarin. I find it hard to believe that CoQ10 can be so near to Vitamin K that it can take over the work of Vitamin K in this process of building the correct active forms of the clotting factors. But I think, if it says everywhere that CoQ10 can be a problem because its structure is so near to Vitamin K, then this must be the case, or? But then I would even say: If you are giving your cat CoQ10 and Warfarin now, do NOT reduce the CoQ10 without reducing the Warfarin as well, because otherwise I would fear bleeding, for the balance between Warfarin and Warfarin antidots would not be there anymore and you would perhaps be giving your cat too much Warfarin ... But the same is of course relevant for Vitamin K in the cat food, I think. it might be a good idea to watch your cat carefully if you change the food, for the new food may contain much more or less vitamin K ... :-(

      > I am interested in this warning as well. Our cat is on Plavix, which
      > is somewhat more forgiving than warfarin or heparin, but it does say
      > in the warnings that CoQ10 may affect Plavix' effectiveness.

      And now this is something that I don't understand: After reading the explanation of vitamin K and Warfarin in Wikipedia (by the way I researched it in German first, much easier for me ;-) and then looked it up in English as well), I don't really understand how CoQ10 could interfere at all with a drug that does not work like a coumarin, inhititing the synthesis of biologically active forms of some calcium-dependent clotting factors.

      http://en.wikipedia.org/wiki/Plavix
      Clopidogrel is a pro-drug whose action may be related to adenosine diphosphate (ADP) receptor on platelet cell membranes. The specific subtype of ADP receptor that clopidogrel irreversibly inhibits is P2Y12 and is important in platelet aggregation and the cross-linking of platelets by fibrin. The blockade of this receptor inhibits platelet aggregation by blocking activation of the glycoprotein IIb/IIIa pathway. The IIb/IIIa complex functions as a receptor mainly for fibrinogen and vitronectin but also for fibronectin and von Willebrand factor. Activation of this receptor complex is the "final common pathway" for platelet aggregation, and is important in platelet aggregation, the cross-linking of platelets by fibrin.

      To me this looks like a mechanism very different from the one in coumarins. So how can CoQ10 interfere with this drug? I reas it but have difficulties understanding how ...

      > I have decided to gradually reduce the amount of CoQ10 we have been
      > giving--

      Hmmmmm, *if* CoQ10 really interferes with plavix and your cat is on its personal, optimal dose of Plavix now, then I would probably rather not dare change anything ... (Sorry, I know that these thoughts of mine are very late now ...)


      By the way, now I was curious and looked up Aspirin as well:
      http://en.wikipedia.org/wiki/Aspirin
      Aspirin's ability to suppress the production of prostaglandins and thromboxanes is due to its irreversible inactivation of the cyclooxygenase (COX) enzyme. Cyclooxygenase is required for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the COX enzyme.
      [...]
      Low-dose, long-term aspirin use irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation.

      Does anyone understand, how CoQ10 could interfere in this process ???


      I haven't tried now to find out anything about Nattokinase, I remember my last research where I wasn't really able to find out how *exactly* Nattokinase prevents clotting. And if I don't know that, I can't know which other drugs / supplements could interfere with the anti-clotting effect of Nattokinase either ... :-(


      Hm, as I said in the beginning, I'm not an expert, so there might be wrong conclusions in my mail here ... But to me it looks very much like CoQ10 can hardly interfere with other drugs than coumarin. And I would not reduce CoQ10 in the therapy of a cat getting Warfarin without reducing Warfarin as well or at least watching my cat very, very carefully afterwards ...


      Sorry, this has become very long now ... Typically me ... ;-)

      Greetings
      Bettina with 2 1/2 heart kitties
      and more of them without heart problems
      http://www.pristine-paws.de
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