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23-06-2010 | Cardiology | Article

Intestinal bacteria may predict warfarin dose requirements


Free abstract

MedWire News: An excess of bacteria in the small intestine may increase the amount of warfarin necessary to achieve a therapeutic anticoagulant effect, Italian researchers believe.

It has been widely observed that the dose of vitamin K antagonists (VKA) – such as warfarin – necessary to achieve an anticoagulant effect varies greatly between individuals.

“Acquired conditions, such as concomitant administration of interacting drugs, other diseases, variation in dietary intake of vitamin K, and genetic polymorphisms can partly explain this variability,” explain Vittorio Giuliano (Ospedale S Maria della Misercordia, Perugia) in the journal Thrombosis Research.

Previous studies have reported that production of vitamin K by intestinal bacteria can greatly influence VKA requirements, the researchers add.

To test this idea, Giuliano and team tried to find links between the dose of warfarin necessary to achieve stable anticoagulation and intestinal bacteria levels in 30 patients on chronic VKA therapy for atrial fibrillation, venous thromboembolic disease, or after aortic valve replacement.

The group was split evenly between individuals requiring low (≤17.5 mg/wk), high (35–70 mg/wk), and very high (≥70 mg/wk) doses of VKA to maintain stable anticoagulation.

Specifically, excessive intestinal bacteria levels, or small-intestine bacterial overgrowth (SIBO), was diagnosed using a lactulose breath test.

Testing revealed that of the five of the six patients with a breath test indicating SIBO required very high doses of warfarin . The remaining patient with an abnormal breath test required a high dose of warfarin, and none of the patients receiving low doses of warfarin had an abnormal breath test.

The researchers also found that factors predictive of SIBO were more prevalent in patients receiving very high doses of warfarin, while warfarin interfering variables were not.

The team also found that patients requiring very high doses of warfarin were also younger than other patients, and had a higher plasma levels of dietary-derviced vitamin K1 but lower, flora-derived plasma vitamin K2 levels.

Cautioning that their findings should be confirmed in larger studies, the authors conclude that their results “suggest a role for intestinal bacterial flora as a cause for warfarin variability.”

“The quantitative or qualitative modulation of intestinal flora through prebiotics, probiotics, or dietary supplements might, therefore, positively affect the response to vitamin K antagonists and help to avoid potentially fatal abrupt variation of International Normalized Ratio values.”

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Philip Ford

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