Small intestinal bacterial overgrowth and warfarin dose requirement variability

Abstract 

The dose of warfarin needed to obtain a therapeutic anticoagulation level varies widely among patients and can undergo abrupt changes for unknown reasons. Drug interactions and genetic factors may partially explain these differences. Intestinal flora produces vitamin K₂ (VK₂) and patients with small intestinal bacterial overgrowth (SIBO) rarely present reduced INR values due to insufficient dietary vitamin K. The present study was undertaken to investigate whether SIBO occurrence may affect warfarin dose requirements in anticoagulated patients. Based on their mean weekly dose of warfarin while on stable anticoagulation, 3 groups of 10 patients each were defined: low dose (LD, ≤17.5mg/wk of warfarin); high dose (HD, from 35-70mg/wk); and very high dose (VHD ≥70mg/wk). Each patient underwent a lactulose breath test to diagnose SIBO. Plasma levels of warfarin and vitamin K-analogues were also assessed. Patients with an altered breath test were 50% in the VHD group, 10% in the HD group, and none in the LD group (P=0.01). Predisposing factors to SIBO were more frequent in the VHD group, while warfarin interfering variables were not. VHD patients were younger and had a higher plasma vitamin K₁ (VK₁) concentration (P>0.05). On the contrary, the plasma VK₂ levels tended to be lower. This pilot study suggests that SIBO may increase a patient's warfarin dose requirement by increasing dietary VK₁ absorption through the potentially damaged intestinal mucosa rather than increasing intestinal VK₂ biosynthesis. Larger studies are needed to confirm these preliminary data and to evaluate the effects of SIBO decontamination on warfarin dosage.

Abbreviations: SIBO, small intestinal bacterial overgrowth, VK₂, vitamin K₂ or menaquinone, LD, low dose, HD, high dose, VHD, very high dose, VK₁, vitamin K₁ or phyloquinone, VKAs, vitamin K antagonists, INR, International Normalized Ratio, LBT, lactulose breath test, PPI, proton pump inhibitors, MKs, menaquinone-n, OR, odds ratio, CI, confidence interval, BMI, body mass index, SEM, standard error of the mean

Keywords: Anticoagulants, Bacterial overgrowth, Lactulose breath test, Menaquinone, Phylloquinone, Warfarin