Small intestinal bacterial overgrowth and warfarin dose requirement variability

• Published in: Thrombosis research 2010-07, Vol.126 (1), p.12-17
• Main Authors: Giuliano, Vittorio, Bassotti, Gabrio, Mourvaki, Evangelia, Castellani, Danilo, Filippucci, Esmeralda, Sabatino, Giuseppe, Gizzi, Stefania, Palmerini, Francesco, Galli, Francesco, Morelli, Olivia, Baldoni, Monia, Morelli, Antonio, Iorio, Alfonso
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Anticoagulants; Anticoagulants - administration & dosage; Anticoagulants - pharmacology; Anticoagulants - therapeutic use; Bacteria - drug effects; Bacterial overgrowth; Biological and medical sciences; Blood and lymphatic vessels; Breath Tests; Cardiology. Vascular system; Cardiovascular system; Cohort Studies; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug Interactions; Female; Hematology, Oncology and Palliative Medicine; Humans; International Normalized Ratio; Intestinal Mucosa - drug effects; Intestine, Small - microbiology; Lactulose; Lactulose breath test; Male; Medical sciences; Menaquinone; Middle Aged; Pharmacology. Drug treatments; Phylloquinone; Pilot Projects; Vascular wall; Vitamin K - administration & dosage; Vitamin K 1 - pharmacology; Warfarin; Warfarin - administration & dosage; Warfarin - pharmacology
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2009.11.032

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, ≤ 17.5 mg/wk of warfarin); high dose (HD, from 35-70 mg/wk); and very high dose (VHD ≥ 70 mg/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.