Gastrointestinal and Hepatology Section, Department of Clinical and Experimental Medicine, Ospedale S. Maria della Misericordia, and Department of Biochemistry Science and Molecular Biotechnologies, University of Perugia, Italy.
Thromb Res. 2010 Jul;126(1):12-7. doi: 10.1016/j.thromres.2009.11.032. Epub 2010 Jan 3.
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, <or=17.5 mg/wk of warfarin); high dose (HD, from 35-70 mg/wk); and very high dose (VHD>or=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.
华法林的剂量需要获得治疗性抗凝水平有很大的差异在患者之间，并且可以进行突然的变化，原因不明。药物相互作用和遗传因素可能部分解释这些差异。肠道菌群产生维生素 K2（VK2）和小肠细菌过度生长（SIBO）的患者很少出现由于饮食中维生素 K 不足导致的 INR 值降低。本研究旨在探讨 SIBO 的发生是否会影响抗凝患者对华法林剂量的需求。根据他们在稳定抗凝时每周平均华法林剂量，将 30 名患者分为 3 组，每组 10 名：低剂量（LD，华法林≤17.5mg/周）；高剂量（HD，35-70mg/周）；和超高剂量（VHD>70mg/周）。每位患者都接受乳果糖呼气试验以诊断 SIBO。还评估了华法林和维生素 K 类似物的血浆水平。在 VHD 组中，改变呼吸试验的患者占 50%，在 HD 组中占 10%，在 LD 组中占 0%（P=0.01）。SIBO 的易患因素在 VHD 组中更为常见，而华法林干扰变量则不然。VHD 患者更年轻，血浆维生素 K1（VK1）浓度更高（P>0.05）。相反，血浆 VK2 水平往往较低。这项初步研究表明，SIBO 可能通过增加通过潜在受损的肠黏膜吸收的膳食 VK1 来增加患者对华法林的剂量需求，而不是增加肠道 VK2 生物合成。需要更大的研究来证实这些初步数据，并评估 SIBO 去污对华法林剂量的影响。
