The impact of acute diarrhea on the coagulation status of patients with vitamin K antagonists

Johannes Schweinfurth,Alexander Bauer,Ulrik Stervbo,Benjamin Rohn,Timm Henning Westhoff,Nina Babel,Sebastian Bertram,Maximilian Seidel,Frederic Bauer,Felix Sebastian Seibert

doi:10.1038/s41598-021-91316-x

Johannes Schweinfurth, Alexander Bauer + Show 8 more

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https://doi.org/10.1038/s41598-021-91316-x

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Abstract

Acute diarrhea is associated with a reduced absorption of both vitamin K antagonists (VKA) and vitamin K itself. To date, the net effect on the coagulation status of subjects with VKA remains elusive. We performed a systematic retrospective single-center analysis using an electronic data extraction approach to identify subjects with plasmatic anticoagulation (either VKA or direct oral anticoagulant (DOAC)) and diarrhea in a German University Hospital over a period of eight years. Acute diarrhea and complete documentation of coagulation status on admission were defined as inclusion criteria, anticoagulation other than VKA/DOAC and obvious inadherence as exclusion criteria. Subjects with VKA/DOAC admitted for hypertension served as control group. Data extraction yielded 356 subjects with gastrointestinal diagnoses and 198 hypertensive subjects, 55 and 83 of whom fulfilled all in- and exclusion criteria. INR values of subjects with VKA were significantly higher in subjects with diarrhea than in hypertensive controls (4.3 ± 3.7 vs. 2.3 ± 0.7, p < 0.001). The distribution of subjects having INR values lower, higher or within the target range differed significantly among groups with a substantially higher prevalence of overanticoagulation in the diarrhea group (46.4% vs. 14.3%, p < 0.001). In a multinomial logistic regression model, acute diarrhea was significantly associated with overanticoagulation (odds ratio 7.2, 95% confidence interval 2.163–23.921; p < 0.001), whereas age, sex, creatinine, and indication of anticoagulation were not (p > 0.05 each). Acute diarrhea is associated with a highly increased risk for overanticoagulation in patients with VKA. Thus, gastroenteritis necessitates a close monitoring of INR in order to identify subjects needing a temporary pause of VKA therapy.

Highlights

Abbreviations VKA Vitamin K antagonists international normalized ratio (INR) International normalized ratio direct oral anticoagulant (DOAC) Direct oral anticoagulant CRP C-reactive protein
These drugs have been standard of care for decades, little is known about the effects of acute episodes of diarrhea on the coagulation status of subjects with VKA
Acute diarrhea was defined as mandatory inclusion criterion, obvious inadherence, anticoagulation other than VKA/DOAC, and lack of INR data at admission were defined as exclusion criterion

Summary

Introduction

Abbreviations VKA Vitamin K antagonists INR International normalized ratio DOAC Direct oral anticoagulant CRP C-reactive protein. E. g., antibiotics like chinolons and contrimoxazole are associated with an increased risk of haemorrhage[2] These drugs have been standard of care for decades, little is known about the effects of acute episodes of diarrhea on the coagulation status of subjects with VKA. Diarrhea reduces the absorption of vitamin K itself, which could lead to temporary overanticoagulation. It remains elusive, which effect overweighs the other. In 1994, a physician reported about himself taking warfarin and suffering from overanticoagulation with excessively increased international normalized ratio (INR) values during an episode of giardiasis[3]. Over the following 20 years four further case reports indicated that diarrhea may lead to overanticoagulation in subjects taking V KA4–7.

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