EUH Resident Report: Vitamin k administration routes for prevention of thrombosis

Bottom line: Evidence that is of low and moderate quality, respectively, is used in a guideline that recommends against routine vitamin K supplementation for patients taking vitamin K antagonists (VKAs) (grade 2c) and against routine vitamin K supplementation for patients taking VKAs with international normalized ratios (INRs) between 4.5 and 10 and no evidence of bleeding (grade 2b). Low-quality evidence resulted in a guideline recommendation of oral vitamin K for patients taking VKAs with INRs > 10 with no evidence of bleeding (grade 2c) and of the additional use of a slow IV injection rather than reversal with coagulation factors alone for patients with VKA-associated major bleeding (grade 2c) (Holbrook et al., 2012).


Holbrook, A., Schulman, S., Witt, D., Vandvik, P., Fish, J., Kovacs, M., . . . Guyatt, G. (2012). Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, 141(2 Suppl), E152S-E184S.

Crowther, M., Douketis, J., Schnurr, T., Steidl, L., Mera, V., Ultori, C., . . . Ageno, W. (2002). Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy. A randomized, controlled trial. Annals of Internal Medicine, 137(4), 251-254.

Raj, G., Kumar, R., & McKinney, W. (1999). Time course of reversal of anticoagulant effect of warfarin by intravenous and subcutaneous phytonadione. Archives of Internal Medicine., 159(22), 2721-2724.

Rivosecchi, R., Garavaglia, J., & Kane-Gill, S. (2015). An evaluation of intravenous vitamin k for warfarin reversal: Are guideline recommendations being followed? Hospital Pharmacy., 50(1), 18-24.

Guyatt, G., Cook, D., Jaeschke, R., Pauker, S., & Schünemann, H. (2008). Grades of recommendation for antithrombotic agents: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest., 133(6 Suppl), 123S-131S.


Literature states that IV vitamin K is effective more rapidly in reversing anticoagulation than oral and subcutaneous vitamin K routes (Raj, Kumar, & McKinney, 1999; Rivoscchi, Garavaglia, & Kane-Gill, 2015), and oral vitamin K is effective more rapidly than subcutaneous vitamin K (Crowder et al, 2002). Different routes have different issues. Commentary on whether the 9th edition of the guidelines are being followed states, “Subcutaneous injection is generally not recommended due to erratic absorption and unpredictable results….Intravenous administration requires the medication to be given over 30 minutes, which could prevent other medications from being administered…anaphylaxis…approximately 3 cases per 10,000 administrations…remains a risk that must be considered…if anticoagulation is reversed to below subtherapeutic levels unnecessarily, patients are at risk for thrombotic events until anticoagulation is resumed” (Rivoscchi, Garavaglia, & Kane-Gill, 2015).

Explanations of grades that were provided with 8th edition of American College of Chest Physicians’ guidelines state: “Grade 2 recommendation. For grading methodologic quality, randomized controlled trials (RCTs) begin as high-quality evidence (designated by “A”), but quality can decrease to moderate (“B”), or low (“C”) as a result of poor design and conduct of RCTs, imprecision, inconsistency of results, indirectness, or a high likelihood for reporting bias. Observational studies begin as low quality of evidence (C) but can increase in quality on the basis of very large treatment effects. Strong (Grade 1) recommendations can be applied uniformly to most patients. Weak (Grade 2) suggestions require more judicious application, particularly considering patient values and preferences and, when resource limitations play an important role, issues of cost” (Guyat, Cook, Jaeschke, Pauker, & Schunemann, 2008).


About Lisa

I have been a Clinical Informationist (aka Medical Librarian) for Emory University since September 2013. Prior to that, I was a Medical Librarian for Lincoln Memorial University (LMU) from March 2007 to August 2013 and served its DeBusk College of Osteopathic Medicine, Caylor School of Nursing, and allied health programs. From January 2002 - March 2007, I served the Medical Assisting (MA), Occupational Therapy Assistant, Physical Therapy Assistant, Radiologic Technologist, and Nursing programs at South College in Knoxville, Tennessee. I graduated from The University of Tennessee School of Information Sciences with a Master of Science degree in December 2000.
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