Causes of an elevated international normalized ratio in the intensive care unit and the implications for plasma transfusion

Abstract

Background: The presence of an elevated international normalized ratio (INR) is common in patients in the intensive care unit (ICU), but the cause rarely determined. These patients are at risk to receive prophylactic plasma prior to invasive procedures.Study design and methods: Samples from patients with an INR of 1.5 or greater were frozen and subsequently thawed and assayed for procoagulant and anticoagulant clotting factors and anti-Xa to determine the likely cause of the INR. Samples showing a low FVII, FX, PC, and PS were categorized as a vitamin K deficiency pattern. Samples showing a low FV, low or normal fibrinogen, and high FVIII were categorized as a liver disease pattern. Samples showing an anti-Xa >0.01 IU/ml were assayed for anti-Xa DOACs. Samples which could not be categorized were grouped as equivocal. Results: A total of 48 samples were obtained over a 6-month period. Nineteen showed a Vitamin K deficiency pattern, 17 a liver disease pattern, 7 showed an anti-Xa DOAC and 5 were equivocal. High FVIII and D-dimers and reduced levels of the anticoagulant proteins were present in the majority of the samples. FVII levels correlated inversely with the INR (r = À0. 81), as did FX (r = À0.67) but not FV (r = À0.04) nor fibrinogen (r = À0.15). Conclusion:Transfusion of plasma to reverse an elevated INR in the ICU should be discouraged since such a practice is either avoidable by the use of vitamin K or inappropriate in the case of liver disease or an anti-Xa DOAC.

Vitamin K: a potential missing link in critical illness–a scoping review

“…This scoping review is the first to explore the mechanisms and consequences of vitamin K deficiency in this population. Six studies analyzing ICU patients' vitamin K status indicate many patients may have (sub)clinical deficiency upon admission and during their stay [ 14 – 16 , 83 , 114 , 115 ]. Deficiency may appear subclinical with normal PT but high PIVKA levels, possibly masking extrahepatic vitamin K function due to hepatic carboxylation favoring [ 15 ].…”

Elevated INR in the ICU and plasma transfusion

“…3 In a recent study, we have observed that a large percentage of these patients (40%) have a clotting factor pattern more consistent with vitamin K deficiency. 5 Therefore, we believe that before a study of prophylactic plasma should be performed, the cause of the elevated INR should be identified in order to avoid the "one intervention (prophylactic plasma) fits all elevated INRs approach. "…”