FFPA 55 year old woman presents as the driver of a motor vehicle collision. She has moderate abdominal tenderness diffusely and a seat belt sign, but has a negative abdominal/pelvis CT. Her INR, however, was noted to be 2.1. She is not on any vitamin K antagonists. The surgeons admit her to the hospital to observe for a potential hollow viscus injury and requests that you order 2 units of FFP for her. Seems reasonable… or is it? What is the logic?

Background 

In patients NOT taking vitamin K antagonists, an elevated international normalized ratio (INR) is presumed to represent bleeding risk and therefore be a useful measurement in traumatic and surgical patients. It is not clear, due to the limited scope of the INR to measure actual bleeding/clotting homeostasis as opposed to the extrinsic pathway, that the INR directly reflects the underlying bleeding risk of acutely ill patients. As a corollary, patients with chronic liver disease frequently have elevations in their INR due to insufficient protein synthesis but are still at increased risk for clotting. In spite of this, indications for FFP transfusions in surgical and traumatically injured patients center on the assessment and subsequent normalization of the INR. 

Is there a better marker for bleeding risk?

Thromboelastography (TEG)

TEG is a point of care test that measures multiple parameters of bleeding hemostasis from blood clot initiation to lysis at a given patient body temperature (more on TEG on LIFTL). After the calculation of multiple data points, the final reading is provided as a coagulation index (CI), or overall state of coagulation. The normal reference range is -3 to 3. Values <-3 represent a bleeding risk (hypocoagulable state) and >3 represent a thrombotic risk (hypercoagulable state).

Article

McCully SP et al.  The International Normalized Ratio overestimates coagulopathy in stable trauma and surgical patients. J Trauma Acute Care Surg. 2013 Dec;75(6):947-53. Pubmed

Objective

  • To compare INR versus TEG prior to and after the administration of FFP in trauma and surgical patients 

Study Method

  • Single center prospective observational study of trauma and surgical patients who were > 16 years of age, hemodynamically stable, and received FFP transfusions
  • Exclusion criteria: 
    • Patients undergoing massive transfusions
    • Blood was unable to be collected
    • Patient had ingested an antiplatelet agent within 10 days. 
  • A total of 106 patients (35% traumatic, 65% surgical) were included in the final analysis. 

Results

  • INR monitoring:
    • Before transfusion of FFP, patients’ average INR = 1.83
    • After transfusion of FFP (range of 1-4 units FFP/patient), patients’ average INR = 1.53
  • TEG: 
    • Before transfusion of FFP, patients average CI= -0.1
    • After transfusion of FFP, patients average CI = 0.4
    • Despite the change in slight decrease in INR (1.83 to 1.53), the pre- and post-FFP CI’s (-0.1 to 0.4) were all in the normal range. 

Analysis

As with various other indirect measurements of patient disease burden (e.g. LDL cholesterol), the INR in these patients not taking vitamin K antagonists did not reflect patient-oriented disease specifics– in particular the need for FFP transfusions. Following the established recommendations likely exposed these patients to harm via the unnecessary transfusions based upon a surrogate marker that does not directly assess actual bleeding risk. The study is however predicated upon the TEG as the gold standard of bleeding homeostasis, and this is far from established. 

Future Directions 

The study is intriguing and should be reproduced utilizing a primary cohort of emergency department specific disease entities and in particular traumatic injuries. It raises further speculations regarding the applicability of INR to patients not on vitamin K antagonists and harkens to the litany of prothrombin complex concentrates (PCC) studies that are predicated upon a more rapid correction of INR than FFP. Should INR not adequately reflect true bleeding risk in this cohort, it is imperative that guideline-based medicine for the management of bleeding risk derive its basis on demonstrable patient oriented outcomes rather than surrogates.   

Take Home Points

  1. The INR overestimated bleeding risk in a small cohort of surgical and trauma patients not on vitamin K antagonists.
  2. Utilizing the INR likely leads to unnecessary FFP transfusions in this cohort.
William Paolo, MD

William Paolo, MD

Residency Program Director
Assistant Professor of Emergency Medicine
SUNY-Upstate Medical Center
William Paolo, MD

@paolomd1

Residency Program Director, Obsessed with Philosophy, Science, Evidence Based Medicine, and Pizza