The international normalized ratio (INR) plays a major role in clinical decision-making, based upon the Model for End-Stage Liver Disease score and international guidelines, but it is unreliable in determining a patient’s need for fresh frozen plasma (FFP) and should not be used to estimate coagulopathy risk, according to a recent study.
Instead, thrombelastography’s (TEG) ability to measure clotting in real time makes it a superior assay for determining coagulopathy risk and reducing unnecessary FFP transfusions, the researchers found.
Originally developed to guide warfarin dosing needs, the INR only identifies deficiencies in several specific procoagulant factors in the extrinsic pathway, ignoring anticoagulant factors and intrinsic pathway procoagulant factors which together may balance out the extrinsic pathway abnormalities.
"Evidence-based research does not justify reliance on the INR to determine the need for FFP transfusion in hemodynamically stable patients," wrote Dr. Sean P. McCully and his colleagues at Oregon Health & Science University, Portland, in the December issue of the Journal of Trauma and Acute Care Surgery.
Dr. Sean P. McCully
"Transfusion of FFP should be limited to bleeding patients with evidence of coagulopathy or stable patients with evidence of a hypocoagulable state on TEG who are at risk for bleeding," they wrote (J. Trauma Acute Care Surg. 2013;75:947-53 [doi:10.1097/TA.0b013e3182a9676c]).
McCully’s team used three coagulation assay methods on blood samples before and after FFP transfer from 106 hemodynamically stable trauma (35%) and surgical (65%) patients. The patients, 59% males, ranged in age from 16 to 92 years (median age, 60 years) and were assessed from February 2010 through August 2012.
Patients were excluded if they had received a massive transfusion or had taken antiplatelet agents within 10 days of admission. Overall, 262 U of fresh frozen plasma were transfused, with patients receiving from 1-4 U each.
The three methods included TEG, clotting factor activity levels, and a collection of conventional coagulation tests that included INR values. While the median INR dropped from 1.87 before FFP transfusion to a still elevated 1.53 after transfusion (P less than .001), TEG values remained in the normal range with little change before and after transfusion. The researchers found all procoagulant factor activities to exceed 30% of normal values preceding transfusions.
The overall coagulation index, calculated from the four main TEG assay variables, was -0.1 before transfusion and -0.4 after (P less than.05). The R value, representing soluble clotting factor activity with the number of minutes to initial fibrin formation, went from 7.2 before transfusion to 6.9 afterward. K time represents a combination of soluble factor activity and fibrin cross-linking, measured at 1.7 minutes before transfusion and 1.6 minutes after.
Values for alpha-angle, the rate of clot strengthening, were 66.7 degrees before transfusion and 66.5 after. Clot strength measured by maximum amplitude of tracing, representing platelet function, went from 66.1 mm before to 66.6 mm after transfusion. Clot lysis at 30 minutes, assessing fibrinolysis, was 0.2% before and 0.3% after transfusion.
Among the other conventional coagulation tests, small changes were seen: a slight reduction in partial thromboplastin time but remaining within normal range before and after transfusion, decreases in hematocrit and platelet counts and increases in D-dimer and fibrinogen levels.
The clotting factors assay revealed median values within the normal range before and after transfusion for factors VIII, IX, XI and XII (intrinsic pathway), but median values for factors II, V and X (common pathway) were below normal range before and after FFP transfer.
The below-normal factor VII median values (extrinsic pathway) before and after transfusion corresponded with the abnormal INR values but were sufficient to maintain hemostasis.
"Our data suggest that an isolated abnormal INR does not reflect coagulopathy," the researchers wrote.
"Despite transfusion-related changes, TEG continued to reflect normal coagulation in a setting without clinical evidence of bleeding," the researchers wrote. "Based on a normal TEG and functional intrinsic pathway, we believe these patients had the potential to form a robust clot and should not have received FFP."
The researchers cited past research finding that anywhere from 10% to 73% of FFP transfusions are inappropriately administered. FFP transfusion complication risks can include acute lung injury, transfusion-associated circulatory overload, anaphylactic reactions, and infections transmission.
The study was limited by the lack of a control group who did not receive FFP, the determination of the bleeding events retrospectively instead of prospectively, and lack of indications for FFP transfusion from the treatment teams.
The study was funded by Dr. Schreiber within the Trauma Research Institute of Oregon. The authors reported no conflicts of interest.