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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 2  |  Issue : 1  |  Page : 27-31

Point-of-care international normalized ratio testing is rapid and reliable: A prospective observational cohort study


1 Department of Pharmacy, Grant Medical Center, 111 South Grant Ave, Columbus, OH, USA
2 Department of Grant Medical Center, 111 South Grant Ave, Columbus, OH, USA

Date of Submission10-Nov-2015
Date of Acceptance19-Jan-2016
Date of Web Publication2-Jun-2016

Correspondence Address:
Jennifer Hartwell
Grant Medical Center, 111 South Grant Ave, Columbus, OH 43215
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2455-5568.183322

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  Abstract 

Background: International normalized ratio (INR) >1.5 may indicate need for reversal of coagulopathy or massive transfusion (MT) in trauma patients. Thus, obtaining INR values as early as possible would expedite both clinical decisions. This study evaluates the reliability of using a point-of-care (POC) device to obtain INR results more rapidly.
Methods: A trained pharmacist used the CoaguChek® XS Plus (Roche Diagnostics, Basel, Switzerland) device to determine POC INRs in venous blood from adult (>18 years) trauma patients not transfused prior to arrival. POC and laboratory INR (lab INR) values and times to availability were compared. The POC INR value was not used for clinical treatment decisions.
Results: POC INR was performed on 177 patients; 43 were excluded due to missing lab INR or later recognition of prehospital blood transfusion. The mean lab INR was 1.163, and the mean POC INR was 1.167. The paired samples correlation was 0.958 (P < 0.001). The mean difference was − 0.0045 (±0.1268), P = 0.683. Ninety-four percent of all patients had POC INR within ±0.2 of the lab INR. POC INR results were available in < 1 min; 37.2 ± 20.0 min faster than the lab INR was reported.
Conclusion: This study confirms that POC INR is a rapid, reliable tool to detect patients who may need prompt reversal of anticoagulant medications or initiation of MT.
The following core competencies are addressed in this article: Patient care, Medical knowledge, Systems based practice

Keywords: Coagulopathy, international normalized ratio, massive transfusion protocol, point-of-care testing, trauma resuscitation


How to cite this article:
Weyrauch E, Walliser G, Hartwell J. Point-of-care international normalized ratio testing is rapid and reliable: A prospective observational cohort study. Int J Acad Med 2016;2:27-31

How to cite this URL:
Weyrauch E, Walliser G, Hartwell J. Point-of-care international normalized ratio testing is rapid and reliable: A prospective observational cohort study. Int J Acad Med [serial online] 2016 [cited 2022 Nov 29];2:27-31. Available from: https://www.ijam-web.org/text.asp?2016/2/1/27/183322


  Introduction Top


In children and adults ages 1–44, trauma is the leading cause of death.[1] Over 80% of operating room deaths following traumatic events and almost 50% of deaths in the first 24 h are attributable to hemorrhage.[2] Acute traumatic coagulopathy is present in almost 25% of cases upon arrival to the Emergency Department following trauma.[3] Patients may also be taking oral anticoagulants that can increase their risk of hemorrhage. There is a large volume of literature to support rapid recognition and reversal of coagulopathy in trauma patients. MacLeod et al. found a 35% increased adjusted odds of dying if the prothrombin time is >14 s.[4] Rapid reversal of international normalized ratio (INR) in warfarin-treated patients with intracranial hemorrhage decreases mortality from 48% to 10% (P< 0.001). For every 30 min delay in initiating fresh frozen plasma (FFP), there is a 20% decreased odds of definitive (INR < 1.4) reversal within 24 h.[5] Compared to the other triggers, INR has the highest predictive value for the need to initiate massive transfusion (MT) (adjusted odds ratio [OR] 2.5 [1.7–3.7]), with an INR > 1.5 strongly predicting the need for MT.[6]

It is clear that reversal of coagulopathy is essential to improve morbidity and mortality in trauma patients. Intuitively, rapid determination of the patient's INR would expedite the initiation of MT or reversal of oral anticoagulants. When every minute counts,[5] delays in treatment while waiting for formal laboratory values to result can cause harm to the patient. For this reason, there has been robust interest in the use of point-of-care (POC) devices such as POC INR machines, thromboelastography (TEG) and handheld arterial blood gas (ABG) machines. Since there has been mixed data regarding the use of POC INR testing to determine treatment for trauma patients,[7],[8] we sought to sample the general trauma population to determine if POC INR testing can rapidly and reliably determine the INR value in the acute setting.


  Methods Top


This prospective observational study was performed from January to May 2013 in our level one trauma center where we admit over 4300 patients annually. Institutional review board approval with a waiver of consent was obtained for this validation study, which used only discarded patient blood and did not direct clinical decision making. Currently, pharmacists respond to all “Category 1” trauma alerts, and to “Category 2” trauma alerts [Table 1] during periods of pharmacist emergency department coverage, on days and early evenings.
Table 1: Trauma activation criteria

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Patients were included if they were 18 years or older, presented with increased risk of bleeding per history or mechanism of injury, and were going to have a laboratory INR (lab INR) drawn [Table 2]. Signs and symptoms of increased risk of bleeding included hypotension, penetrating injury, blunt trauma arrest or patients with abdominal pain, pelvic fracture or traumatic brain injury. Exclusion criteria included ages <18, administration of blood products prior to arrival, and no plan for lab draw of INR level [Table 2].
Table 2: Laboratory work ordered per trauma activation level

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After a bedside caregiver (nurse or paramedic) collected the necessary amount of blood for the lab work requested by the trauma team, including an INR, a trained pharmacist immediately applied discarded venous blood from the additive free syringe to the prepared POC INR test strip. Pharmacists responsible for responding to traumas as described above were trained on the CoaguChek ® XS Plus device (Roche Diagnostics, Basel, Switzerland). With the involvement of a manufacturer representative, a training program was developed with two pharmacists having the ability to verify that users were proficient at performing the POC INR test. The program involved an overview of the device and example testing. Then, each pharmacist was responsible for passing an examination and performing the test under direct observation.

The POC INR value and result time were recorded but not used for the determination of treatment. Only the INR determined by the laboratory was used for clinical treatment decisions. All healthcare providers, except for the pharmacist, were blinded to the POC INR result.

The INR value from the POC device was then correlated with the lab INR value to determine if the device could be used reliably for the determination of treatment decisions. POC INR ±0.2 compared to the lab INR value was determined to be the desired goal if the device were to be used to potentially dose concentrated blood products. Time interval for the availability of POC INR values were compared to those of the lab INR values. The timing of the lab INR was determined by the time that the value was reported in the electronic medical record (EMR).

The primary outcome was the correlation between the POC INR and the lab INR. The secondary outcome was to compare the time of availability of the POC and lab INR. This was determined by comparing the time of known POC result and the time of laboratory result reporting in the EMR. Since the POC INR was available within seconds on the device, this was considered “time zero.”

Demographic information, including age, gender, injury severity score (ISS), and use of oral anticoagulants, was also recorded. Descriptive statistics were produced using means, medians, ranges and standard deviations (SDs) for continuous variables and percentages for categorical variables. Paired sample t-test and correlation analysis was used to compare POC INR values with lab INR values. Statistical significance was evaluated at the 5% (α = 0.05) level. A preinvestigation sample size calculation was performed. With a patient population of 128 patients, there would be 80% power to show POC INR us within ±0.2 of the lab INR.


  Results Top


POC INR was performed on 177 patients. Of these, 134 patients were included in the final analysis. Forty-three patients were excluded due to missing lab INR values or later recognition of prehospital blood transfusion. Demographic data are summarized in [Table 3].
Table 3: Patient demographics

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The sample included mostly male (61.2%) patients with an average age of 51.1 years. Average ISS was 10 (range 1–75, SD 10). About 10% of the patients had documented oral anticoagulant use prior to admission.

Primary outcome

The mean lab INR was 1.163, and the mean POC INR was 1.167. The paired samples correlation was 0.958 (P< 0.001). The mean difference between the POC INR and the lab value was −0.0045 (±0.1268), P = 0.683. Ninety-four percent of all patients had POC INR within ±0.2 of the lab INR.

Subgroup analysis when groups were divided into “high” (INR > 1.5) and “low” (INR ≤ 1.5) reveals correlations as follows: The low group (n = 124) had a mean lab INR of 1.071 with mean POC INR 1.063, paired samples correlation 0.725 (P< 0.001). Mean difference is 0.0081 (±0.0993), P = 0.367. The high group (n = 10) had a mean lab INR of 2.300 with mean POC INR 2.460, paired samples correlation 0.906 (P = 0.001), mean difference −0.1600 (±0.2716), P = 0.095. These results are summarized in [Table 4].
Table 4: Point-of-care international normalized ratio and lab international normalized ratio correlation

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Only one patient had a POC INR noted to be < 1.5 but with a lab INR ≥ 1.5; conversely, only one patient had a POC INR ≥ 1.5 but with a lab INR < 1.5. These results are summarized in [Table 5]. As a result, the sensitivity and specificity of the POC INR are 91.7% and 99.2%, respectively, as noted in [Table 6].
Table 5: Point-of-care international normalized ratio correlation with lab international normalized ratio

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Table 6: Sensitivity and specificity of point-of-care international normalized ratio

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Secondary outcome

Average time to reporting of lab INR in the EMR was 37 min (range 3–119 min, SD 20 min). Time to POC INR result is <1 min on the handheld device. This resulted in an average of 37 min of time savings by using POC INR testing compared to waiting for the result in the EMR.


  Discussion Top


This study demonstrates that, overall, the POC INR performed by the CoaguChek ® XS Plus device correlates very well with the lab INR and saves, on average, 37 min over waiting for the lab INR. This key piece of data can guide the immediate bedside decision for MT or prompt the clinician to be immediately prepared to reverse anticoagulant medications when lab INR values are available. Due to a very small number of patients with elevated INR values >1.5, we cannot comment with assurance about the validity of POC INR in this subgroup, but we do feel confident that when the POC INR is reported at <1.5, the lab INR will also result at <1.5, with a negative predictive value of 0.992.

Rapid clinical decision making is essential in the care of the critically injured trauma patient. During the time elapsed before the lab INR is available, the patient's status could have significantly changed, rendering the value irrelevant to the treatment plan. INR is a significant predictor for the need for MT. In fact, the INR is the best individual trigger with the highest OR for the need for MT, followed by systolic blood pressure, base deficit, and hemoglobin.[6] POC INR, in conjunction rapid ABG, which provides hemoglobin and base deficit results, rounds out the resources which can provide the clinician with immediate data to help guide the clinical decision for MT.

Our institution recently developed a clinical practice guideline in which we seek to reverse the effects of oral anticoagulants within 2 h in our patients with intracranial hemorrhage. This is the recommendation from the American College of Surgeons in the recently released resources for the Optimal Care of the Injured Patient (6th edition). We believe the use of POC INR testing in the initial assessment of the trauma patient may help detect correctable coagulopathies earlier than standard lab testing, and we may be able to develop protocols to reduce the time to reversal of an elevated INR. However, at this time, we would caution against abandoning the use of formal lab INR test, which remains the gold standard, and should be used in the calculation for the dosing of prothrombin complex concentrate (PCC). Increased variability between the lab INR and the POC INR at values >1.5 introduce potential errors in PCC dosing. This is a limitation of the POC device noted both in the current study and is a known limitation noted by the manufacturer.[9]

We recognize there are several other limitations to our study. This was a convenience sample including nonconsecutive patients at trauma alerts that involve pharmacy response. This patient selection process gleaned lower than the expected percentage of elevated INRs and no critical values (INR > 4). Based on this, the POC INR would need to be confirmed with the lab INR if the POC INR reports a value >4. This is already current practice in the outpatient setting. Furthermore, our data collection did not reap many elevated INR values, and more variability was seen in this group with INR > 1.5. Though the sample size of elevated INRs was small, the trend of wider variance is consistent with known limitations of the device as reported by the manufacturer.[9] This would be of concern if potentially using the POC device to dose concentrated blood products such as PCC, which requires the patients' weight and INR value to calculate the dose to be administered. In addition, only the CoaguChek ® XS Plus system was evaluated in this study so the data may not be applicable to other makes and models.

This study is also limited, by its design, to restrict us from commenting on management or outcomes. While we demonstrated that the use of POC INR is reliable and can save time over waiting for the lab INR, we did not examine outcomes such as mortality, hospital or Intensive Care Unit length of stay or complications. This represents an area for future study: To evaluate whether knowing the INR value immediately with the POC INR device changes the management of the patient such as time to initiation of MT, decision for or time to operative intervention, time to receiving reversal agents such as PCC or FFP, and whether these interventions correlate to differences in outcomes.

While much has been discussed recently about the use of TEG, use of such devices require significant capital ($21,600–$34,600) for the purchase of the device and training to interpret the results.[10] The device used in our study has a list price of $1100.[11] The cost of a 1 time use POC INR cartridge, as reported to the authors by our laboratory staff, is $4.06. The formal lab INR test materials cost $0.68 ($0.59 for cartridge +$0.09 for citrated blood collection tube). However, costs associated with administration, and personnel performing the lab INR test, and reporting the result are not calculated in this lab INR estimate and would significantly increase the overall cost.[12] Use of POC INR allows clinicians to use a device which is easy to use, already present in many institutions, and the results are readily interpreted by most clinicians without specific training. Use of POC INR testing may allow a wide range of clinicians to earlier recognize a coagulopathy and the need for escalation to definitive trauma care or initiation of MT.

Though our sample of patients with INR > 1.5 was small and we cannot, based upon this current work, recommend the use of POC INR for dosing of concentrated blood products, we do feel confident that POC INR can reliably detect patients who meet the threshold value of INR 1.5 for rapid identification of those who may need MT.[6] Data from the group in Cincinnati suggests that POC INR correlates well with TEG but is faster and less expensive than TEG.[13]


  Conclusion Top


This study confirms that POC INR is a rapid and reliable tool to detect patients with elevated INR values, which would aid in time sensitive clinical decision making for reversal of anticoagulants and initiation of MT protocols.

Acknowledgments

We would like to thank Jamie Jenkins for statistics support and M. Shay O'Mara for reviewing the manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Access to Trauma Centers in the United States. US Department of Health and Human Services; September, 2009. Available from: http://www.cdc.gov/traumacare, [Last accessed on 2015 Dec 22].  Back to cited text no. 1
    
2.
Nunez TC, Cotton BA. Transfusion therapy in hemorrhagic shock. Curr Opin Crit Care 2009;15:536-41.  Back to cited text no. 2
    
3.
Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma 2003;54:1127-30.  Back to cited text no. 3
    
4.
MacLeod JB, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma 2003;55:39-44.  Back to cited text no. 4
    
5.
Ivascu FA, Howells GA, Junn FS, Bair HA, Bendick PJ, Janczyk RJ. Rapid warfarin reversal in anticoagulated patients with traumatic intracranial hemorrhage reduces hemorrhage progression and mortality. J Trauma 2005;59:1131-7.  Back to cited text no. 5
    
6.
Callcut RA, Cotton BA, Muskat P, Fox EE, Wade CE, Holcomb JB, et al. Defining when to initiate massive transfusion: A validation study of individual massive transfusion triggers in PROMMTT patients. J Trauma Acute Care Surg 2013;74:59-65, 67-8.  Back to cited text no. 6
    
7.
David JS, Levrat A, Inaba K, Macabeo C, Rugeri L, Fontaine O, et al. Utility of a point-of-care device for rapid determination of prothrombin time in trauma patients: A preliminary study. J Trauma Acute Care Surg 2012;72:703-7.  Back to cited text no. 7
    
8.
Mitra B, O'Reilly G, Collecutt M, Cameron PA, Phillips L, Davis A. Prospective comparison of point-of-care international normalised ratio measurement versus plasma international normalised ratio for acute traumatic coagulopathy. Emerg Med Australas 2012;24:363-8.  Back to cited text no. 8
    
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10.
Jackson GN, Ashpole KJ, Yentis SM. The TEG vs the ROTEM thromboelastography/thromboelastometry systems. Anaesthesia 2009;64:212-5.  Back to cited text no. 10
    
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12.
Email and Telephone Communication: Ohio Health Laboratory Services; 22 December, 2015.  Back to cited text no. 12
    
13.
Goodman MD, Makley AT, Hanseman DJ, Pritts TA, Robinson BR. All the bang without the bucks: Defining essential point-of-care testing for traumatic coagulopathy. J Trauma Acute Care Surg 2015;79:117-24.  Back to cited text no. 13
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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