Feature | Point of Care Testing | May 05, 2017| Nicholas C. Vanderslice, Ph.D., and Arnol S. Rios

Advances in Point-of-Care Coagulation Analyzer Technology

New POC coagulation testing systems can provide reassurance of lab-accurate patient PT/INR results   

Siemens Xprecia Stride anticoagulation, coagulation PT/INR or INR testing at the point of care (POC)

Point-of-care coagulation PT/INR testing with handheld devices can help improve outcomes with more convenient and frequent measurements to keep patients within the therapeutic range of anticoagulant agents.

Point-of-care (POC) coagulation analyzers that measure prothrombin time/international normalized ratio (PT/INR) on fingerstick capillary blood are used to support the monitoring of patient oral anticoagulant therapy (OAT) with vitamin K antagonists. These agents include warfarin (Coumadin), phenprocoumon (Marcumar) and acenocoumarol (Sintrom, also sold as other brand names). 

The agents have a narrow therapeutics window and their effectiveness can be impacted by the patient’s diet if they eat vitamin K-rich foods like green, leafy vegetables, so regular monitoring is necessary. POC coagulation analyzers offer many clinically useful advantages in the treatment of a growing patient population requiring OAT, most notably the provision of near-instant test results. 

The therapeutic range of warfarin is very narrow so PT/INR result without the wait that laboratory testing incurs allows physicians to make immediate and often more frequent adjustments to anticoagulant dosage. This increases the patient’s time in the therapeutic range and potentially lowering the risk of adverse events.[1] Accordance between POC PT/INR and clinical laboratory PT/INR measurement has repeatedly been shown to be good, despite a cloud on the POC testing horizon cast by the 2016 withdrawal from market of one manufacturer’s PT/INR monitoring systems for reportedly generating inaccurate low readings.[2] Healthcare professionals and patients seeking reassurance that POC PT/INR testing remains safe and effective for the monitoring of OAT can be confident in the advances the industry continues to make to ensure accuracy of device results.  

 

Oral Anticoagulant Therapy

OAT is prescribed on a long-term basis for people who have experienced recurrent abnormal blood clotting, or for those who are at high risk of developing clots. For example, patients with atrial fibrillation, a common cardiac arrhythmia that affects an estimated 2.7-6.1 million people in the USA,[3] are at risk for blood clots, including those that cause ischemic stroke. OAT is frequently prescribed to reduce these stroke risks, but use of these medications typically necessitates frequent patient monitoring through blood tests. More than 800 million PT/INR tests are conducted annually worldwide.[4] An increasing population of patients on warfarin therapy and the trend toward testing outside of the laboratory have escalated demand for reliable PT/INR results on convenient, easy-to-use POC analyzers.

 

Prothrombin Time and the International Normalized Ratio

PT is a measure of clotting time subject to differences in type and sensitivity of the various commercial thromboplastin reagents used in its determination. Monitoring of OAT is usually based on the INR, a mathematical adjustment of the PT introduced to standardize values and the interpretation of results. An INR calculation relies on a thromboplastin manufacturer’s international sensitivity index (ISI) number, which mathematically compares a thromboplastin reagent lot to an international reference standard.[5] Commercial POC analyzers report both in PT seconds and INR units utilizing handy and biosafe disposable reagent test strips.

 

POC Coagulation Testing Allows Rapid Patient Interventions

Although laboratory determination of PT/INR remains the gold standard of reference in instances of an unexpected patient result, POC PT/INR measurement offers significant advantages as a decision and management tool both in and out of the hospital. In the emergency room, in the coronary care unit, in surgery, and in procedure suites when time is paramount, POC PT/INR analyzers provide immediate, actionable results. These devices also can help expedite patient management in a range of settings as diverse as outpatient clinics, physicians’ offices and surgeries, pharmacies, care centers and patients’ homes. 

Some POC PT/INR analyzers are convenient, lightweight, handheld devices designed to require a minimum of instruction or expertise to use effectively. They do not require an invasive venous blood draw, and in outpatient settings, can reduce a warfarin anticoagulant therapy patient’s visit from three hours or more to as few as 30 minutes. Since there is no wait for a lab result, a dosage adjustment can be made, when indicated, during the patient visit. No delay, and the greater frequency of assessment and adjustment in treatment that POC PT/INR testing supports, helps ensure that a patient has the best chance of maintaining time in therapeutic range (TTR). Studies have shown that fast POC coagulation testing improves TTR.[6,7,8] More time in TTR is reported to reduce likely incidence of stroke. Less time in TTR is associated with increased rates of recurrent venous thromboembolism and major bleeding, and in atrial fibrillation patients, an increased risk of ischemic stroke. 

A low TTR has also been shown to be predictive, in patients on vitamin K antagonist therapy, of death, systemic embolism and myocardial infarction. Vitamin K antagonist therapy treatment after a stroke, blood clot, or heart valve issue, for instance, inevitably balances between prevention of further complications and avoidance of hemorrhage. More frequent patient monitoring can help reduce the odds of adverse events.

 

POC Coagulation Testing Remains Accurate

A solitary device withdrawal from the market in 2016 is unlikely to adversely impact growing demand for, and confidence in, POC coagulation testing. Scores of studies comparing POC with laboratory PT/INR testing have affirmed its accuracy, validity, clinical efficiency and overall safety.[6,7,8] Furthermore, other studies have shown that patient compliance with appointments improves verses laboratory result timescales.[9] POC PT/INR analyzers remain safe and effective for the monitoring of OAT when supported by validated reference lab methods and testing regimes. 

This acknowledges some known limitations. Systematic bias compared to laboratory measurement is possible, variable bias often resulting from the local laboratory calibration method. PT/INR results from different methods are not always equal (for many reasons, including varieties of clot detection, thromboplastin reagent and endpoint detection), yet POC PT/INR remains effective, correlating with important outcomes in multiple clinical trials and improving patient management.

 

Manufacturer Developments Continue to Advance the Quality of Results

The latest POC coagulation analyzers generate timely results without sacrificing the diagnostic quality controls provided by the central lab. POC testing has to balance the quest for fast results against the absolute for accuracy and QC that the lab assures. A recent FDA-cleared POC PT/INR device is the Xprecia Stride Coagulation Analyzer from Siemens Healthineers. This device has demonstrated PT/INR testing performance equivalency with the Roche CoaguChek XS POC system, and also reference laboratory analysis.[10] The system employs the same Dade Innovin thromboplastin test reagent as many reference laboratory platforms, an industry advance which eliminates a potential source of variability in the correlation and comparison of results. Another industry safeguard is auto-detection of adequate application of fingerstick blood to the device test strip to prevent an erroneous read. 

Recent POC PT/INR devices provide both electronic and internal QC checks on test strips. Convenient device test strip eject mechanisms allow safe disposal of used strips to minimize operator exposure to potential contamination from patient blood.             

POC PT/INR testing remains a safe and effective option for the monitoring of patients on OAT, although clinicians need to be aware of the reasons why both POC and laboratory PT/INR results from different methods are not always equal, despite the implementation of the INR standard. Manufacturers continue to advance accuracy and quality control in this growing sector of the POC testing marketplace, but nevertheless need to educate clinicians as to the reasons behind differences observed in PT/INR method comparisons.

 

Read the related article "Advances in Point-of-Care Anticoagulation Testing Systems."

 

Read about newer anticoagulants that do not require INR testing "Advantages and Disadvantages of Novel Oral Anticoagulants."

 

Watch the video "Editor’s Choice of the Most Innovative Cardiology Technology at TCT 2016," which includes a segment on the latest POC INR testing system from Siemens.
 

 

Editor’s note: Nicholas C. Vanderslice, Ph.D., is senior scientist, point of care diagnostics at Siemens Healthineers.  Arnol S. Rios, is senior manager of global marketing, point of care diagnostics at Siemens Healthineers 

References:

1.    Ryan, F., S. O’Shea, and S. Byrne. "The reliability of point‐of‐care prothrombin time testing. A comparison of CoaguChek S and XS INR measurements with hospital laboratory monitoring." International Journal of Laboratory Hematology 32.1p1 (2010): e26-e33.
2.    https://www.fda.gov/Safety/Recalls/ucm510746.htm
3.    https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_atrial_fibrillation.htm
4.    Jackson, Craig M., and M. Peter Esnouf. "Has the time arrived to replace the quick prothrombin time test for monitoring oral anticoagulant therapy?" Clinical Chemistry 51(3) (2005): 483-485.
5.    WHO Expert Committee on Biological Standardization. "Guidelines for thromboplastins and plasma used to control oral anticoagulant therapy." World Health Organ Tech Rep Ser 889 (1999): 64-93.
6.    Newall, Fiona, Paul Monagle, and Linda Johnston. "Home INR monitoring of oral anticoagulant therapy in children using the CoaguChek S point-of-care monitor and a robust education program." Thrombosis Research 118.5 (2006): 587-593.
7.    Gardiner, Chris, et al. "Patient self‐testing is a reliable and acceptable alternative to laboratory INR monitoring." British Journal of Haematology 128.2 (2005): 242-247.
8.    Ansell, Jack, et al. "Guidelines for implementation of patient self-testing and patient self-management of oral anticoagulation. International consensus guidelines prepared by International Self-Monitoring Association for Oral Anticoagulation." International Journal of Cardiology 99.1 (2005): 37-45.
9.    Gialamas, Angela, et al. "Does point-of-care testing lead to the same or better adherence to medication? A randomised controlled trial: the PoCT in General Practice Trial." Medical Journal of Australia 191.9 (2009): 487.
10.    White Paper, Fernando R, Jacobson AK, Kennedy S, Lessard C, Olson K, Scribner A, “PT/INR Test Performance of the Xprecia Stride Coagulation Analyzer Demonstrates Equivalency with Established Laboratory Hemostasis and Point-of-care Methods.”

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