Periods of ‘severe bleeding’ after trauma or during surgery require real-time management of hemostasis to preserve life. Due to their ability to produce rapid results and a multitude of other characteristics, POCT is becoming the gold standard in hemostatic management. In recent years there has been an increasing demand for POC hemostatic tests and as a result of such, along with advancements in technology, there has been a significant increase in both the spectrum of tests available and the number of tests performed (1). Following is a review of the main groups of clinically available POC hemostasis tests.
Viscoelastic POC techniques are based on thromboelastography, they are used to measure the time until clot formation begins, the dynamics of clot formation, and the solidity and stability of clots over time. Viscoelastic tests are of an advantage in acute situations such as trauma-induced coagulopathy, transfusions management, intra- and postoperative bleeding and targeted hemostatic therapy. Guidance obtained by using viscoelastic methods in the detailed settings has resulted in the improved outcome of the patients. One unique advantage of viscoelastic techniques is that they can directly detect hyperfibrinolysis; no conventional coagulation test can do this reliably (2). Additionally, unlike most convectional laboratory hemostasis tests, viscoelastic tests use whole blood samples. This initially reduces the need for sample preparation, but most importantly gives this method its greatest advantage. It provides results that most closely resemble that of in vivo hemostasis, whereas laboratory tests are often regarded as producing a highly artificial measurement of hemostasis. However, there is still room for development with viscoelastic tests. Development of new sensor technology could help increase the accuracy and sensitivity of the tests, an area that is sometimes questioned. Additionally, the cost of reagents used in these POC devices drive up costs, whilst the complexity of use and understanding of results finds that many hospitals do not use them at the point of care. Instead they have a live feed of results in which the healthcare professionals have access to at the point of care.
Platelet function tests (PFT)
Platelets are one of the key components of hemostasis, and there is a variety of assay methods available for the quantitative assessment of their function. Light transmission aggregometry has remained the gold standard for over 60 years, however, due to its cumbersome protocol that includes a series of tests, several point of care devices have been developed (3). The POC devices work based on the concept that an individual’s thrombotic profile could be assessed in vitro by assessing the response to stimulation of platelet aggregation by specific, usually solo agonists such as adenosine diphosphate (ADP), collagen and thrombin. Advances in research and understanding of platelet function have left current clinically available POC PFTs with many limitations. Most tests still rely on specific agonist-induced platelet aggregation using citrate-anticoagulated blood under static conditions, while the significance of high flow, shear and locally-generated thrombin is ignored. To reflect physiological processes, POC tests should assess non-anticoagulated blood at high shear, to reflect and assess the dynamics of thrombus formation, platelet reactivity and thrombus stability, as well as the rate of endogenous thrombolysis of the occlusive thrombus (4).
Blood gas analysers
Although they do not actually assess hemostasis, blood gas analysers are most commonly grouped with hemostatic POCT due to the physiological parameters they assess. In principle, all blood gas analysers are actually POC devices. They primarily aim to measure the oxygen and carbon dioxide levels in the blood as well as the acid-base equilibrium, however, there is now a range of parameters that can be assessed. They are most commonly used in a critical care setting and can provide a more complete picture for coagulation management (5). However, blood gas analysis fails to yield a specific diagnosis, a patient with asthma for example may present similar results to another patient with pneumonia. Furthermore, one of the greatest drawbacks comes with the narrow operational temperature range (6). The process of blood gas analysis involves heating of the blood to normal body temperature. Recent advancements in sensing technology have required smaller samples of blood that can be used at room temperature, boasting a massive advantage in the production of rapid results.
Internationalised Normalised Ratio (INR)
POC testing in hemostasis is not confined to acute care settings. The most obvious example is the out of hospital monitoring of patients who are administered an anticoagulant, such as warfarin. The dose of warfarin is depended on the results of a blood test called the internationalised normalised ratio (INR). The INR measures the length of time taken for an individual’s blood to clot. The longer the clotting time takes, the higher the INR. The majority of POC INR testing is performed using fully automated machines (7). This has given patients more control over their drug regimens and reduced disruption to their lives caused by frequent visits to the hospital for testing. Furthermore, the POCT requires only a finger prick to retrieve a blood sample, as opposed to the full venous blood sample usually required, which has been found to be a great advantage to many patients.
However, there are several interfering factors that can cause variations in the results produced by at home INR testing. The volume of capillary blood required can vary on the test/manufacturer used, this can range from 3 to 50 µl (8). Often the larger volumes can be difficult to obtain without squeezing the finger. Furthermore, the test strips have a time constraint between ‘warm-up’ and the application of the blood. In situations where there are difficulties obtaining the sample as with the larger volumes in the range, this can affect the time constraint and ultimately affect results. Finally, the tests do not account for abnormalities in the sample such as increased viscosity, haemolysis or hyperbilirubinemia which can all have varying effects on the results (9).
Electrochemical sensing is an ideal method to develop highly accurate, robust, and cost-effective point of care (POC) devices. A platform that utilises electrochemical parameters to measure clotting blood as well as multi-sensing applications in blood, is one that holds significant potential for a low-cost, scalable diagnostic device development. Electrochemical biosensors embedded inside microfluidic chips facilitate multiplexed sensing of different parameters, such as pH, oxygen, glucose, lactate, and chloride; allowing for the development of multiplexed microfluidic chips for blood coagulation monitoring and other blood tests.
At Integrated Graphene we have a host of solutions including microfluidic and bespoke lab-on-a-chip development, as well as our novel 3D Graphene Foam biosensor, Gii-Sens, that are primed to be incorporated into your next rapid diagnostic platform. Contact us today to find out about the potential of our solutions to develop low cost and multiplexed blood assessments.
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- Self-monitoring of oral anticoagulation: does it work outside trial conditions? Gardiner, C, et al. 2, s.l. : Journal of Clinical Pathology, 2009, Vol. 62.
- Point-of-care testing in haemostasis. Perry, D J, et al. 5, s.l. : British Society for Haematology, 2010, Vol. 150.
- Hemolyzed Samples Should be Processed for Coagulation Studies: The Study of Hemolysis Effects on Coagulation Parameters. Arora, S, Kolte, S and Dhupia, J. 2, s.l. : Annals of Medical and Health Sciences research, 2014, Vol. 4.