Hemostasis and Coagulation in Acute/Intensive Care
Author: Luca Vita
Hemostasis is a tightly regulated natural process which leads to cessation of bleeding after damage to a blood vessel has occurred. It is regarded as the initial step of wound healing and can be broken down into three main steps. Vasoconstriction is the initial stage which restricts blood flow to the damaged area. Platelet plug formation is the second stage and is regarded as primary hemostasis. The final stage is coagulation and is regarded as secondary hemostasis.
Abnormalities in hemostasis are commonplace amongst individuals who are deemed critically ill with cardiovascular disease and admitted to an intensive care unit (ICU). Furthermore, hemostatic abnormalities also frequently occur during anaesthetic and surgery. As such, precise hemostatic monitoring is compulsory in both a critical care and perioperative setting. Currently hemostatic management is done via traditional laboratory testing, most commonly the prothrombin time (PT) test or at the point-of-care via viscoelastic methods (VEM).
Laboratory Testing
With hemostasis and coagulation being such an intricate, multi-step process, a multitude of laboratory tests are available that target different parts of the process. Prothrombin time was one of the first tests developed, around 75 years ago and continues to be the most commonly used. There are two variations of PT currently used, Quick-time PT and Owren-type PT (4). The test measures the time taken for a fibrin clot to form in platelet-poor plasma stimulated with a high amount of tissue factor and anionic phospholipid at the optimal concentration of calcium (5). One of the biggest advantages with the PT test is its ease of ability to be automated which reduces variability between tests and reduces the time taken by manual operators. However, even with automation, laboratory PT tests have roughly a 90-minute result turnaround time (6). Additionally, due to the plethora of reagents that can be used to perform the test there can often be large variation in the results produced from lab to lab, or sometimes even within the same lab. To overcome this an internationalised normalised ratio (INR) was developed to standardise the results.
POC testing
More recently evidence has suggested that the use of point-of-care testing in the management of hemostasis results in the need for fewer blood transfusions, increased overall patient outcome and a reduction in healthcare costs. Viscoelastic methods have allowed for the development of such tests. Thromboelastography and thromboelastometry are the two most common point-of-care assays that use viscoelastic technologies (7). The assays work by measuring the change in viscoelastic properties of the whole blood whilst a clot is forming. With a firmer clot producing greater resistance against the movement of rotating particles in the measuring device (8). Like any point-of-care device, the greatest advantage they pose over traditional laboratory testing is the quickness of results and the ease of use. VEM can be performed by minimally trained individuals and can provide results in as little as 3 minutes. Furthermore, the lack of need for expensive laboratory equipment helps cut costs. However, the greatest disadvantage with using VEM is that they only assess secondary hemostasis and therefore does not give the complete picture of hemostasis. Additionally, as the majority of the generally used antiaggregant medication targets primary hemostasis, VEM assays are blind to them (9).
Future of Hemostasis Testing
As stated, POCT boast the advantage of having reduced costs over traditional laboratory tests, Gii-Sens takes this further. Its patented one step production process and ease of integration into any assay ensure costs are kept to a minimum whilst our fully cooperative assay development guarantees an easy integration. Fortunately, low cost does not come at the sacrifice of other key qualities. Gii is the words first 3D graphene foam, due to this structure it has a large electrochemically active area allowing for a higher saturation of recognition molecules, lowering the limit of detection. Not only does the structure of Gii enhance assay quality, but its composition does too. With over 98% carbon purity, Gii is able to surpass the electrochemical quality of commonly used noble metals permitting assay development with higher sensitivities. However, POCT is not the only application of our novel sensing technology. With current technologies traditional laboratory blood tests still exceed the accuracy and sensitivity of that achievable by POCT. Integration of Gii-Sens into laboratory scale tests can help reduce some of the large costs whist maintaining the expert quality they provide.
However, the most significant characteristic is that Gii-Sens also has the potential for multiplexing. This is the ability to measure multiple analytes in a single experiment, which is possible due to the embedment of electrochemical biosensors inside microfluidic chips. Furthermore, microfluidic centrifugal technology has allowed for miniaturisation of traditional laboratory processes such as blood plasma separation whilst different fluorescent probes provide monitoring of different blood coagulation factors such as thrombin and fibrin. This innovative multiplexed sensing technology is a promising development in the production of low cost, multiplexed blood analysis.
Are you developing a hemostasis point of care test? Do you want to explore the possibilities opened up by utilising a high-performing electrochemical platform? Contact us today
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