It was identified that HTPR was associated with ischemia risk, while LTPR was associated with bleeding risk in patients who underwent DAPT. For example, ADAPT - DES (Assessment of Dual Antiplatelet Therapy With Drug - Eluting Stents) research data show that high platelet reactivity under clopidogrel treatment had significant positive correlation with stent thrombosis and myocardial infarction, while had negative correlation with hemorrhage following PCI. It prompts that the detection of platelet activity has potential value on monitoring, adjustment and individualization of antiplatelet therapy during P2Y12 inhibitor treatment . Why didn't we get the results we had guessed in this study? The possible reasons are as follows.
The first is that this retrospective study reflected the situation in the real world. The TEG results analyzed were the baseline condition under DAPT during perioperative period of PCI. Subsequent individualized adjustment of antithrombotic drugs was probably applied following an unsatisfied result of TEG, which might be the main reason to correct the underlying risk of thrombus or bleeding. For example, if TEG suggested HTPR following PCI, clopidogrel was replaced with ticagrelor or a doubled dose for a least one month after discharge. On the contrary, patients with LTPR who presented with bleeding tendency might have altered DAPT plan and duration during follow-up. And this is the purpose of PFT, the individualized adjustment of anti-platelet therapy. Therefore, the negative results of this study may be instead encouraging. Despite differences in platelet reactivity at baseline, it is not surprising that there was no difference in five-year outcomes after the most likely individualized adjustment of antithrombotic strategies. If the inference holds, the value of TEG cannot be negated easily in guiding antithrombotic therapy in patients with ACS and TP.
Secondly, it is still important to acknowledge the technical advantages and limitations of TEG, as well as other PFT technologies. Currently, there are a variety of commonly used methods for PFT in clinical practice, with different detection standards. Different experimental methods have their own advantages and disadvantages. Currently, no detection method has been found to be comprehensively superior to other methods [28-35]. Since the platelet aggregation method has a certain dependence on the platelet count, the detection results have a large deviation in patients with TP . The application value of flow cytometry detection has been reported, and it has been confirmed in patients with idiopathic thrombocytopenic purpura (ITP) that the platelet longevity and protease-activated receptor-1 related activity was significantly associated with bleeding fraction in patients with ITP, independent of platelet count . Due to many factors such as clinical availability and cost, optical turbidity assay and TEG detection are carried out in most domestic centers, while VerifyNow rapid analyzer, flow cytometry, PFA-100 and Plateletworks analyzer are seldom used in clinical practice [34, 35].
TEG was used to detect the changes of thrombus viscosity and elasticity during coagulation. During the detection, the oscillating cup containing the blood sample rotates at a uniform speed. When the blood clot forms, current generates due to the coupling motion of the metal needle placed in it to cut the magnetic induction line. After computer processing, it is depicted as a TEG curve. The main parameter of the curve, R time, is from the time the blood sample is put into the oscillating cup to the time the fibrin clot begins to form. MA, the maximum size of the thrombus, reflects the maximum intensity of the clot being formed. On this basis, AA and ADP were added respectively, and the MA values increased in the presence of activators, namely MAAA and MAADP, so as to calculate the inhibition degree of platelet reactivity by aspirin or P2Y12 receptor inhibitors.
TEG has many advantages over traditional coagulation function detection, such as reflecting the whole process of sample blood from clot formation to fiber dissolution, and the interaction between clotting factors and platelets. However, there are also some drawbacks. First, as an in vitro detection project, the detection environment is still different from the actual environment of the body. It can reflect the interaction between coagulation factors and platelets but cannot simulate the influence of vascular wall related factors such as vascular endothelial cells on the coagulation process. Secondly, TEG is used to detect the whole coagulation function of the body but cannot be used to distinguish one specific abnormal coagulation process. For example, abnormal MA in TEG represents abnormal platelet or fibrinogen, quality or quantity defect, which is unable to be identified respectively and still need routine coagulation function test. Thirdly, there is still a lack of standardized operation and evaluation guidelines. The quality control of TEG is not ideal. And the selection of threshold value for guiding treatment decision is not consistent, which needs to be further improved.
Therefore, one of the research directions on whether PFT can play a positive role in the individualization of antiplatelet therapy is the improvement of detection technology and quality control. On the other hand, the limitation of the study itself was also an important reason for the failure of PFT to achieve positive results in the individualization of antiplatelet therapy. A high proportion of low-risk patients were included in the Gauging Responsiveness with A VerifyNow assay-Impact on diabetes And Safety (GRAVITAS) study . The Testing platelet Reactivity In patients underGoing elective stent placement on clopidogrel to Guide the alternative thErapy with pRasugrel (TRIGGER–PCI) study, only 0.4% suffered ischemic events and it was terminated . In the Assessment by a Double Randomization of a Conventional Antiplatelet Strategy versus a Monitoring-guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption versus Continuation One Year after Stenting (ARCTIC) study, 15% of patients were still in the state of high platelet reactivity after adjusting the treatment regimen according to PFT . Only 4% of patients in Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC) study had an enhanced DAPT regimen . Large cohort studies are still under way in the hope of producing stronger results. However, this study was carried out in a special group of patients with ACS and TP, which reflects the real-world situation. So even if the positive results of clinical studies have drawn on the PFT-directed individualized antiplatelet therapy, the existence of real-world complications cannot be negated. Clinical trials are ideal, after all.
Several limitations should be taken into consideration. Firstly, no antiplatelet drugs data was available during follow-up, as well as PFT data. Thus, we cannot analyze the change of therapy and TPR for 5 years, which likely attributes to alter their adverse events risk. Secondly, in reality, the delivery company delivered the blood to the blood transfusion department for TEG testing within two hours, more than the required optimal time, which might affect the test results to some extent. Finally, there may be additional confounders that were not controlled for within our model. Nevertheless, this is a relatively large core laboratory analysis comparing cases with baseline HTPR, LTPR and NTPR tested by TEG in patients with ACS and TP underwent PCI, a less common interdisciplinary situation, in terms of both long-term outcomes and angiographic data, and we believe that we have accounted for the most clinically relevant variables in our model.