Viscoelastic Hemostatic Assays and Platelet Function Testing in Patients with Atherosclerotic Vascular Diseases
Abstract
:1. Introduction
2. Viscoelastic Hemostatic Assays and Platelet Function Testing
2.1. Platelet Dysfunction and Adverse Vascular Events
2.2. Platelet Function Testing in Cardiovascular Medicine
2.3. Thromboelastography and Thromboelastometry: Assays Principle, Advantages and Disadvantages
2.4. Platelet Function Testing with Thromboelastography
2.5. Platelet Function Testing with Thromboelastometry
2.6. Clinical Experiences with Viscoelastic Hemostatic Assays (VHA) for Platelet Function Testing and Gaps in Evidence
3. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ACS | acute coronary syndromes |
ADP | adenosinediphosphate |
ADPRB | ADP receptor blockers |
ASA | acetylsalicylic acid |
CABG | coronary artery bypass graft |
CI | confidence interval |
GRAVITAS | Gauging Responsiveness with a VerifyNow P2Y12 assay: Impact on Thrombosis and Safety |
HPR | high on-treatment platelet reactivity |
HR | hazard ratio |
LTA | light transmission aggregometry |
MPR | maximal platelet reactivity |
PCI | percutaneous coronary interventions |
PFA | Platelet Function Analyzer |
PFT | platelet function testing |
POC | point-of-care |
PRI | platelet reactivity index |
PRP | platelet rich plasma |
PRU | platelet response units |
ROTEM® | thromboelastometry |
SCAD | stable coronary artery disease |
STEMI | ST elevation myocardial infarction (MI) |
TEG® | thromboelastography |
TRAP | thrombin receptor activating peptide |
VASP-P | vasodilator-stimulated phosphoprotein (VASP) phosphorylation |
VHA | viscoelastic hemostatic assays |
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Assay Principle | Viscoelastic hemostatic assay, uses 340 µL of whole blood in a rotating cylindrical cup while a fixed pin on a torsion wire is suspended in the blood, coagulation is activated by selected activators in a pre-defined assay | |
Manufacturer | Haemoscope, Haemonetics, Niles, IL, USA. | |
Platelet Function Testing | Yes (Platelet mapping assay specifically designed for thromboelastography is commercially available) | |
Parameter | Calculation | Information Provided |
R (Reaction rate) | the time elapsed from the coagulation trigger until the formation of a clot of 2 mm | Time from initiation of clotting process until clot starts to form |
K (Kinetics time) | the time elapsed from 2 to 20 mm | Flags the speed of formation of a solid clot |
MA (Maximum amplitude) | the maximum amplitude of the signal | Reflects the maximum clot strength |
LY30 (Lysis 30) | percentage of remaining clot stability in relation to the MA value at 30 min after R | Reflects loss of clot stability |
Assay | Description | |
Kaolin | Kaolin acts as contact activators. | |
Rapid TEG | Reagent contains tissue factor and kaolin as inducers. | |
HTEG | Reagent with lipophilized heparinase to neutralize unfractionated heparin. Used in conjunction with kaolin to measure heparin effect. | |
Functional fibrinogen | Reagent with tissue factor and abciximab (glycoprotein IIb/IIIa platelet receptor blocker), inhibiting platelet contribution to clot formation. Allows qualitative measurement of the fibrinogen contribution to clot strength independent of platelets. | |
Native | Native whole blood sample analyzed following only recalcification. Impractical for clinical use given long R time. | |
Platelet mapping | Assay uses heparinized blood mixed with ActivatorF (reptilase and activated factor XIII). Sufficient heparin is present to entirely suppress the generation of thrombin while fibrinogen is converted to fibrin and cross- linked due to the presence of reptilase and activated factor XIII. Subsequent addition of either arachadonic acid (AA) or adenosine diphosphate (ADP) allows measurement of the platelet activation response to these inducers in the absence of thrombin. These results are compared to kaolin analysis to determine platelet response to AA and ADP. |
Assay Principle | Viscoelastic hemostatic assay, uses 340 µL of whole blood in a fixed cylindrical cup while a pin suspended on a ball-bearing mechanism oscillates with the application of a constant force, coagulation is activated by selected activators in a pre-defined assays | |
Manufacturer | Instrumentation Laboratory, Bedford, MA, USA | |
Platelet Function Testing | No (FIBTEM indirectly assesses platelet function, platelet mapping assay could be adapted for ROTEM®) | |
Parameter | Calculation | Information Provided |
CT (Clotting time) | the time elapsed from the coagulation trigger until the formation of a clot of 2 mm | Time from initiation of clotting process until clot starts to form |
CFT (Clot forming time) | the time elapsed from 2 to 20 mm | Flags the speed of formation of a solid clot |
MCF (Maximum clot firmness) | the maximum amplitude of the signal | Reflects the maximum clot strength |
LI 30 (Lysis index after 30 min) | percentage of remaining clot stability in relation to the MCF value at 30 min after CT | Reflects loss of clot stability |
Assay | Activator/Inhibitor | Information Provided |
INTEM | Contact activation | Fast assessment of clot forming, fibrin polymerization, and fibrinolysis through the intrinsic pathway |
HEPTEM | Contact activation + heparinase | ROTEM measurement without heparin contribution: specific detection of heparin (compared to INTEM), measurement of clotting in heparinized ones |
EXTEM | Tissue factor activation | Fast assessment of clot forming, fibrin polymerization, and fibrinolysis through the extrinsic pathway |
FIBTEM | Tissue factor activation + platelet inhibition | ROTEM measurement without platelets: qualitative measurement of fibrinogen status |
APTEM | Tissue factor activation + aprotinin | In vitro fibrinolysis inhibition: fast detection of lysis when compared with EXTEM |
NATEM | Recalcification only = classical TEM (thromboelastometry) | Sensitive measurement of the equilibrium of coagulation activation or inhibition |
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Samoš, M.; Škorňová, I.; Bolek, T.; Stančiaková, L.; Korpallová, B.; Galajda, P.; Staško, J.; Kubisz, P.; Mokáň, M. Viscoelastic Hemostatic Assays and Platelet Function Testing in Patients with Atherosclerotic Vascular Diseases. Diagnostics 2021, 11, 143. https://doi.org/10.3390/diagnostics11010143
Samoš M, Škorňová I, Bolek T, Stančiaková L, Korpallová B, Galajda P, Staško J, Kubisz P, Mokáň M. Viscoelastic Hemostatic Assays and Platelet Function Testing in Patients with Atherosclerotic Vascular Diseases. Diagnostics. 2021; 11(1):143. https://doi.org/10.3390/diagnostics11010143
Chicago/Turabian StyleSamoš, Matej, Ingrid Škorňová, Tomáš Bolek, Lucia Stančiaková, Barbora Korpallová, Peter Galajda, Ján Staško, Peter Kubisz, and Marián Mokáň. 2021. "Viscoelastic Hemostatic Assays and Platelet Function Testing in Patients with Atherosclerotic Vascular Diseases" Diagnostics 11, no. 1: 143. https://doi.org/10.3390/diagnostics11010143