Measuring Thrombus Stability at High Shear, Together With Thrombus Formation and Endogenous Fibrinolysis: First Experience Using the Global Thrombosis Test 3 (GTT-3)
Thrombus formation in a severely stenosed artery is initiated by high shear activation of platelets, with soluble platelet agonists, such as ADP and thromboxane, playing only a secondary role in the growth and stability of the thrombus. Conventional platelet function tests, however, assess only the...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2023-08-01
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| Series: | Clinical and Applied Thrombosis/Hemostasis |
| Online Access: | https://doi.org/10.1177/10760296231181917 |
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| author | Rahim Kanji MB BS, MRCP Joshua Leader MB BS Vassilios Memtsas MB BS Diana A Gorog MD, PhD, FRCP, FESC |
| author_facet | Rahim Kanji MB BS, MRCP Joshua Leader MB BS Vassilios Memtsas MB BS Diana A Gorog MD, PhD, FRCP, FESC |
| author_sort | Rahim Kanji MB BS, MRCP |
| collection | DOAJ |
| description | Thrombus formation in a severely stenosed artery is initiated by high shear activation of platelets, with soluble platelet agonists, such as ADP and thromboxane, playing only a secondary role in the growth and stability of the thrombus. Conventional platelet function tests, however, assess only the soluble agonist-dependent pathway of platelet aggregation. As the thrombus evolves, its stability and ability to withstand dislodgement by arterial flow will determine whether complete and persistent vessel occlusion will occur. The Global Thrombosis Test (GTT), an automated point-of-care technique, simulates the formation of thrombus in whole blood under high shear flow (shear rate >12 000 s −1 ) and measures the time for occlusive thrombus formation and spontaneous, endogenous thrombolysis/fibrinolysis. The latest GTT-3 model subjects the growing thrombus to upstream pressure, resembling that in a medium-sized artery, and provides an additional assessment of thrombus stability and fibrinolysis rate. It can be used in 3 programs, including a new “hypershear” mode, whereby repetitive cycles of pressure are applied to the growing thrombus, increasing shear rate to ∼22 000 s −1 , such as that in patients on mechanical circulatory support. In addition to assessing the risk of arterial thrombosis, the GTT-3 could be used to assess the impact of antithrombotic medications on thrombus stability at high shear. Although current antiplatelet medications target the biochemical axis of platelet aggregation (soluble agonists) and also increase bleeding risk, novel shear-selective antiplatelet therapies may prevent thrombosis while preserving hemostasis. Future studies are needed to assess the usefulness of assessing thrombus stability on cardiovascular and pharmacological evaluation. |
| first_indexed | 2024-03-12T16:46:01Z |
| format | Article |
| id | doaj.art-e18aee7a69114dc6af245e1890528a3c |
| institution | Directory Open Access Journal |
| issn | 1938-2723 |
| language | English |
| last_indexed | 2024-03-12T16:46:01Z |
| publishDate | 2023-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Clinical and Applied Thrombosis/Hemostasis |
| spelling | doaj.art-e18aee7a69114dc6af245e1890528a3c2023-08-08T12:33:19ZengSAGE PublishingClinical and Applied Thrombosis/Hemostasis1938-27232023-08-012910.1177/10760296231181917Measuring Thrombus Stability at High Shear, Together With Thrombus Formation and Endogenous Fibrinolysis: First Experience Using the Global Thrombosis Test 3 (GTT-3)Rahim Kanji MB BS, MRCP0Joshua Leader MB BS1Vassilios Memtsas MB BS2Diana A Gorog MD, PhD, FRCP, FESC3 Cardiology Department, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK Cardiology Department, East and North Hertfordshire NHS Trust, Stevenage, Hertfordshire, UK Cardiology Department, East and North Hertfordshire NHS Trust, Stevenage, Hertfordshire, UK Centre for Health Services and Clinical Research, School of Life and Medical Sciences, University of Hertfordshire, Hertfordshire, UKThrombus formation in a severely stenosed artery is initiated by high shear activation of platelets, with soluble platelet agonists, such as ADP and thromboxane, playing only a secondary role in the growth and stability of the thrombus. Conventional platelet function tests, however, assess only the soluble agonist-dependent pathway of platelet aggregation. As the thrombus evolves, its stability and ability to withstand dislodgement by arterial flow will determine whether complete and persistent vessel occlusion will occur. The Global Thrombosis Test (GTT), an automated point-of-care technique, simulates the formation of thrombus in whole blood under high shear flow (shear rate >12 000 s −1 ) and measures the time for occlusive thrombus formation and spontaneous, endogenous thrombolysis/fibrinolysis. The latest GTT-3 model subjects the growing thrombus to upstream pressure, resembling that in a medium-sized artery, and provides an additional assessment of thrombus stability and fibrinolysis rate. It can be used in 3 programs, including a new “hypershear” mode, whereby repetitive cycles of pressure are applied to the growing thrombus, increasing shear rate to ∼22 000 s −1 , such as that in patients on mechanical circulatory support. In addition to assessing the risk of arterial thrombosis, the GTT-3 could be used to assess the impact of antithrombotic medications on thrombus stability at high shear. Although current antiplatelet medications target the biochemical axis of platelet aggregation (soluble agonists) and also increase bleeding risk, novel shear-selective antiplatelet therapies may prevent thrombosis while preserving hemostasis. Future studies are needed to assess the usefulness of assessing thrombus stability on cardiovascular and pharmacological evaluation.https://doi.org/10.1177/10760296231181917 |
| spellingShingle | Rahim Kanji MB BS, MRCP Joshua Leader MB BS Vassilios Memtsas MB BS Diana A Gorog MD, PhD, FRCP, FESC Measuring Thrombus Stability at High Shear, Together With Thrombus Formation and Endogenous Fibrinolysis: First Experience Using the Global Thrombosis Test 3 (GTT-3) Clinical and Applied Thrombosis/Hemostasis |
| title | Measuring Thrombus Stability at High Shear, Together With Thrombus Formation and Endogenous Fibrinolysis: First Experience Using the Global Thrombosis Test 3 (GTT-3) |
| title_full | Measuring Thrombus Stability at High Shear, Together With Thrombus Formation and Endogenous Fibrinolysis: First Experience Using the Global Thrombosis Test 3 (GTT-3) |
| title_fullStr | Measuring Thrombus Stability at High Shear, Together With Thrombus Formation and Endogenous Fibrinolysis: First Experience Using the Global Thrombosis Test 3 (GTT-3) |
| title_full_unstemmed | Measuring Thrombus Stability at High Shear, Together With Thrombus Formation and Endogenous Fibrinolysis: First Experience Using the Global Thrombosis Test 3 (GTT-3) |
| title_short | Measuring Thrombus Stability at High Shear, Together With Thrombus Formation and Endogenous Fibrinolysis: First Experience Using the Global Thrombosis Test 3 (GTT-3) |
| title_sort | measuring thrombus stability at high shear together with thrombus formation and endogenous fibrinolysis first experience using the global thrombosis test 3 gtt 3 |
| url | https://doi.org/10.1177/10760296231181917 |
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