Diagnosis of atrial fibrillation as the source of cryptogenic retrieved clots by a novel thrombin secretion assay
Related Experiment Video
Updated: Jun 4, 2025
Leveraging Turbidity and Thromboelastography for Complementary Clot Characterization
Published on: June 4, 2020
Lamis Qassim1, David Orion1, Joab Chapman2
1Department of Neurology, The Chaim Sheba Medical Center, Ramat Gan, Israel; Department of Neurology and Neurosurgery, Faculty of Medicine and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Insights
A new assay measuring thrombin secretion from clots can identify the source of cryptogenic strokes, differentiating between atrial fibrillation (AF) and atherosclerosis (AS) to improve secondary prevention strategies.
Area of Science:
- Biochemistry
- Cardiovascular Medicine
- Neurology
Background:
- Secondary stroke prevention requires identifying the source of cryptogenic clots.
- Previous research indicated differing thrombin activity in atrial fibrillation (AF) versus atherosclerosis (AS) clots.
Purpose of the Study:
- To validate and optimize thrombin secretion measurements for diagnosing clot sources.
- To improve the accuracy of differentiating AF from AS in stroke patients.
Main Methods:
- Developed and compared manual and column-based assays for measuring thrombin secretion from artificial clots modeling AS and AF.
- Classified strokes as AS, AF, or cryptogenic, with AF/non-AF determined by long-term follow-up.
- Analyzed thrombin secretion patterns using the ratio of maximal initial to minimal baseline values.
Main Results:
- The column-based assay was faster and more informative than manual methods.
- A thrombin secretion ratio cutoff of 0.52 demonstrated 78.9% specificity and 90.0% sensitivity for differentiating clot sources.
- This method identified 84% of cryptogenic patients who later developed AF, correlating with cardiac monitoring outcomes.
Conclusions:
- A rapid and sensitive thrombin secretion assay was developed for determining cryptogenic clot sources.
- The assay effectively differentiates between AF and AS clot origins.
- This method shows strong correlation with long-term clinical outcomes, aiding secondary stroke prevention.
Background:
Secondary prevention of acute ischemic stroke depends on identifying the source of cryptogenic clots. We previously reported that secreted thrombin activity from endovascularly retrieved clots is significantly different in atrial fibrillation (AF) vs atherosclerosis (AS), probably due to the in vivo biology of the clots.
Objectives:
The purpose of this study was to validate and optimize thrombin secretion for clot source diagnosis.
Methods:
Strokes were defined as either AS, AF, or cryptogenic, with the latter group defined as AF or non-AF by long-term clinical follow-up. Artificial venous blood clots were either prewashed or unwashed to model AS and AF sources. Thrombin secretion from the clot was measured fluorometrically by manually transferring the clots between wells or by washing them in an agarose bead column, collecting samples manually, or by using the fraction collector. The secretion pattern was represented as the ratio of maximal initial values to minimal baseline.
Results:
The new column-based assay was faster and more informative than the manually transferring approach. Significant differences in thrombin secretion ratios were observed between prewashed and unwashed artificial clots, and between AF and AS clots, with a cutoff ratio of 0.52 showing 78.9% specificity and 90.0% sensitivity. This cutoff identified 84% of cryptogenic patients who developed definite AF, and lifetable analysis found significantly more definite AF confirmation by cardiac monitoring in this group than in patients with a probable non-AF ratio (P = .021 by log-rank [Mantel-Cox] test).
Conclusion:
We developed a rapid and sensitive method for determining cryptogenic clot sources that correlates well with long-term clinical outcomes.
Related Concept Videos
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:16Clot Retraction and Fibrinolysis