Qassim Lamis, Orion David, Chapman Joab, Yaniv Gal, Itsekson-Hayosh Zeev, Weinberg Nitai, Shavit-Stein Efrat
Department 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.
Department 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; Robert and Martha Harden Chair in Mental and Neurological Diseases, Faculty of Medicine and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Heart Rhythm. 2025 Jul;22(7):1629-1636. doi: 10.1016/j.hrthm.2024.12.028. Epub 2024 Dec 19.
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.
The purpose of this study was to validate and optimize thrombin secretion for clot source diagnosis.
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.
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).
We developed a rapid and sensitive method for determining cryptogenic clot sources that correlates well with long-term clinical outcomes.
急性缺血性中风的二级预防取决于确定隐源性血栓的来源。我们之前报道过，血管内取出的血栓分泌的凝血酶活性在房颤（AF）和动脉粥样硬化（AS）中存在显著差异，这可能是由于血栓的体内生物学特性所致。
本研究的目的是验证和优化用于血栓来源诊断的凝血酶分泌检测方法。
中风被定义为AS、AF或隐源性，后者通过长期临床随访定义为AF或非AF。人工静脉血栓分为预洗或未洗，以模拟AS和AF来源。通过在孔间手动转移血栓或在琼脂糖珠柱中洗涤血栓，手动收集样本或使用分部收集器，用荧光法测量血栓的凝血酶分泌。分泌模式表示为最大初始值与最小基线值的比值。
新的基于柱的检测方法比手动转移方法更快且信息更丰富。预洗和未洗的人工血栓之间以及AF和AS血栓之间的凝血酶分泌率存在显著差异，截断比值为0.52时，特异性为78.9%，敏感性为90.0%。该截断值识别出84%发展为明确AF的隐源性患者，生存表分析发现，该组通过心脏监测确诊为明确AF的患者明显多于可能为非AF比值的患者（对数秩[Mantel-Cox]检验，P = 0.021）。
我们开发了一种快速、灵敏的方法来确定隐源性血栓来源，该方法与长期临床结果相关性良好。
