Usefulness of ADAMTS13 to predict response to recanalization therapies in acute ischemic stroke

Abstract

Objective: We aimed to analyze ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in relation to arterial recanalization in patients treated with IV tissue plasminogen activator (tPA) and in relation to futile recanalization in patients treated with mechanical thrombectomy.

Methods: Acute ischemic stroke patients (n = 108) with documented arterial occlusions treated with IV-tPA were selected. ADAMTS13 activity was measured by ELISA in samples collected before treatment. Recanalization was assessed at 2 hours by transcranial Doppler. In 78 consecutive patients treated with endovascular thrombectomy, ADAMTS13 antigen was measured by ELISA and futile recanalization was defined as complete recanalization plus modified Rankin Scale score >2 at 3 months. Independent predictors of recanalization and futile recanalization were determined by logistic regression, adjusted by age, NIH Stroke Scale score, and time from stroke onset.

Results: Patients who achieved tPA-induced recanalization had higher baseline ADAMTS13 activity (78.1% [68%-88%] vs 70.1% [61%-79%], p = 0.021). In logistic regression analysis, ADAMTS13 activity >75% was an independent predictor of recanalization (odds ratio = 6.76 [1.52-30.02], p = 0.012), together with absence of early ischemic signs and Oxfordshire Community Stroke Project classification. Regarding endovascular therapies, a reduced ADAMTS13 concentration (<982 ng/mL) was an independent predictor of futile recanalization (odds ratio = 67.4 [1.4-3,282.1], p = 0.034), together with age and diabetes mellitus. The addition of ADAMTS13 to clinical predictors of tPA-induced recanalization and futile recanalization improved discrimination and reclassification (integrated discrimination improvement = 10.06% and 28.4%, net reclassification improvement = 61.0% and 107.4%, respectively).

Conclusions: A reduced ADAMTS13 was associated with poor response to recanalization therapies. If confirmed in future prospective studies, a panel of blood biomarkers including ADAMTS13 might be a useful tool to guide reperfusion therapies.

Figure 1. ADAMTS13 according to the main outcomes after recanalization therapies

(A) Comparison of ADAMTS13 activity between stroke patients who achieved recanalization 2 hours after IV tissue plasminogen activator and those who did not. (B) Comparison of ADAMTS13 antigen between patients with futile or successful recanalization after endovascular recanalization. (C) Applying a cutoff point of ADAMTS13 activity of 75%, patients over this cutoff were more likely to recanalize (59.1% vs 36.7%) than those with lower ADAMTS13 activity. (D) Applying a cutoff point of ADAMTS13 antigen of 982 ng/mL, patients below this cutoff were more likely to have futile recanalization (42.3% vs 14.3%) than those with higher levels. In A and B, boxplots represent median and interquartile range between the different subgroups. In C and D, the blue bars represent the percentage of patients who recanalized and the green bars those who did not. ADAMTS13 = a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13.