Permeable Thrombi Are Associated With Higher Intravenous Recombinant Tissue-Type Plasminogen Activator Treatment Success in Patients With Acute Ischemic Stroke

Abstract

Early complete recanalization of an occluded artery is a strong predictor of favorable functional outcome in patients with acute ischemic stroke.1 To increase the chance of favorable outcome, guidelines recommend the use of intravenous thrombolysis with recombinant tissue-type plasminogen activator (r-tPA) in eligible patients.2 Because intravenous r-tPA treatment results in a relatively low rate of recanalization, 3 it might be useful to estimate the likelihood of failure or success of intravenous r-tPA before treatment initialization.Preclinical studies have shown that thrombus permeability influences r-tPA efficacy. Permeability reflects the ability of soluble molecules to move within the gaps between adjacent platelets, fibrin filaments, and red blood cells.4,5 A high permeability might result in more effective activation of recombinant tissue-type plasminogen because of an improved surface contact area and might, therefore, increase the dissolution of the fibrin filaments and consequently the thrombus.6 These preclinical findings have not yet been studied in a clinical setting. We recently proposed a method to assess thrombus Background and Purpose-Preclinical studies showed that thrombus permeability improves recombinant tissue-type plasminogen activator (r-tPA) efficacy. We hypothesize that thrombus permeability estimated from radiological imaging is associated with improved recanalization after treatment with intravenously administered r-tPA (r-tPA) and with better functional outcome. Methods-We assessed thrombus attenuation increase (TAI) in patients from the Dutch Acute Stroke Study with an occlusion of an intracranial artery on computed tomographic angiography. Patients were included within 9 hours after the stroke onset. After dichotomization of TAI as pervious or impervious, logistic regressions analyses were performed to estimate associations of intravenous r-tPA therapy with complete recanalization and with favorable functional outcome (modified Rankin Scale score of ≤2). Results-Three hundred eight patients matched the inclusion criteria. The median TAI was 20.1 (interquartile range, 8.5-37.8) Hounsfield unit (HU). We found a significant increase in the odds of complete recanalization with increasing TAI for patients treated with intravenous r-tPA (P=0.030). One hundred thirty-one (42%) thrombi were classified as pervious with TAI of ≥23 HU. In patients with a pervious thrombus, complete recanalization was more frequent after treatment with intravenous r-tPA than after conservative treatment (odds ratio, 6.26; 95% confidence interval, 2.4-16.8; P<0.001). In patients with an impervious thrombus, the effect of intravenous r-tPA was not significant (odds ratio, 1.4; 95% confidence interval, 0.5-4.1; P=0.47). Favorable outcome was more common in patients with a pervious thrombi than without (odds ratio, 2.1; 95% confidence interval, 1.3-3.4; P=0.001). Conclusions-Thrombus perviousness, as measured on computed tomography in the acute stage of ischemic stroke, is strongly associated with recanalization...

Clots, Collaterals, and the Intracranial Arterial Tree

“…Moreover, thrombus permeability is also associated with better clinical outcome in their study. Santos et al 8 thus substantiate previous evidence about thrombus porosity identified using such imaging constructs like residual flow through thrombus on CT angiography and occult anterograde flow through thrombus on CT perfusion that are imaging markers of early thrombus lysis with alteplase. 3,7 Other imaging constructs like thrombus location on CTA and Trans-cranial Doppler, thrombus length on noncontrast CT and CTA, clot burden score on CTA, forward flow through clot on dynamic CTA, collateral status on CTA and CT perfusion, Gradient Echo blooming on magnetic resonance imaging have all been shown to be markers of thrombus lysis with alteplase.…”

“…3,7 Other imaging constructs like thrombus location on CTA and Trans-cranial Doppler, thrombus length on noncontrast CT and CTA, clot burden score on CTA, forward flow through clot on dynamic CTA, collateral status on CTA and CT perfusion, Gradient Echo blooming on magnetic resonance imaging have all been shown to be markers of thrombus lysis with alteplase. [2][3][4][5][6][7][8] Taken together, this growing body of literature is helping treating physicians who predict the likelihood of treatment success with alteplase in patients with acute ischemic stroke.…”

“…Thrombus porosity Empirical evidence from studies in patients with acute ischemic stroke supporting this theoretical framework of thrombus lysis is accumulating. [3][4][5][6][7][8] In their article, Santos et al 8 showed that thrombus permeability as measured by comparing attenuation increase within the thrombus on computed tomographic angiography (CTA) when compared with attenuation of thrombus on the noncontrast CT is associated with increased likelihood of recanalization (measured at 24-48 hours) in patients administered with alteplase. Moreover, thrombus permeability is also associated with better clinical outcome in their study.…”

Thrombus Permeability on Dynamic CTA Predicts Good Outcome after Reperfusion Therapy

“…[9][10][11] It has been suggested that thrombus permeability might be related to the physical porosity of thrombus and might reflect the ability of soluble molecules to move within the gaps among adjacent platelets, fibrin filaments, and red blood cells. 8,9,12,13 Preclinical studies have demonstrated that high permeability of the thrombus within the occluded artery allowed residual blood to flow through the thrombus, 9,10 which may have a positive effect on neurologic outcome after acute ischemia due to the compensating oxygenation of brain tissue distal to the occluded artery. Recently, thrombus attenuation increase (TAI) was used to assess the thrombus permeability on conventional single-phase CT angiography and noncontrast CT. A pervious thrombus with a high TAI was found to be associated with better neurologic outcome after reperfusion therapy in patients with AIS.…”

“…Recently, thrombus attenuation increase (TAI) was used to assess the thrombus permeability on conventional single-phase CT angiography and noncontrast CT. A pervious thrombus with a high TAI was found to be associated with better neurologic outcome after reperfusion therapy in patients with AIS. 8,12 The enhancement of arteries on conventional single-phase CTA is affected by the acquisition time because the contrast filling of the occlusion site is delayed compared with that in the normal condition. 14 Therefore, the permeability of the thrombi may be underestimated if single-phase CTA is acquired before contrast completely penetrates the thrombus.…”