Ravinder-Jeet Singh, MBBS, DM

Alves HC, Treurniet KM, Jansen IGH, Yoo AJ, Dutra BG, Zhang G, et al. Thrombus Migration Paradox in Patients with Acute Ischemic Stroke. Stroke. 2019; 50:3156-3163.

Thrombus is a dynamic structure with constantly changing size, morphology and location over time, to variable extent in each patient, before recanalization occurs. Recently, there is interest in understanding dynamic clot features, especially regarding thrombus movement — defined as change in the occlusion site — between initial (typically CT angiogram) and follow-up vascular imaging (usually catheter angiogram for mechanical thrombectomy). Whether thrombus migration before recanalization is of any clinical or functional significance remains under investigation. The thrombus migration was studied in the past.1 It underlies a clinical phenomenon called “spectacular shrinking deficit,” in which a patient with major hemispheric syndrome shows rapid (over minutes to hours) and dramatic improvement or disappearance of most clinical deficits.1 Use of regular “vascular imaging” now allows investigating the concept in reverse order, i.e., the incidence thrombus migration and correlate it with clinical change or functional outcome. Different factors determine the dynamic behavior of the clot, including source of thrombus (etiology of stroke), composition of the thrombus, initial thrombus location within arterial tree (for example, proximal vs distal occlusion), angioarchitecture around the thrombus and use of intravenous thrombolysis (IVT).1-4

In the paper published by Alves et al., the authors studied thrombus migration within ICA-MCA axis among patients enrolled in the MR CLEAN registry.4 Initial occlusion site was recorded on the initial CTA as the most proximal thrombus location, and it was compared to thrombus location seen on conventual angiogram performed later at the time of endovascular treatment.

Among 1349 included patients, thrombus migration was seen in 302 (22%). Overall, use of intravenous thrombolysis was associated with increased rate of thrombus migration and resolution. Further, presence of thrombus migration predicted lower likelihood of successful and complete reperfusion, while thrombus resolution predicted higher reperfusion rates. Counterintuitively, despite lower rate of successful and complete reperfusion, thrombus migration does not negatively influence functional outcomes.

The authors conclude that in patients with acute ischemic stroke, thrombus location regularly changes between computed tomography angiography and digital subtraction angiography (DSA). Administration of intravenous alteplase almost doubled the rate of thrombus migration (adjusted odds ratio 2.01; CI, 1.29–3.11) and increased the chance of thrombus resolution (aOR, 1.85; CI, 1.22–2.80). Thrombus migration reduced the rate of complete reperfusion (aOR, 0.57; CI, 0.42– 0.78 for complete reperfusion, and 0.74; CI, 0.55–0.99 for successful reperfusion), but was associated with better functional outcome, especially when initial occlusion involved M1.

The present study suggests that migration of thrombus is not really “bad” from a functional outcome perspective even though it reduces reperfusion quality after EVT. This contrasts with other studies, which noted negative association of thrombus migration with clinical improvement or functional outcome.5,6 Therefore, more data is needed to draw definite conclusions. Further, initial CTA in the study was single phase with its inherent limitations. As assessment of thrombus migration relied on change in proximal end of the thrombus, therefore, not accounting for phenomenon of pseudo-occlusion. Patients with terminal ICA or M1 occlusion may have slow flow of contrast in the cervical- intracranial ICA, thus, single phase CTA may result in overestimation of proximal extent of the thrombus compared to DSA. This might have led to difference in thrombus location seen between two modalities and overestimation of thrombus migration rates in both ICA and M1 locations unlike distal occlusions. This phenomenon and accurate clot location are better defined on multiphase CTA or CTA with a delayed phase. Finally, patients with spectacular shrinking deficit or “sufficient clinical recovery” are likely underrepresented in the study, as these patients may not undergo EVT, as acknowledged by the authors. Despite limitations, the study highlights the phenomenon of thrombus dynamics and its interaction with different reperfusion modalities (IVT and mechanical thrombectomy). More studies are needed to inform the interventional and functional implications of thrombus dynamics.

References:

  1. Minematsu K, Yamaguchi T, Omae T. ‘Spectacular shrinking deficit’: rapid recovery from a major hemispheric syndrome by migration of an embolus. Neurology. 1992; 42:157-62.
  2. Qazi EM, Sohn SI, Mishra S, Almekhlafi MA, Eesa M, d’Esterre CD, et al. Thrombus characteristics are related to collaterals and angioarchitecture in acute stroke. Can J Neurol Sci. 2015; 42:381–388.
  3. Maegerlein C, Friedrich B, Berndt M, Lucia KE, Schirmer L, Poppert H, et al. Impact of histological thrombus composition on preinterventional thrombus migration in patients with acute occlusions of the middle cerebral artery. Interv Neuroradiol. 2018; 24:70-75.
  4. Alves HC, Treurniet KM, Jansen IGH, Yoo AJ, Dutra BG, Zhang G, et al. Thrombus migration paradox in patients with acute ischemic stroke. Stroke. 2019; 50:3156-3163.
  5. Kaesmacher J, Maegerlein C, Kaesmacher M, Zimmer C, Poppert H, Friedrich B, et al. Thrombus migration in the middle cerebral artery: incidence, imaging signs, and impact on success of endovascular thrombectomy. J Am Heart Assoc. 2017;6:e005149.
  6. Ohara T, Menon BK, Al-Ajlan FS, Horn M, Al Sultan AS, Letteri F, et al. Abstract: Thrombus migration is a common phenomenon with IV tPA and may have negative effects on outcome when tPA treatment is given before endovascular thrombectomy in proximal occlusions. Stroke. 50:A82.