An MRI study of the differences in the rate of thrombolysis between red blood cell‐rich and platelet‐rich components of venous thrombi ex vivo

Abstract

Purpose: To test whether T 1 -weighted MRI can detect the differences in the rate of thrombolysis induced by recombinant tissue plasminogen activator (rt-PA) between platelet-rich regions and red blood cell (RBC)-rich regions of venous thrombi ex vivo. Materials and Methods:Each of 21 venous thrombi ex vivo (8 pulmonary emboli and 13 in situ thrombi) was dissected along the longitudinal axis. Half of it was analyzed for the presence of platelet, fibrin, and RBC components by immunohistochemistry and the other half was imaged serially by high-resolution T 1 -weighted three-dimensional MRI to assess the progression of thrombolysis. The MR images were analyzed for proportions of the remaining platelet-rich and RBC-rich regions.Results: Laminated platelet-rich regions, corresponding to Zahn lines, were confirmed immunohistochemically and by MRI in 18/21 venous thrombi. In T 1 -weighted MR images (TE/TR ¼ 10/105 ms) the mean signal intensity of platelet-rich regions was on average 2.3 higher than that of RBC-rich regions. The rate of thrombolysis in plateletrich regions was on average 30% lower than in RBC-rich regions. After 120 min of thrombolysis the proportion of lysed platelet-rich regions was 0.27 6 0.04 versus 0.40 6 0.08 in RBC regions, which resulted in 1.4% decrease of lysed thrombus volume per 1% increase of platelet-rich content.Conclusion: Venous thrombi are most often composed of interspersed platelet-rich and RBC-rich regions. T 1 -weighted MRI is capable of noninvasive discrimination between those two components of venous thrombi ex vivo which have a different susceptibility to thrombolysis by rt-PA.

Enhanced Fibrinolysis with Magnetically Powered Colloidal Microwheels

“…These conditions are relevant both to deep vein thrombosis where fibrin‐rich thrombi several centimeters in length can form, attenuating any pressure difference across the thrombus, as well as in to arterial thrombosis where low permeability platelet‐rich thrombi result in very low interstitial flows even for significant pressure gradients . In both cases, heterogeneities in thrombus structure can result in regions that are more permeable and more susceptible to fibrinolysis under pressure‐driven flow . In our studies, the size of individual colloids and small µwheels is on the same order of magnitude as dense fibrin gel pores and may benefit from convective transport by either enhancing µwheel penetration or by conveying plasmin deeper into a thrombus.…”

Fluid and Solute Transport in the Interstitial Space of Blood Clots

“…For example, at pressures typical of large human arteries one would except fibrinolytic agents like tissue plasminogen activator (tPA) to penetrate no further than ∼100 μm over 1 hr into the interior platelet rich clot. This is too slow for most clinical applications and supports reports that fibrinolytic drugs have limited success on platelet rich clots [24]. In addition, the hindrance of transport of coagulation proteins and platelet agonists out of clots is a potential mechanism for the arrest of clots growth.…”

Evaluation of thrombolysis by using ultrasonic imaging: an in vitro study

“…The distribution of platelets in a thrombus is actually an important factor in thrombolysis. For instance, the laminations of coalescent platelets mixed with the fibrin network (known as Zahn lines 41 42 ) in in vivo thrombi may result in a stronger resistance to thrombolysis 43 . For these reasons, the performance of using Nakagami imaging to evaluate the lysis of thrombus in vivo should be investigated using animal models.…”