Dependence of Blood Clot Lysis on the Mode of Transport of Urokinase into the Clot - A Magnetic Resonance Imaging Study in Vitro

Abstract

SummaryMagnetic resonance imaging was employed to study the dependence of clot lysing patterns on two different modes of transport of urokinase into whole blood clots. In one group of clots (nonperfused clots, n1 = 10), access of urokinase to the fibrin network was possible by diffusion only, whereas in the other group (perfused clots, n2 = 10) bulk flow of plasma containing urokinase was instituted through occlusive clots by a pressure difference of 3 .7 kPa (37 cm H2O) across 3 cm long clots with a diameter of 4 mm. It was determined separately that this pressure difference resulted in a volume flow rate of 5.05 ± 2.4 × 10−2 ml/min through occlusive clots. Perfused clots diminished in size significantly in comparison to nonperfused ones already after 20 min (p <0.005). Linear regression analysis of two-dimensional clot sizes measured by MRI showed that the rate of lysis was more than 50-times faster in the perfused group in comparison to the nonperfused group. It was concluded that penetration of the thrombolytic agent into clots by perfusion is much more effective than by diffusion. Our results might have some implications for understanding the differences in lysis of arterial and venous thrombi.

Biochemical and biophysical conditions for blood clot lysis

“…1). When a pressure gradient of 1-2 Wdcm of clot length was applied along occlusive cylindrical clots channels of lysed areas penetratedinto non-retracted clots with a velocity of 60-100 mm/h [2] and into retracted clots with a velocity of about 5 mm/h (Fig.2) [3]. Bulk flow of plasminogen and UK into clots thus accelerated the rate of lysis up to 100-fold in comparison to transport by diffusion.…”

Prospective Evaluation of Blood Coagulability and Effect of Treatment in Patients with Stroke Using Rotational Thromboelastometry

“…8 It has been suggested that this variation in response to treatment depends on clot size, composition, and source 33 and that old platelet-rich, well-organized thrombi formed under flow conditions are more resistant to lysis than fresh fibrin and red cell-rich clots formed under stasis. [34][35][36] It is important to highlight that citrated blood is used and ROTEM parameters measured reflect the activity of rt-PA on the clot that occurs ex vivo at the time of citrate reversal. Hence, we cannot be certain that these measurements exactly reflect the effect of rt-PA on clot kinetics in vivo.…”

Shorter time to intervention improves recanalization success and clinical outcome post intra-arterial intervention for basilar artery thrombosis

“…It is possible that the changes in clot composition over time result in older fibrin-rich clots to be more organized and hence more resistant to thrombolysis, decreasing the likelihood for the occluded arteries to be recanalized. [19][20][21][22] Recanalization is associated with a significant survival benefit. 7,8 Our study showed that 30/41 (73.2%) patients who were recanalized survived at 90 days, compared to 3/8 (37.5%) non-recanalized patients (p = 0.094).…”

“…Fresh newly formed clots are more red blood cell dominant and less resistant to thrombolysis, while older clots are more fibrin-rich and well-organized and hence more resistant to thrombolysis. [19][20][21][22] Furthermore, shortening the delay to intervention is vital in ensuring the survival of penumbral tissue. 23 Successful intervention to attenuate the growth of the ischaemic core positively contributes to good clinical outcomes.…”