tPA Thrombolysis Research Articles

Intravenous Recombinant Tissue Plasminogen Activator in a Pregnant Woman With Cardioembolic Stroke

Historically, the use of tissue plasminogen activator (tPA) thrombolysis in pregnancy has been regarded as relatively contraindicated. Underlying this stance has been the concern over the risk of bleeding complications in both mother and child. We report the successful use of intravenous recombinant tPA (rtPA) thrombolysis in a pregnant woman with acute cardioembolic stroke. The patient improved clinically, did not develop complications after receiving rtPA, and at 37 weeks' gestation, delivered a healthy infant, demonstrating that rtPA thrombolysis may be used safely in pregnant women.

In Vitro Models for Assessing Transcranial Ultrasound-Enhanced Thrombolysis

To the Editor: Contrary to the promising results of recent clinical studies, Pfaffenberger et al conclude from in vitro data that diagnostic ultrasound (US) is not suitable for transcranial enhancement of tissue plasminogen activator (tPA) thrombolysis.1 Their contention is based on surprising control data showing significant clot lysis without tPA and plasminogen and relatively modest increases in clot dissolution with tPA. Interestingly, their reported clot weight loss of 21.8% after 1 hour of incubation in saline alone is much higher than that which they recently reported in another journal using the same methods (2.8%±1.8%2 and 11.0%±3.8%3). Likewise, the effect of tPA alone (27.4%) also differs with earlier results of 19.9%±4.3%3 and 22.7%±9.0%.2 These discrepancies seem important, because a 19.9% effect of tPA alone would have been lower than combined US and recombinant tPA through the skull (26.2%), thus encouraging the authors to positively assess transcranial US thrombolysis. Because clot dissolution is dependent on the amount of plasminogen present and on the amount of tPA available for activation of the plasminogen, little clot lysis should occur during the first 60 minutes of incubation in saline, with or without tPA. To study our hypothesis, we used experimental conditions similar to those of Pfaffenberger et al. 1.5 mL of citrated …

Ca 2+-regulated secretion of tissue-type plasminogen activator and von Willebrand factor in human endothelial cells

von Willebrand factor (vWF) and tissue-type plasminogen activator (tPA) are products of endothelial cells which are secreted into the bloodstream upon a stimulus-induced rise in intracellular Ca 2+. Although the release of both factors appears to be regulated similarly, they exhibit opposing physiological effects in the vasculature with vWF inducing coagulation and platelet aggregation and tPA triggering fibrinolysis and thrombolysis. To analyze possible differences in the regulated secretion of vWF and tPA in more detail, we recorded the Ca 2+-triggered exocytosis of both factors in cultured human endothelial cells. We demonstrate that vWF and tPA which are stored in different granules within endothelial cells are released with different kinetics following endothelial stimulation with histamine or the Ca 2+ ionophore A23187. While the stimulus-induced release of vWF increases with time over a course of 30 min, maximal acute secretion of tPA is observed 5 min following stimulation and subsequently drops to background levels. In the case of vWF, secretion can also be monitored indirectly through an antibody-reinternalization assay which indicates an incomplete release of vWF during single exocytotic fusion events. Our data thus point to differences in the Ca 2+-triggered secretion of vWF and tPA which could allow a fine-tuning of their release thereby ensuring a balanced physiological action.

Recommendations for tPA Thrombolysis in Children

Recommendations for tPA Thrombolysis in Children

Evaluation of thrombolysis and surgery in the emergency management of the acutely ischaemic limb

Acute limb ischaemia has a significant morbidity and mortality. In selected cases, the use of catheter directed tPA thrombolysis offers the surgeon an alternative to emergency surgery. This approach does not demonstrate any increase in the rate of limb loss.

Thrombosis in Children: Current Perspective and Distinct Challenges

Coincident with a true increase in the incidence of thrombosis in childhood has come an appreciation of the impact of thromboembolic events upon children. In part, the greater awareness of childhood thrombosis reflects improved diagnostic imaging, which allows more sensitive identification of clots in infants and children. At the same time, advances in supportive care have meant that more children are being exposed to, surviving and living with thromboembolic risk factors and complications than previously. Because data regarding pediatric thrombosis have been lacking, treatment strategies have been extrapolated from experience in adults. This approach, however, results in diagnostic and therapeutic pitfalls. An understanding of issues unique to pediatric thrombosis is required; recent insights and the ongoing challenges are reviewed.

Thrombosed Hemodialysis Grafts: Lyse and Wait with Tissue Plasminogen Activator or Urokinase Compared to Mechanical Thrombolysis with the Arrow-Trerotola Percutaneous Thrombolytic Device

To determine if the lyse and wait (L&W) technique with a 4-mg dose of alteplase (tissue plasminogen activator; tPA) is a safe and effective method of declotting dialysis grafts as compared to use of the Arrow-Trerotola Percutaneous Thrombectomy Device (PTD) or the L&W technique with use of urokinase (UK). Forty patients were randomized prospectively to undergo L&W declotting with use of 4 mg of tPA or mechanical thrombolysis with the PTD. The time interval to restored graft flow, total procedure time, hemostasis time, and anatomic success, clinical success, complications, and patency rates were analyzed. These were compared with historic results in 20 patients treated with the L&W technique with use of 250,000 U UK. The immediate anatomic success rate was 95% in the tPA L&W and PTD groups. The mean in-room lysis time with restored flow was 10 minutes for L&W with tPA and 19 minutes for PTD (P = .002). The mean in-room procedure time was 39 minutes for L&W and 45 minutes for PTD (P = NS). Mean hemostasis time with use of manual compression was 44 minutes for L&W with tPA and 23 minutes for PTD (P = .057). The historic group of 20 patients who underwent L&W with UK had a 95% anatomic success rate, a mean of 14 minutes of lysis time, a mean of 34 minutes of procedure time, and a mean of 26 minutes of time to hemostasis. No bleeding complications occurred in the PTD group. Seven episodes of bleeding occurred in six patients given tPA; four were delayed 60-90 minutes after the procedure, one necessitated hospitalization, and two required additional therapies. Four of the 20 patients undergoing L&W with UK had minor puncture site bleeding during the procedure. The 3-month primary patency rates were 65%, 65%, and 60% for L&W with tPA, PTD, and L&W with UK, respectively (P = NS). The 4-mg dose of tPA is effective but results in more bleeding complications and longer hemostasis times than mechanical thrombolysis with use of the PTD. Unlike in our experience with UK, bleeding complications with tPA were both major and delayed.

Enhancement of ultrasound-accelerated thrombolysis by echo contrast agents: dependence on microbubble structure

The combination of ultrasound (US) exposure and ultrasound contrast agent (UCA) further increases the amount of drug-mediated thrombolysis. The aim of this study was to examine the efficacy of the combination of US and UCA on tissue plasminogen activator (tPA) thrombolysis, and the dependence on the microbubble structure. A catheter-type transducer capable of US emission (10 MHz, spatial peak temporal average intensity = 1.02 W/cm 2 and peak negative pressure = 0.33 MPa) in the continuous-wave mode was employed. In 28 artificial white thrombi, serial changes in acoustic properties monitored by echography and histopathology during the tPA-mediated thrombolysis were analyzed. The thrombi were assorted to 4 groups; UCA nontreated (Control), sonicated albumin (A)-, SH-U508A (SH)- and dodecafluoropentane emulsion (DDFP)-treated groups. Persistence of microbubble opacification and thrombus weight were also measured. After the sample was suspended in a beaker with tPA (8000U) and 100 mL of saline, the UCA was administered and the mixture exposed to US for 10 min. Weight reduction of the thrombus was greatest in the DDFP Group (−49 ± 8%), and that in the A Group (−8 ± 5%) was not significantly different from that in the Control Group (−5 ± 1%). The persistence of the microbubbles expressed as the decay of the time-intensity curve, was longest in the DDFP Group. The echo intensity of the superficial layer of the thrombus exposed to US was high and weight loss was marked. Multiple cavity formation was observed histopathologically. The stability of the microbubbles was an important factor of the US and UCA enhancement effect on tPA-mediated thrombolysis. This combination therapy has potential for clinical application in patients with thrombotic arterial and venous occlusion and left arterial thrombus.