Antihypertensive Treatment Prolongs Tissue Plasminogen Activator Door-to-Treatment Time

Background: Ultrasound has been shown to enhance thrombolysis when used in conjunction with a thrombolytic agent. We have loaded echogenic liposomes (ELIP) with tissue plasminogen activator (tPA) and shown that mechanical non-imaging 1 MHz ultrasound can enhance thrombolysis in an in vitro clot model. This study aimed to evaluate the efficacy of clinical Doppler ultrasound to enhance the thrombolytic effect of our tPA-ELIP. Materials and Methods: A standard reproducible whole blood porcine clot model was used. Clots were blotted dry, weighed, and placed in 10 ml fresh frozen porcine plasma. Clots were treated with tPA-ELIP with and without Doppler ultrasound (pulsed wave ultrasound, 6.6 MHz, 2 minute-treatment time). After 30 minutes, clots were similarly weighed. Data are reported as percent clot mass loss. Samples of the plasma were assayed for D-dimer levels. Results: Exposure of tPA-ELIP to clinical Doppler ultrasound enhanced thrombolysis (p=0.015 vs. tPA alone or Doppler ultrasound alone; Figure ). There was a trend towards higher D-dimer levels in the clots treated with tPA-ELIP + clinical Doppler ultrasound, corresponding to the higher percent clot mass loss seen in this treatment group. Conclusions: This study demonstrates the ability of clinical Doppler ultrasound to enhance the thrombolytic effect of our tPA-ELIP in an in vitro clot model. This demonstrates the potential to translate our novel thrombolytic technique of combining a thrombolytic-loaded contrast agent and ultrasound to patient care.

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Abstract 64: Feasibility and safety on intravenous tissue Plasminogen Activator in the Pre-Hospital Acute Neurological Therapy and Optimization of Medical Care in Stroke Patients - Study (PHANTOM-S) Results of the Phantom-S pilot study

Stroke ◽

10.1161/str.43.suppl_1.a64 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Joachim E Weber ◽

Martin Ebinger ◽

Michal Rozanski ◽

Carolin Waldschmidt ◽

Matthias Wendt ◽

...

Keyword(s):

Pilot Study ◽

Acute Stroke ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Treatment Time ◽

Hospital Setting ◽

Ct Scanner ◽

Time To Treatment ◽

Intravenous Tissue Plasminogen Activator ◽

Tissue Plasminogen

Background: Beneficial effects of intravenous tissue Plasminogen Activator (tPA) in acute ischemic stroke (AIS) are strongly time-dependent. In PHANTOM-S, we use a specialized stroke ambulance equipped with a CT-scanner and point-of-care laboratory in order to shorten time-to-treatment. We report feasibility and safety of the 3-months pilot phase. Methods: The ambulance (staffed by a neurologist, paramedic and technician) is deployed by the dispatch center when the emergency call algorithm yields a suspected acute stroke. The pilot study was restricted to patients able to give informed consent. Preliminary Results: Between February 8 and April 30, 2011, the ambulance was deployed 208 times. Specific medical management was provided for 108 patients. 54 patients (50%) had a stroke while 31 (29%) had other neurological and 23 (21%) non-neurological diseases. 24 (48%) (median-NIHSS: 8; mean-age: 75±12) of 50 patients with AIS ambulance diagnosis received tPA (23 in the pre-hospital setting and one patient after admission for CT dysfunction). One of the tPA treated patients had a final non-stroke diagnosis (sepsis). Mean alarm-to-treatment time of pre-hospital tPA application was 58 minutes (62 minutes including the in-hospital tPA-application) compared to 98 minutes in 50 consecutive patients treated with tPA in Charité hospitals in 2010. Two (8%) of the tPA patients suffered a symptomatic intracranial hemorrhage and one patient (4%) died in-hospital. Technical failures comprised one CT dysfunction and two delayed CT-image transmissions Conclusions: Pre-hospital acute stroke management including tPA-application is feasible and the results suggest a significant shortening of time-to-treatment without obvious safety concerns. Final data will be presented at the ISC.

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Symptomatic Intracerebral Hemorrhage Among Eligible Warfarin-Treated Patients Receiving Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke

Yearbook of Neurology and Neurosurgery ◽

10.1016/j.yneu.2011.03.014 ◽

2011 ◽

Vol 2011 ◽

pp. 10-11

Author(s):

A.A. Rabinstein

Keyword(s):

Ischemic Stroke ◽

Intracerebral Hemorrhage ◽

Acute Ischemic Stroke ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Intravenous Tissue Plasminogen Activator ◽

Symptomatic Intracerebral Hemorrhage ◽

Tissue Plasminogen

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Thrombolytic therapy with tissue plasminogen activator for superior vena cava thrombosis in an infant with sepsis

Acta Paediatrica ◽

10.1080/08035250410020163 ◽

2005 ◽

Vol 94 (2) ◽

pp. 239-241 ◽

Cited By ~ 1

Author(s):

H. Tan ◽

M. Kizilkaya ◽

F. Alper ◽

N. Becit ◽

H. Kürşat

Keyword(s):

Thrombolytic Therapy ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Superior Vena Cava ◽

Superior Vena ◽

Vena Cava ◽

Tissue Plasminogen ◽

Vena Cava Thrombosis

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Tissue plasminogen activator as a novel diagnostic aid in acute pulmonary embolism

VASA ◽

10.1024/0301-1526/a000392 ◽

2014 ◽

Vol 43 (6) ◽

pp. 450-458 ◽

Cited By ~ 1

Author(s):

Julio Flores ◽

Ángel García-Avello ◽

Esther Alonso ◽

Antonio Ruíz ◽

Olga Navarrete ◽

...

Keyword(s):

Pulmonary Embolism ◽

Negative Predictive Value ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Predictive Value ◽

Acute Pulmonary Embolism ◽

Enzyme Linked Immunosorbent Assay ◽

Diagnostic Utility ◽

Tissue Plasminogen ◽

D Dimer

Background: We evaluated the diagnostic efficacy of tissue plasminogen activator (tPA), using an enzyme-linked immunosorbent assay (ELISA) and compared it with an ELISA D-dimer (VIDAS D-dimer) in acute pulmonary embolism (PE). Patients and methods: We studied 127 consecutive outpatients with clinically suspected PE. The diagnosis of PE was based on a clinical probability pretest for PE and a strict protocol of imaging studies. A plasma sample to measure the levels of tPA and D-dimer was obtained at enrollment. Diagnostic accuracy for tPA and D-dimer was determined by the area under the receiver operating characteristic (ROC) curve. Sensitivity, specificity, predictive values, and the diagnostic utility of tPA with a cutoff of 8.5 ng/mL and D-dimer with a cutoff of 500 ng/mL, were calculated for PE diagnosis. Results: PE was confirmed in 41 patients (32 %). Areas under ROC curves were 0.86 for D-dimer and 0.71 for tPA. The sensitivity/negative predictive value for D-dimer using a cutoff of 500 ng/mL, and tPA using a cutoff of 8.5 ng/mL, were 95 % (95 % CI, 88–100 %)/95 % (95 % CI, 88–100 %) and 95 % (95 % CI, 88–100 %)/94 %), respectively. The diagnostic utility to exclude PE was 28.3 % (95 % CI, 21–37 %) for D-dimer and 24.4 % (95 % CI, 17–33 %) for tPA. Conclusions: The tPA with a cutoff of 8.5 ng/mL has a high sensitivity and negative predictive value for exclusion of PE, similar to those observed for the VIDAS D-dimer with a cutoff of 500 ng/mL, although the diagnostic utility was slightly higher for the D-dimer.

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The L-Arginine: Nitric Oxide Pathway Contributes to the Acute Release of Tissue Plasminogen Activator in vivo in Man

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(97)87918-1 ◽

1998 ◽

Vol 31 (2) ◽

pp. 442A

Author(s):

D Newby

Keyword(s):

Nitric Oxide ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Tissue Plasminogen ◽

Nitric Oxide Pathway

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Desmopressin Stimulates Parallel Norepinephrine and Tissue Plasminogen Activator Release in Normal Subjects and Patients with Diabetes Mellitus

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642768 ◽

1988 ◽

Vol 59 (02) ◽

pp. 269-272 ◽

Cited By ~ 13

Author(s):

M B Grant ◽

C Guay ◽

R Lottenberg

Keyword(s):

Diabetes Mellitus ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Time Course ◽

Vascular Endothelial Cells ◽

Normal Subjects ◽

Plasma Norepinephrine ◽

Endogenous Catecholamine ◽

Tissue Plasminogen ◽

Patients With Diabetes

SummaryDesmopressin acetate administration markedly stimulates release of tissue plasminogen activator (t-PA) from vascular endothelial cells. The mechanism for this effect is unknown. Because infusion of epinephrine has been shown to increase t-PA levels, we examined the role of endogenous catecholamine mediation of t-PA release by desmopressin. Intravenous desmopressin acetate (0.3 μg/kg) was infused over 30 min in 9 controls and 11 subjects with diabetes mellitus, a condition associated with abnormalities of the fibrinolytic system. Plasma was collected in the supine, overnight fasted state at 15 min intervals (0-60 min) for measurement of t-PA activity, t-PA antigen and fractionated catecholamines. t-PA activity peaked at 30-45 min and subsequently decreased. The norepinephrine levels paralleled the t-PA activity. t-PA activity increased 10-fold from 0.14 ± .12 to 1.49 ± 0.79 IU/ml (Mean ± SD) and plasma norepinephrine increased 2- fold from 426 ± 90 to 780 ± 292 pg/ml. However, epinephrine and dopamine levels did not change significantly. The response to desmopressin of control and diabetic subjects was not shown to differ and their data were combined. We conclude that desmopressin increases plasma norepinephrine in addition to t-PA and that the parallel time course of change suggests a possible role for norepinephrine in mediating endothelial cell t-PA release.

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