scholarly journals The syndrome of hepatic veno-occlusive disease after marrow transplantation

Blood ◽  
1995 ◽  
Vol 85 (11) ◽  
pp. 3005-3020 ◽  
Author(s):  
SI Bearman
Keyword(s):  
Serum Bilirubin ◽  
Recombinant Tissue Plasminogen Activator ◽  
Clinical Syndrome ◽  
Therapeutic Drug ◽  
High Dose ◽  
Cellular Mechanisms ◽  
Tissue Plasminogen ◽  
Pharmacologic Prophylaxis ◽  
Supportive Management ◽  
To Receive

The clinical syndrome of VOD is a frequent cause of nonrelapse mortality among patients receiving high-dose cytoreductive regimens. Patients likely to develop VOD have existing liver dysfunction, evidence of infection before conditioning, tend to receive more intensive preparative regimens, and often receive marrow from alternative donors. Therapeutic drug monitoring of busulfan and pharmacokinetic dose adjustments appear to be useful in reducing the incidence of VOD in patients receiving this agent. Data are contradictory as regards whether pharmacologic prophylaxis is effective. Patients who will develop severe VOD are characterized by a rapid increase in serum bilirubin as well as weight. Supportive management of these patients should attempt to preserve respiratory as well as renal function, sometimes a very difficult task. Treatment with recombinant tissue plasminogen activator has promise. However, given its potential for toxicity, a prospective randomized trial should be performed. Hopefully, as more data regarding the molecular and cellular mechanisms of this illness are elucidated, more thoughtful prevention strategies will be developed. This will be necessary, particularly as newer, more intensive preparative regimens are being developed, as access to alternative donors increases, and as more diseases will be treated with this approach.

scholarly journals Preparation of Peptide and Recombinant Tissue Plasminogen Activator Conjugated Poly(Lactic-Co-Glycolic Acid) (PLGA) Magnetic Nanoparticles for Dual Targeted Thrombolytic Therapy

2020 ◽  
Vol 21 (8) ◽  
pp. 2690 ◽  
Author(s):  
Huai-An Chen ◽  
Yunn-Hwa Ma ◽  
Tzu-Yuan Hsu ◽  
Jyh-Ping Chen
Keyword(s):  
Magnetic Nanoparticles ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Glycolic Acid ◽  
Blood Clot ◽  
Recombinant Tissue Plasminogen Activator ◽  
Clot Lysis ◽  
High Dose ◽  
Tissue Plasminogen

Recombinant tissue plasminogen activator (rtPA) is the only thrombolytic agent that has been approved by the FDA for treatment of ischemic stroke. However, a high dose intravenous infusion is required to maintain effective drug concentration, owing to the short half-life of the thrombolytic drug, whereas a momentous limitation is the risk of bleeding. We envision a dual targeted strategy for rtPA delivery will be feasible to minimize the required dose of rtPA for treatment. For this purpose, rtPA and fibrin-avid peptide were co-immobilized to poly(lactic-co-glycolic acid) (PLGA) magnetic nanoparticles (PMNP) to prepare peptide/rtPA conjugated PMNPs (pPMNP-rtPA). During preparation, PMNP was first surface modified with avidin, which could interact with biotin. This is followed by binding PMNP-avidin with biotin-PEG-rtPA (or biotin-PEG-peptide), which was prepared beforehand by binding rtPA (or peptide) to biotin-PEG-maleimide while using click chemistry between maleimide and the single –SH group in rtPA (or peptide). The physicochemical property characterization indicated the successful preparation of the magnetic nanoparticles with full retention of rtPA fibrinolysis activity, while biological response studies underlined the high biocompatibility of all magnetic nanoparticles from cytotoxicity and hemolysis assays in vitro. The magnetic guidance and fibrin binding effects were also confirmed, which led to a higher thrombolysis rate in vitro using PMNP-rtPA or pPMNP-rtPA when compared to free rtPA after static or dynamic incubation with blood clots. Using pressure-dependent clot lysis model in a flow system, dual targeted pPMNP-rtPA could reduce the clot lysis time for reperfusion by 40% when compared to free rtPA at the same drug dosage. From in vivo targeted thrombolysis in a rat embolic model, pPMNP-rtPA was used at 20% of free rtPA dosage to restore the iliac blood flow in vascular thrombus that was created by injecting a blood clot to the hind limb area.

Sex differences in IV thrombolysis treatment for acute ischemic stroke

Neurology ◽  
2020 ◽  
Vol 95 (1) ◽  
pp. e11-e22
Author(s):  
Brent Strong ◽  
Lynda D. Lisabeth ◽  
Mathew Reeves
Keyword(s):  
Sex Differences ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Sex Difference ◽  
Meta Analysis ◽  
Recombinant Tissue Plasminogen Activator ◽  
Pooled Data ◽  
Lower Treatment ◽  
Tissue Plasminogen ◽  
To Receive

ObjectiveA prior meta-analysis of reports published between 2000 and 2008 found that women were 30% less likely to receive IV recombinant tissue plasminogen activator (rtPA) treatment for stroke than men; we updated this meta-analysis to determine if this sex difference persisted.MethodsWe identified studies that reported sex-specific IV rtPA treatment rates for acute ischemic stroke published between 2008 and 2018. Eligible studies included representative populations of patients with ischemic stroke from hospital-based, registry-based, or administrative data. Random effects odds ratios (ORs) were generated to quantify sex differences.ResultsTwenty-four eligible studies were identified during this 10-year period. The summary unadjusted OR based on 17 studies with data on all ischemic stroke patients was 0.87 (95% confidence interval [CI], 0.82–0.93), indicating that women had 13% lower odds of receiving IV rtPA treatment than men. However, substantial between-study variability existed. Lower treatment odds in women were also observed in 7 studies that provided data on the subgroup of patients eligible for IV rtPA treatment, although the summary OR of 0.95 (95% CI, 0.88–1.02) was not statistically significant. Examination of time trends across 33 studies published between 2000 and 2018 found evidence that the sex difference had narrowed in more recent years.ConclusionsAlthough there is considerable variability in the findings of individual studies, pooled data from recent studies show that women with acute stroke are less likely to be treated with IV thrombolysis compared with men. However, the size of this difference has narrowed compared to studies published before 2008.

scholarly journals Frequency of stroke patients qualified for recombinant tissue plasminogen activator (r-TPA) and constraints in Zahedan 2016

2017 ◽  
Vol 7 (1) ◽  
pp. 7 ◽  
Author(s):  
Alireza Khosravi ◽  
Mohammad-taghi Farzadfard ◽  
Arezoo Abdollahpour
Keyword(s):  
Ischemic Stroke ◽  
Ct Scan ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Demographic Data ◽  
Recombinant Tissue Plasminogen Activator ◽  
City Hospital ◽  
Stroke Patients ◽  
Tissue Plasminogen ◽  
To Receive

Background: Brain stroke is one of the common causes of mortality and disability. By introducing r-TPA into the global drug market and its effect on the patients’ prognosis, using this drug is recommended in all patients with ischemic stroke who visited less than 4.5 hours after start stroke symptoms. The aim of this study was to investigate the frequency of stroke patients qualified for recombinant tissue plasminogen activator (r-TPA) and its constraints.Methods: In this descriptive cross-sectional study, 244 patients examined with stroke admitted to the neurology of Zahedan city hospital in 2016. Information form were completed with demographic data, transmission method, referral time, CT scan preparation time, and the response of the patients' trials, and finally the data were inserted in SPSS.16 software and analysed by statistical methods.Results: Out of all patients with ischemic stroke, 28 (11.5%) patients had contraindication to receive drug. Of 216 remain patients, 201 patients (93.1%) had no possibility to receive r-TPA due to the loss of gold time and only 15 patients (6.9%) had possibility to receive drug because of visited 4.5 hours before the beginning of symptoms. Of them, 3(20%) patients due to delay in CT scan and test results, had no possibility to receive r-TPA. In summary, of all patients with inclusion criteria, only 12 (5.5%) patients could use the r-TPA in this study.Conclusions: The most important barrier to using r-TPA has been the loss of golden time and training to raise awareness of the society can lead to early referral from the onset of stroke symptoms.

Recombinant Tissue Plasminogen Activator Therapy for Pacemaker-Induced Thrombosis

1998 ◽  
Vol 6 (2) ◽  
pp. 125-126
Author(s):  
Erdoĝan Ilkay ◽  
Ilgin Karaca ◽  
Selami Serhatlioglu ◽  
Nadi Aslan ◽  
Mutlu Cihangiroglu
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Subclavian Vein ◽  
Recombinant Tissue Plasminogen Activator ◽  
High Dose ◽  
Vein Thrombosis ◽  
Subclavian Vein Thrombosis ◽  
Short Period ◽  
Tissue Plasminogen

A 50-year-old male who developed subclavian vein thrombosis following insertion of a demand pacemaker was treated with a short period of high-dose recombinant tissue plasminogen activator (100 mg over 3 hours). Total thrombolysis was achieved without complications.

Investigation by HPLC of the Catabolism of Recombinant Tissue Plasminogen Activator in the Rat

1988 ◽  
Vol 60 (01) ◽  
pp. 107-112 ◽  
Author(s):  
Roy Harris ◽  
Louis Garcia Frade ◽  
Lesley J Creighton ◽  
Paul S Gascoine ◽  
Maher M Alexandroni ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Half Life ◽  
Recombinant Tissue Plasminogen Activator ◽  
Rat Plasma ◽  
High Molecular Weight Complex ◽  
Molecular Weights ◽  
Major Activity ◽  
Tissue Plasminogen

SummaryThe catabolism of recombinant tissue plasminogen activator (rt-PA) was investigated after injection of radiolabelled material into rats. Both Iodogen and Chloramine T iodination procedures yielded similar biological activity loss in the resultant labelled rt-PA and had half lives in the rat circulation of 1 and 3 min respectively. Complex formation of rt-PA was investigated by HPLC gel exclusion (TSK G3000 SW) fractionation of rat plasma samples taken 1-2 min after 125I-rt-PA injection. A series of radiolabelled complexes of varying molecular weights were found. However, 60% of the counts were associated with a single large molecular weight complex (350–500 kDa) which was undetectable by immunologically based assays (ELISA and BIA) and showed only low activity with a functional promoter-type t-PA assay. Two major activity peaks in the HPLC fractions were associated with Tree t-PA and a complex having a molecular weight of ̴ 180 kDa. HPLC fractionation to produce these three peaks at various timed intervals after injection of 125I-rt-PA showed each to have a similar initial rate half life in the rat circulation of 4-5 min. The function of these complexes as yet is unclear but since a high proportion of rt-PA is associated with a high molecular weight complex with a short half life in the rat, we suggest that the formation of this complex may be a mechanism by which t-PA activity is initially regulated and finally cleared from the rat circulation.

Bioavailability in Rats of Human Recombinant Tissue Plasminogen Activator After Subcutaneous and Intramuscular Injection

1986 ◽  
Vol 56 (03) ◽  
pp. 299-301 ◽  
Author(s):  
L J Garcia Frade ◽  
S Poole ◽  
S Hanley ◽  
L J Creighton ◽  
A D Curtis ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Inferior Vena ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Vena Cava ◽  
Recombinant Tissue Plasminogen Activator ◽  
Fibrin Plate ◽  
Tissue Plasminogen

SummaryThe bioavailability of human recombinant tissue plasminogen activator (rt-PA) in rats was measured after subcutaneous (s.c.) and intramuscular (i.m.) injection. Rt-PA was absorbed after both i.m. and s.c. injection, giving peak plasma concentrations within 30 min and 1 h, respectively, with detectable concentrations up to 6 h. These peak values of bioavailable t-PA were obtained in a functional fibrin plate assay of euglobulin precipitates and expressed as +88% and +243% (for s.c. and i.m. routes respectively) above basal rat fibrinolytic activity. Prior injection of rt-PA, s.c. or i.m., significantly reduced the weights of thrombi induced in the inferior vena cava after injection.

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