Tissue plasminogen activator in chronic subdural hematomas as a predictor of recurrence

2006 ◽  
Vol 104 (1) ◽  
pp. 79-84 ◽  
Author(s):  
Hiroyuki Katano ◽  
Ken Kamiya ◽  
Mitsuhito Mase ◽  
Motoki Tanikawa ◽  
Kazuo Yamada
Keyword(s):  
Growth Factor ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Venous Blood ◽  
Angiogenic Factors ◽  
Subdural Hematomas ◽  
Initial Surgery ◽  
Significant Difference ◽  
Tissue Plasminogen ◽  
Endothelial Growth Factor

Object Chronic subdural hematomas (CSDHs) recur in 7 to 18% of cases. The present study was conducted to determine whether serum or lesion concentrations of coagulofibrinolytic and angiogenic factors, which have been reported to be potential markers of CSDH development, might predict such recurrences. Methods Sixty consecutive patients (mean age 71.5 years) with CSDHs (74 affected sides) were studied. Samples of serum in preoperative peripheral venous blood and of hematomas (obtained during surgery) were collected and analyzed. The CSDH recurred in six (8.1%) of the 74 affected sides in six patients. None of the values of the coagulative factors or tests in serum showed significant variation between cases with and those without recurrence. Among coagulofibrinolytic factors, tissue plasminogen activator (TPA) in hematomas demonstrated significantly greater levels in recurrent than in nonrecurrent cases; a similar tendency was noted for α2-plasmin inhibitor–plasmin complex in hematomas. Both factors were greater in the lesions than in the serum. Among the angiogenic factors, levels of hepatic growth factor (HGF) and vascular endothelial growth factor (VEGF) in hematomas were significantly greater than in serum, whereas those of basic fibroblast growth factor were rather lower. Note that comparisons between recurrent and nonrecurrent cases revealed no significant difference. Conclusions Patients harboring CSDHs with high TPA concentrations on sampling at the initial surgery have a relatively high probability of recurrence and require follow up with computerized tomography scanning. Angiogenic factors, such as HGF and VEGF, might be candidate markers of CSDH enlargement but are not useful as predictors of recurrence.

Management of Large Submacular Hemorrhages Due to Exudative AMD Utilizing Pars Plana Vitrectomy, Subretinal Tissue Plasminogen Activator, and Gas Insertion Compared With Antivascular Endothelial Growth Factor Alone

2017 ◽  
Vol 1 (1) ◽  
pp. 34-40 ◽  
Author(s):  
Enchun M. Liu ◽  
Rithwick Rajagopal ◽  
Bradley T. Smith ◽  
M. Gilbert Grand
Keyword(s):  
Growth Factor ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Pars Plana Vitrectomy ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Tissue Plasminogen ◽  
Pars Plana ◽  
Endothelial Growth Factor ◽  
Surgical Group

Purpose: To assess the outcomes of patients with large submacular hemorrhage (SMH) due to age-related macular degeneration in this era of anti-vascular endothelial growth factor (VEGF). Methods: Retrospective analysis of 149 eyes of 149 patients receiving pars plana vitrectomy, subretinal tissue plasminogen activator, and gas injection (“surgical group”; n = 80) or anti-VEGF alone (“anti-VEGF group”; n = 69). Changes in visual acuity (VA), number of anti-VEGF injections, and percentage of patients with ≥3 line VA gains are compared between groups. Results: Patients in the surgical group had larger SMH than those in the anti-VEGF group, 30.35 versus 14.57 mm2 ( P < .0001). Both groups experienced similar visual gains (−0.35 logarithm of the minimal angle of resolution [logMAR] vs −0.23 in logMAR, surgical vs anti-VEGF group; P = .36). The percentage of patients gaining ≥3 lines of VA was 55% in the surgical group and 54% in the anti-VEGF group. The surgical group achieved best-recorded VA sooner (3.7 compared to 4.6 months; P = .04) and required fewer injections (3.4 injections vs 4.7 in the anti-VEGF group; P = .001). Conclusion: Surgical intervention was favored for larger hemorrhages of shorter duration. Despite extensive hemorrhage and poor baseline VA, both groups showed similar rate of significant VA improvement.

scholarly journals Management of acute submacular hemorrhage using intravitreal injection of tissue plasminogen activator and gas: A case series

2020 ◽  
Vol 8 ◽  
pp. 2050313X2097033
Author(s):  
Athanasios Karamitsos ◽  
Vasileios Papastavrou ◽  
Tsveta Ivanova ◽  
David Cottrell ◽  
Kevin Stannard ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Visual Acuity ◽  
Growth Factor ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Case Series ◽  
Recombinant Tissue Plasminogen Activator ◽  
Vascular Endothelial ◽  
Tissue Plasminogen ◽  
Endothelial Growth Factor

The objective of this case series is the evaluation of the efficacy and visual outcomes after displacement of subretinal hemorrhage using intravitreal injection of recombinant tissue plasminogen activator, expansile gas, and in some cases an anti-vascular endothelial growth factor agent. A case series of 28 eyes of 28 patients (16 men and 12 women with age range 67–95 years) suffering from subretinal hemorrhage (duration range 1–15 days) caused by age-related macular degeneration or retinal macroaneurysm is presented. All the patients were treated with intravitreal injection of recombinant tissue plasminogen activator and gas and some of them received an anti-vascular endothelial growth factor agent between January 2013 and December 2016. The outcomes assessed were visual acuity (preoperatively 1 week, and 1 month postoperatively) with respect to duration and dimension of hemorrhage, displacement of hemorrhage, and possible complications of the procedure. Successful displacement of hemorrhage was achieved in 25 patients (89.3%), 18 of 28 patients had significant improvement in visual acuity 1 week after the treatment, and 22 of 28 patients had significant improvement in visual acuity 1 month after the treatment. The mean improvement of all patients with anatomical displacement of the hemorrhage in visual acuity was 0.7 ± 0.5 (LogMAR) in 1 month. Two patients developed vitreous hemorrhage after the procedure and one retinal detachment. Visual outcome a month after therapy displayed week correlation with duration, diameter, and thickness of hemorrhage. The results lead to the conclusion that intravitreal treatment of recombinant tissue plasminogen activator and expansible gas with or without injection of anti-vascular endothelial growth factor agent is effective in improving visual acuity and displacing submacular hemorrhage secondary to age-related macular degeneration and retinal macroaneurysm. The best functional outcomes can be expected in patients regardless of the size and duration of the hemorrhage.

Immunoreactivity of Tissue Plasminogen Activator and of Its Inhibitor Complexes

1989 ◽  
Vol 61 (03) ◽  
pp. 409-414 ◽  
Author(s):  
M Rånby ◽  
G Nguyen ◽  
P Y Scarabin ◽  
M Samama
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Degradation Products ◽  
Gel Filtration ◽  
Free Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Plasma Samples ◽  
Significant Difference ◽  
Tissue Plasminogen ◽  
Pai 1

SummaryAn enzyme linked immunosorbent assay (ELISA) based on goat polyclonal antibodies against human tissue plasminogen activator (tPA) was evaluated. The relative immunoreactivity of tPA in free form and tPA in complex with inhibitors was estimated by ELISA and found to be 100, 74, 94, 92 and 8l% for free tPA and tPA in complex with PAI-1, PAI-2, α2-antiplasmin and C1-inhibitor, respectively. Addition of tPA to PAI-1 rich plasma resulted in rapid and total loss of tPA activity without detectable loss of ELISA response, indicating an immunoreactivity of tPA in tPA/PAI-1 complex of about l00%. Three different treatments of citrated plasma samples (acidification/reneutralization, addition of 5 mM EDTA or of 0.5 M lysine) prior to determination by ELISA all resulted in increased tPA levels. The fact that the increase was equally large in all three cases along with good analytical recovery of tPA added to plasffi, supported the notion that all tPA antigen present in plasma samples is measured by the ELISA. Analysis by ELISA of fractions obtained by gel filtration of plasma from a patient undergoing tPA treatment identified tPA/inhibitor complexes and free tPA but no low molecular weight degradation products of tPA. Determinations of tPA antigen were made at seven French clinical laboratories on coded and randomized plasma samples with known tPA antigen content. For undiluted samples there was no significant difference between the tPA levels found and those known to be present. The between-assay coefficient of variation was 7 to 10%. In conclusion, the ELISA appeared suited for determination of total tPA antigen in human plasma samples.

scholarly journals Analisis pengaruh pemberian virgin coconut oil (VCO) terhadap adhesi intraperitoneal

2016 ◽  
Vol 8 (2) ◽  
Author(s):  
Erwin . ◽  
Jimmy Panelewen ◽  
Ishak Lahunduitan
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Rattus Norvegicus ◽  
Adhesion Formation ◽  
Coconut Oil ◽  
Virgin Coconut Oil ◽  
Chi Square ◽  
Significant Difference ◽  
Tissue Plasminogen ◽  
Anti Inflammation

Abstract: Intraperitoneal adhesion is an attachment between intraperitoneal tissue and organ in the form of fibrosis. The occurences of intraperitoneal adhesion are 67-93% after laparotomy and 97% after gynecological operation. Adhesion between wound and omentum occurs in 80% of patients; 50% involve the intestines. Prevention and inhibition of adhesion formation can be done by decreasing post traumatic inflammation. There are several substances that can be used for that purpose, inter alia: anti-inflammation, anti-histamine, anti-coagulant (heparin), anti-oxidant, proteolytic enzymes, and tissue plasminogen activator. It is already known that virgin coconut oil (VCO) has several important roles, such as: anti-inflammation, antithrombosis, mechanical barrier, and antioxidant due to its tocopherol content. This study aimed to obtain the influence of several doses of intraperitoneal VCO on intraperitoneal adhesion macroscopically and microscopically after laparotomy. This was an analytical interventional study using control. Samples were male Wistar rats (Rattus norvegicus) with an average body weight of 175-200 g. The results of Kruskal-Wallis chi-square tests were 16.381, df = 4, and Asymp sig = 0.003 (P < 0.05) for macroscopical grading (Zühlke) meanwhile 15.160, df = 4, and Asymp sig = 0.004 (P < 0.01) for microscopical grading (Yilmaz). Conclusion: There was a statistically significant difference in macroscopical grades according to Zühlke and in microscopical grades according to Yalmiz among the five groups concerning the occurence of intraperitoneal adhesion in Rattus norvegicus.Keywords: intraperitoneal adhesion, virgin coconut oil (VCO).Abstract: Adhesi intraperitonial adalah timbulnya perlengketan berupa fibrosis antara jaringan dan organ di dalam rongga abdomen. Kejadian adhesi intraperitoneal sekitar 67-93% setelah operasi laparotomi bedah dan mencapai 97% pada operasi ginekologi. Adhesi antara luka dan omentum terjadi pada 80% pasien dan sekitar 50% melibatkan usus. Untuk mencegah atau mengurangi pembentukan adhesi dapat dilakukan dengan menurunkan inflamasi pasca trauma melalui bahan atau obat anti-inflamasi, anti-histamin, anti-koagulan (heparin), anti-oksidan, enzim proteolitik, dan tissue plasminogen activator. Virgin Coconut Oil (VCO) telah diketahui berperan sebagai antiinflamasi, antitrombotik, barier mekanik, dan antioksidan dengan bahan aktif utama tokoferol. Penelitian ini bertujuan untuk mengetahui pengaruh VCO secara makroskopik dan mikroskopik terhadap adhesi intraperitoneal dengan menganalisis perbandingan dosis VCO yang diberikan intraperitoneal pada hewan coba tikus Wistar. Jenis penelitian ini analitik intervensional dengan kontrol. Hewan coba ialah tikus Wistar (Rattus norvegicus) yang diseragamkan berat badan 175-200 g, jenis kelamin jantan, dan variannya. Hasil uji Kruskal-Wallis chi-square ialah 16,381 dengan df = 4 dan Asymp sig = 0,003 (P < 0,05) untuk penilaian makroskopik (Zühlke) sedangkan nilai 15,160, dengan df = 4 dan Asymp sig = 0,004 (P < 0,01) untuk penilaian mikroskopik (Yilmaz). Simpulan: Terdapat perbedaan bermakna dalam derajat makroskopik menurut Zühlke dan derajat mikroskopik menurut Yilmaz pada ke-5 perlakuan dalam kejadian adhesi intraperitoneal pada Rattus norvegicus.Kata kunci: adhesi intraperitoneal, VCO

A Comparison of Thromboelastography with Heparinase or Protamine Sulfate Added In Vitro during Heparinized Cardiopulmonary Bypass

1997 ◽  
Vol 78 (02) ◽  
pp. 820-826 ◽  
Author(s):  
Bruce D Spiess ◽  
Michael H Wall ◽  
Bruce S Gillies ◽  
Jane C K Fitch ◽  
Louise O Soltow ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Postoperative Hemorrhage ◽  
Sensitive Indicator ◽  
Blood Samples ◽  
Significant Difference ◽  
Tissue Plasminogen ◽  
Heparin Neutralization

SummaryThromboelastography (TEG) has been used after cardiopulmonary bypass (CPB) to diagnose excessive postoperative hemorrhage. Conventional TEG during CPB is not possible due to the sensitivity of the TEG to even small amounts of heparin, which produces a nondiagnostic tracing. The purpose of this study was to compare heparin neutralization using heparinase or protamine in TEG blood samples obtained during CPB. TEG testing was performed on 48 patients before, during and after CPB. Tissue plasminogen activator activity and antigen were measured on a subset of 32 patients. We found: 1) heparinase neutralized at least 10 IU/ml heparin while 1.6 ug/ml protamine neutralized up to 7 IU/ml heparin, 2) in samples with complete heparin neutralization by both methods, there was no significant difference in the R values, 3) while there was good correlation for other TEG parameters between heparinase and protamine treated samples, heparinase treatment produced shorter K values and higher angle, MA and A60, 4) while fibrinolysis was detected using both methods, heparinase treatment suppressed fibrinolysis in the TEG in both samples from patients and after in vitro addition of tissue plasminogen activator, 5) TEG was not a sensitive indicator of t-PA activity, detecting only 21% of samples with increased t-PA activity during bypass, and 5) heparinase was at least 100 times more expensive than protamine. We conclude that while both heparinase and protamine can be used to neutralize heparin in TEG samples obtained during CPB, protamine neutralization is more sensitive to fibrinolysis and less expensive, but the protamine dose must be carefully selected to match the heparin level used at individual institutions.

scholarly journals Biological effect of tissue plasminogen activator (t-PA) and DNase intrapleural delivery in pleural infection patients

2019 ◽  
Vol 6 (1) ◽  
pp. e000440 ◽  
Author(s):  
Nikolaos I Kanellakis ◽  
John M Wrightson ◽  
Rob Hallifax ◽  
Eihab O Bedawi ◽  
Rachel Mercer ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Treatment Period ◽  
Tissue Plasminogen Activator ◽  
Statistical Significance ◽  
Significant Rise ◽  
Monocyte Chemoattractant Protein 1 ◽  
Significant Difference ◽  
Tissue Plasminogen ◽  
Pleural Infection ◽  
Intrapleural Administration

BackgroundPleural infection (PI) is a major global disease with an increasing incidence, and pleural fluid (PF) drainage is essential for the successful treatment. The MIST2 study demonstrated that intrapleural administration of tissue plasminogen activator (t-PA) and DNase, or t-PA alone increased the volume of drained PF. Mouse model studies have suggested that the volume increase is due to the interaction of the pleura with the t-PA via the monocyte chemoattractant protein 1 (MCP-1) pathway. We designed a study to determine the time frame of drained PF volume induction on intrapleural delivery of t-PA±DNase in humans, and to test the hypothesis that the induction is mediated by the MCP-1 pathway.MethodsData and samples from the MIST2 study were used (210 PI patients randomised to receive for 3 days either: t-PA and DNase, t-PA and placebo, DNase and placebo or double placebo). PF MCP-1 levels were measured by ELISA. One-way and two-way analysis of variance (ANOVA) with Tukey’s post hoc tests were used to estimate statistical significance. Pearson’s correlation coefficient was used to assess linear correlation.ResultsIntrapleural administration of t-PA±DNase stimulated a statistically significant rise in the volume of drained PF during the treatment period (days 1–3). No significant difference was detected between any groups during the post-treatment period (days 5–7). Intrapleural administration of t-PA increased MCP-1 PF levels during treatment; however, no statistically significant difference was detected between patients who received t-PA and those who did not. PF MCP-1 expression was not correlated to the drug given nor the volume of drained PF.ConclusionsWe conclude that the PF volume drainage increment seen with the administration of t-PA does not appear to act solely via activation of the MCP-1 pathway.

Vascular endothelial growth factor receptor-2 (VEGFr-2) genetic polymorphisms as predictors to antiangiogenic therapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14561-e14561
Author(s):  
J. Jurado ◽  
J. A. Ortega ◽  
P. Iglesias ◽  
J. L. García-Puche ◽  
J. Belon
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Overall Survival ◽  
Growth Factor ◽  
Antiangiogenic Therapy ◽  
Venous Blood ◽  
Metastatic Breast ◽  
Severe Toxicity ◽  
Vascular Endothelial ◽  
Significant Difference ◽  
Endothelial Growth Factor

e14561 Background: Vascular endothelial growth factor (VEGF) and its receptors (VEGFr-2) have important roles in angiogenesis, predicting risk and prognosis in several solids tumor. VEGFr-2 located on chromosome 4 (4q11-q12) is organized into 30 exons separated by 29 introns. Recently the VEGF-2578 AA and VEGF-1154 AA genotypes were associated with a superior median overall survival when using bevacizumab in metastatic breast cancer. We investigated the association of VEGFr-2 polymorphisms to efficacy and toxicity in patients with antiangiogenic therapy. Methods: We performed genotype for selected VEGFr-2 polymorphisms in promoter regions 5’UTR, 3’UTR; in exons 7, 8, 9, 11, 16, 17, 18, 21, 27, 30 and introns 9, 17, 20. DNA was extracted from venous blood of 44 patients with non-curable solid tumors who have received treatment with bevacizumab (B) N=20 (45%) or raf kinase inhibitors 55%; vatalanib (PTK-787) N=3, sunitinib (SU011248) N=6, sorafenib (BAY 43–9006) N= 13, ZD6474 N=1 and AMG706 N= 1. Kaplan-Meier survival analysis was used to assess the association between VEGFr-2 staining and either progression-free survival (PFS) or overall survival (OS). Results: 44 patients have received a median of 6 (1–19) cycles of treatment, 72% was used simultaneously with QT. According to the criteria of NCI-CTC the severe toxicity G3–4 occurred in 47%, 9% with a definite suspension of the drug. The toxicity was not associated with VEGFr-2 genotypes. Efficacy; 5/44 patients (11%) had complete response and 11/ 44 (22%) partial responses by RECIST criteria. With a median follow up of 12 months, the ILP was 8.5 months dt (5.8). The analysis of VEGFr-2 polymorphisms identifies the variant AA of the intron-20 rs2219471 with a significant difference in PFS and OS regarding their ancestral variant AG. Conclusions: Our data suggest that VEGFR polymorphism can be a predictor of clinical outcomes in antiangiogenic therapy. No significant financial relationships to disclose.

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