Changes in Fibrinogen After rt-PA Administration

1996 ◽  
Vol 2 (1) ◽  
pp. 43-50
Author(s):  
Justine Meehan Carr ◽  
Edwin G. Bovill ◽  
Russell P. Tracy ◽  
Martin Mankowski ◽  
Kenneth G. Mann ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Recombinant Tissue Plasminogen Activator ◽  
Low Molecular Weight ◽  
Tissue Plasminogen ◽  
Group A ◽  
Group B ◽  
Plasmin Inhibitor ◽  
D Dimer ◽  
Qualitative Changes ◽  
Time Point

Among patients participating in the TIMI-II protocol, there was a variability in the fibrinolytic re sponse to recombinant tissue plasminogen activator (rt- PA). A cohort of 20 TIMI-II patients was selected for detailed study because their responses to rt-PA varied widely in the degree of fibrin(ogen)olysis. Patient plasmas were analyzed by immunoblotting for changes in fibrino gen and plasminogen. Measurements of fibrinogen, fibrin ogen degradation product (FDP), D-dimer, Bβ 1-42, plas minogen, and t-PA were also correlated. Three patterns of response to rt-PA were identified: Group A ( n = 4) had fibrinogenolysis without fibrinolysis; Group B ( n = 11) had fibrinolysis and mild fibrinogenolysis; and Group C ( n = 5) had fibrinolysis with intense fibrinogenolysis. Group C patients also demonstrated qualitative changes in high- molecular-weight (HMW) and low-molecular-weight (LMW) fibrinogens, whereas Group A and B patients demonstrated only mild alterations in fibrinogen compo sition. Plasmin-inhibitor complexes were identified in all three groups. All patients had both plasmin-α2-anti plasmin and plasmin-α2-macroglobulin complexes at the 50-min time point. The concentration of pretreatment plasminogen correlated with the degree of fibrinogenoly sis.

Adjusted Versus Fixed Doses of the Low-Molecular-Weight Heparin Fragmin in the Treatment of Deep Vein Thrombosis

1994 ◽  
Vol 71 (05) ◽  
pp. 698-702 ◽  
Author(s):  
M Alhenc-Gelas ◽  
C Jestin-Le Guernic ◽  
J F Vitoux ◽  
A Kher ◽  
M Aiach ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Deep Vein Thrombosis ◽  
Low Molecular Weight Heparin ◽  
Factor Xa ◽  
Heparin Therapy ◽  
Low Molecular Weight ◽  
Vein Thrombosis ◽  
Group A ◽  
Group B ◽  
Deep Vein

SummaryTreatment monitoring based on a laboratory parameter increases the efficacy and safety of standard heparin therapy, but it is not known if this also applies to low-molecular-weight heparin (LMWH) therapy of acute deep vein thrombosis (DVT). In a prospective randomized trial involving 122 consecutive patients, group A (58 patients) received a weight adjusted dose of Fragmin (100 IU/kg) subcutaneously twice a day throughout the treatment period (10 days ± 1), while in group B (64 patients) the dosage was based on the results of an anti factor Xa (anti Xa) amidolytic assay to obtain a target concentration from 0.5 to 1 IU/ml. AntiXa and antithrombin activities were also measured retrospectively on frozen plasma from all patients. The two regimens were comparable in terms of hemorrhagic complications (4 in group A and 3 in group B). Bilateral ascending phlebography was performed before inclusion and at the end of LMWH treatment. Treatment efficacy, based on Marder’s score, did not differ between the two groups (p = 0.3). Dosage adjustment to between 0.5 to 1IU anti-Xa/ml does not therefore appear to improve the efficacy or safety of LMWH tieatment. However, correlations between the change in Marder’s score and both anti-Xa (p <0.001) and antithrombin activity (p <0.001) were observed, suggesting a relationship between the degree of FXa or thrombin inhibition and antithrombotic activity.

scholarly journals Simultaneous Combined Intravenous Recombinant Tissue Plasminogen Activator and Endovascular Therapy for Hyperacute Middle Cerebral Artery M1 Occlusion

2011 ◽  
Vol 17 (1) ◽  
pp. 115-122 ◽  
Author(s):  
S. Toyota ◽  
S. Sugiura ◽  
K. Iwaisako
Keyword(s):  
Middle Cerebral Artery ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Cerebral Artery ◽  
Endovascular Therapy ◽  
Recombinant Tissue Plasminogen Activator ◽  
Simultaneous Treatment ◽  
Tissue Plasminogen ◽  
Group A ◽  
Group B

We investigated the efficacy and safety of combined intravenous (IV) recombinant tissue plasminogen activator (rtPA) and simultaneous endovascular therapy (ET) for hyperacute middle cerebral artery (MCA) M1 occlusion. Between October 2005 and April 2007, in the combined group, 22 patients eligible for IV rtPA, who were diagnosed as having MCA M1 occlusion, were treated with IV rtPA and simultaneous ET was initiated as soon as possible. The other patients were treated with IV rtPA alone (IV group A: n = 11). Between May 2007 and November 2008, all patients eligible for IV rtPA, who were diagnosed as having MCA M1 occlusion, underwent thrombolysis by IV rtPA alone (IV group B: n = 24). The improvement of the National Institutes of Health Stroke Scale score at 24 hours was highest in the combined group (10 ± 4.1). In contrast, it was 5.1 ± 4.7 in the IV group A (P = 0.017) and 5.6 ± 5.6 in IV group B (P = 0.006). In the combined group, successful recanalization was observed in 18 of 22 patients with one symptomatic intracranial hemorrhage. The rate of mRS0–2 at three months was highest in the combined group, 36% in the IV group A and 33% in the IV group B (P = 0.008). Simultaneous treatment with IV rtPA and ET improved the clinical outcome of MCA M1 occlusion without a significant increase of adverse effects in our study.

scholarly journals Doppler Ultrasound under Image Denoising Algorithm in the Diagnosis and Treatment of Fetal Growth Restriction Using Aspirin Combined with Low-Molecular-Weight Heparin

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Huiling Liu ◽  
Huiyuan Niu ◽  
Wenqiong Zeng
Keyword(s):  
Molecular Weight ◽  
Blood Flow ◽  
Image Denoising ◽  
Doppler Ultrasound ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Doppler Ultrasound Imaging ◽  
Group A ◽  
Group B ◽  
Calcium Injection

Objective. This study explored the clinical application value of image denoising algorithm combined with Doppler ultrasound imaging in evaluation of aspirin combined with low-molecular-weight heparin (LMWH) on fetal growth restriction (FGR). Method. A two-stage image denoising by principal component analysis (PCA) with local pixel grouping (LPG-PCA) denoising algorithm was constructed in this study. Eighty FGR pregnant women were included in the study, and they were rolled into an experimental group (aspirin enteric-coated tablets + LMWH calcium injection) and a control group (LMWH calcium injection) according to the different treatment plans, with 40 cases in each group. All patients were performed with Doppler ultrasound imaging. The blood flow parameters (BFPs) were recorded and compared before and after the treatment in two groups, including power index (PI), resistance index (RI), high systolic blood flow velocity (S), high diastolic blood flow velocity (D), S/D value, and peak systolic velocity (PSV). In addition, the middle cerebral artery (MCA) BFPs, cerebral placental rate (CPR), amniotic fluid index (AFI) and perinatal outcome (PO) of the two groups were compared. Results. The total effective rate of treatment in group A (87.5%) was greatly higher than that in group B (62.5%), showing statistical difference (P < 0.05). The PI (0.72 ± 0.19), RI (0.57 ± 0.17), and S/D values (2.26 ± 0.43) in group A were dramatically lower than those in group B, which were 0.92 ± 0.21, 0.75 ± 0.14, and 2.64 ± 0.45, respectively (P < 0.05), and the AFI was higher (13.71 ± 2.2 cm vs 11.38 ± 2.16 cm) (P < 0.05). The Apgar score (9.17 ± 0.26), weight (3.57 ± 1.08), and gestational age (38.85 ± 2.50) of group A were all higher in contrast to those of group B, which were 7.33 ± 0.25, 2.61 ± 1.13, and 36.18 ± 2.25, respectively (P < 0.05). In addition, the fetal double parietal diameter (2.4 ± 0.9 mm), femur diameter (2.2 ± 0.6 mm), head circumference (1.2 ± 0.4 mm), abdominal circumference (1.3 ± 0.7 mm), and uterine height (0.8 ± 0.3 mm) in group A were obviously superior to those in group B, which were 1.8 ± 0.4 mm, 1.7 ± 0.5 mm, 0.8 ± 0.2 mm, 0.9 ± 0.4 mm, and 0.4 ± 0.6 mm, respectively, showing statistically observable differences (P < 0.05). Conclusion. Doppler ultrasound based on image denoising algorithm can accurately evaluate the effect of aspirin combined with LMWH on the improvement of FGR and showed good application value.

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.

scholarly journals Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Bing-xin Kang ◽  
Hui Xu ◽  
Chen-xin Gao ◽  
Sheng Zhong ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trial ◽  
Total Knee Arthroplasty ◽  
Blood Loss ◽  
Tranexamic Acid ◽  
Randomized Controlled ◽  
Group A ◽  
Total Knee ◽  
Group B ◽  
D Dimer

Abstract Background We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA). Methods For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50–75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay. Results The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P <  0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05). Conclusion In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA. Trial registration The trial was registered in the Chinese Clinical Trial Registry (ChiCTR1900025013).

New coronavirus infection, hemostasis and heparin dosing problems: It is important to say now

2020 ◽  
Author(s):  
А.Ю. Буланов ◽  
Е.В. Ройтман
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight ◽  
Evidence Based ◽  
Low Molecular Weight Heparins ◽  
Heparin Resistance ◽  
Hospital Patients ◽  
Expert’S Opinion ◽  
Coronavirus Infection ◽  
Based Medicine ◽  
D Dimer

В отсутствие достаточной базы доказательной медицины самым ценным становится мнение экспертов, опирающихся на свой опыт и опыт коллег. COVID-19-ассоциированная коагулопатия имеет характер тромбовоспаления. Назначение гепаринов — нефракционированного или, главным образом, низкомолекулярного (НМГ) призвано преодолеть его, поскольку гепарин обладает не только антикоагулянтным эффектом, но и оказывает непрямое и прямое противовоспалительное дейст вие. Поэтому назначение НМГ как минимум в профилактических дозах показано всем госпитализированным пациентам. Система гемостаза у пациентов с COVID-19, прежде всего у тяжелых, требует лабораторной оценки количества тромбоцитов, содержания Д-димера, протромбинового отношения или процентов протромбина по Квику и концентрации фибриногена. Анализ данных показал, что своеобразие коронавирусного гемостаза формирует гиперфибриногенемия, которая становится явным фактором гепаринорезистентности. Для преодоления последней назначение увеличенных (промежуточных или лечебных) доз НМГ выглядит перспективным решением. Достаточность назначения уместно определить либо по анти- Ха активности или (как экспресс-оценка) по тромбоэластрограмме. In the absence of a suffi cient base of evidence-based medicine, the most valuable becomes the expert’s opinion as a mirror of both personal and collegial experience. COVID-19-associated coagulopathy has a character of a thromboinfl ammation. The heparins — unfractionated or mainly low molecular weight heparins (LMWH) are intended to overcome it, since heparins have not only an anticoagulant effect but both an indirect and direct anti-infl ammatory effects as well. So that LMWH are indicated for all in-hospital patients. Patients with COVID-19, especially in severe cases, require laboratory testing of platelet count, D-dimer, prothrombin ratio or prothrombin percents by Quick and fi brinogen. Data analysis showed that a feature of coronavirus hemostasis is hyperfibrinogenemia that becomes an overt factor for heparin resistance. To overcome the latter, an adjusting doses of LMWH toward intermediate or therapeutic looks like a promising way. The suffi ciency of the adjusted LMWH dose is appropriate determining either with anti- Xa activity or thromboelastographically as express testing. Key words: hemostasis, COVID-19-associated coagulopathy, fibrinogen, low molecular weight heparins

The effects of low-molecular-weight heparin at two different dosages on thrombin generation in cancer patients.

2010 ◽  
Vol 104 (07) ◽  
pp. 92-99 ◽  
Author(s):  
Ludwig Traby ◽  
Alexandra Kaider ◽  
Rainer Schmid ◽  
Alexander Kranz ◽  
Peter Quehenberger ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Cancer Patients ◽  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
Low Molecular Weight ◽  
Prothrombotic State ◽  
Coagulation Activation ◽  
Thrombotic Risk ◽  
Baseline Levels ◽  
D Dimer

SummaryNon-surgical cancer patients are at high thrombotic risk. We hypothesised that the prothrombotic state is reflected by elevated thrombin generation and can be mitigated by increasing the low-molecularweight heparin (LMWH) dose. Non-surgical cancer patients were randomised to enoxaparin 40 or 80 mg. D-dimer, prothrombin fragment F1+2 (F1+2) and peak thrombin (PT) were measured 2, 4, 6 hours (h) after LMWH (day 1) and daily for 4 days. A total of 22 and 27 patients received enoxaparin 40 and 80 mg, respectively. D-dimer and F1+2 moderately decreased after 6 h in both groups. After enoxaparin 80 mg, D-dimer baseline levels [median (quartiles)] decreased from day 1 to 4 [1054.9 (549.5, 2714.0) vs. 613.0 (441.1, 1793.5) ng/ml] (p<0.0001), while no difference was seen after 40 mg. Baseline PT levels [median (quartiles)] were 426.2 nM (347.3, 542.3) (40 mg) and 394.0 nM (357.1, 448.8) (80 mg). After 80 mg, PT significantly decreased to 112.4 nM (68.5, 202.4), 57.1 nM (38.0, 101.2) and 43.6 nM (23.4, 112.8) after 2, 4 and 6 h, which was lower than after 40 mg (p=0.003). After 80 mg, PT decreased from day 1 to 4 [358.6 nM (194.2, 436.6); p=0.06] while no difference was seen after 40 mg. In conclusion, in cancer patients coagulation activation and thrombin generation is substantially increased. Peak thrombin levels are sensitive to the anticoagulant effects of LMWH at different dosages. The prothrombotic state is substantially attenuated by higher LMWH doses.

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