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Low-Dose Tissue Plasminogen Activator Thrombolysis in Children

Low-Dose Tissue Plasminogen Activator Thrombolysis in Children,Michael Wang,Taru Hays,Vinod Balasa,Rochelle Bagatell,Ralph Gruppo,Eric F. Grabowski,Le

Low-Dose Tissue Plasminogen Activator Thrombolysis in Children   (Citations: 25)
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Purpose: To compare results of low-dose tissue plasminogen ac- tivator (TPA) in children with arterial and venous thrombi relative to standard published dosing. Methods: Subjects consisted of all consecutive children with ob- jectively confirmed thrombi for whom TPA thrombolysis was clinically ordered by the authors. Initial dosing used published standard dose (0.1-0.5 mg/kg per hour). With experience, a low- dose regimen (0.01-0.06 mg/kg per hour) was given in an attempt to derive a minimal effective dose. Results: Thirty-five children were treated with TPA. Either stan- dard or low-dose infusions of TPA resulted in complete throm- bolysis of 28 of 29 (97%) acute thrombi, while all 6 chronic thrombi had a partial response. In contrast to the recommended adult-derived dosages of 0.1 to 0.5 mg/kg per hour, the authors found that initial doses of less than 0.01 mg/kg per hour were effective in 12 of 17 patients with acute thrombosis. Neonates required 0.06 mg/kg per hour. Route of administration (local or systemic) did not affect efficacy. Major bleeding occurred in only one extremely preterm infant. Minor bleeding, primarily oozing at intravenous sites, occurred in 27% of children during TPA infu- sions. Prophylactic unfractionated or low-molecular-weight hepa- rin was infused concomitant with TPA in 42% of the children and did not increase the risk of bleeding. Conclusions: TPA in very low doses appears to be safe and ef- fective for thrombolysis of acute thromboses in most children, given appropriate patient selection.
Published in 2003.
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    • ...respond to thrombolysis with lower doses of tPA than used in adults [48] . As it is unknown to what extent developmental hemostasis will impact thrombolysis and risk of hemorrhage, the TIPS trial will start with a conservative dose of intravenous tPA and increase in small increments: 0.6, 0.75, 0.9, and 1.0 mg/kg...

    Catherine Amlie-Lefondet al. Thrombolysis in Acute Childhood Stroke: Design and Challenges of the T...

    • ...Lower doses of systemic thrombolysis have been effective in achieving clot lysis in children and neonates and may expose patients to less bleeding risk, but the experience remains limited [22]...
    • ...Wang et al. demonstrated improved results with Alteplase treatment of acute clots of less than 2 weeks’ duration [22]...
    • ...Others have also used different dosage regimens of rt-PA, starting with very low doses (0.01‐0.3 mg/kg/hr in non-neonates) and increasing the initial rt-PA dose in a stepwise fashion, according to the clinical situation [22, 39]...
    • ...Lower dose infusions have been used in other cases of CDT in neonates (Table 1). A reduced dose of concomitant heparin therapy at 10 units/kg/hr during Alteplase therapy was used to avoid clot progression, as employed by previous studies [22, 40]...
    • ...Wang et al., 2003 [22] 1 Term 3 days Left pulmonary artery rt-PA ‐ 0.1 mg 16 C = 1/1 ‐ a The series of Ryan et al. and Ries et al. have been included in Tables 1 and 2 because both systemic and local thrombolysis were carried out...
    • ...Wang et al. also used a low dose of Alteplase (0.01‐ 0.06 mg/kg/hr) locally and systemically to treat acute clots in neonates and children successfully [22]...

    Jawad U. Khanet al. Catheter-Directed Thrombolysis of Inferior Vena Cava Thrombosis in a 1...

    • ...Recently, the efficacy of administering a very low dose of rt-PA (0.01-0.06 mg/Kg/h) in continuous infusion for 12 to 96 hours was reported [59] in a small and varied series of children with thrombosis...
    • ...Notably, a recently published paper reports the efficacy of thrombolysis with rt-PA at very low doses [59]...

    Paola Giordanoet al. A Practical Approach to Diagnosis and Treatment of Symptomatic Thrombo...

    • ...Although local rtPA instillation is efficacious and safe, optimal patency rates (80–90%) are often seen only after two to three boluses have been administered, which may require up to 48 h [5, 6, 7, 8, 9]. On the other hand, short-term (intracatheter) rtPA infusion has been widely and successfully used in interventional radiology units and pediatric hematology-oncology pediatric patients [5, 6, 7, 8, 9, 10, 11]...
    • ...Available data suggest that in children lower doses of rtPA are required for thrombolysis when it is administered as an infusion compared to the local instillation of boluses [11, 18, 19]...
    • ...Although the doses of rtPA used in this and other studies in pediatric populations have been extrapolated from adult (standard) dosing of 0.1–0.5 mg/kg, recent studies have shown that much lower doses (0.01– 0.06 mg/kg/h) could be administered as a continuous infusion [11]...
    • ...In a recent trial designed to determine minimal effective dose in the treatment of acute thrombosis in children, 0.01 mg was adequate in 70.5% of the subjects [11]...
    • ...The cost of rtPA can be a major hindrance to its widespread application for catheter clearance in dialysis units [11, 17]...

    Oluwatoyin F. Bamgbolaet al. Recombinant tissue plasminogen activator infusion for hemodialysis cat...

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