Details

Autor(en) / Beteiligte

• Fanikos, John
• Marquis, Kathleen
• Buckley, Leo
• Tran, Lena K.
• McLaughlin, Kevin
• Golash, Abby Jane
• Campia, Umberto
• Piazza, Gregory
• Connors, Jean M.
• Goldhaber, Samuel Z.

Titel

Stability of alteplase for ultrasound-facilitated catheter-directed thrombolysis

Ist Teil von

• Blood advances, 2021-12, Vol.5 (23), p.5283-5289

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Ultrasound-facilitated catheter-directed thrombolysis is used with low-dose alteplase to treat pulmonary embolism. This reduces the risk of bleeding that accompanies systemic administration of higher alteplase doses. Some studies suggest that alteplase given over 2 to 6 hours is safe and effective, but there are few data to support the stability of alteplase under these conditions. Therefore, we undertook this in vitro study to determine the duration of alteplase stability. Alteplase was prepared in solutions of 8 mg in 100 mL, 6 mg in 150 mL, and 8 mg in 200 mL. Solutions were administered through the EkoSonic Endovascular System (with and without ultrasound) to simulate administration over 2, 4, and 6 hours. Alteplase was assessed with reversed-phase high-performance liquid chromatography (RP-HPLC). Assays were performed at time 0 and at 30-minute intervals during simulated infusion. An enzyme-linked immunosorbent assay was used to measure alteplase concentrations at time 0 and at 15-minute intervals during simulated infusion. By using RP-HPLC in the absence of ultrasound, the alteplase concentration remained within 1% of the original concentration through 120, 240, and 360 minutes of infusion. By using RP-HPLC for measurement, alteplase in the presence of ultrasound degraded steadily over time to ∼90% of its original amount in 120 minutes, ∼80% in 240 minutes, and ∼70% in 360 minutes. The remaining alteplase was available for enzymatic activity. Alteplase solutions of 0.04 and 0.08 mg/mL degraded steadily over time during simulated ultrasound-facilitated catheter-directed administration. Alteplase that did not degrade remained available for enzymatic activity. •Alteplase solutions degrade steadily over time during simulated ultrasound-facilitated catheter-directed administration.•Remaining nondegraded alteplase proteins retained functional activity. [Display omitted]