Letter to the editor: Reduced doses of systemic thrombolysis in acute pulmonary embolism

Abstract

To the editorWe read with interest the systematic review by Rojas-Murguia et al. 1 We congratulate the authors and would like to share some thoughts.In resource-limited settings where catheter-directed therapies may not be available, or interhospital transfer of patients with pulmonary embolism (PE) faces barriers, 2 lowdose systemic thrombolysis (ST) could be considered as an option. However, when contemplating the use of half-doses ST in acute PE, clinicians face a strict benefit vs risk assessment, particularly for major bleeding (MB) events. Generally, intravenous (IV) unfractionated heparin (UFH) is the preferred anticoagulation (AC) agent when ST are planned, given its very short half-life and reversibility. 3 It is important to start AC as soon as the clinical suspicion of PE arises, since a delay may worsen clot propagation; 4 moreover, worsens mortality. 5 How should heparins be managed in the peri-ST infusion setting? A variety of strategies have been utilized regarding IV UFH in the peri-ST phase; some are conservative (e.g. holding IV UFH during ST infusion), others more aggressive (e.g. continuation of UFH infusion with accelerating infusions of alteplase in 15 min and/or 2 h infusions). 6,7 Given the paucity of data, there is a need to perform a randomized, controlled-trial comparing continuation of IV UFH infusion vs holding it while infusing ST, focusing on the primary safety end-point, MB.What are the authors' thoughts in regards the use of ultralow doses of ST (e.g. bolus of alteplase, followed by infusions at 1 mg/h for 8-12 h)? 8 In our opinion, prolonged times of ST could increase MB events, especially, when IV UFH is concurrently infused. Case series and reports have suggested duration of infusions to be no more than 4-6 h. 8 In our opinion, infusions of ST should not exceed 4-6 h, clinicians should avoid concurrent UFH infusion with ST and careful monitoring should be implemented. Another caveat is to avoid an ST bolus as it is associated with increased bleeding risk, 9 particularly in patients with intermediate-risk PE when evidence supporting its use remains weak. It is important to take with a "grain of salt" such strategies until more robust data are published.

Letter to the Editor: Reduced-Dose Thrombolysis for Acute Pulmonary Embolism

“…The use of concomitant heparin infusion while administering thrombolysis is indeed a controversial topic. We agree with the authors 1 that different regimens have been published. It is important to emphasize that the concomitant use of heparin and thrombolytic differs in acute myocardial infarction (concomitant use of therapeutic heparin, due to the concern for re-occlusion of the coronary artery), vs venous thromboembolism (VTE) (usually thrombolytic without heparin and heparin afterward, or concomitant heparin at a lower dose).…”

“…We agree with the authors 1 that coagulation parameters should be monitored during and after thrombolytic infusion.…”

“…We also agree with the authors 1 that the dose–response relationship of thrombolysis for VTE is unknown. “Ultra-low” doses of a thrombolytic should only be used in experienced centers with a shared-decision-making approach and an open and careful case-by-case risk–benefit evaluation.…”

“…This is the reason why currently at our institution, heparin is withheld during thrombolytic infusion (as recommended by the Food and Drug Administration [FDA]) 6 and is re-started based on activated partial thromboplastin time, once the infusion is complete. We agree with the authors 1 that this is an area that needs more robust and high-level evidence.…”

“…We appreciate the comments made by Porres-Aguilar 1 regarding our publication “Reduced-Dose Thrombolysis in Acute Pulmonary Embolism: A Systematic Review.” 2…”