Case Series: rTPA Infusion as Salvage Therapy for Prolonged Critically Ill COVID-19 Patients

First Author(s)

• 

  Pramma Elayaperumal, MD

  Pulmonary and Critical Care Medicine Fellow
  State University of New York Downstate Medical Center
  Brooklyn, NY

  Disclosure information not submitted.

  Slides and Audio

Co-Author(s)

• GM

  Gregory Margolin, DO, FCCM

  Visiting Professor
  NYC Emergency Management, United States

  Disclosure information not submitted.
• AY

  Alice Yau, MD

  IM Resident
  NYCHH - Woodhull, United States

  Disclosure information not submitted.
• MC

  Michael Caputo, DO

  IM Resident
  NYCHH - Woodhull, United States

  Disclosure information not submitted.
• JR

  J. Timothy Riley, MD

  Visiting Professor
  NYC Emergency Management, United States

  Disclosure information not submitted.

Title: Case Series: rTPA Infusion as Salvage Therapy for Prolonged Critically Ill COVID-19 Patients

Introduction:
Attributable to microangiopathic thrombosis in situ, COVID-19 may effect any organ system. Severe hypoxemia, preserved lung compliance and a hypercoaguable states related to these small vessel clots place thrombolysis followed by anti platelet agents and full-dose anticoagulation as an attractive strategy to mitigate disease. Because these micro circulation clots are not routinely embolic in origin, but rather continuous in situ formation, we hypothesized a continuous rTPA infusion may be superior to other single-dose regimens attempted. As a pilot endeavor in patients declining after 10 days of hospitalization, we review a salvage strategy in 5 patients with severe, near-death COVID-19.

Methods:
Following IRB approval, retrospective data was collected from 5 patients with severe, prolonged ( >10 days hypoxemia) COVID-19, from April to May, 2020 that received bolus and infusion rTPA followed by apixaban and clopidogrel at conclusion of rTPA infusion. Chart records ethically document MPOA informed consent in advance of the rTPA. rTPA cessation occurred at either improvement of P:F >150 or patient death. rTPA regimen was approximated in each patient to receive a bolus of 0.5-1 mg/kg and a subsequent infusion rate of 1-5mg/kg/hr actively titrated by the ICU Attending physician, guided by serial fibrinogen levels. Each of the five patients had severe hypoxemia (P:F< 75), fibrinogen >600mg/dL and AKI.

Results:
2 of the 5 patients encountered bleeding at central lines within 6 hours of rTPA bolus, to prompt the Intensivist to pause the rTPA infusion and apply PRBC support. TPA was resumed after hemostasis. No bleeding events occurred with apixaban and clopidigrel once the rTPA infusion was stopped. 4 of 5 patients reversed their severe ARDS and shock. 2 of those 4 survived to hospital discharge. 4 of 5 patients reversed their AKI. Of 3 patients that received RRT, 2 were able to stop dialysis during or following their rTPA.

Conclusions:
In this retrospective case series, rTPA infusion until P:F >150, followed by clopidigrel and apixaban was associated with improved mortality, reduction in shock support and renal recovery trends. Whether similar results could be achieved with some other combination/dose or without the loading rTPA boluses, clopidigrel and/or apixaban requires further investigation.