Case Study Looks at tPA Use for COVID-19 Coagulopathy

Could so-called clot-busters play a role in treating severe symptoms of the novel coronavirus? That remains a possibility, although correct dosing still needs to be established, according to a new report. Find out what happened when clinicians gave off-label intravenous tPA (Alteplase) ton three patients with COVID-19 who had ARDS and respiratory failure.

MANHASSET, NY – Coagulopathy is appearing as an extremely dangerous manifestation of COVID-19, with 71.4% of patients who die of the infection meeting criteria for disseminated intravascular coagulation (DIC) while only 0.6% of patients who survive meet these criteria, according to a recent article.

The report in the Journal of Thrombosis and Haemostasis adds that, over time, clinicians have recognized that the patients don’t have a bleeding diathesis but rather a predominantly pro-thrombotic DIC with high venous thromboembolism rates, elevated D-dimer levels, high fibrinogen levels in concert with low anti-thrombin levels, and pulmonary congestion with microvascular thrombosis and occlusion on pathology.

In addition, according to the Northwell Health-led authors, healthcare professionals who care for critically ill COVID-19 patients are witnessing high rates of central line thrombosis and vascular occlusive events (e.g. ischemic limbs, strokes, etc.).

“There is evidence in both animals and humans that fibrinolytic therapy in Acute Lung Injury and ARDS improves survival, which also points to fibrin deposition in the pulmonary microvasculature as a contributory cause of ARDS and would be expected to be seen in patients with ARDS and concomitant diagnoses of DIC on their laboratory values such as what is observed in more than 70% of those who die of COVID-19,” the authors explain.

That led them to test off-label intravenous administration of tPA (Alteplase) in three patients with COVID-19 who had ARDS and respiratory failure. In all three cases, the authors note the patients demonstrated an initial improvement in their P/F ratio, with improvements ranging from a 38% improvement (Case 3) to a nearly 100% improvement (Case 1).

However, they add, “The observed improvements were transient and lost over time in all 3 patients after completion of their tPA infusion.”

The authors cite past research indicating redosing of the fibrinolytic agent in patients who had transient responses such as were observed in their cases, which led to more durable responses. The study team also describes precedent for using much larger bolus doses of tPA, while patients remain on a therapeutic heparin drip, including in sub-massive pulmonary embolism where the use of a 100mg bolus of tPA (Alteplase) while on a therapeutic heparin drip has been shown to be highly effective in reducing mortality and only increases bleeding risk by 1.2%.

“Such an approach using larger bolus-dose tPA (50mg or 100mg bolus) without holding anticoagulation in order to prevent recurrence of the suspected pulmonary microvascular thrombosis underlying COVID-19 ARDS is worthy of further consideration and study, and while the mortality in COVID-19 ARDS is exceptionally high the risks of tPA must still be carefully considered given the ~1% risk of catastrophic bleeding from tPA in non-stroke patients,” according to the authors, who add that formal studies are needed to determine the optimal dosing regimen of tPA with or without therapeutic anticoagulation in COVID-19 ARDS and should include whether a re-dosing protocol is needed if the benefits are transient.

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