In Situ Thrombolysis With tPA and Inflow Perfusion Analysis in Patient With Severe Covid-19 Infection
Condition: COVID-19
MeSH terms: COVID-19
Study type: Interventional

Summary: 
      To estimate the pulmonary response microvascular thrombosis in critical patients due to
      SARS-Cov-2., at the Hospital General de México "Dr. Eduardo Liceaga", a 15 patients
      compassionate treatment study was authorized and approved by the ethics and research
      committee DI-222-2020. Because of the severity of the illness the legal representative sign
      informed consent in all the patients for performing in-situ thrombolysis with alteplase
      selectively by catheter in each main pulmonary artery, under fluoroscopic guidance and
      acquiring images with the iFlow software to assess immediate and post-procedure response.
    

Detailed description: 
      The main clinical characteristic of patients with severe SARS-Cov-2 infection is hypoxemic
      respiratory failure that requires Mechanical Ventilation. The Acute Respiratory Syndrome
      model has been proposed as the cause of this significant deterioration in lung function and
      all management has focused on ventilatory support management. As for ventilatory failure, it
      has been attributed to the presence of severe pulmonary inflammation evolving to fibrosis,
      which is the clinical characteristic of patients with Primary Respiratory Distress Syndrome
      (which would be the case of this as it is considered a respiratory virus).

      Several autopsy studies demonstrated microthrombi in pulmonary circulation. The major
      limitation of these investigations is that the autopsy provided static information. Some of
      these alterations could be secondary to the disseminated intravascular coagulation (DIC)
      observed as the standard route to the multisystem organ failure exhibited in critically ill
      patients.

      With this comes the contradictory results of high doses of anticoagulants in the survival of
      these patients. This intermediate to high doses can reduce organ support treatments in
      moderate cases, however, in critically ill patients the benefit of high dose of
      anticoagulants, once again failed to produce benefit on survival. Different publication on
      biopsies made in these patients have report the presence of thrombosis in the
      microcirculation and finally recently has been published the demonstration by direct
      examination with Citoscam, the presence of this thrombosis of the microcirculation in vivo in
      11 of 13 test (85% of the sample). Studies performed with viscoelastic coagulation tests
      present evidence of three key alterations in coagulation

        1. EXTEM and INTEM Hypercoagulable states represented by a maximum amplitude (A5, A10 and
           MCF) greater than 70mm, short clot formation time.

        2. Hyperfibrinogenemia A5 A10 MCF in FIBTEM greater than 30mm

        3. Absence of fibrinolytic activity (ML% Lys 30 and Lys 60) 100% Taking this into account
           plus the large number of publications regarding the thrombotic phenomenon of the patient
           with COVID-19, this could be explained by the presence of a phenomenon of ventilation
           perfusion (V / Q) that is observed in patients with Massive Pulmonary Thromboembolism
           (PE) which is known as the infinite relationship, that is, the lung is with normal
           aeration, but no perfusion, there is no adequate gas exchange, with presence of hypoxia,
           increment of death space and ultimately obstructive shock.

      In patients with COVID-19, this phenomenon is observed in patients with absence of massive or
      submassive PE that explains this phenomenon.

      The high mortality of critically ill patients with SARS-Cov-2 infection, the presence of
      thrombosis of the microcirculation and the lack of efficacy of anticoagulation in some cases
      suggests that this phenomenon could be the cause of the behavior between perfusion
      ventilation observed in SARS-Cov-2 patients.

      For these reasons, a probe of concept research was developed to find out if pulmonary
      perfusion alteration by microthrombosis and secondary V / Q abnormalities could be linked to
      the pathophysiology of the patient with severe SARS-Cov-2 infection.

      To estimate the pulmonary response microvascular thrombosis in critical patients due to
      SARS-Cov-2., at the Hospital General de México "Dr. Eduardo Liceaga", a 15 patients
      compassionate treatment study was authorized and approved by the ethics and research
      committee DI-222-2020. Because of the severity of the illness the legal representative sign
      informed consent in all the patients for performing in-situ thrombolysis with alteplase
      selectively by catheter in each main pulmonary artery, under fluoroscopic guidance and
      acquiring images with the iFlow software to assess immediate and post-procedure response.
    

Intervention name(s): tPA
Intervention type(s): Drug
Intervention description(s): Selectively catheter thrombolysis with alteplase in each main pulmonary
Other intervention name(s): in situ thrombolysis
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Covid-19; Acute Respiratory Distress Syndrome; Thrombosis