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INCLUSION OF FIBRINOLYTICS IN THE THERAPEUTIC PLAN FOR COVID-19.

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Abstract

INCLUSION OF FIBRINOLYTICS IN THE THERAPEUTIC PLAN FOR COVID-19. Thrombosis in COVID is not solved only with Anticoagulants, the early use of Fibrinolytics and Antiplatelet Agents is necessary. Since March 2020, after studies that included autopsies were published in which it was found that the main cause of complications and deaths from COVID-19 was the presence of micro and macrothrombosis, from that date the indication of anticoagulants became a standard and were included in the Treatment Protocols for moderate and severe cases of COVID-19. More than 1 year has passed since the use of anticoagulants such as heparins in COVID became widespread, however, despite their use, new studies that include autopsies continue to frequently identify micro and macro thrombosis at the pulmonary and the systemic microvasculature. This evidence makes it necessary to review the therapeutic indication of using only anticoagulants in COVID-19. Several studies have already identified that the state of hypercoagulability and thrombophilia that occurs in COVID-19 is mainly associated with abnormal hyperactivity of platelets and their precursors, megakaryocytes, which are the largest cells in the bone marrow. For a few years it has been identified that megakaryocytes are not only produced at the bone marrow level, but are also produced in the lungs, and in COVID, pathology studies have identified an increase in the number of megakaryocytes at the lung level, which has led to increased production of platelets and thrombi [1]. Similarly, in autopsy studies performed on patients with COVID, the abnormal presence of megakaryocytes has been identified at the brain level. observing that the nuclei of megakaryocytes generate embolisms at the level of the microvasculature of the brain, with the consequent decrease in blood circulation at the cerebral level. Other alterations that are generated is the greater release of extracellular vesicles, and the greater release of existing serotonin reserves within platelets, with the consequent increase in plasma serotonin [2]. These findings support the recommendation to include antiplatelet and fibrinolytic agents in the Treatment Scheme for the different stages of COVID. Since mid-2020, we have included the use of Acetylsalicylic Acid (Aspirin) in the Therapeutic Plan that we publish for Acute COVID, as it is the most widely available antiplatelet agent, at the lowest cost, and with decades of experience in its use. [3]. Subsequently, we expanded its indication and since July 2020 we included ASA in the "Therapeutic Test" prepared for Post-Acute COVID Syndrome or Long COVID [4], and later in November 2020 we have included ASA in Post-Exposure Prophylaxis aimed at Contacts of sick people, and for “People at Higher Risk” in Pre-Exposure Prophylaxis [5]. Regarding Fibrinolytics, we have included them since the Therapeutic Plan that we published in January 2021 [6]. In this, the inclusion of Fibrinolytics for oral use such as Lumbrokinase, which is a proteolytic enzyme from Lumbricus rubellus, a species of earthworm, has been recommended. This enzyme favors the breakdown of clots and thrombi [1,6]. Other oral alternatives for fibrinolytic enzymes are Serrapeptase and Nattokinase, which can be indicated together. We reaffirm the importance of the use of fibrinolytics in COVID-Acute, and we maintain the indication to take antiplatelet agents from the first day of symptoms in COVID-Acute, and we also maintain their indications for their prophylactic use. The most frequent presentation of Lumbrokinase is that of 20 mg tablets, the recommended dose for COVID being between 4 to 6 tablets per day, it is marketed as a supplement and does not require a prescription. We indicate it together with an antiplatelet agent such as ASA at a dose of between 100 and 300 mg per day to be taken after food, always accompanied by Famotidine to reduce the risk of digestive bleeding and due to its favorable effects observed in patients with COVID. It should be taken into account that the simultaneous use of drugs with effects on reducing coagulation can cause bleeding, more so due to the use of ASA. Oral fibronolytics have a significantly lower risk of causing bleeding than ASA. In Acute Post COVID Syndrome (PACS), Persistent COVID or Long COVID we also frequently indicate 1 or 2 Fibrinolytics together with an Antiplatelet [6]. The details of the doses of the Fibrinolytics and Antipaquetes, according to the severity of the disease and the weight of the patient, are available in the documents of references 6 and 7.
INCLUSION OF FIBRINOLYTICS IN THE THERAPEUTIC PLAN
FOR COVID-19
Thrombosis in COVID is not solved only with Anticoagulants, the early use of
Fibrinolytics and Antiplatelet Agents is necessary.
Aguirre-Chang, Gustavo and Trujillo Aurora. ResearchGate. April 27, 2021.
Since March 2020, after studies that included autopsies were published in which it was
found that the main cause of complications and deaths from COVID-19 was the presence
of micro and macrothrombosis, from that date the indication of anticoagulants became a
standard and were included in the Treatment Protocols for moderate and severe cases of
COVID-19.
More than 1 year has passed since the use of anticoagulants such as heparins in COVID
became widespread, however, despite their use, new studies that include autopsies
continue to frequently identify micro and macro thrombosis at the pulmonary and the
systemic microvasculature. This evidence makes it necessary to review the therapeutic
indication of using only anticoagulants in COVID-19.
Several studies have already identified that the state of hypercoagulability and
thrombophilia that occurs in COVID-19 is mainly associated with abnormal hyperactivity of
platelets and their precursors, megakaryocytes, which are the largest cells in the bone
marrow.
For a few years it has been identified that megakaryocytes are not only produced at the
bone marrow level, but are also produced in the lungs, and in COVID, pathology studies
have identified an increase in the number of megakaryocytes at the lung level, which has
led to increased production of platelets and thrombi [1].
Similarly, in autopsy studies performed on patients with COVID, the abnormal presence of
megakaryocytes has been identified at the brain level. observing that the nuclei of
megakaryocytes generate embolisms at the level of the microvasculature of the brain, with
the consequent decrease in blood circulation at the cerebral level [2].
Other alterations that are generated is the greater release of extracellular vesicles, and the
greater release of existing serotonin reserves within platelets, with the consequent
increase in plasma serotonin [2].
These findings support the recommendation to include antiplatelet and fibrinolytic agents
in the Treatment Scheme for the different stages of COVID.
Since mid-2020, we have included the use of Acetylsalicylic Acid (Aspirin) in the
Therapeutic Plan that we publish for Acute COVID, as it is the most widely available
antiplatelet agent, at the lowest cost, and with decades of experience in its use. [3].
Subsequently, we expanded its indication and since July 2020 we included ASA in the
"Therapeutic Test" prepared for Post-Acute COVID Syndrome or Long COVID [4], and
later in November 2020 we have included ASA in Post-Exposure Prophylaxis aimed at
Contacts of sick people, and for “People at Higher Risk” in Pre-Exposure Prophylaxis [5].
Regarding Fibrinolytics, we have included them since the Therapeutic Plan that we
published in January 2021 [6]. In this, the inclusion of Fibrinolytics for oral use such as
Lumbrokinase, which is a proteolytic enzyme from Lumbricus rubellus, a species of
Inclusion of Fibrinolytics in the Therapeutic Plan for COVID-19. Aguirre-Chang, Gustavo and Trujillo, Aurora.
ResearchGate. April 2021.
2
earthworm, has been recommended. This enzyme favors the breakdown of clots and
thrombi [1,6].
Other oral alternatives for fibrinolytic enzymes are Serrapeptase and Nattokinase, which
can be indicated together.
We reaffirm the importance of the use of fibrinolytics in COVID-Acute, and we maintain the
indication to take antiplatelet agents from the first day of symptoms in COVID-Acute, and
we also maintain their indications for their prophylactic use.
The most frequent presentation of Lumbrokinase is that of 20 mg tablets, the
recommended dose for COVID being between 4 to 6 tablets per day, it is marketed as a
supplement and does not require a prescription. We indicate it together with an antiplatelet
agent such as ASA at a dose of between 100 and 300 mg per day to be taken after food,
always accompanied by Famotidine to reduce the risk of digestive bleeding and due to its
favorable effects observed in patients with COVID. It should be taken into account that the
simultaneous use of drugs with effects on reducing coagulation can cause bleeding, more
so due to the use of ASA. Oral fibronolytics have a significantly lower risk of causing
bleeding than ASA.
In Acute Post COVID Syndrome (PACS), Persistent COVID or Long COVID we also
frequently indicate 1 or 2 Fibrinolytics together with an Antiplatelet [6].
The details of the doses of the Fibrinolytics and Antipaquetes, according to the severity of
the disease and the weight of the patient, are available in the documents of references 6
and 7.
References
1. Aguirre-Chang G. The use of Platelets and Clots for Persistent Intracellular Infections
including SARS CoV-2 Infection and Neoplasms. ResearchGate. Diciembre 2020.
https://www.researchgate.net/publication/348080280
2. Aguirre-Chang G. and Trujillo F. COVID-19: a viral thrombogenic disease due to platelet
hyperactivity, extracellular vesicle release, NETs and other factors. ResearchGate.
Septiembre 2020. https://www.researchgate.net/publication/346051348
3. Aguirre-Chang G., Trujillo A. and Cordova JA. COVID-19: Treatment Plan and Potential
Therapies. ResearchGate. August 2020.
https://www.researchgate.net/publication/343392304
4. Aguirre-Chang G. and Trujillo F. COVID-19: "Therapeutic Test" for Patients with Persistent
Symptoms of COVID. For Long hauler, Long COVID, Post-Acute and Chronic COVID.
ResearchGate. Septiembre 2020. https://www.researchgate.net/publication/344325326
5. Aguirre-Chang G. and Trujillo F. COVID-19: Inclusion of Acetylsalicylic Acid in prophylaxis
for “people at increased risk” of developing severe illness and of mortality. ResearchGate.
November 2020. https://www.researchgate.net/publication/345416543
6. Aguirre-Chang G., Trujillo A. and Cordova JA. COVID-19: Therapeutic Plan and Potential
Therapies, Table 2021. ResearchGate. January 2021.
https://www.researchgate.net/publication/348268812
7. Aguirre-Chang G. and Trujillo F. Sub-Acute and Chronic COVID: Therapeutic Plan for
patients with with Post Acute COVID Syndrome (PACS) or Long COVID. ResearchGate.
Abril 2021. https://www.researchgate.net/publication/351274265
8. Other publications are available at:
https://www.researchgate.net/profile/Gustavo-Aguirre-Chang
ResearchGate has not been able to resolve any citations for this publication.
Data
Full-text available
TABLE 2021, COVID-19: THERAPEUTIC PLAN AND POTENTIAL THERAPIES. January 2021. Early treatment is important, and in those who do not have a rapid therapeutic response, the doses of drugs should be increased to reduce Viral Load. After 27 to 30 hours of starting treatment, the response to this should be evaluated. If it does not present a significant improvement in symptoms, it indicates that the Viral Load is High and there is a tendency to make a Persistent Infection, so it is worth increasing doses and medications.
The use of Platelets and Clots for Persistent Intracellular Infections including SARS CoV-2 Infection and Neoplasms. ResearchGate. Diciembre
  • G Aguirre-Chang
Aguirre-Chang G. The use of Platelets and Clots for Persistent Intracellular Infections including SARS CoV-2 Infection and Neoplasms. ResearchGate. Diciembre 2020. https://www.researchgate.net/publication/348080280
COVID-19: a viral thrombogenic disease due to platelet hyperactivity, extracellular vesicle release, NETs and other factors
  • G Aguirre-Chang
  • F Trujillo
Aguirre-Chang G. and Trujillo F. COVID-19: a viral thrombogenic disease due to platelet hyperactivity, extracellular vesicle release, NETs and other factors. ResearchGate. Septiembre 2020. https://www.researchgate.net/publication/346051348
COVID-19: Treatment Plan and Potential Therapies. ResearchGate
  • G Aguirre-Chang
  • A Trujillo
  • J A Cordova
Aguirre-Chang G., Trujillo A. and Cordova JA. COVID-19: Treatment Plan and Potential Therapies. ResearchGate. August 2020. https://www.researchgate.net/publication/343392304
COVID-19: Inclusion of Acetylsalicylic Acid in prophylaxis for "people at increased risk" of developing severe illness and of mortality. ResearchGate
  • G Aguirre-Chang
  • F Trujillo
Aguirre-Chang G. and Trujillo F. COVID-19: Inclusion of Acetylsalicylic Acid in prophylaxis for "people at increased risk" of developing severe illness and of mortality. ResearchGate. November 2020. https://www.researchgate.net/publication/345416543
Sub-Acute and Chronic COVID: Therapeutic Plan for patients with with Post Acute COVID Syndrome (PACS) or Long COVID. ResearchGate. Abril
  • G Aguirre-Chang
  • F Trujillo
Aguirre-Chang G. and Trujillo F. Sub-Acute and Chronic COVID: Therapeutic Plan for patients with with Post Acute COVID Syndrome (PACS) or Long COVID. ResearchGate. Abril 2021. https://www.researchgate.net/publication/351274265