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Posts Tagged ‘atypical hemolytic uremic syndrome’


Why Blood Clots Are a Major Problem in Severe COVID-19

Reporter: Aviva Lev-Ari, PhD, RN

 

  • Clotting in uninjured blood vessels is a common occurrence in hospital patients, especially those in the intensive care unit.

  • In a July report in the journal Blood, Al-Samkari and colleagues found that nearly 10 percent of 400 people hospitalized for Covid-19 developed clots. In a February report by researchers in China, about 70 percent of people who died of Covid-19 had widespread clotting, while few survivors did.
  • people who died of Covid-19 were nine times as likely to be speckled with tiny clots as those of people who died of influenza
  • SARS-CoV-2 infects and damages the cells lining blood vessels, it could expose the tissue underneath
  • clotting results from inflammation. And here, many experts are eyeing a set of proteins called the complement system
  • These proteins, known collectively as complement, attack invaders and call in other parts of the immune system to assist. They also can activate platelets and promote clotting.
  • Claudia Kemper1,2,3 said “complementologists think that this is a massive part of the disease”  signs of complement activity in the lungs and livers of people who died from Covid-19
  • Laurence found several active complement proteins in the skin and blood vessels of his early Covid-19 clotting cases
  • a New York team found that patients were more likely to become very ill and die if they had a history of clotting or bleeding, or if they had macular degeneration, which can indicate complement problems.
  • Genes involved in complement and clotting responses were more active when the virus was present in patients’ nasal swabs.
  • immune element may promote clotting in severe Covid-19 cases: an overreaction called a cytokine storm, in which the body releases an excess of inflammation-promoting cytokine molecules.
  • Body’s response in need of control: (1) control the clotting, (2) control the inflammation, (2) control the complement pathway in tandem with antiviral Remdesivir that controls the viral replication thus the viral load.
  • Balance the risk of clotting with the danger of bleeding (bleeds into the digestive system for these patients, but they may also hemorrhage in the lungs, brain or spots where medical devices pierce the skin)
  • Dosage of blood thinners is debated – 40 Studies found for: anticoagulation | Covid19
    Also searched for COVID and SARS-CoV-2See Search Details
  • there is no evidence that people with less severe Covid-19, who do not require hospitalization, should take blood thinners or aspirin to ward off clots.
  • Management of Clotting: Argatroban, for example, is a Food and Drug Administration-approved anticoagulant that interferes with thrombin, an element of the clotting cascade. Eculizumab, which blocks one of the complement proteins, is approved for certain inflammatory conditions.
  • Clinical judgement is used in light of lack of evidence

 

SOURCES

Why Blood Clots Are a Major Problem in Severe Covid-19

SMITHSONIANMAG.COM

https://www.smithsonianmag.com/science-nature/why-blood-clots-are-major-problem-severe-covid-19-180975678/

Complement and the Regulation of T Cell Responses

Annual Review of Immunology

Vol. 36:309-338 (Volume publication date April 2018)
https://doi.org/10.1146/annurev-immunol-042617-053245

Complement Dysregulation and Disease: Insights from Contemporary Genetics

M. Kathryn Liszewski,1 Anuja Java,2

Elizabeth C. Schramm,3 and John P. Atkinson1

1Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110; email: j.p.atkinson@wustl.edu

2Division of Nephrology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110

3Serion Inc., St. Louis, Missouri 63108

 

Keywords

atypical hemolytic uremic syndrome, age-related macular degeneration,

alternative complement pathway, C3 glomerulopathies, factor H, CD46,

factor I, C3, factor B

Abstract

The vertebrate complement system consists of sequentially interacting proteins that provide for a rapid and powerful host defense. Nearly 60 proteins comprise three activation pathways (classical, alternative, and lectin) and a terminal cytolytic pathway common to all. Attesting to its potency, nearly half of the system’s components are engaged in its regulation. An emerging theme over the past decade is that variations in these inhibitors predispose to two scourges of modern humans. One, occurring most often in childhood, is a rare but deadly thrombomicroangiopathy called atypical hemolytic uremic syndrome. The other, age-related macular degeneration, is the most common form of blindness in the elderly. Their seemingly unrelated clinical presentations and pathologies share the common theme of overactivity of the complement system’s alternative pathway. This review summarizes insights gained from contemporary genetics for understanding how dysregulation of this powerful innate immune system leads to these human diseases.

CONCLUSIONS AND PERSPECTIVES

Over the last decade, a remarkable advance has been the elucidation of the role of mutations in complement regulators and components in aHUS, AMD, and C3G. Next-generation sequencing has led theway to these discoveries, but functional assessments are the critical factors in definitively associating pathogenesis with genetic variants.

Most exciting has been the development and approval by the FDA of the monoclonal antibody, eculizumab, as the new standard of care for treatment of aHUS. Challenges remain, however because eculizumab is costly and the duration of treatment remains uncertain and warrants further prospective studies. The use of eculizumab in C3G should also be prospectively addressed.

Furthermore, given the increasing number of mutations in the complement regulatory proteins identified in aHUS and C3G and the heterogeneity in the mechanisms leading to dysregulation of the AP, there is a need for further assessment of the genetic variants of unknown significance. As yet, no complement inhibitor has been approved to treat AMD.

These analyses coupled with the anticipated new developments of complement therapeutics will help establish patient-tailored therapies based on each patient’s specific alteration. The future holds much promise for the further delineation of complement-disease associations and for novel complement-targeted therapeutic agents.

SOURCE

Annu. Rev. Pathol. Mech. Dis. 2017. 12:25–52

https://www.annualreviews.org/doi/10.1146/annurev-pathol-012615-044145

 

 

Other related articles published in this Open Access Online Scientific Journal include the following: 

 

Is SARS-COV2 Hijacking the Complement and Coagulation Systems?

Reporter: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2020/08/04/is-sars-cov2-hijacking-the-complement-and-coagulation-systems/

 

New Etiology for COVID-19: Death results from Immune-Mediation (virus-independent immunopathology: lung and reticuloendothelial system) vs Pathogen-Mediation causing Organ Dysfunction & Hyper-Inflammation – Immunomodulatory Therapeutic Approaches (dexamethasone)

Curators: Stephen J. Williams and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2020/07/12/new-etiology-for-covid-19-death-results-from-immune-mediation-virus-independent-immunopathology-lung-and-reticuloendothelial-system-vs-pathogen-mediation-causing-organ-dysfunction-hyper-infl/

Corticosteroid, Dexamethasone Improves Survival in COVID-19: Deaths reduction by 1/3 in ventilated patients and by 1/5 in other patients receiving oxygen only

Reporter: Aviva Lev-Ari, PhD, RN – bold face and color fonts added

https://pharmaceuticalintelligence.com/2020/06/27/corticosteroid-dexamethasone-improves-survival-in-covid-19-deaths-reduction-by-1-3-in-ventilated-patients-and-by-1-5-in-other-patients-receiving-oxygen-only/

SAR-Cov-2 is probably a vasculotropic RNA virus affecting the blood vessels: Endothelial cell infection and endotheliitis in COVID-19

Reporter: Aviva Lev-Ari, PhD, RN – Bold face and colors are my addition

https://pharmaceuticalintelligence.com/2020/06/01/sar-cov-2-is-probably-a-vasculotropic-rna-virus-affecting-the-blood-vessels-endothelial-cell-infection-and-endotheliitis-in-covid-19/

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