Inflammatory Anemia Associated Parameters in Septic Patients

NCT ID: NCT04281888

Last Updated: 2020-02-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-03-20

Study Completion Date

2021-05-20

Brief Summary

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1. To observe the changes in the inflammatory anemiaassociated parameters of patients with sepsis in the early stage of intensive care unit (ICU) admission.
2. To evaluate their association with 28-days mortality
3. To evaluate the effect of blood transfusion on these parameters and the survival of the studied patients

Detailed Description

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Anemia is one of the most common complications in patients with sepsis in the intensive care unit (ICU), as well as sepsis is a major cause of high mortality in ICU. Studies demonstrated that sepsis-related anemia can be caused by fluid loading related hemodilution, iatrogenic blood loss, decreases in iron supply, erythropoietin (EPO) production and erythrocyte lifespan .

However, sepsis related anemia has been demonstrated to be associated mainly with inflammation (i.e., "anemia of inflammation"). Anemia of inflammation is usually a mild to moderately severe anemia (hemoglobin rarely \< 8 g/dL) . It develops in the setting of infection, inflammatory disease or malignancy, together with low serum iron despite adequate systemic iron stores, decreased serum transferrin, normal size of erythrocytes and hemoglobin content or mildly decreased size and hemoglobin content of erythrocytes if the inflammatory disease is longstanding .

Impaired iron homeostasis and the suppressive effects of proinflammatory cytokines on erythropoiesis, together with alterations in the erythrocyte membrane that impair its survival may result, ultimately, in inflammation-associated anemia .

Hepcidin is a key regulator of inflammation-associated anemia. Hepcidin reduces the iron level in plasma through:

1. direct inhibition of intestinal absorption of iron.
2. promotion of iron storage in macrophages by down regulating expression of ferroprotein in intestinal mucosae and macrophages.

Increased interleukin-6 (IL-6) in patients with sepsis can induce an abruptly increased synthesis of hepcidin, causing decreased plasma iron. Plasma iron can be depressed by inflammation markedly (more than 50%) and rapidly ( with in 24 hrs). Also, the interaction between inflammation and iron metabolism may interfere with other inflammatory anemia associated parameters and complicate iron metabolism in patients with sepsis.

Typically, plasma ferritin (which stores iron) is reduced in iron deficiency anemia but can increase in the acute phase of sepsis. Anemia usually results in an increased synthesis of EPO in kidneys in minutes to hours, but the response to EPO is blunted in patients with sepsis . The soluble transferrin receptor (sTfR), an early and sensitive biomarker for diagnosing iron deficiency , is particularly useful for identification of concomitant iron deficiency in patients with inflammation. The sTfR is not affected by inflammation, which is a significant advantage over other biomarkers. Plasma sTfR reflects the degree of iron availability for cells, whereas plasma ferritin reflects iron storage. Hence, the ratio of sTfR to log ferritin (hereafter termed "sTfR/log ferritin") provides the efficacy of sTfR alone or ferritin alone in the diagnosis of iron deficiency. These cytokines have the propensity to promote iron restricted erythropoiesis, characterized by functional rather than absolute iron deficiency, occurring secondary to dysregulation of iron metabolism.

Associations among inflammatory cytokines, EPO, and anemia in critically ill septic patients remain unclear.

The inflammatory anemia-associated parameters mentioned above may change with the severity of inflammation in patients with sepsis. The sensitivity and specificity of these parameters can be modified if inflammation and iron deficiency are present concomitantly. This may complicate the diagnosis, evaluation, and treatment of inflammatory anemia.

Hence, a better understanding of changes in the inflammatory anemia and associated parameters in patients with sepsis at the early stage of ICU admission is needed urgently. In addition, although severe anemia is associated with adverse outcomes in critical illness, a lowered plasma iron is part of the natural defense against pathogens.

EPO has also been demonstrated to exert protective effects in the kidneys and lungs of mice with sepsis, but EPO deficiency contributes to anemia development in patients with sepsis. As a result of these effects, inflammatory anemia-associated parameters have been speculated to be associated with the prognosis of patients with sepsis , but relevant studies are lacking

Conditions

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Inflammatory Response

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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Exclusion Criteria

1. patients less than18 years of age.
2. patients have chronic liver dysfunctions or chronic kidney disease resulting from different causes.
3. patients with known iron related diseases (e.g., hemochromatosis), immunologic diseases or malignancies upon hospital admission; all types of anemia (aplastic, iron deficiency, hemolytic, megaloblastic).
4. patients with overt blood loss (e.g., gastrointestinal bleeding) upon admission and during the ICU stay.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Heba Mohamed Ahmed

Hematologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yousreiya A Ahmad, Professor

Role: STUDY_DIRECTOR

Assuit University Hospital

Central Contacts

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Heba M Ahmed, Hematologist

Role: CONTACT

00201061343995

References

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Ganz T, Nemeth E. Iron homeostasis in host defence and inflammation. Nat Rev Immunol. 2015 Aug;15(8):500-10. doi: 10.1038/nri3863. Epub 2015 Jul 10.

Reference Type BACKGROUND
PMID: 26160612 (View on PubMed)

Hegde A. Approach to an Anemic Critically Ill Patient. Indian J Crit Care Med. 2019 Sep;23(Suppl 3):S178-S180. doi: 10.5005/jp-journals-10071-23247.

Reference Type BACKGROUND
PMID: 31656373 (View on PubMed)

Weiss G, Ganz T, Goodnough LT. Anemia of inflammation. Blood. 2019 Jan 3;133(1):40-50. doi: 10.1182/blood-2018-06-856500. Epub 2018 Nov 6.

Reference Type BACKGROUND
PMID: 30401705 (View on PubMed)

Other Identifiers

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Heba

Identifier Type: -

Identifier Source: org_study_id

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