Procalcitonin

Procalcitonin
Presenter: Dr Nazuk Sharma

Objectives of our today topic…..
 Relevant Anatomy
 History related to PCT
 What is PCT?
 What are clinical situations where PCT may be useful?
 Why are we studying PCT?
 How we detect PCT?
 PCT levels in various disease and the pitfalls
 Some evidences published…

History of Procalcitonin
 In 1975, Moya F et al. suggested the existence of a precursor for calcitonin in chicken. The
large biosynthetic molecule splits intracellularly to generate the hormone, and they named
it as procalcitonin
 Allison’s study (1981) in RNA isolated from human medullary carcinoma demonstrated the
synthesis of calcitonin as a precursor protein molecule in human
 Later studies show that calcitonin is secreted after a sequential Co and post translational
modification like glycosylation proteolytic cleavage
 “Lancet” “1993”
“ High serum PCT concentrations in patients with sepsis and infection”

What is PCT ?
 Member of CAPA protein family
 PCT is produced in thyroid C cells, from a CALC-1 gene located on
chromosome 11
 116 amino acid peptide that belongs to the calcitonin (CT) superfamily
of peptides.
 ~MW of 14.5 kDa

 It is detectable within 2-4 hours and peaks within 6-24 hours (as
opposed to CRP which begins to rise after 12-24 hours and peaks at
48 hours).
 PCT production is not impaired by neutropenia or other
immunosuppressive states.
 PCT levels parallel the severity of the inflammatory insult or infection
meaning those with more severe disease have higher levels.
 it has some utility as a prognostic indicator with higher serum
concentrations related to the risk of mortality

Why are we studying PCT?
There is an alarming number of 18 million new sepsis cases
reported each year worldwide with mortality rate ranging
from 30–50%.
In India  28.3% of patients contact sepsis during ICU stay
and have 34% mortality rate

Early diagnosis and prompt
antimicrobial therapy is crucial in
the treatment of sepsis for saving
lives
PCT

Reference range
 Normal:
<0.1 ng/mL (infants >72 hours – adults)
or healthy subjects  10–50 pg/ ml
 Suspected Lower Respiratory Tract Infection:
0.1 – 0.25 ng/mL - Low likelihood for bacterial infection; Antibiotics discouraged.
>0.25 ng/mL - Increased likelihood bacterial infection; Antibiotics encouraged.
 Suspected Sepsis:
Strongly consider initiating antibiotics in all unstable patients.
0.1 – 0.5 ng/mL - Low likelihood for sepsis; Antibiotics discouraged.
>0.5 ng/mL – Increased likelihood sepsis; Antibiotics encouraged.
>2.0 ng/mL – High risk of sepsis/septic shock; Antibiotics strongly encouraged.

What are clinical situations where PCT
may be useful?
Differentiation of bacterial versus viral respiratory
tract infection
Determination of antibiotic treatment length in
respiratory infections
Diagnosis, risk stratification, and monitoring of sepsis
and septic shock

 Diagnosis of systemic secondary infection post-surgery, post-
organ transplant, and in severe burns, multiorgan failure, and
severe trauma
 Diagnosis of bacteremia and sepsis in adults and children
(including neonates)
 Differentiating bacterial versus viral meningitis

Detection of PCT
 Short half life of 25-30 hours along with its virtual absence in health and specificity for bacterial
infections, gives it a clear advantage over the other markers of bacterial infection.
 Using a quantitative homogenous assay (BRAHMS, Hennigsdorf, Germany).
 The assay is based on Time Resolved Amplified Cryptate Emission (TRACE) technology .
 Samples suitable for the assay can be serum or plasma using either EDTA or heparin as the
anticoagulants but not citrate since this has been shown to underestimate PCT levels

PCT Measurements in Other Diseases
 MALARIA
Becker and co-workers
PCT levels are elevated in both severe and uncomplicated Plasmodium falciparum malaria but
could not be used to differentiate between the 2 types and was thus of limited use in its diagnosis.
 PULMONARY TUBERCULOSIS (PTB)
Baylan and co-worker
Found that serum PCT levels were slightly high on admission in patients with active PTB in
comparison with controls and patients on anti-tuberculous chemotherapy.
Although this difference was statistically significant, the PCT levels of most cases with PTB (58.7%)
were below the usual cut-off level (0.5 ng/mL)
Hence, PCT was not a reliable indicator in the diagnosis of active PTB and could not be substituted
for microbiological, epidemiological, clinical, and radiological data

 COMMUNITY ACQUIRED PNUEMONIA
Nyamande and Lalloo,
Their study showed that PCT levels differ significantly in patients with CAP due to TB,
PJP, and bacteria.
 LIVER TRANSPLANT
Mendonca and colleague
Liver transplant recipients, plasma PCT levels were significantly increased in infected
patients in comparison to those that had acute liver rejection.

Situations where the PCT elevations may be due to a non-bacterial cause:
 Newborns (<48-72 hours; after 72 interpret levels as usual)
 Massive stress (severe trauma, surgery, cardiac shock, burns)
In absence of infection PCT levels trend down after inciting event
 Treatment with agents which stimulate cytokines (OKT3, anti-lymphocyte
globulins, alemtuzumab, IL-2, granulocyte transfusion)
 Malaria and some fungal infections
 Prolonged, severe cardiogenic shock or organ perfusion abnormalities
Pitfalls in PCT Measurement

Pitfalls in PCT Measurement
 Addisonian crisis caused by adrenal failure has been associated with
elevated PCT levels.
 Some forms of vasculitis and acute graft vs. host disease
 Paraneoplastic syndromes due to medullary thyroid and small cell lung
cancer
 Brodska and colleagues reported marked elevations in PCT and CRP
levels in patients scheduled for hematopoietic stem cell transplantation
and receiving anti-thymocyte globulin during conditioning

PCT as a tool for antibiotic therapy

Procalcitonin in sepsis and systemic inflammation: a harmful
biomarker and a therapeutic target
British Journal of Pharmacology
Volume 159, Issue 2, pages 253-264, 27 NOV 2009 DOI: 10.1111/j.1476-5381.2009.00433.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2009.00433.x/full#f3

© 2000 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 7
Muller and colleagues conducted a study in consecutive critically ill patients to compare the
usefulness of serum concentration of calcitonin precursor, CRP, IL-6 and lactate for the diagnosis of
sepsis.
Blood samples were collected at variable intervals during the course of treatment, they concluded
that PCT is the most reliable marker for
Calcitonin precursors are reliable
markers of sepsis in a medical
intensive care unit.
Muller, Beat; Becker, Kenneth; MD,
PhD; Schachinger, Hartmut;
Rickenbacher, Peter; Huber, Peter;
Zimmerli, Werner; Ritz, Rudolf
Critical Care Medicine. 28(4):977-
983, April 2000.
Evaluation of laboratory parameters for the diagnosis of sepsis in a medical intensive care unit (%)

Procalcitonin in sepsis and systemic inflammation: a harmful
biomarker and a therapeutic target

Procalcitonin in sepsis and systemic inflammation: a harmful biomarker and a therapeutic target

PCT is among the most promising sepsis
markers, capable of complementing clinical
signs and routine lab parameters
of severe infection.

References
 Meisner M. Pathobiochemistry and clinical use of procalcitonin. Clinica chimica
acta. 2002 Sep 30;323(1):17-29.
 Jin M, Khan AI. Procalcitonin: uses in the clinical laboratory for the diagnosis of
sepsis. Laboratory Medicine. 2015 Oct 22;41(3):173-7.
 Vijayan AL, Ravindran S, Saikant R, Lakshmi S, Kartik R. Procalcitonin: a promising
diagnostic marker for sepsis and antibiotic therapy. Journal of intensive care. 2017
Dec;5(1):51.
 Read :https://www.nebraskamed.com/for-providers/asp/procalcitonin-pct-
guidance

Procalcitonin

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