Authors: Wang Yixin, Sun Yunhui
Affiliation: The First Affiliated Hospital of Jiamusi University
1. Procalcitonin
Procalcitonin (PCT) is a non-hormonal precursor peptide glycoprotein that is released into the patient’s circulatory system as a soluble protein under conditions of severe systemic infection, particularly bacterial infections. Under normal physiological conditions, PCT, transcribed from the CALC-1 gene, is localized to the C cells of the thyroid and the neuroendocrine cells of the lungs, with very low concentrations in healthy individuals [(0.033±0.003) ng/ml], and PCT levels are generally higher in males than in females.
Clinical Application Value of PCT
(1) PCT can be used for the diagnosis and differential diagnosis of sepsis
The 2012 expert consensus on the emergency clinical application of procalcitonin stated that PCT levels in sepsis patients are significantly higher than in non-sepsis patients, and bacterial sepsis patients have significantly higher PCT levels than non-bacterial sepsis patients. The elevation of PCT is highly specific for bacterial infections leading to sepsis, making it a biological marker for diagnosing sepsis and differentiating severe bacterial infections, and it has been approved by the U.S. Food and Drug Administration as a potential indicator of mortality in patients with severe sepsis.
PCT levels increase sequentially in patients with SIRS, sepsis, severe sepsis, and septic shock, showing statistical significance and correlating with the severity of the condition. When PCT levels rise from 0.5 ng/ml to over 2 ng/ml, it indicates a severe bacterial infection or sepsis. However, in cases of severe liver and kidney dysfunction or during the initial days post-surgery or trauma, PCT may remain within the range of 0.5-2 ng/ml. When PCT levels exceed 2 ng/ml or even 10 ng/ml, the likelihood of sepsis, severe sepsis, or septic shock is very high, exceeding 90%. High levels of PCT indicate a severe systemic inflammatory response and a high risk of death, necessitating immediate antibiotic and other targeted treatments.
(2) PCT has been used to guide empirical antibiotic treatment for bacterial infections in respiratory diseases such as acute exacerbations of chronic bronchitis and community-acquired pneumonia
Acute exacerbations of chronic bronchitis and community-acquired pneumonia are often caused by bacterial infections, with PCT levels higher than those caused by viral, atypical pathogens, and tuberculosis. PCT levels correlate positively with the positive rate of sputum bacterial cultures and the severity of the condition. Low PCT levels (<0.1 ng/ml) suggest mild pulmonary infections with a good prognosis, while infections caused by viruses or atypical pathogens are indicators for not using or stopping antibiotics. High initial PCT levels that continue to rise or do not decrease during treatment are signs of poor prognosis.
(3) PCT levels can be used to determine the effectiveness of empirical antibacterial treatment
Dynamic monitoring of PCT levels can assess disease progression; therefore, for patients receiving antibiotic treatment, it is essential to monitor PCT changes daily to determine whether to continue or discontinue antibiotic therapy and to monitor infection sites. If PCT levels decrease by more than 30% within 72 hours of treatment initiation, the treatment is considered effective; if PCT levels continue to rise, it indicates worsening infection or treatment failure, while a decrease in PCT levels can be seen as improvement and successful treatment.
(4) Monitoring PCT levels to determine when to initiate antibacterial treatment
If a patient’s PCT is <0.1 ng/ml, antibiotic use is not recommended; if PCT >0.5 ng/ml, it indicates severe bacterial infection or sepsis, necessitating the initiation of antibiotic treatment; in emergency situations, PCT >0.25 ng/ml may also indicate infection, and if there is other supporting evidence of infection, antibiotics can be started.
(5) PCT can serve as a tumor marker
In tumor diseases, PCT levels <0.5 ng/ml generally do not induce PCT production, but caution should be exercised for medullary thyroid carcinoma or follicular thyroid carcinoma, where PCT can serve as one of the tumor markers. Widespread metastasis can lead to mild elevations in PCT, notably in liver metastasis patients, where PCT can be around 0.5 ng/ml, and can reach up to 1 ng/ml in cases of systemic metastasis.
(6) PCT can reflect the severity of pancreatitis
Some researchers divided 50 patients with acute pancreatitis into mild and severe pancreatitis groups and measured serum PCT, CRP, and WBC levels. The results showed that the PCT level in the severe pancreatitis group [1.86 (0.52-3.98) μg/L, P<0.01] was significantly higher than that in the mild pancreatitis group [0.42 (0.00-1.67) μg/L], indicating a positive correlation between PCT and the severity of acute pancreatitis (r=0.745, P<0.05). High levels of PCT indicate severe conditions, organ dysfunction, and poor prognosis. If PCT in pancreatitis patients is >1 ng/ml, it strongly suggests the possibility of infectious necrosis.
(7) Monitoring for bacterial infection complications after major surgeries and severe trauma
PCT can increase after surgical procedures and trauma, typically peaking 1-2 days post-operation, with peak values reaching 2 ng/ml. Wu Wenchuan et al. conducted a prospective analysis of 432 patients undergoing major abdominal surgery and found that PCT levels significantly increased in patients with infectious complications on the third postoperative day, while PCT only slightly increased in those with non-infectious complications. In patients without postoperative complications, the critical PCT values on days 1, 3, and 5 post-operation were 1.8, 0.7, and 0.4 μg/L, respectively, similar to findings from Novonty’s study. The increase in PCT post-surgery or trauma is hypothesized to be related to hematoma formation in the surgical area and increased release of intestinal toxins. If bacterial infection occurs post-surgery or trauma, serum PCT levels will remain elevated or high; if infection or sepsis is effectively controlled, PCT will quickly decrease to normal levels.
Reference Values for PCT
The plasma PCT concentration in healthy individuals is less than 0.05 ng/ml. In elderly individuals, patients with chronic diseases, and about 10% of healthy individuals, plasma PCT concentrations can exceed 0.05 ng/ml, with a maximum of 0.1 ng/ml, but generally not exceeding 0.3 ng/ml. The diagnostic threshold for PCT in sepsis patients is greater than 0.5 ng/ml, while severe sepsis and septic shock patients have PCT concentrations fluctuating between 5-500 ng/ml. In rare cases of severe infections, plasma PCT levels can exceed 1000 ng/ml.
2. C-Reactive Protein
C-Reactive Protein (CRP) is a protein that reacts with the polysaccharide component C-polysaccharide of Streptococcus pneumoniae and appears during acute infections. When the body is under stress, inflammatory factors such as IL-6, IL-1, and TNF-α can induce hepatocytes to synthesize CRP. In normal patients, CRP levels are extremely low, usually not exceeding 5 mg/L, and remain stable in the body over time, so even minor changes in CRP can indicate alterations in physiological status.
Clinical Application Value of CRP
(1) Can be used to differentiate bacterial infections from viral infections
During acute inflammatory responses, CRP is synthesized at a rate of 1 g per day, beginning to rise 6-8 hours after infection, peaking at 24-48 hours, and can increase hundreds to thousands of times compared to normal values, with the degree of elevation correlating with the severity of the infection. After the disease is cured, CRP levels can return to normal within a week. In viral infections, CRP often does not increase (except for some severely invasive viruses that cause tissue damage, such as adenovirus and herpes virus).
(2) Can reflect the severity of the body’s inflammation
Different concentrations of CRP can reflect the severity of inflammation. CRP levels between 10-50 mg/L generally indicate mild inflammation, including local bacterial infections (such as bronchitis, tonsillitis, cystitis), surgical and accidental trauma, deep vein thrombosis, myocardial infarction, inactive connective tissue diseases, malignant tumors, and most viral infections; CRP levels between 50-100 mg/L indicate more severe diseases, and intravenous antibiotic treatment may be necessary; CRP levels >100 mg/L should raise high suspicion of severe diseases, often accompanied by bacterial infections.
(3) Can be used to detect connective tissue diseases
Connective tissue diseases are autoimmune diseases affecting multiple systems, including systemic lupus erythematosus (SLE), rheumatoid arthritis, and others. Studies have shown that in certain connective tissue diseases such as SLE, systemic sclerosis, and dermatomyositis, serum CRP levels may be only mildly elevated or even not elevated at all. Notably, CRP can increase during SLE disease activity and infections, but the levels of increase differ. CRP often rises significantly during infections, while in patients with very active SLE, CRP may only be mildly elevated (generally <60 mg/L). However, regardless of whether there is an accompanying infection, CRP can be moderately elevated (average 76 mg/L) in SLE patients with serositis. Therefore, CRP levels are significant for differentiating SLE disease activity.
(4) Can predict the prognosis of malignant tumors
A large body of literature suggests that CRP levels can predict the prognosis of malignant tumors. Some studies indicate that a preoperative CRP/albumin ratio ≥0.025 is a prognostic indicator for gastric cancer patients undergoing radical resection. A CRP/albumin ratio ≥0.037 is closely related to the progression of liver cancer and the decline of liver reserve function, serving as a prognostic indicator for liver cancer. A preoperative CRP/albumin ratio ≥0.0271 is associated with poor postoperative prognosis in colon cancer patients, and compared to the modified Glasgow prognostic score, the CRP/albumin ratio may better predict postoperative survival in colon cancer patients. A CRP/albumin ratio >0.03 is an indicator of poor prognosis for pancreatic cancer patients undergoing resection. CRP levels, along with the neutrophil/lymphocyte ratio, can also serve as prognostic indicators for pancreatic cancer.
(5) Predicts the risk of cardiovascular diseases
Atherosclerotic plaques are primarily composed of fibrous caps and lipids, with significant infiltration of inflammatory cells, stimulating the liver to produce CRP, leading to a sustained mild elevation of CRP, which can be used to predict the occurrence of atherosclerosis. The Physicians’ Health Study (PHS) showed that hs-CRP levels in the highest group of atherosclerosis patients had a twofold increased risk of future disease compared to the normal group, and a threefold increased risk of myocardial infarction. During acute myocardial infarction, severe reactions occur in the areas of myocardial injury and necrosis, leading to elevated hs-CRP levels, which are even higher when there is complete blockage of the coronary artery associated with the infarction. CRP levels greater than 10 mg/L pose a significantly greater risk than those less than 10 mg/L, making CRP a prognostic indicator for ischemic stroke.
Reference Values for CRP
Serum CRP is measured using enzyme-linked immunosorbent assay, with normal values for adults and children ranging from 0.068-8.2 mg/L; values of 10-99 mg/L indicate localized or superficial infections; ≥100 mg/L indicates sepsis or invasive infections, with a sensitivity of up to 100%.
CRP is used for assessing the risk of cardiovascular diseases: hs-CRP<1 mg/L indicates low risk, 1-3 mg/L indicates moderate risk, and >3 mg/L indicates high risk. Studies have shown that hs-CRP≥2.0 mg/L is an effective predictor of cardiovascular disease in the Chinese population.
3. Conclusion
As an acute phase protein, CRP can be elevated in response to any inflammatory reaction, making it difficult to distinguish whether it is an infectious disease based solely on this indicator; a comprehensive consideration of the body’s immune function and defense mechanisms, along with clinical manifestations and other relevant auxiliary examinations, is necessary.
In contrast, PCT, as a new inflammatory marker, is not influenced by non-infectious factors, thus its diagnostic value for bacterial infectious diseases is significantly superior to that of white blood cell counts and CRP. It is recognized as the most sensitive diagnostic indicator for sepsis, with high value in diagnosing early infections, differentiating infection types and severity, and guiding antibiotic use, making it highly significant in clinical practice.
[References]
[1] Expert Consensus Group on the Emergency Clinical Application of Procalcitonin. Expert Consensus on the Emergency Clinical Application of Procalcitonin (PCT) [J]. Chinese Journal of Emergency Medicine, 2012, 21(9).
[2] Yu Shifei, Li Fangqiu. Advances in the Clinical Application of Procalcitonin [J]. Journal of Medical Postgraduates, 2016, 29(2): 206-209.
[3] Wang Yongbo, Qian Jing. Advances in the Biochemical Properties and Clinical Applications of Procalcitonin [J]. Medical Review, 2016, 22(3): 493-496.
[4] Zhou Yuqing, Chen Xiang. Analysis of PCT, CRP, and WBC Levels and Their Correlation in Patients with Acute Pancreatitis [J]. Medical Review, 2017, 23(4): 795-797.
[5] Wu Wenchuan, Lou Wenhui. Advances in the Relationship Between Procalcitonin and Postoperative Infectious Complications [J]. Chinese Journal of Practical Surgery, 2016, 36(2): 245-247.
[6] Ma Yating, Li Xinjun, Yang Ming, et al. Advances in Research and Clinical Application of C-Reactive Protein [J]. Clinical Laboratory Journal (Electronic Edition), 2015, 4(4): 997-1002.
[7] Huang Li, Wang Qingmei, Hu Jian, et al. Advances in the Relationship Between C-Reactive Protein and Malignant Tumors [J]. Journal of Translational Medicine (Electronic Edition), 2017, 4(2): 65-70.
[8] Tong Hai, Tu Yulin. High-Sensitivity C-Reactive Protein and Atherosclerosis [J]. Literature Review, 2010, 18(9): 746-750.
Source: Medical Community Respiratory Channel
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