C-Reactive Protein (CRP), High-Sensitivity C-Reactive Protein (hs-CRP), Acute Phase Protein

Acute-phase protein (Acute Phase Reactants)
- Acute-phase proteins are raised in inflammatory conditions.
- When there is an increase in an acute phase protein called positive acute-phase protein.
- In the case of a decrease in the acute phase protein, it is called negative phase protein.
- The acute phase proteins (positive) are proteins whose concentration increases in the plasma, and after the disease episode is over, it decreases and may become normal.
C-Reactive Protein (CRP)
Sample
- The venous blood of the patient is needed to prepare the serum.
- A fasting sample is preferred.
- A random sample can be taken.
- Analyze the fresh sample.
- Or can store at 4 °C for <72 hours.
- At -20 °C for six months.
Indications
- Advised in bacterial infection.
- It is advised in rheumatic fever.
- It is advised in rheumatoid arthritis.
- It may be advised after the surgery.
Precautions
- This may be raised in cigarette smoking.
- Avoid hemolysed and lipemic samples.
- Raised values are seen in hypertension, diabetes mellitus, metabolic syndrome, gingivitis, and bronchitis.
- Decreased values have seen weight loss, moderate consumption of alcohol, and exercise.
- Estrogens and progesterone increase value.
- Niacin, statin, and fibrates decrease value.
Pathophysiology
- Definition:
- CRP is produced in the liver, and its name is derived from its reaction with streptococcal capsular polysaccharides.
- CRP level supporting bacterial endocarditis, appendicitis, and active collagen diseases was >10 mg/L.
- There are changes in the plasma protein in response to:
- Acute illness.
- Trauma.
- Necrosis.
- Infarction.
- Burns.
- Chemical injury.
- Malignant tumors.
- The acute reaction proteins pattern is also called:
- Acute inflammatory response pattern.
- Acute stress pattern.
- Acute-phase protein pattern.
- CRP is found in the Gamma-region band on serum electrophoresis.
- CRP is absent from the healthy person.
- CRP increased after any injury (trauma, bacterial infection, surgery, neoplasm, and inflammation) to 100 times.
- CRP was given the name in 1941 that it is protein.
- This is a nonspecific acute-phase protein.
- CRP starts rising after 4 to 6 hours of the infection, while other proteins rise after 12 to 36 hours of the initiating cause.
- CRP is functionally analogous to IgG, except it is not antigen-specific.
- This protein is synthesized in the liver and released into blood circulation after tissue injury in a few hours.
- The synthesis of the CRP is initiated by:
- Antigen immune complexes.
- Bacterial infection.
- Fungal infection.
- Trauma or tissue injury.
- The synthesis of the CRP is initiated by:
- High-sensitivity CRP (hs-CRP):
- It detects the lower level of CRP, which is important to find the risk of cardiac events.
- The sensitivity is 0.01 mg/dL.
- In the case of raised hs-CRP, follow-up serial measurements are needed.
- hs-CRP is useful for the risk of developing acute myocardial infarction with a history of the acute coronary syndrome.
- Value ≥1.0 mg/L indicates subclinical infection/inflammation; this needs to repeat the test in 3 to 4 weeks.
- Coronary risk grades:
- Low-risk = <1.0 mg/L
- Average risk = 1.0 to 3.0 mg/L.
- High-risk = ≥3.0 mg/L.
- It is the first acute phase protein raised in inflammatory diseases, and its level increases tremendously.
- It is raised in acute and chronic inflammation.
- This promotes the binding of Complement and helps in phagocytosis.
- Its formation is initiated by the antigen-antibody immune complex.
- This can induce the production of cytokines.
- This can cause inhibition of chemotaxis and modulation of the WBC function.
- The normal CRP level is <2 to 3 mg/L.
- The markedly raised level of >10 mg/L indicates an active inflammatory condition like collagen diseases and infection.
- Its level does not rise consistently in the virus infection.
- CRP vs. ESR:
- More sensitive and rapidly responding than the ESR.
- Other physiologic factors influence ESR, but CRP does not.
- CRP tends to increase before the increase in ESR and the rise in antibodies titer.
- In the acute inflammatory process, CRP shows an earlier and more rapid increase than the ESR.
- In recovery, it becomes normal before the ESR.
- It disappears when the disease is treated with cortisone or salicylates.
- This is useful for the assessment of risk for developing myocardial infarction in patients presenting with acute coronary signs and symptoms.
- It may be advised after the surgery when its level increases in 4 to 6 hours.
- It starts going down after a 3rd postoperative day.
- If it persists raised level which indicates a complication of infection or pulmonary infarction.
- It helps in the differential diagnosis of bacterial or viral meningitis.
- In viral meningitis, it will not be raised.
- Normal value excludes bacterial meningitis.
- In myocardial infarction (AMI):
- CRP is raised, and it correlates with CK-MB isoenzyme in AMI.
- Its peak level occurs 1 to 3 days later than CK-MB.
- hs-CRP values >10 mg/L within 6 to 24 hours after the symptom onset indicates an increased risk for a recurrent cardiac event within 30 days to 1 year.
- In unstable angina, hs-CRP values >10 mg/L will predict a higher chance of myocardial infarction/death as compared to the group of patients where hs-CRP <10 mg/L.
- CRP may remain increased in AMI for at least three months.
- If the level persists to be raised indicates ongoing damage to myocardial tissue.
- The baseline level is a good marker for future cardiovascular disease.
- CRP is a strong predictor of cardiovascular diseases than the low-density-lipoprotein (LDL) and cholesterol.
- In patients with stable coronary disease, CRP is a good marker for assessing the likelihood of recurrent myocardial infarction, restenosis, or death.
- Its level is normal in the case of angina.
- Serology of CRP:
- CRP appears after 24 to 48 hours of the onset of infection.
- Peak level reaches 72 hours.
- It disappears from circulation after seven days.
- Based upon CRP level, there are the following categories:
- Normal level = <3 mg/L.
- High level CRP = >10 mg/L (active inflammation).
- Low level CRP = 3 to 10 mg/L. (Cellular stress).
Normal
- <1.0 mg/dL
- Source 2
- <1.0 mg/dL or <10.0 mg/L
- Cardiac disease risk:
- Low = <1.0 mg/dL
- Average = 1.0 to 3.0 mg/dL
- High = >3.0 mg/dL
- Source 4
- CRP = <0.8 mg/dL (<8.0 mg/L) (by nephelometry)
- CRP repotable value = 0.3 to 20 mg/dL
- hs-CRP = 0.020 to 0.800 mg/dL (o.2 to 8.0 mg/L) (by immunoassay)
The raised level is seen in:
-
- Soft tissue Trauma.
- Infection.
- Tissue necrosis.
- Patients with Rheumatoid arthritis.
- In Rheumatic fever.
- Patients with systemic lupus erythematosus.
- Patient with pneumonia.
- Patient with malignancies.
- In pregnant ladies.
- Pulmonary tuberculosis.
- Urinary tract infection.
- Myocardial infarction.
- Vasculitis syndrome.
- Bacterial meningitis.
Decreased CRP level is seen in:
- This may be seen in the moderate use of alcohol.
- In weight loss.
- Excessive exercise.
- Medicine like Niacin, and a statin.
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