Welcome to the course “An Introduction to Canine C-Reactive Protein (CRP)”.

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This course will take approximately 15 minutes to complete.

After this course, you will be able to:

1. Understand the key clinical benefits of CRP testing for dogs

2. Identify and monitor systemic inflammation in dogs by using CRP testing

Inflammation is a physiologic response to tissue injury due to trauma, infection or other causes. A localized inflammation is limited to one organ or site in the body. When inflammation cannot be retained locally, the inflammation becomes systemic. This process is characterized by the total inflammatory reactivity of multiple organs and tissue.

Traditionally, diagnostic approaches to systemic inflammation include examining the changes in white blood cells and various plasma proteins, such as fibrinogen.

Another approach to systemic inflammation is to evaluate the role of acute phase proteins in the body. As a first response to an inflammatory stimulus, innate immune cells – such as macrophages and neutrophils – respond by mediating the release of inflammatory cytokines at the site of tissue injury. These cytokines, which are small proteins involved in cell signaling, trigger changes in the production of acute phase proteins, primarily in the liver.

Acute phase proteins can increase or decrease during an acute phase response. Negative acute phase proteins, such as albumin and transferrin, decrease in concentration during an acute phase response. Positive acute phase proteins, such as CRP, serum amyloid A, serum amyloid P and haptoglobin, increase in concentration during an acute phase response and are released into the bloodstream. Therefore, a high level of positive acute phase proteins and a low level of negative acute phase proteins in the blood is an indication of an acute phase response by the body.

Depending on the degree of increase in concentration, positive acute phase proteins can be further categorized as major, moderate or minor:

• Major acute phase proteins increase 10- to 100-fold upon stimulation, peak between 24 and 48 hours and then decrease rapidly.

• Moderate acute phase proteins increase 1- to 10-fold upon stimulation, peak between 48 and 72 hours and then decrease at a slower rate than major acute phase proteins.

• Minor acute phase proteins increase only slightly and at a gradual rate.

Major and moderate acute phase proteins differ per animal species. CRP is a major acute-phase protein found in dogs.

As part of the acute phase response in dogs, the amount of CRP in the body rises within four to six hours after the inflammatory stimulus. If there is no progression in the inflammatory process, CRP will peak between 24 and 48 hours.

The amount of CRP in the body then drops rapidly after systemic inflammation begins to subside. It can decrease as much as 50% of the peak value within 24 hours, making CRP a sensitive means of monitoring progression or regression of an active inflammatory process.

Following the cessation of the inflammatory process, the CRP level in the body returns to the baseline level. This may take one to two weeks, depending on the severity of the inflammatory process.

The CRP concentration in dogs is not significantly affected by gender, breed, stress or diet.

However, several factors can elevate the CRP concentration in dogs without disease. These are

• pregnancy and lactation

• young age - dogs younger than three months may have CRP values that are above the upper reference interval limit, and

• strenuous exercise - dogs that are very active may have elevated CRP concentrations as a result of exercise-induced inflammation

The Catalyst® CRP Test is a quantitative, canine-specific assay that can be used to determine the presence and severity of systemic inflammation in a patient. For this test, you can use serum, plasma or whole blood using a lithium heparin whole blood separator.

It is available as a separate slide and can be run as a stand-alone test or with a chemistry profile. A recent study by IDEXX found that there is minimal, and clinically insignificant, interference by hemolysis, lipemia and icterus on the mean CRP concentration.

CRP testing cannot be used to determine the cause of the inflammation or to distinguish between infectious and non-infectious inflammatory disease. Therefore, it is recommended that the CRP test result should always be evaluated in conjunction with a comprehensive patient history, physical examination and a Minimum DataBase when systemic inflammation is suspected.

To determine the severity of the systemic inflammation, we usually refer to a dynamic range between 0 and 100 mg/L for the Catalyst® CRP Test. This dynamic range includes three main interpretive ranges:

• 0 to 10 mg/L

• 10 to 30 mg/L, and

• 30 to 100 mg/L

Click on each range of results to learn more.

A value between 0 and 10 mg/L indicates that there is no evidence of systemic inflammation present in the body. This is the current reference interval for clinically normal dogs.

A value between 10 and 30 mg/L indicates that there is a mild active inflammatory process, an early developing systemic inflammation in the body or that a previous systemic inflammatory process is now resolving. Patients with CRP values within this range should be monitored to determine if the active inflammation is progressing or regressing.

A value greater than 30 mg/L indicates the presence of significant systemic inflammation. Increasing CRP is directly related to increasing severity of systemic inflammation.

CRP testing provides excellent value in point-of-care patient assessment. CRP testing can be used for the following patients:

• Patients who are clinically unwell: A CRP test can be used to determine if systemic inflammation is present. High CRP concentrations are likely with a wide variety of conditions, such as pyometra, pneumonia, pancreatitis, immune-mediated diseases, inflammatory bowel disease, systemic bacterial infections, and many more.

• Patients undergoing treatment: CRP testing can be used to monitor the regression or progression of systemic inflammation during treatment, hospitalization or recheck visits.

• Patients undergoing invasive surgery: CRP testing can help you to monitor the post-operative response of a patient and quickly detect inflammatory complications.

• Patients who are being treated with any immunosuppressive drug that become clinically unwell.

• Patients with vague signs of illness or those who are “under the weather”: You could consider CRP testing when assessing patients who are “under the weather” as a CRP value above the reference interval would warrant further investigation.

The Catalyst® CRP Test also complements the results of other diagnostic tests, such as a Complete Blood Count, run on a hematology analyzer. For example, you’ll receive immediate and straightforward insight into the severity of the systemic inflammation from the CRP test as well as detailed information on the body’s response to the inflammation from the CBC results and graphics.

By running a CRP test in-house, you can quickly establish if systemic inflammation is present in your patient, allowing you to make immediate decisions for therapy or further testing. This also means that you can discuss the results and treatment options with the pet owner during the same patient consultation.

CRP test results can be fully integrated with other test results for a comprehensive diagnostic view. While a single CRP test result is useful, the real value of the test lies in its ability to illustrate a trend in the systemic inflammation over a period of time. This allows you to monitor how the systemic inflammation is changing in real-time.

In summary, CRP is a major acute-phase protein which is produced rapidly during the onset of systemic inflammation in the body. Because of this rapid response, CRP can be used as a real-time biomarker for systemic inflammation and acts as an early indicator as well as an objective monitor of active inflammation. By using in-house testing, rapid and accurate results are generated in real time allowing for immediate communication with clients and superior medical management of patients.

Thank you for taking the course: “An Introduction to Canine C-Reactive Protein (CRP)”.