C-reactive protein: point-of-care testing in the pediatrician’s office

August 2005

Evidence of serious pediatric infections includes high peak temperature and duration of fever, the well-known generalized clinical signs of a “sick kid” and sometimes red flag focal clinical signs, such as nuchal rigidity or a purpuric rash. The primary care pediatrician in the office setting often encounters ill-looking children without any focus of infection.

Which children can be observed at home, which children should go directly to the reference laboratory and which children must be sent to the nearest capable emergency medicine department are vexing questions frequently facing the office-based pediatrician. With the passage of the Clinical Laboratory Improvement Act (CLIA), many non-CLIA-waived tests for acute phase reactants, including leukocyte counts and sedimentation rate, are performed at the a reference laboratory, away from the point of care. For the small pediatric office, a CLIA-certified clinical laboratory is usually too expensive to equip and maintain.

Coulter counters and other technology for automated determination of leukocyte count cost at least $15,000 to purchase new.

Wouldn’t it be helpful if an accurate and inexpensive test for acute phase reactants could be performed in a few minutes without a major financial investment in equipment or supplies and without the requirement of a venipuncture?

Point-of-care testing has been in use since Thomas Willis (1621-1675) used the taste test to determine the presence of glucosuria.

Recent FDA approvals

Recently, several benchtop instruments, which inexpensively and accurately measure the concentration of C-reactive protein (CRP), have been approved by the FDA and are available for point-of-care use in primary care offices. These include NycoCard CRP (Axis-Shield PoC AS, Oslo Norway, distributed by PRIMUS Corp., Kansas City, Mo., 1-800-377-4752) and QuikRead 101 CRP (Orion Diagnostics, Espoo, Finland, QAS, Orlando, Fla., 1-407-563-2405). These and perhaps other compact desktop instruments are currently commercially available and affordable, costing approximately $1,500. Reagents cost about $5 per test and are sold in lots of 48 to 50 tests. CRP can be performed in two or three minutes on small amounts (5 µl) of serum, plasma or whole blood specimens. Point-of-care CRP tests are currently not-CLIA-waived and require CLIA approval for a moderately complex or highly complex office laboratory, a licensed laboratory director and participation in an approved quality assurance program, which costs about $150 annually for CRP unknowns sent three times per year by the accreditation organization.

Point-of-care testing is familiar to pediatricians who use rapid tests for identification of group A streptococcal pharyngotonsillitis, Epstein-Barr infectious mononucleosis, influenza virus and respiratory syncytial virus and for determination of hemoglobin, blood glucose and total cholesterol. Such tests are relatively inexpensive to purchase, require no financial outlay for durable equipment, are easy to perform, offer short turn around time, reduce injudicious prescriptions of antibiotics for viral infections and are approved by CLIA. Points-of-care tests for CRP are a novel concept for small in-office CLIA-approved pediatric laboratories. The manufacturers have applied for CLIA-waived status, and they predict that CLIA will grant their request within the next 12 months.

NycoCard is a solid phase immunometric assay using immobilized human-CRP specific mouse monoclonal antibodies.

According to the manufacturer’s insert, compared with reference standard methods of turbidimetry or nephelometry, NycoCard performed well with a correlation coefficient of 0.99. Results of a clinical study conducted in general practice primary care clinics at the University of Oslo found a close correlation (r=0.85) with the reference standard. CRP values above 20 mg/L are clinically not important and 20-50 mg/L are borderline. Values 60 mg/L or above suggest a pronounced increase in inflammatory response or a more severe infection.

In emergency department settings and on hospital wards, markedly elevated CRP tests are of great value to help select those patients who might be sicker than they appear. CRP tests complement the decision-making value of the sedimentation rate and blood leukocytes. In our small primary care pediatric office, we purchased one of the point-of care CRP instruments and performed more than 250 tests in little over 18 months. We use the test with an automated complete blood count when a febrile child looks sick and/or when the child has fever more than 72 hours.

Both tests are rapidly performed with small amounts of fingerstick capillary blood. Results for both tests are available in about five minutes. Parents of our patients are given an option of signing a release form, which states that they assume full responsibility for paying for the tests if they elect to have them performed at our office. Neither the parents nor our business office submits the bill to a managed care organization for reimbursement. We charge $25 for both tests. Payment is by cash, credit card or billed directly to the patient’s account for prompt collection later.

For more information:

• Dahler-Eriksen BS, Lauritzen T, Lassen JF, et al. Near-patient test for C-reactive protein in general practice: assessment of clinical, organizational, and economic outcomes. Clin Chem. 1999;4(4)5:478-485.
• Hansson LO, Carlsson I, Hansson E, et al. Measurement of the C-reactive protein and the erythrocyte sedimentation rate in general practice. Scand J Prim Health Care. 1995;13(1):39-45.
• Hjortdahl P, Landaas S, Urdal P, et al. C-reactive protein: a new rapid assay for managing infectious disease in primary health care. Scand J Prim Health Care. 1991;9(1):3-10.
• Hobbs, R. Near patient testing in primary care. Brit Med J. 1996;312(7026):263-264.

• Richard H. Schwartz, MD, is from the department of pediatrics at Inova Fairfax Hospital for Children, Falls Church, Va.