College of American Pathologists
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  Q and A





March 2009

Fredrick L. Kiechle, MD, PhD

Question Q. Can high-sensitivity C-reactive protein measurements replace the time-honored erythrocyte sedimentation rate?

A. C-reactive protein, or CRP, is a nonspecific acute-phase reactant. CRP is in the sera of healthy individuals at levels of less than 1 mg/dL, and the levels can rise markedly (20–50 mg/dL) in response to tissue injury and inflammation. CRP is thus used to monitor disease activity and progression in inflammatory conditions such as rheumatologic autoimmune disease, in postoperative recovery, and in cases of bacterial infection.

In recent years, the utility of measuring CRP has been expanded from its historical use as a sensitive marker of acute inflammation to include assessment of risk for cardiovascular disease.1 This is done with the help of the high-sensitivity C-reactive protein test. The hsCRP test is a more sensitive assay for measuring very low levels of CRP that cannot be measured with the traditional CRP assay.

The erythrocyte sedimentation rate essentially measures the rate at which erythrocytes sediment to the bottom of a tube. Normally, erythrocytes sediment slowly because red cells have a net negative charge and repel each other. On the other hand, acute-phase reactants such as fibrinogen and other positively charged proteins can neutralize the surface charge of erythrocytes and promote aggregation. As a result, red cell aggregation increases the rate of sedimentation.2

CRP and the ESR are different measures of an acute-phase response. CRP measures a specific protein involved in the acute-phase response, whereas the ESR is a broader measure of the acute-phase response. Walsh, et al.,3 noted that the ESR and CRP had a linear relationship in patients with rheumatoid arthritis, but high-dose prednisone therapy caused a greater reduction in CRP than in the ESR. They suggested CRP was the more sensitive test, but elevated levels of CRP and the ESR do not have identical clinical significance after treatment with drugs such as gold, penicillamine, and prednisone. In another study4 on hsCRP, CRP, and the ESR in rheu­matoid arthritis, the authors concluded hsCRP could detect low levels of systemic inflammation that were not picked up by CRP. They also concluded that hsCRP performed better than the ESR in predicting some disease activity variables. Steinvil,5 however, identified low-grade inflammation in individuals without elevated hsCRP (<5 mg/L) levels. Mok, et al., investigated CRP and the ESR6 as predictors of infectious complications in the postoperative period following spinal surgery. The authors concluded CRP was more applicable, predictable, and responsive in the early postoperative period following surgery and was superior to the ESR as a diagnostic test.

This sampling of studies suggests that hsCRP can, in most cases, replace the ESR as a diagnostic test for acute inflammation. However, before implementing such a practice, several other factors must be considered. Using hsCRP is more expensive than using the ESR. Additionally, the linear range of the hsCRP assay is more limited (0.02–8 mg/dL or 0.2–80 mg/L) than that of the traditional CRP assay. This means patients with high CRP levels would need several rounds of dilution on the autoanalyzer. This could be wasteful and time-consuming. In our own lab, we offer both assays.


  1. May A, Wang TJ. Evaluating the role of biomarkers for cardiovascular risk prediction: focus on CRP, BNP, and urinary microalbumin. Expert Rev Mol Diagn. 2007;7:793–804.
  2. Sox HC, Liang MH. The erythrocyte sedimentation rate. Guidelines for rational use. Ann Intern Med. 1986;104:515–523.
  3. Walsh L, Davies P, McConkey B. Relationship between erythrocyte sedimentation rate and serum C-reactive protein in rheumatoid arthritis. Ann Rheum Dis. 1979;38:362–363.
  4. Dessein PH, Joffe BI, Stanwix AE. High-sensitivity C-reactive protein as a disease activity marker in rheumatoid arthritis. J Rheumatol. 2004;31:1095–1097.
  5. Steinvil A, Shapira I, Arbel Y, et al. Determinants of the erythrocyte sedimentation rate in the era of microinflammation: excluding subjects with elevated C-reactive protein levels. Am J Clin Pathol. 2008;129:486–491.
  6. Mok JM, Pekmezci M, Piper SL, et al. Use of C-reactive protein after spinal surgery: comparison with erythrocyte sedimentation rate as predictor of early postoperative infectious complications. Spine. 2008;33:415–421.

Suzanne Arinsburg, DO
Resident in Clinical Pathology
New York-Presbyterian Hospital–Weill Medical College of Cornell University

Yash P. Agrawal, MD, PhD
Director, Central Laboratory
New York-Presbyterian Hospital–Weill Medical College of Cornell University
Member, CAP Toxicology
Resource Committee

Question Q. What is the CAP Hematology/Clinical Micro­scopy Resource Committee’s opinion about clinicians requesting a “pathologist review” without any flags from the hematology analyzer?

A. The committee’s consensus is that if a clinician strongly suspects a condition that will manifest specific changes on the blood smear, it is reasonable to ask for a morphologic review of the blood smear to seek those changes even if the analyzer has not generated flags. Examples cited were intracellular parasites and rare fragmented cells early in the course of HUS/TTP. The committee felt that while educating clinicians is useful in avoiding excessive and unnecessary morphologic reviews, it is essential that the astute clinician be able to suggest that a smear review be performed, communicated in such a way, it is hoped, that the laboratory can understand and focus on the clinician’s concerns.

Robert Novak, MD
Department of Pathology
Children’s Hospital
Medical Center of Akron
Akron, Ohio

Immediate past chair,
CAP Hematology/Clinical Microscopy Resource Committee

Dr. Kiechle is medical director of clinical pathology, Memorial Healthcare, Hollywood, Fla.