The effect of diurnal variation on erythrocyte sedimentation rate

Introduction

Erythrocyte sedimentation rate (ESR) is a nonspecific, simple and inexpensive laboratory test that demonstrates inflammatory reaction or tissue damage [1], [2]. ESR is one of the most commonly used parameters in evaluating acute phase response. It rises 24 h after the onset of inflammation and has an average half-life of 6 days [3].

Increased ESR is used in the clinic to determine whether the disease is present, to monitor the course of the known disease, and to evaluate response to treatment. ESR is still a very valid test in the diagnosis and follow-up of several diseases such as polymyalgia, rheumatoid arthritis, SLE, multiple myeloma, Hodgkin’s disease, septic arthritis, and osteomyelitis. Especially high ESR, polymyalgia rheumatica and temporal arteritis are among the diagnostic criteria [4], [5], [6], [7]. High ESR values in oncology are indicative of poor prognosis in various types of cancer such as Hodgkin’s disease, gastric carcinoma, renal cell carcinoma, chronic lymphocytic leukemia, breast, prostate and colorectal cancers. In patients with solid tumors, ESR values above 100 mm/h are generally considered as signs of metastasis. Several studies have shown that ESR can be used as a tool to screen for specific infections such as orthopedic prosthetic infections, bacterial infections in children and pelvic inflammatory disease. However, it should not be used as a screening test in asymptomatic patients, but only as a diagnostic supportive test in symptomatic patients because it is affected by various factors and has low sensitivity and specificity [4], [8], [9]. The degree of sedimentation elevation helps plan the dose and duration of corticosteroid therapy to treat patients with polymyalgia rheumatica and temporal arteritis that maximize ESR [10]. Although ESR reaches very high values in some patients with active SLE, the same patients CRP may be at normal levels [11].

Normal sedimentation values vary according to age and sex. Women have a higher basal ESR value than men and the upper limit of normal for both sexes increases with age [12], [13].

The International Council for Standardization in Hematology (ICSH) has suggested the “Westergren method” for ESR measurement [14]. The logic of the test is that when the well-mixed venous blood with anticoagulant is kept in an upright position in a special tube, the erythrocytes collapse downwards by gravity because they have higher specific weight than plasma [5], [15]. In today’s medical biochemistry laboratories, ESR is checked with automated devices that have a temperature correction and hold the tubes exactly 90° up to half an hour [16], [17].

It is known that some laboratory tests show diurnal variation and are affected by fasting-satiety state. Information on diurnal variation and satiety status of ESR is controversial in the literature [18], [19], [20], [21]. This study aimed to investigate the diurnal changes of ESR with fasting and satiety.

Materials and methods

Results

The mean age of the volunteers was 34.4 ± 5.7 (mean ± standard deviation). The ESR distribution by hours is shown in Figure 1. ESR results were the lowest at 09:00 [Mean = 7.9 ± 5.9 mm/h, median = 5.5 mm/h, 3.9–9.8 (25th percentile and 75th percentile)] and 15:00 [Mean = 9.0 ± 6.6 mm/h, median = 5.5 mm/h, 4.4–12.1 (25th percentile and 75th percentile)]. In the nonparametric Friedman variance analysis performed because more than two measurements were made and the distribution was not normal, it was found that ESR did not change during the day (p = 0.179) (Table 1). The test results obtained at 10:00, 11:00, and 12:00 am for the assessment of fasting and satiety status on ESR, were higher than baseline, but there were no statistical significance (6.2, 6.0, and 7.8 mm/h, respectively). Also, ESR results at 18:00 and 24:00 to evaluate diurnal variation were higher than baseline, but did not show statistical significance (5.7, and 6.6 mm/h, respectively). Descriptive statistics and comparing between groups are shown in Table 1.

Figure 1:

The ESR distribution by hours.

Discussion

According to the current statistics of our laboratory, five out of every 100 patients are tested for ESR. Although high-sensitivity CRP testing is common and popular, ESR remains an indispensable test in medical laboratories. Unlike CRP, ESR is also elevated in the presence of abnormal plasma proteins such as monoclonal immunoglobulins, cryoglobulins, and cryofibrinogens without an acute phase response [2], [18].

Studies on diurnal variation of ESR in the literature show different results. In a study of diurnal changes in acute phase response, including 35 acute infected patients with fever and 25 patients without fever, ESR was reported to have diurnal changes and the highest ESR values were found at 15:00 [19]. In that study, they may have reached this conclusion because blood sampling for ESR was performed two consecutive days and three times a day (07:00, 15:00, and 23:00). If more intraday samples were taken, different results could be encountered. In the study of Perdiz et al., ESR was reported to show the diurnal variation that is not synchronized with parameters such as body temperature, complete blood count, fibrinogen [19]. Bouvenot et al. studied this with 40 male patients between the ages of 40–60, who had no hepatic and inflammatory disease and were treated in hospital for different reasons and performed ESR with five blood samples at 07:00, 13:00, 19:00, 01:00, and 07:00 to complete the 24-h cycle and reported that ESR did not show diurnal variation [20]. Although the results were controversial, it was thought that because of the reasons that study performed in the patient group and patients had a high age range, and the disease and age caused high ESR could mask diurnal variation.

In a comparative study of examining morning variability of ESR, ESR studied with blood samples taken at 07:00, 09:00, 10:00, and 12:00 from 90 patients with the osteoarticular disease. Although the average values were high at 07:00 in the morning, no significant difference was reported. It was emphasized that patients’ anti-inflammatory drug use duration, dose, and multidrug use may affect the diurnal variation of ESR [21].

Mallya et al., seven patients with active rheumatoid arthritis (4 F, 3 M) between 08:00 and 20:00 between 2 h in the series of nine ESR measurements were reported to show diurnal variation. The ESR diurnal variation of the fasting-satiety cycle was higher in five of the seven patients and the mean values were statistically significant, although less in four patients who did not eat during the day [18]. In patients with active disease and the lowest initial ESR value was 35 mm/h, the difference between the mean higher ESR values was found to be higher than ours. The diurnal variation of ESR associated with food digestion is thought to occur in a variety of ways, particularly intra-day changes in plasma content.

The primary goal of this study was to determine the optimal blood sampling time for accurate results in diagnosis and follow-up by examining diurnal changes in ESR, and the second aim was to improve our knowledge of preanalytical variables. The weaknesses of our study were the low number of volunteers and unequal gender distribution. Baseline ESR results in 10 volunteers who participated in our study were between 3.0 and 10.2 mm/h. The other two female volunteers measured approximately 20 mm/h (Figure 2).

Figure 2:

Individual ESR results of volunteers.

In this study, it was found that ESR did not show a change during the day, and it was found to be the lowest level at 9:00 am and 3:00 pm. Elevations at noon and midnight are not significant, but it should be kept in mind that ESR may be more likely to occur during intra-day changes in the case of tissue damage and inflammatory disease.

In conclusion, although it is known that routine biochemistry tests should be performed from the blood sample taken in the morning in case of starvation, blood sampling can be done for ESR during the day if necessary. Taking into consideration the changes in ESR used in the diagnosis and follow-up of patients during the day, it should be considered that taking blood samples at any hour during working hours may not affect the results.