Diagnostic Performance of Serum Erythropoietin to Discriminate Polycythemia Vera from Secondary Erythrocytosis through Established Subnormal Limits
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Population
2.2. Serum Erythropoietin Assay
2.3. Statistical Analysis
3. Results
3.1. Basic Demographics of the Study Population
3.2. Determination of Reference Interval and Influencing Factors for Serum Erythropoietin in Healthy Donors
3.3. Determination of Clinical Decision Limit and Functional Reference Limit of Serum Erythropoietin
3.4. Diagnostic Performance of Serum Erythropoietin in Differential Diagnosis of Polycythemia Vera and Secondary Erythrocytosis Using Different ‘Subnormal’ Limits
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | Healthy Donor (n = 393) | Polycythemia Vera (n = 41) | Secondary Erythrocytosis (n = 49) | p-Value (PV vs. SE) | p-Value (SE vs. HD) |
---|---|---|---|---|---|
Males, n (%) | 172 (43.8) | 23 (56.1) | 38 (77.6) | 0.031 | <0.001 |
Age, years, median (range) | 51 (19–77) | 56 (26–89) | 46 (18–74) | 0.001 | 0.020 |
Body mass index 1, kg/m2 | 23.7 (22.0–26.4) | 23.5 (21.4–26.4) | 26.8 (24.4–28.9) | 0.002 | <0.001 |
Systolic BP 1, mmHg | 122 (116–132) | 131 (124–145) | 136 (123–148) | 0.443 | <0.001 |
Diastolic BP 1, mmHg | 76 (69–82) | 89 (78–95) | 89 (82–98) | 0.192 | <0.001 |
Heart rate 1, /min | 74 (67–81) | 81 (75–89) | 86 (77–96) | 0.229 | <0.001 |
Smoking history, n (%) | |||||
Yes | 52 (13.2) | 5 (12.2) | 14 (28.6) | 0.003 | 0.001 |
No | 95 (24.2) | 15 (36.6) | 5 (10.2) | - | - |
Unknown | 246 (62.6) | 21 (51.2) | 30 (61.2) | - | - |
Comorbidities, n (%) | |||||
Hypertension | 54 (13.7) | 14 (34.1) | 16 (32.7) | - | - |
Diabetes Mellitus | 9 (2.3) | 4 (9.8) | 6 (12.2) | - | - |
Dyslipidemia | 44 (11.2) | 4 (9.8) | 5 (10.2) | - | - |
Pulmonary disease | 0 (0.0) | 0 (0.0) | 0 (0.0) | - | - |
Others | 16 (4.1) 2 | 7 (17.1) 3 | 5 (10.2) 4 | - | - |
None | 286 (72.8) | 18 (43.9) | 23 (46.9) | - | - |
Laboratory data, median (IQR) | |||||
Erythropoietin, IU/L | 10.1 (7.9–13.1) | 1.7 (1.1–3.0) | 7.0 (3.8–11.2) | <0.001 | <0.001 |
White blood cell, ×1000/μL | 5.89 (4.82–7.03) | 11.53 (9.88–13.77) | 7.35 (5.82–9.23) | <0.001 | <0.001 |
ANC, ×1000/μL | 3.20 (2.44–4.10) | 8.55 (6.73–10.79) | 4.55 (3.12–6.19) | <0.001 | <0.001 |
Hemoglobin, g/dL | 14.0 (13.2–15.2) | 18.7 (17.9–19.4) | 18.4 (17.6–18.7) | 0.102 | <0.001 |
Hematocrit, % | 42.1 (39.6–45.1) | 58.9 (54.2–61.8) | 53.7 (51.7–55.8) | <0.001 | <0.001 |
Platelet, ×1000/μL | 256 (226–292) | 515 (352–700) | 243 (204–288) | <0.001 | 0.201 |
Glucose, mg/dL | 96 (91–103) | 93 (87–103) | 100 (90–130) | 0.025 | 0.025 |
HbA1C, % | 5.5 (5.3–5.7) | 5.6 (5.4–6.2) | 6.4 (5.6–7.7) | 0.161 | 0.004 |
BUN, mg/dL | 13.2 (11.0–15.5) | 13.4 (10.9–16.0) | 12.8 (10.1–15.7) | 0.545 | 0.397 |
Creatinine, mg/dL | 0.73 (0.64–0.85) | 0.83 (0.72–0.94) | 0.91 (0.76–1.04) | 0.073 | <0.001 |
eGFR, mL/min/1.73 m2 | 101 (95–110) | 95 (81–103) | 99 (84–111) | 0.227 | 0.086 |
Total cholesterol, mg/dL | 199 (172–223) | 162 (141–182) | 191 (160–218) | <0.001 | 0.304 |
Triglyceride, mg/dL | 100 (69–149) | 101 (79–150) | 128 (82–168) | 0.307 | 0.035 |
C-reactive protein, mg/dL | NT | 0.07 (0.04–0.16) | 0.07 (0.04–0.15) | 0.972 | - |
Cutoff Value (IU/L) | Sensitivity, % (95% CI) | Specificity, % (95% CI) | PPV, % (95% CI) | NPV, % (95% CI) |
---|---|---|---|---|
3.1 * | 80.5 (65.1–91.2) | 87.8 (75.2–95.4) | 84.6 (71.9–92.2) | 84.3 (74.1–91.0) |
4.3 † | 92.7 (80.1–98.5) | 73.5 (58.9–85.1) | 74.5 (64.5–82.4) | 92.3 (79.9–97.3) |
5.3 ‡ | 97.6 (87.1–99.9) | 65.3 (50.4–78.3) | 70.2 (61.5–77.6) | 97.0 (82.0–99.6) |
7.0 § | 97.6 (87.1–99.9) | 46.9 (32.5–61.7) | 60.6 (54.1–66.8) | 95.8 (76.4–99.4) |
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Yoon, J.S.; Kang, H.; Jekarl, D.W.; Lee, S.-E.; Oh, E.-J. Diagnostic Performance of Serum Erythropoietin to Discriminate Polycythemia Vera from Secondary Erythrocytosis through Established Subnormal Limits. Diagnostics 2024, 14, 1902. https://doi.org/10.3390/diagnostics14171902
Yoon JS, Kang H, Jekarl DW, Lee S-E, Oh E-J. Diagnostic Performance of Serum Erythropoietin to Discriminate Polycythemia Vera from Secondary Erythrocytosis through Established Subnormal Limits. Diagnostics. 2024; 14(17):1902. https://doi.org/10.3390/diagnostics14171902
Chicago/Turabian StyleYoon, Ji Sang, Hyunhye Kang, Dong Wook Jekarl, Sung-Eun Lee, and Eun-Jee Oh. 2024. "Diagnostic Performance of Serum Erythropoietin to Discriminate Polycythemia Vera from Secondary Erythrocytosis through Established Subnormal Limits" Diagnostics 14, no. 17: 1902. https://doi.org/10.3390/diagnostics14171902