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Clinical Investigations: CARDIOLOGY |

Evaluation of Intravascular Hemolysis With Erythrocyte Creatine in Patients With Cardiac Valve Prostheses*

Toshika Okumiya, PhD; Mitsuko Ishikawa-Nishi; Tadafumi Doi; Mikio Kamioka, MD; Hiroaki Takeuchi, PhD; Yoshinori Doi, MD; Tetsuro Sugiura, MD, FCCP
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*From the Department of Laboratory Medicine (Drs. Okumiya, Kamioka, Sugiura, Ms. Ishikawa-Nishi, and Mr. T. Doi) and Geriatric Medicine (Dr. Y. Doi), Faculty of Medicine, Kochi Medical School, Nankoku; and the Department of Laboratory Sciences (Dr. Takeuchi), Yamaguchi University School of Medicine, Ube, Japan.

Correspondence to: Toshika Okumiya, PhD, Department of Laboratory Medicine, Faculty of Medicine, Kochi Medical School, Oko-cho, Nankoku, Kochi 783-8505, Japan; e-mail: okumiyat@med.kochi-u.ac.jp



Chest. 2004;125(6):2115-2120. doi:10.1378/chest.125.6.2115
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Study objectives: To detect intravascular hemolysis in patients with cardiac valve prostheses. Erythrocyte creatine, a marker of erythrocyte age that increases with shortening erythrocyte survival, was evaluated with other hemolytic markers and hemodynamic parameters.

Design: Prospective study.

Patients and measurements: Erythrocyte creatine was enzymatically assayed in 33 patients with prosthetic valves, including 15 patients with aortic valve replacement, 13 patients with mitral valve replacement, and 5 patients with double-valve (aortic and mitral) replacement, and 33 control subjects. Blood flow velocity and valvular regurgitation were determined by Doppler echocardiography. Other hemolytic markers (lactate dehydrogenase [LDH], reticulocyte count, and haptoglobin) and cardiac muscle markers (myoglobin and myosin light chain 1) were also measured.

Results: Erythrocyte creatine and LDH levels were significantly higher (p < 0.0001) and the haptoglobin level was lower (p < 0.0001) in patients with a prosthetic valve as compared with control subjects. However, there were no significant differences in these markers between those with (n = 17) and without (n = 16) regurgitation. Patients with high erythrocyte creatine levels (> 1.8 μmol/g hemoglobin) exhibited significantly higher total peak flow velocity (sum of peak flow velocities at mitral and aortic valves) than those with normal erythrocyte creatine levels (p = 0.006). Erythrocyte creatine had a significant correlation with total peak flow velocity (r = 0.64, p < 0.0001), but LDH and haptoglobin had no significant correlation with total peak flow velocity. Patients with high LDH levels (> 460 IU/L) showed significantly higher myoglobin (p = 0.008) and myosin light chain 1 (p = 0.02) than those with normal LDH levels, whereas erythrocyte creatine was not related to cardiac muscle markers.

Conclusions: Erythrocyte creatine is a quantitative and reliable marker for intravascular hemolysis in patients with prosthetic valves. Mild hemolysis is ascribable to valvular flow velocity rather than regurgitation.

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