J Korean Med Sci.  2024 Mar;39(8):e81. 10.3346/jkms.2024.39.e81.

Impact of Lactate Dehydrogenase and Hemoglobin Levels on Clinical Outcomes in Patients With Paroxysmal Nocturnal Hemoglobinuria: Results From the National Korean PNH Registry

• Jang JH
• Kim JS
• Lim CTK
• Kleinman NJ
• Myren KJ
• Wang A
• Patel Y
• Lee JW

• KMID: 2553330
• DOI: http://doi.org/10.3346/jkms.2024.39.e81

Abstract

Background
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder caused by uncontrolled terminal complement activation, which leads to intravascular hemolysis (IVH), thromboembolism (TE), renal failure, and premature mortality.
Methods
We performed a secondary analysis of data collected from patients enrolled in the Korean National PNH Registry to assess the relative importance of risk factors, specifically lactate dehydrogenase (LDH) and hemoglobin (Hb), in predicting the incidence of TE, impaired renal function, and death in complement inhibitor-naïve patients with PNH.
Results
Multivariate regression modeling indicated that LDH ≥ 1.5 × upper limit of normal (ULN), male sex, and pain were associated with increased risk of TE (P = 0.016, 0.045, and 0.033, respectively), hemoglobinuria and pain were associated with an increased risk of impaired renal function (P = 0.034 and 0.022, respectively), and TE was associated with an increased incidence of death (P < 0.001). Hb < 8 g/dL was not a predictor of TE, impaired renal function, or death in multivariate regression analyses. Standardized mortality ratio analysis indicated that LDH ≥ 1.5 × ULN (P < 0.001), Hb < 8 g/dL (P < 0.001), and Hb ≥ 8 g/dL (P = 0.004) were all risk factors for death; in contrast, patients with LDH < 1.5 × ULN had similar mortality to the general population.
Conclusion
In complement inhibitor-naïve patients with PNH, LDH ≥ 1.5 × ULN was a significant predictor of TE, and TE was a significant predictor of death. Hb was not a significant predictor of TE, impaired renal function, or death. Therefore, controlling IVH will improve clinical outcomes for patients with PNH.

Keyword

Paroxysmal Nocturnal Hemoglobinuria; Anemia; Hemolysis; Mortality

Figure

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  Fig. 1 Signs and symptoms related to paroxysmal nocturnal hemoglobinuria and clinical outcomes stratified by levels of (A) LDH and (B) Hb.Hb = hemoglobin, LDH = lactate dehydrogenase, TE = thromboembolism, ULN = upper limit of normal.*P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001.

• 

  Fig. 2 SMR of the PNH population compared with age- and sex-matched general Korean population.a CI = confidence interval, Hb = hemoglobin, LDH = lactate dehydrogenase, PNH = paroxysmal nocturnal hemoglobinuria, SMR = standardized mortality ratio, TE = thromboembolism, ULN = upper limit of normal.aPatients with missing age/sex are excluded from calculation of SMR (nine patients).bOne patient with TE had missing age/sex.cOne patient with impaired renal function had missing age/sex.dThree patients with classic PNH and six patients with PNH-cytopenia had missing age/sex.*P ≤ 0.01, **P ≤ 0.001.

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