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

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.
Competing Interests: Jun Ho Jang has no conflicts of interest to declare. Jin Seok Kim has received fees from Alexion, AstraZeneca Rare Disease. Cindy Thiow Koon Lim is an employee of IQVIA. Nora J. Kleinman is an employee of IQVIA. Karl-Johan Myren is an employee of and shareholder in Alexion, AstraZeneca Rare Disease. Alice Wang was an employee of and shareholder in Alexion, AstraZeneca Rare Disease at the time of study completion. Yogesh Patel is an employee of and shareholder in Alexion, AstraZeneca Rare Disease. Jong Wook Lee has received grants and fees from Alexion, AstraZeneca Rare Disease, and has served as a member of an advisory board for Alexion, AstraZeneca Rare Disease.
(© 2024 The Korean Academy of Medical Sciences.)