J Korean Med Sci.  2016 Feb;31(2):214-221. 10.3346/jkms.2016.31.2.214.

Predictive Factors of Mortality in Population of Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH): Results from a Korean PNH Registry

• Jang JH
• Kim JS
• Yoon SS
• Lee JH
• Kim YK
• Jo DY
• Chung J
• Sohn SK
• Lee JW

• KMID: 2360045
• DOI: http://doi.org/10.3346/jkms.2016.31.2.214

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive, systemic, life-threatening disease, characterized by chronic uncontrolled complement activation. A retrospective analysis of 301 Korean PNH patients who had not received eculizumab was performed to systematically identify the clinical symptoms and signs predictive of mortality. PNH patients with hemolysis (lactate dehydrogenase [LDH] > or = 1.5 x the upper limit of normal [ULN]) have a 4.8-fold higher mortality rate compared with the age- and sex-matched general population (P < 0.001). In contrast, patients with LDH < 1.5 x ULN have a similar mortality rate as the general population (P = 0.824). Thromboembolism (TE) (odds ratio [OR] 7.11; 95% confidence interval [CI] (3.052-16.562), renal impairment (OR, 2.953; 95% CI, 1.116-7.818) and PNH-cytopenia (OR, 2.547; 95% CI, 1.159-5.597) are independent risk factors for mortality, with mortality rates 14-fold (P < 0.001), 8-fold (P < 0.001), and 6.2-fold (P < 0.001) greater than that of the age- and sex-matched general population, respectively. The combination of hemolysis and 1 or more of the clinical symptoms such as abdominal pain, chest pain, or dyspnea, resulted in a much greater increased mortality rate when compared with patients with just the individual symptom alone or just hemolysis. Early identification of risk factors related to mortality is crucial for the management of PNH. This trial was registered at www.clinicaltrials.gov as NCT01224483.

Keyword

Paroxysmal Nocturnal Hemoglobinuria; PNH; Risk Factors; Mortality

MeSH Terms

Adolescent
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal/therapeutic use
Antibodies, Monoclonal, Humanized/therapeutic use
Area Under Curve
Child
Dyspnea/etiology
Female
Hemoglobinuria, Paroxysmal/*diagnosis/drug therapy/mortality
Hemolysis
Humans
Kaplan-Meier Estimate
Kidney Diseases/complications/diagnosis
L-Lactate Dehydrogenase/metabolism
Male
Middle Aged
Odds Ratio
ROC Curve
Registries
Republic of Korea
Retrospective Studies
Risk Factors
Thromboembolism/complications/diagnosis
Young Adult
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
L-Lactate Dehydrogenase

Figure

• 

  Fig. 1 Impact of LDH in PNH patients. (A) Receiver operating characteristic curve of LDH cutoff for mortality, (B) Logistic regression analysis of the association of LDH ≥ 1.5, ≥ 3.0× and ≥ 5.0× ULN at diagnosis and mortality.

• 

  Fig. 2 Kaplan-Meier survival of PNH patients compared with age- and gender-matched general population. (A) Patients with TE had a 14-fold higher mortality rate compared with the general population (standard mortality ratio [SMR]=13.9; 95% confidence interval [CI], 8.2-19.6; P < 0.001). (B) Patients with cytopenia had a mortality rate 6.2-fold greater than the age- and gender-matched general population (SMR=6.2; 95% CI, 4.7-9.3; P < 0.001). (C) Patients with impaired renal function (IRF) had a mortality rate 7.8-fold greater than the age- and gender-matched general population (SMR=7.8; 95% CI, 3.9-11.8; P < 0.001). (D) PNH patients with lactate dehydrogenase (LDH) ≥1.5 times the upper limit of normal (ULN) had a 5.0-fold greater risk for mortality compared with patients with LDH <1.5×ULN (95% CI, 1.15-21.70; P = 0.009). PNH patients with LDH ≥1.5×ULN had a 4.8-fold higher mortality rate compared with the general population (SMR=4.8; 95% CI, 3.0-6.6; P < 0.001).

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