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

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] ≥ 1.5 × 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 × 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.

Eculizumab in paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome: 10‐year pharmacovigilance analysis

“…In the only double‐blind, randomised, placebo‐controlled trial of eculizumab in 87 patients with PNH (Hillmen et al , ), serious nonmeningococcal infections were reported in similar proportions of eculizumab‐treated and untreated patients with PNH (2% vs. 6%, respectively). Outside of the clinical trial programme, severe infections have been reported in up to 18% (Nishimura et al , ) and were identified as the cause of death in 25–40% of mortalities reported in untreated patients with PNH (Jang et al , ; Yu et al , ). Infections have been identified as precipitating events in patients with aHUS (Noris et al , ; Schifferli et al , ; Geerdink et al , ; Fremeaux‐Bacchi et al , ; Campistol et al , ); it is important to note that immunosuppression may play a role in these infections because many aHUS patients receive dialysis or renal transplantation (Noris et al , ; Schifferli et al , ; Geerdink et al , ; Fremeaux‐Bacchi et al , ; Lok & Foley, ; Campistol et al , ).…”

“…Paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS) are rare, chronic, diseases that may be life‐threatening without treatment (Brodsky, ; Jang et al , ; Loschi et al , ; Fakhouri et al , ). Both diseases are caused by uncontrolled complement activation, resulting in intravascular haemolysis in PNH and systemic thrombotic microangiopathy (TMA) in aHUS (Noris & Remuzzi, ; Brodsky, ).…”

Clinical benefit of eculizumab in patients with no transfusion history in the International Paroxysmal Nocturnal Haemoglobinuria Registry

“…This is an important finding as several studies have identified LDH ≥ 1.5 × ULN as an independent prognostic factor in PNH. 3,20 Clinical symptoms, such as those that define HDA, further aggravate this negative prognostic predictor.…”

Outcomes of allogeneic stem cell transplantation in patients with paroxysmal nocturnal hemoglobinuria with or without aplastic anemia

“…1 The clinical manifestations of PNH are thromboembolism (TE) driven by intravascular hemolysis and bone marrow (BM) failure. [2][3][4][5][6] Although eculizumab, a humanized monoclonal antibody directed against complement component C5, has been increasingly used to control intravascular hemolysis in patients with hemolytic PNH, this treatment does not improve BM failure. 7,8 Moreover, patients with PNH frequently exhibit an element of BM failure such as aplastic anemia (AA), 5,9 and about half of all patients with AA have been found to have a detectable population of PNH clones.…”