Paroxysmal nocturnal hemoglobinuria: Diagnosis and management protocol

Al-Momen, Abdul Kareem; Bakistani, Abdul Ghani Al; Alsaeed, Ahmad; Olama, Asma Al; Hejazi, Ayman; Awarji, Christian; Almhareb, Fahed; Alsayegh, Faisal; Alzahrani, Hazzaa; Almarashly, Mahmoud; Qari, Mohammed H.; Aslam, Mohammad; Seliem, Rania M.; Kindi, Salam Al; Abuharbesh, Saud; Owaidah, Tarek; Bassuni, Wafaa

doi:10.4103/1658-5127.137081

Cited by 2 publications

(3 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In clinical practice, patients treated with eculizumab who had experienced BTH due to suboptimal C5‐inhibition (ranging from 11% to 27%) have been successfully managed by adjusting either the dosage or frequency of maintenance doses to achieve and maintain efficacy of treatment, adjustments that may differ from the approved regimen 20–24 . As shown in these clinical studies, the overall incidence of BTH (defined as one or more new or worsening signs or symptoms of intravascular haemolysis in the presence of LDH ≥2 × ULN after prior reduction of LDH to <1·5 × ULN on treatment) 5 observed with ravulizumab in Study 301 [4·0% of ravulizumab patients vs. 10·7% of eculizumab patients, between‐group difference [95% confidence interval (CI), −6·7% (−14·21, 0·180; P inf <0·0001], 5 and Study 302 [0% of ravulizumab patients vs. 5·1% of eculizumab patients, between‐group difference (95% CI) 5·1% (−8·89, 18·99); P inf <0·0004] 4 showed non‐inferiority between treatment groups.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised, multicentre studies

et al. 2020

View full text Add to dashboard Cite

Ravulizumab, a novel long‐acting complement component 5 (C5) inhibitor administered every 8 weeks (q8w), was non‐inferior to eculizumab for all efficacy outcomes in two randomised, open‐label, phase 3 trials in C5 inhibitor‐naïve (Study 301) and eculizumab‐experienced (Study 302) adult patients with paroxysmal nocturnal haemoglobinuria (PNH). This pre‐specified analysis characterised ravulizumab pharmacokinetics (PK), pharmacodynamics (PD; free C5 levels), and PD differences between medications (Study 301, n = 246; Study 302, n = 195). Ravulizumab PK parameters were determined using non‐compartmental analysis. Serum free C5 was quantified with a Gyros‐based fluorescence assay (ravulizumab) and an electrochemiluminescence ligand‐binding assay (eculizumab). Ravulizumab PK parameters were numerically comparable in both studies; the median time to maximum concentrations ranged from 2·3 to 2·8 and 2·3 to 2·6 h in studies 301 and 302, respectively. Ravulizumab steady‐state serum concentrations were achieved immediately after the first dose and sustained throughout treatment. For ravulizumab, the mean (SD) post hoc terminal elimination half‐life was 49·7 (8·9) days. Serum free C5 concentrations <0·5 µg/ml were achieved after the first ravulizumab dose and sustained throughout treatment in both studies. In a minority of patients, free C5 concentrations <0·5 µg/ml were not consistently achieved with eculizumab in either study. Ravulizumab q8w was more consistent in providing immediate, complete, sustained C5 inhibition than eculizumab every‐2‐weeks in patients with PNH.

show abstract

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised, multicentre studies

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The classical presentation is intravascular haemolysis accompanied by unusual site thrombosis or smooth muscle dystonia in the form of abdominal pain, oesophageal spasm, or erectile dysfunction. The other two categories are subclinical PNH and PNH in the context of marrow failure syndrome, including aplastic anaemia (AA) and myelodysplastic syndrome (MDS) [ 1 , 4 ].…”

Section: Discussionmentioning

confidence: 99%

“…There is an intimate overlap between aplastic anaemia and PNH, with 40–60% of patients with aplastic anaemia having a PNH clone. However, there is an anecdotal report about a similar overlap between PNH and other marrow disorders [ 1 , 2 ]. We report a case of primary myelofibrosis (PMF) with concomitant subtle PNH predicted by the presence of new-onset erectile dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Primary myelofibrosis with concurrent paroxysmal nocturnal haemoglobinuria presenting with erectile dysfunction

Alsalman

Albesher

et al. 2022

Oxford Medical Case Reports

View full text Add to dashboard Cite

Primary myelofibrosis and paroxysmal nocturnal haemoglobinuria (PNH) are uncommon clonal blood disorders that are rarely found together. We report a case of primary myelofibrosis (PMF) with concomitant subtle PNH in a 42-year-old man who presented with a 4-week history of fatigue, unexplained chest pain, and new-onset erectile dysfunction. Bone marrow biopsy showed severe fibrosis consistent with PMF. However, smooth muscle dystonia symptoms in the form of new-onset erectile dysfunction and oesophageal spasm were not fully explained by PMF but were clues for PNH, confirmed by flow cytometric assays. Routine PNH testing for patients with new-onset PMF and clinical symptoms suggestive of PNH, as well as those with refractory anaemia despite effective therapy, is crucial since these two conditions can coexist. As a result, a lack of early testing may cause a delay in diagnosis, increasing the patient’s transfusion load and the facility’s costs.

show abstract

Paroxysmal nocturnal hemoglobinuria: Diagnosis and management protocol

Cited by 2 publications

References 2 publications

Pharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised, multicentre studies

Pharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised, multicentre studies

Primary myelofibrosis with concurrent paroxysmal nocturnal haemoglobinuria presenting with erectile dysfunction

Contact Info

Product

Resources

About