Treatment

Treatment is largely symptomatic:

• red cell transfusions for anaemia
• iron for iron deficiency
• platelet transfusions for thrombocytopenia
• anticoagulants for thromboses
  • long-term anticoagulation with a target INR of 2·5 is recommended for patients with large PNH clones (PNH granulocytes >50%) and a platelet count greater than 100 × 10^9/l
  • anticoagulation can also be considered for patients with smaller clones and platelet counts less than 100 × 10^9/l dependent on additional risk factors for thrombosis and bleeding

Severe cases may require bone marrow transplantation.

NICE state that (2):

• ravulizumab is recommended, within its marketing authorisation, as an option for treating paroxysmal nocturnal haemoglobinuria in adults:
  • with haemolysis with clinical symptoms suggesting high disease activity, or
  • whose disease is clinically stable after having eculizumab for at least 6 months

NICE state that (3):

• iptacopan is recommended, within its marketing authorisation, as an option for treating paroxysmal nocturnal haemoglobinuria (PNH) in adults with haemolytic anaemia
• the NICE committee stated that:
  • "...Evidence from clinical trials shows that iptacopan increases the level of haemoglobin in the blood and reduces the need for blood transfusions. For people who have not had a C5 inhibitor, an indirect comparison suggests that iptacopan is more effective than eculizumab and ravulizumab, but these results are uncertain.For people who still have anaemia after having a C5 inhibitor, clinical trial evidence shows that iptacopan is more effective than eculizumab and ravulizumab. An indirect treatment comparison suggests that iptacopan is more effective than pegcetacoplan, but the results are uncertain..."

Splenectomy is of little value

Notes (4):

• eculizumab, which is indicated to treat patients with paroxysmal nocturnal hemoglobinuria (PNH), is a life-changing, life-saving therapy that decreases intravascular hemolysis and thrombosis and improves survival.
• some eculizumab-treated patients, however, experience breakthrough hemolysis; and overall, the burden of the treatment schedule (intravenous infusions every 2 weeks) is substantial
• ravulizumab is a long-acting, second-generation complement component 5 (C5) inhibitor that is administered intravenously every 8 week
• ravulizumab has been shown to be as safe and efficacious as eculizumab, to be associated numerically with lower rates of breakthrough hemolysis (p for non-inferiority <0.0004), and to be preferred over eculizumab by most patients
• ravulizumab is likely to replace eculizumab as the first-line treatment for PNH both in patients who are naive to eculizumab treatment and in patients who are clinically stable on eculizumab

Reference:

1. Baglin TP et al. the British Committee for Standards in Haematology (2006) Guidelines on oral anticoagulation (warfarin): third edition - 2005 update British Journal of Haematology 2006; 132 (3): 277-285.
2. NICE (May 19th 2021). Ravulizumab for treating paroxysmal nocturnal haemoglobinuria
3. NICE (September 2024). Iptacopan for treating paroxysmal nocturnal haemoglobinuria
4. Lee JW, Kulasekararaj AG. Ravulizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Expert Opin Biol Ther. 2020 Mar;20(3):227-237