treatment

Last edited 03/2022 and last reviewed 03/2022

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):

• pegcetacoplan is recommended, within its marketing authorisation, as an option for treating paroxysmal nocturnal haemoglobinuria (PNH) in adults who have anaemia after at least 3 months of treatment with a C5 inhibitor
• the NICE committee note that "...Current treatments for PNH include C5 inhibitors such as eculizumab and ravulizumab. Some people still experience anaemia and symptoms of PNH while having these treatments. Clinical trial evidence suggests that pegcetacoplan improves haemoglobin levels (a measure of anaemia) and haematological symptoms of PNH for people who have anaemia while taking eculizumab. Pegcetacoplan is likely to have the same clinical benefits for people who have anaemia while taking ravulizumab, because ravulizumab is very similar to eculizumab...For adults with anaemia while having a C5 inhibitor, pegcetacoplan is more effective and costs less than ravulizumab and eculizumab..."

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 (March 2022). Pegcetacoplan 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