PNH

 When to suspect PNH?

- unexplained cytopenias

-unusual site thrombosis

-Coomb's neg hemolytic anemia

- smooth muscle dystonia--> abd pain, renal dysfunction, erectile dysfunction, pulm HTN

Investigations: Flow cytometry for CD55 and CD59. bmbx to rule out AA, MDS and bone marrow failure. If only hemolytic anemia, bmbx may not be needed. However if low WBC or plt, do a bmbx.

Classical PNH- only hemolysis, no bone marrow failure

PNH with bone marrow failure

Subclinical PNH- mild hemolysis,PNH clone < 20%

Treatment

1. C5 inhibitors: For symptomatic PNH- Ravulizumab q 8 weeks. Rav is also approved for children over 1 month.

Other C5i eculizumab ( IV q 2 weeks on maintenance) and crovalimab ( s/c) weekly for first month, then q 4 weeks.

Available through REMS program.

2.  Alternative pathway inhibitors: Iptacopan ( oral) pegcetacopan ( sub cut).  Can be used for those who have persistent or breakthrough hemolysis on eculizumab not responding to increased frequency of administration.

Can be used upfront. Avoid in those with hx of thrombosis, or excess ETOH use.

Complement-amplifying conditions, such as infection, surgery, vaccinations, or excessive alcohol consumption can worsen hemolysis when on alternative pathway inhibitors.

Danicopan--> alternative pathway inhibitor of factor D. Oral agent. Prescribe if someone on C5i has significant extravascular hemolysis.

Picture ASH Feb 2025