The long-term monitoring of patients with paroxysmal nocturnal hemoglobinuria (PNH) depends on patient- and disease-related factors, such as the patient’s presentation, clone size, and receipt of anticomplement therapy. Special monitoring situations to consider include bone marrow failure syndrome, hemolytic PNH, and pregnancy.

Long-term monitoring in PNH varies among patients, depending on the presentation, clone size, and whether they are on anticomplement therapy. In general, I assess the patient’s symptoms, particularly fatigue, both qualitatively and quantitatively via the patient interview, a 0 to 10 scale, and blood work, including a complete blood count, kidney function tests, bilirubin, lactate dehydrogenase (LDH), complement assay, and flow cytometry to check clone size. Intermittently, I order additional tests, such as an iron panel to assess for iron deficiency anemia and a D-dimer test to assess whether the coagulation system is activated. Additionally, I educate the patient on PNH symptoms and how we work to decrease the risk of thrombosis, infections, and breakthrough hemolysis.

If the clone size is small (ie, <10%), anticomplement therapy usually is not needed, and I will follow up with the patient every 6 months. Patients with PNH who are initiating anticomplement therapy receive vaccinations and antibiotics against encapsulated bacteria, in addition to having more frequent visits. As the patient stabilizes, the frequency of visits decreases to every 3 months or so, and I will recheck clone size once or twice per year.

Some special monitoring situations include bone marrow failure syndrome and hemolytic PNH. For patients with PNH in the context of bone marrow failure syndrome, we monitor more for the bone marrow failure syndrome than for the PNH because the clone tends to be quite small. More important, I think, is monitoring patients with hemolytic PNH. These individuals are almost always on anticomplement therapy. Initially, when they start therapy, they need to be monitored every week. Some of them will have had a thrombotic event, and we will need to ensure that their anticoagulation is appropriate.

Another special monitoring situation is pregnancy. Right now, the only treatment data that we have are with eculizumab. So, a female patient who is planning to become pregnant should be on eculizumab. In the second and third trimesters, I tend to check complement assays frequently because, as the blood volume expands, we need to be sure that we are giving enough of the drug to inhibit complement. In the second trimester, I check every month; in the third trimester, I check every 2 weeks or so. All patients who are pregnant will be on heparin during pregnancy, especially in the third trimester, and for at least 6 weeks after pregnancy because of the risk of thrombosis.

When considering patients who are on complement inhibitors in general, for those whose hemoglobin does not improve and whose reticulocyte counts and bilirubin levels remain elevated, I do additional testing, such as a direct Coombs test. This test is negative in PNH, so a positive test, along with continued anemia, a high reticulocyte count, high bilirubin, reasonably well-controlled LDH, and a suppressed complement assay, are suggestive of extravascular hemolysis and a need to switch from a C5 inhibitor to a proximal inhibitor.

Before a patient who is receiving a C5 inhibitor is due for their next visit and dose of therapy, I check the 50% hemolytic complement (CH50) assay to determine if we are optimally inhibiting complement. If the CH50 is undetectable, we have good control of complement, and any residual anemia is not due to a breakthrough hemolytic event but is instead probably due to some other reason. Those with undetectable CH50 will not benefit from increasing the dose of the C5 inhibitor because we have maximized the drug’s therapeutic benefit. Similarly, for patients who are on a proximal inhibitor such as pegcetacoplan, iptacopan, or danicopan, I check the alternative complement (AH50) assay. Lastly, for patients who are taking iptacopan or danicopan, checking a lipid panel every 6 months or so is recommended because of the risk of hyperlipidemia.