Between 2000 and 2010, a total of 28 patients were tested for PNH using flow cytometry in our department, of whom 22 were found to have the disease. Venous thrombosis was described in five of 16 patients with symptomatic disease (31 %). This is comparable with other datasets, in which 33 – 50 % of patients were found to have thrombosis (5, 7), as were three of the nine patients in our previous study (9). Two patients with PNH were diagnosed with chronic myeloproliferative disease (myelofibrosis). PNH associated with chronic myeloproliferative disease is rare, but has been described previously (17).
PNH itself is a rare disease. Despite centralised diagnosis and treatment at a regional level, our dataset is small and firm conclusions cannot be drawn. Our main aim is to remind others of the disease so that as many patients as possible can be identified.
Whereas nine patients with suspected PNH were referred to the Department of Haematology, Oslo University Hospital in the 20 years prior to 2001 (9), in the course of a decade (2000 – 2010) we received samples from 28 patients and detected PNH clones in 22 of them. The threshold for requesting PNH analysis has probably become lower, and flow cytometry is far more sensitive than Ham’s test (11). Nevertheless, it is surprising that so many patients (79 %) tested positive. This may be an indication that too few tests are being requested because PNH is rarely suspected.
Since 2010, flow cytometry-based diagnosis of PNH has been improved further by combining even more antibodies with FLAER, a fluorochrome-conjugated (Alexa 488) non-lysing mutated proaerolysin, which binds specifically to GPI in the cell membrane (12).
Only six patients were treated with eculizumab, a monoclonal antibody against complement factor C5. In three patients, the drug probably contributed to improvement, in the other three further treatment was not possible because eculizumab was no longer indicated. It is a weakness of the study that we do not have long-term follow-up data from more patients who have been treated with eculizumab.
New and better methods for the diagnosis and treatment of PNH have improved the prognosis for this population (15). The Norwegian guidelines for diagnosis and treatment of PNH have recently been updated (16), and devote significant space to the use of eculizumab. International studies show that the drug reduces transfusion requirements and improves life expectancy among the most severely affected, and is also well tolerated (14, 15).
C5 deficiency is associated with increased risk of meningitis (Neisseria meningitidis) (18). Patients who are to receive eculizumab should therefore be vaccinated against meningococcal disease before the start of treatment. They should also be given phenoxymethylpenicillin for self-treatment and/or a safety information card stating that they should be treated without delay on suspicion of meningococcal disease (19). In Norway, eculizumab is indicated for symptomatic PNH (classic and secondary) with anaemia-related fatigue that impairs social functioning, frequent episodes of abdominal pain, thromboembolism and organ involvement (16).
Pregnancy in these patients entails a high risk of complications for both mother and foetus. Treatment of pregnant women with eculizumab has shown promising results (20). Monitoring of these patients requires close collaboration between the haematologist and specialists in foetal medicine with specific experience.
We have previously called for increased awareness of PNH with direct antiglobulin test (DAT)-negative haemolytic anaemias, aplastic anaemia and Budd-Chiari syndrome of unknown aetiology (9). In our dataset, aplastic anaemia/myelodysplastic syndrome with or without haemolysis was the indication for flow cytometric analysis in 18 of 28 patients, showing that previous efforts probably have contributed to increased awareness of the disease. We continue to urge general practitioners, specialists in internal medicine and haematologists to keep this condition in mind. Although PNH is very rare, and knowledge and experience of it is limited among health professionals, it is important to be aware of the disease because correct treatment improves survival (15). Moreover, the presence of a PNH clone predicts a favourable response to immunosuppressive therapy in aplastic anaemia (21).
More sensitive diagnostic methods that also reveal secondary/subclinical PNH associated with bone marrow disease have transformed the previous view of the disease as a relatively benign condition (9). The dataset presented here illustrates that this is a serious disease, as larger datasets have shown (5), but also a condition with extensive variation in symptoms and severity.