Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolytic anemia and thrombosis and is notoriously associated with aplastic anemia and myelodysplastic syndromes. Rarer associations include myeloproliferative neoplasms (MPNs), which are also burdened by increased thrombotic tendency. The therapeutic management of this rare combination has not been defined so far. Here, we describe a 62-year-old man who developed a highly hemolytic PNH more than 10 years after the diagnosis of MPN. The patient started eculizumab, obtaining good control of intravascular hemolysis but without amelioration of transfusion-dependent anemia. Moreover, we performed a review of the literature regarding the clinical and pathogenetic significance of the association of PNH and MPN. The prevalence of PNH clones in MPN patients is about 10%, mostly in association with JAK2V617F-positive myelofibrosis. Thrombotic events were a common clinical presentation (35% of subjects), sometimes refractory to combined treatment with cytoreductive agents, anticoagulants, and complement inhibitors. The latter showed only partial effectiveness in controlling hemolytic anemia and, due to the paucity of data, should be taken in consideration after a careful risk/benefit evaluation in this peculiar setting.
Highlights
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder caused by the somatic mutations of phosphatidylinositol glycan A (PIGA)
PNH has been described in the context of bone marrow failure (BMF) syndromes, namely, aplastic anemia (AA) and myelodysplastic syndrome (MDS) [4]
The disregarded association of these two conditions may cause a significant delay in PNH diagnosis, as observed in our case
Summary
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder caused by the somatic mutations of phosphatidylinositol glycan A (PIGA). A 62-year-old Caucasian male was diagnosed with Janus kinase (JAK)2-negative essential thrombocythemia (ET) in May 2007 due to isolated asymptomatic thrombocytosis (Table 1) His medical history was unremarkable, except for moderate arterial hypertension on regular treatment; no previous thrombotic events were registered. The patient became strongly symptomatic for anemia, requiring about 1–2 RBC units/month. BM biopsy confirmed increased age-adjusted cellularity, granulocytic hyperplasia, and numerous megakaryocytes in loose and dense clusters, including both mature and atypical, dystrophic cells; fibrosis was stable with diffuse increase in TABLE 1 | Laboratory parameters at different time points of the clinical history of the patient. ET, essential thrombocythemia; MF, myelofibrosis; PNH, paroxysmal nocturnal hemoglobinuria; ECU, eculizumab; Hb, hemoglobin; PLT, platelet; WBC, white blood cell; LDH, lactate dehydrogenase; ULN, upper limit of normal; UB, unconjugated bilirubin; Retics, reticulocytes. The patient is continuing regular fortnightly eculizumab infusions, with subjective benefit, with persistent transfusion dependence
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