Supervisors info:
Κοκόρη Στυλιανή, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Βαλσάμη Σερένα, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Γαβριηλάκη Ελένη, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΑΠΘ
Summary:
Paroxysmal nocturnal hemoglobinuria (PNH) or Marchiafava-Micheli Syndrome is a rare acquired clonal disorder of hematopoietic stem cell that manifests with hemolytic anemia, bonne marrow failure and thrombosis. PNH is related to a somatic mutation in the phosphatydilinositol glycan class A (PIG-A), X-linked gene, responsible for a deficiency in glycosylphosphatidylinositol- anchored proteins (GPI-Aps). The absence of GPI-Aps complement regulatory proteins CD55 and CD59 leads to hemolysis. PNH is classified in three variants by the International PNH Interest Group: The Classic PNH, one form predominantly hemolytic without overt marrow failure, the PNH in the setting of another bone marrow failure syndrome (myelodysplastic syndrome, aplastic anemia or primary myelofibrosis) and the Subclinical PNH, a very mild disease with almost no symptoms. Patients may present with a variety of clinical manifestations, such as anemia, thrombosis, smooth muscle dystonia, extreme fatigue, abdominal pain, dyspnea, kidney disease and hypercoagulability. The delay of diagnosis of PNH increases the risk of mortality and morbidity. Thrombosis in PNH may occur at any site. However, venous thrombosis is more common than arterial. The laboratory findings of PNH include high levels of dehydrogenase (LDH), bilirubin and reticulocytes. Furthermore, patients with PNH have low levels of hemoglobin and haptoglobin. They also suffer from cytopenias such as leucopenia and neutropenia. Nowadays, the diagnosis of PNH is based on flow cytometry analysis (FCM). FLAER (fluorescently labeled aerolysin) is a more sensitive than FCM quantification of antibody binding to CD59. In the past, laboratory diagnosis was including the Sucrose hemolysis test, the Ham test and the Gel card test. Treatment of PNH is mainly supportive consisting of transfusion therapy, anticoagulation or hematopoietic stem cell transplantation. Since 2007, terminal complement inhibitors (C5), such as eculizumab and ravulizumab have revolutionized the treatment of this disease. However, patients treated with these inhibitors can still experience anemia because of C3-mediated extravascular hemolysis. Proximal complement inhibitors (C3), which are only just beginning to emerge, have the potential to address this problem by targeting components of the pathway upstream of C5, thereby protecting patients against both intra- and extravascular hemolysis.
Keywords:
Lactate dehydrogenase, Reticulocytes, Haptoglobin, PNH clone size, Flow cytometry
