Treatment and prognosis of paroxysmal nocturnal hemoglobinuria
- Robert A Brodsky, MD
Robert A Brodsky, MD
- Professor of Medicine and Oncology
- Johns Hopkins University
Therapy for paroxysmal nocturnal hemoglobinuria (PNH) is evolving rapidly, spurred by the availability of biologic therapies that target the underlying hemolytic defect or the abnormal hematopoietic stem cell. However, many questions remain regarding when to initiate these costly therapies and how to balance therapy for symptoms of hemolysis with therapy for bone marrow failure.
This topic review will discuss the treatment and prognosis of PNH. The pathogenesis, clinical manifestations, and diagnosis of PNH are presented separately. (See "Pathogenesis of paroxysmal nocturnal hemoglobinuria" and "Clinical manifestations and diagnosis of paroxysmal nocturnal hemoglobinuria".)
INITIAL EVALUATION AND MONITORING
Baseline evaluations of the newly diagnosed patient — A newly-diagnosed patient may already have laboratory results available that show the degree of hemolysis and the size of the PNH clone. We review all available records to confirm the diagnosis and the presence or absence of an additional bone marrow disorder such as aplastic anemia (AA) or myelodysplastic syndrome (MDS). (See "Clinical manifestations and diagnosis of paroxysmal nocturnal hemoglobinuria", section on 'Diagnostic evaluation'.)
If not obtained as part of the initial diagnostic evaluation, all patients should have baseline testing that includes a complete blood count (CBC) with differential, reticulocyte count, lactate dehydrogenase (LDH), biochemical profile, and flow cytometry for PNH. We also obtain iron studies (serum iron, total iron binding capacity, and ferritin) and a D-dimer level.
Patients with significant pancytopenia and suspected AA or MDS should have an examination of a bone marrow aspirate and biopsy, including cytogenetic studies, a fluorescence in situ hybridization panel for MDS, a quantitative CD34 cell count, and an iron stain. (See "Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis", section on 'Bone marrow examination' and "Clinical manifestations and diagnosis of the myelodysplastic syndromes", section on 'Bone marrow aspirate and biopsy'.)
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- INITIAL EVALUATION AND MONITORING
- Baseline evaluations of the newly diagnosed patient
- Monitoring of the established patient
- OVERVIEW OF APPROACH TO THERAPY
- PAIN FROM SMOOTH MUSCLE DYSTONIA
- Evaluation for thrombosis
- Management of thrombosis
- Prevention of thrombosis
- ANTI-COMPLEMENT THERAPY
- Indications for anti-complement therapy
- Available anticomplement therapies
- - Eculizumab
- Prevention and treatment of meningococcal infection
- Other toxicities and cost
- Anti-complement therapies in development
- HEMATOPOIETIC CELL TRANSPLANTATION
- Conditioning regimen and stem cell product
- SPECIAL POPULATIONS
- Oral contraceptives
- SUMMARY AND RECOMMENDATIONS