From the Guidelines
The initial screening process for paroxysmal nocturnal hemoglobinuria (PNH) should include a comprehensive diagnostic work-up, with paroxysmal nocturnal hemoglobinuria screening being a crucial component, as recommended by the American Society of Clinical Oncology clinical practice guideline 1. When suspecting PNH, the diagnostic work-up should encompass a range of tests, including:
- History and physical examination, with special consideration of new drugs and insect, spider, or snake bites
- Blood chemistry, complete blood count (CBC) with evidence of anemia, macrocytosis, and evidence of hemolysis on peripheral smear
- LDH, haptoglobin, bilirubin, reticulocyte count, and free hemoglobin tests to indicate hemolysis
- Disseminated intravascular coagulation panel, which could include Prothrombin Time and International Normalized Ratio (PT/INR), to rule out infectious causes
- Autoimmune serology and direct and indirect bilirubin tests
- A direct agglutinin test and, if no obvious cause is found, bone marrow analysis and cytogenetic analysis to evaluate for myelodysplastic syndromes Given the complexity of PNH diagnosis, flow cytometry to detect GPI-anchor deficient blood cells is considered the gold standard for PNH diagnosis, as it can detect PNH clones as small as 0.01% of cells 1. Prior to flow cytometry, supportive laboratory tests may include complete blood count showing anemia, elevated reticulocyte count, elevated lactate dehydrogenase (LDH), decreased haptoglobin, and elevated indirect bilirubin, all indicating hemolysis, as outlined in the American Society of Clinical Oncology clinical practice guideline 1. Urinalysis may reveal hemoglobinuria or hemosiderinuria, and the Coombs test is typically negative in PNH, helping distinguish it from autoimmune hemolytic anemia. The importance of a comprehensive diagnostic work-up, including paroxysmal nocturnal hemoglobinuria screening, cannot be overstated, as it enables accurate diagnosis and appropriate management of PNH, ultimately improving patient outcomes 1.
From the Research
Initial Screening Process for Paroxysmal Nocturnal Hemoglobinuria (PNH)
The initial screening process for PNH involves several steps and considerations, as outlined in various studies 2, 3, 4, 5, 6.
- Medical Indications: The current medical indications for PNH screening by flow cytometry (FCM) are highly efficient, with the highest frequency of PNH+ cases observed among patients screened because of bone marrow (BM) failure syndrome, particularly those with aplastic anemia (AA) and myelodysplastic syndrome (MDS) 2.
- Laboratory Tests: Laboratory tests for PNH include flow cytometry, which allows for the detection of very small populations of PNH cells, and can be used to follow the natural course and response to therapy of the disease 3.
- Screening Algorithms: Improved screening algorithms are needed for patients presenting with thrombosis and normal blood cell counts, as only a minor fraction of these patients are positive for PNH 2.
- Monitoring and Treatment: Monitoring for PNH clones can guide the choice of initial treatment, and the treatment of patients with both PNH and aplastic anemia depends on which condition predominates 4.
- Complement System: PNH is a complement-mediated disease, and the latest generation of tests allow for the detection of very small populations of PNH cells, and can be used to follow the natural course and response to therapy of the disease 5, 6.
Key Factors to Consider
When screening for PNH, several key factors should be considered, including:
- Hemolytic Anemia: Hemolytic anemia is a common symptom of PNH, and patients with this condition should be screened for PNH 2, 6.
- Thrombosis: Thrombosis is a common complication of PNH, and patients with unexplained thrombosis should be screened for PNH 2, 5.
- Bone Marrow Failure: Bone marrow failure is a common underlying condition in patients with PNH, and patients with aplastic anemia or myelodysplastic syndrome should be screened for PNH 2, 4.
- Flow Cytometry: Flow cytometry is a highly sensitive and specific test for PNH, and should be used to confirm the diagnosis in patients with suspected PNH 2, 3.