A new diagnostic algorithm could lead to earlier and more accurate diagnosis of paroxysmal nocturnal hemoglobinuria, a life-threatening hematopoietic stem cell disorder. Early diagnosis of PNH is essential to avoid serious, potentially fatal outcomes, but timely identification is complicated by the condition’s rarity and the non-specificity of the attendant symptoms.
To address this gap, a committee of PNH experts developed an algorithm for screening and diagnosis based on consensus from physicians with real-world experience in treating the disorder. The result should help non-specialists derive an appropriate differential diagnosis.
A handful of core signs and symptoms form the foundation of the algorithm. These include symptoms of anemia, such as fatigue, tachycardia, shortness of breath, and headache; thrombotic events; dark-colored urine; intermittent abdominal pain; esophageal spasms; and dysphagia.
PNH should be suspected in patients presenting with any of these symptoms in addition to bone marrow dysfunction. In particular, if a patient has aplastic anemia or unexplained cytopenia, the treating physician should test for PNH with FLAER or high-sensitivity flow cytometry. A patient with myelodysplastic syndrome and an initial diagnosis of hypoplastic marrow, or a young patient with myelodysplastic syndrome should also be tested.
A diagnosis of PNH should also be suspected for patients presenting with any of the core symptoms in addition to hemolysis or thrombosis. Patients presenting with hemoglobinuria or abnormal lab results, such as normocytic or macrocytic anemia, thrombocytopenia, abnormal iron studies, or reticulocytosis, should be tested for hemolysis. This testing should also be performed for a patient presenting with any of the core signs or symptoms and unprovoked or unusual site thrombosis.
Unprovoked thrombosis includes deep vein thrombosis or pulmonary embolism in the absence of major clinical risk factors for venous thromboembolism such as recent surgery, trauma, immobilization, hormonal therapy, or active cancer. Unusual site thrombosis includes the hepatic veins; other splanchnic veins; the cerebral vein; and dermal veins.
If hemolysis testing shows decreased haptoglobin or increases in lactic dehydrogenase, bilirubin, or reticulocytes in addition to a negative direct antiglobulin test, then the patient should undergo testing for PNH with FLAER or high-sensitivity flow cytometry.
This study contributes to the clinical practice by providing a concise and accessible tool that can be utilized by physicians without limitation in regard to their experience level in PNH diagnosis or global region of practice.