Expert Consensus on the Diagnosis and Monitoring of Paroxysmal Nocturnal Hemoglobinuria (PNH): An Algorithmic Approach in an Era of New Treatments

Paroxysmal nocturnal hemoglobinuria Paroxysmal nocturnal hemoglobinuria: (par-uk-SIZ-muhl nok-TURN-uhl hee-muh-gloe-buh-NYOOR-ee-uh) A rare and serious blood disease that causes red blood cells to break apart. Paroxysmal means sudden and irregular. Nocturnal means at night. Hemoglobinuria means hemoglobin in the urine. Hemoglobin is the red part of red blood cells. A… (PNH) is a rare hematologic disorder caused by a defect of glycosylphosphatidyl-anchored proteins, leading to an uncontrolled complement-mediated hemolysis hemolysis: (hi-MOL-uh-suss) The destruction of red blood cells. . The advent of complement inhibitors in clinical practice radically changed patients' outcomes and survival. Despite this significant progress, numerous unmet needs persist in clinical practice. A group of Italian experts explored the main challenges currently associated with PNH diagnosis and monitoring and reached a consensus on screening, diagnosis, initial work-up, and monitoring. The following core questions were examined: (i) Which patients need to be tested? (ii) Which test to use, and how do we define positivity? (iii) Which workup is requested for patients with a newly detected PNH clone clone: To make copies. Bone marrow stem cells clone themselves all the time. The cloned stem cells eventually become mature blood cells that leave the bone marrow and enter the bloodstream. ? (iv) Which monitoring in untreated patients? (v) Which monitoring in C-terminal-inh and C-proximal inh? Each specific clinical question was framed according to the GRADE format. Overall, flow-cytometry for PNH detection was recommended in patients presenting with two or more suggestive signs or symptoms and/or with hematologic conditions known to be associated with PNH clones, including DAT-negative hemolysis, idiopathic idiopathic: Usually refers to any condition with no known cause. venous thrombosis venous thrombosis: Blood clot in a vein (particularly at atypical sites), and primary bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. dysfunction (such as aplastic anemia aplastic anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… or myelodysplastic syndrome). A high-sensitivity flow cytometry flow cytometry: (sy-TOM-uh-tree) A laboratory test that gives information about cells, such as size, shape, and percentage of live cells. Flow cytometry is the test doctors use to see if there are any proteins missing from the surface of blood cells. It is the standard test for confirming a diagnosis of paroxysmal… test in neutrophils and erythrocytes should be preferred (lower limit of quantification 0.01%). Baseline assessment of disease activity (i.e., LDH > 1.5×ULN and PNH signs/symptoms), thrombotic risk, bone marrow (BM) features and imaging for organ dysfunction are suggested. Monitoring comprises blood counts and hemolytic markers with frequency depending on anemia anemia: (uh-NEE-mee-uh) A condition in which there is a shortage of red blood cells in the bloodstream. This causes a low red blood cell count. Symptoms of anemia are fatigue and tiredness. severity and symptoms, as well as annual PNH clone retesting, BM reevaluation in case of cytopenias, and constant education about infectious risk and breakthrough hemolysis in patients on treatment.