Paroxysmal Nocturnal Hemoglobinuria

Published on 04/03/2015 by admin

Filed under Hematology, Oncology and Palliative Medicine

Last modified 22/04/2025

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Chapter 5 Paroxysmal Nocturnal Hemoglobinuria

Robert A. Brodsky

Approach to Diagnosing Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) has an estimated incidence of 2 to 5 per million in the United States. This, coupled with its protean manifestations, makes diagnosing PNH a challenge for even the most astute diagnostician. However, given the ease and specificity of modern diagnostic assays, the most important attribute a physician can possess in diagnosing PNH is to maintain a high level of suspicion and to be cognizant of the various presentations of the disease. A small sample of peripheral blood sent to an experienced flow cytometric laboratory is usually sufficient to establish or exclude the diagnosis of PNH. These assays are fast, reliable, and inexpensive. If monoclonal antibodies are used to establish the diagnosis, it is imperative that two or more antibodies be used on at least two different lineages. Assaying granulocytes is the most reliable method of diagnosing PNH because they are not affected by blood transfusions. The author prefers to use FLAER over monoclonal antibodies on granulocytes and monocytes because of the improved sensitivity and specificity; anti-CD59 is the most reliable marker on erythrocytes.

Classical PNH is usually more conspicuous than hypoplastic PNH. Patients typically present with direct antiglobulin-negative hemolytic anemia, hemoglobinuria, and mild to moderate cytopenias. Obscure paroxysms of back pain, abdominal pain, fatigue, or headaches are often present. The BM is typically normocellular to mildly hypercellular with intense erythroid hyperplasia and mild to moderate dyserythropoiesis. BM iron stores are frequently, but not always, absent. PNH patients can also present with abrupt, severe abdominal pain and jaundice caused by thrombosis. All patients presenting with unexplained hepatic vein, portal vein, mesenteric vein, or portal vein thrombosis should be screened for PNH.

It is important to distinguish PNH from myelodysplastic syndrome. Most patients with refractory anemia should be screened for PNH, especially those with moderate to severe cytopenias, an elevated lactate dehydrogenase level, and a hypocellular BM. In addition, all patients diagnosed with aplastic anemia should be screened for PNH. As few as 3% PNH erythrocytes may result in an elevated LDH. In rare instances, idiopathic myelofibrosis or autoimmune hemolytic anemias can mimic PNH. Patients with a history of aplastic anemia—especially those managed with immunosuppressive therapy—should be monitored closely for the outgrowth of PNH.

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