A 30-year-old woman comes to the emergency department with sudden-onset abdominal pain and ascites. Laboratory studies show anemia, reticulocytosis, leukopenia, and thrombocytopenia. Flow cytometry of the patient's peripheral blood cells using the appropriate monoclonal antibodies shows CD55 and CD59 deficiency. CT scan of the abdomen shows hepatic vein thrombosis. Which of the following is the most likely cause of this patient's anemia?

Question

A 30-year-old woman comes to the emergency department with sudden-onset abdominal pain and ascites.  Laboratory studies show anemia, reticulocytosis, leukopenia, and thrombocytopenia.  Flow cytometry of the patient's peripheral blood cells using the appropriate monoclonal antibodies shows CD55 and CD59 deficiency.  CT scan of the abdomen shows hepatic vein thrombosis.  Which of the following is the most likely cause of this patient's anemia?

Quizplus · Accepted Answer

11ec160b_3af7_0070_9249_59c11af2b76f_MD0001_00 This patient's combination of hemolytic anemia, hypercoagulability (eg, hepatic vein thrombosis), and pancytopenia are characteristic of paroxysmal nocturnal hemoglobinuria (PNH). Despite the name, hemolysis has been shown to occur at low baseline levels throughout the day, with exacerbations caused by a variety of inflammatory triggers (eg, infections, surgery). PNH is caused by an acquired mutation of the PIGA gene within a clonal population of multipotent hematopoietic stem cells. This gene is involved in the synthesis of the glycosylphosphatidylinositol (GPI) anchor, a glycolipid necessary for the attachment of several cell-surface proteins, including CD55 (decay-accelerating factor) and CD59 (MAC inhibitory protein). These proteins help inactivate complement and prevent the membrane attack complex from forming on normal cells. Absence of the GPI anchor results in CD55 and CD59 deficiency and complement-mediated hemolysis. The hemolysis occurs more often at night because complement activity is increased during sleep due to lower blood pH. Patients also develop thrombotic complications (eg, Budd-Chiari syndrome), likely due to release of free hemoglobin and other prothrombotic factors from lysed red blood cells and platelets. PNH is often associated with pancytopenia and aplastic anemia (possibly due to autoimmune attack against GPI-antigens on stem cells). Flow cytometry is the gold standard for the diagnosis of PNH and will show absence of the GPI anchor and CD55 and CD59 deficiency. (Choice B) Factor V mutation can result in an aberration called factor V Leiden, which is resistant to cleavage by activated protein C. Patients with factor V Leiden are at increased risk of thrombotic events, but hemolytic anemia and pancytopenia are not seen. (Choice C) Intracellular dehydration occurs during the pathogenesis of sickle cell anemia and spherocytosis. (Choice D) Mutations affecting the beta globin chain cause β-thalassemia. (Choice E) Splenic sequestration is a common complication of sickle cell anemia. Educational objective: The triad of hemolytic anemia, hypercoagulability, and pancytopenia suggests paroxysmal nocturnal hemoglobinuria (PNH). PNH results from an acquired mutation in the PIGA gene that causes absence of the glycosylphosphatidylinositol anchor and associated deficiency of CD55 and CD59 complement inhibitor proteins. __________ References: The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria. (http://www.ncbi.nlm.nih.gov/pubmed/22305531)

A 30-Year-Old Woman Comes to the Emergency Department with Sudden-Onset