A 20-year-old man is evaluated for recurrent episodes of jaundice. He was separated from his parents at a young age and is unaware of any family medical history. The patient resided in several foster homes throughout his childhood but currently lives alone. His temperature is 36.7 C (98 F), blood pressure is 120/80 mm Hg, and pulse is 72/min. Physical examination shows pallor, icterus, and mild splenomegaly. There is no lymphadenopathy or hepatomegaly. The remainder of the physical examination is normal. Laboratory test results are as follows: When the patient's red blood cells are incubated in a hypotonic solution with glycerol, hemoglobin is released. The control sample does not release hemoglobin. This patient is at greatest risk of developing which of the following?

Question

A 20-year-old man is evaluated for recurrent episodes of jaundice.  He was separated from his parents at a young age and is unaware of any family medical history.  The patient resided in several foster homes throughout his childhood but currently lives alone.  His temperature is 36.7 C (98 F), blood pressure is 120/80 mm Hg, and pulse is 72/min.  Physical examination shows pallor, icterus, and mild splenomegaly.  There is no lymphadenopathy or hepatomegaly.  The remainder of the physical examination is normal.  Laboratory test results are as follows:  When the patient's red blood cells are incubated in a hypotonic solution with glycerol, hemoglobin is released.  The control sample does not release hemoglobin.  This patient is at greatest risk of developing which of the following?

Quizplus · Accepted Answer

11ec160b_3980_8d15_9249_d9de20c01fbe_MD0001_00 This patient's presentation with anemia, elevated lactate dehydrogenase, and indirect hyperbilirubinemia suggests hemolytic anemia. The lysing of blood cells when incubated in hypotonic saline with glycerol describes a positive acidified glycerol lysis test, the diagnostic test for hereditary spherocytosis (HS). Spherocytes demonstrate increased osmotic fragility in this test due to their decreased surface area to volume ratio. HS is the most common hemolytic anemia due to a red blood cell (RBC) membrane defect. The mutation in HS most often affects spectrin and ankyrin, the plasma-membrane scaffolding proteins. Patients with HS present with hemolytic anemia, jaundice, and splenomegaly. Pigmented gallstones are a complication of any hemolytic anemia. In chronic hemolysis, the increased bilirubin from lysed RBCs precipitates as calcium bilirubinate, forming pigmented stones in the gallbladder. Patients with HS may also present with aplastic crises due to parvovirus B19 infection. (Choice A) Autoimmune hemolytic anemia (AIHA) results in findings similar to those seen in HS (eg, indirect hyperbilirubinemia, elevated lactate dehydrogenase, spherocytes on peripheral blood smear). In contrast to HS, AIHA is not heritable, and patients have a positive direct antiglobulin (Coombs) test along with a propensity to develop autoimmune disease (eg, systemic lupus erythematosus). (Choices B and C) The abnormal adhesion of sickle cell RBCs to the endothelium and the subsequent obstruction of small blood vessels lead to various injuries, which include splenic autoinfarction and femoral avascular necrosis. A positive acidified glycerol lysis test classically describes HS, not sickle cell anemia. (Choice D) Glucose-6-phosphate dehydrogenase (G6PD) deficiency presents with hemolytic anemia and indirect hyperbilirubinemia usually following oxidative stress. Common triggers include drugs (sulfonamide or antimalarial agents), fava beans, and infections (viral hepatitis, pneumonia, or typhoid). Peripheral smears of G6PD deficiency anemia show bite cells and Heinz bodies, not spherocytes. Educational objective: Hereditary spherocytosis results from red cell cytoskeleton abnormalities, most commonly in the proteins spectrin and ankyrin. Increased osmotic fragility on acidified glycerol lysis testing confirms the diagnosis. Hemolytic anemia, jaundice, and splenomegaly are classic manifestations. Complications include pigmented gallstones and aplastic crises from parvovirus B19 infection. __________ References: Hereditary spherocytosis. (http://www.ncbi.nlm.nih.gov/pubmed/18940465) Disorders of red cell membrane. (http://www.ncbi.nlm.nih.gov/pubmed/18341630) Red cell membrane: past, present, and future. (http://www.ncbi.nlm.nih.gov/pubmed/18988878)

A 20-Year-Old Man Is Evaluated for Recurrent Episodes of Jaundice