A 43-year-old woman comes to the emergency department with abdominal pain and dark urine. Physical examination shows right upper-quadrant tenderness without guarding or rebound. Laboratory results are as follows: Further workup, including MRI of the abdomen, shows hepatic vein thrombosis. Which of the following is the most likely diagnosis?

Question

A 43-year-old woman comes to the emergency department with abdominal pain and dark urine.  Physical examination shows right upper-quadrant tenderness without guarding or rebound.  Laboratory results are as follows:  Further workup, including MRI of the abdomen, shows hepatic vein thrombosis.  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

11ec25c8_d425_8bec_bc81_1fcd475eda0b_MD0003_00 The most likely diagnosis in this case is paroxysmal nocturnal hemoglobinuria (PNH). PNH is an autoimmune hemolytic disorder characterized by intravascular and extravascular hemolysis and hemoglobinuria. The disease is due to an acquired genetic defect that results in lack of the glycosylphosphatidylinositol anchor, which connects proteins, including CD55 and CD59, to the cell surface. These proteins normally inhibit the activation of complement on red blood cells, but their absence allows the complement membrane attack complex to form and results in hemolysis. On average, patients have manifestations in the fourth decade of life resulting from one of the following: Hemolysis leading to hemoglobinuriaCytopenias - fatigue and dyspnea from anemiaHypercoagulable state (eg, portal vein thrombosis) - acute abdominal pain that may be due to severe hemolysis or portal vein thrombosis Hemolysis leading to hemoglobinuria Cytopenias - fatigue and dyspnea from anemia Hypercoagulable state (eg, portal vein thrombosis) - acute abdominal pain that may be due to severe hemolysis or portal vein thrombosis This patient's anemia and low haptoglobin accompanied by elevated bilirubin and lactate dehydrogenase (LDH) are all consistent with intravascular hemolysis. The key to the diagnosis is the patient's hepatic vein thrombosis in conjunction with these signs of hemolysis. Patients with autoimmune hemolytic anemia have a tendency for venous thromboembolism, but those with PNH are at particular risk, especially within intraabdominal or cerebral veins. Flow cytometry tests are used to confirm the diagnosis by assessing for the absence of the CD55 and CD59 proteins on the surface of the red blood cells. (Choice A) Acute intermittent porphyria may also present with abdominal pain and dark red/brown urine. However, the pigmented urine is due to porphyrins and/or porphyrin precursors (not hemoglobinuria), and hematologic abnormalities and thromboembolism are rare. (Choice B) The elevated LDH and bilirubin accompanied by the low haptoglobin make a hemolytic anemia much more likely than an aplastic anemia. (Choice C) G6PD deficiency can cause hemolytic anemia but is more common in male patients, particularly those of African descent. Patients are generally asymptomatic when there is no anemia, but disease can be triggered by medications or infections. Venous thrombosis is unlikely. (Choice D) Symptomatic hereditary spherocytosis would likely have led to some symptoms in this patient before age 43, and it is not usually associated with venous thromboses. Educational objective: Paroxysmal nocturnal hemoglobinuria should be suspected in patients who have a combination of hemolytic anemia, cytopenias, and hypercoagulable state (intraabdominal or cerebral venous thrombosis). Flow cytometry tests are used to confirm the diagnosis by assessing for absence of the CD55 and CD59 proteins on the surface of red blood cells. References: Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry. (http://www.ncbi.nlm.nih.gov/pubmed/24488565) Thrombosis in paroxysmal nocturnal hemoglobinuria. (http://www.ncbi.nlm.nih.gov/pubmed/23610373)

A 43-Year-Old Woman Comes to the Emergency Department with Abdominal