Review Question - QID 106774

This patient has paroxysmal nocturnal hemoglobinuria (PNH) (hemolytic anemia, pancytopenia, and dark urine in the evenings/mornings (positive for hemoglobin and hemosiderin)), in which a deficiency of hematopoietic cell membrane proteins, specifically CD-55 and CD-59 is seen.

The lack of the CD-55 (decay accelerating factor) and CD-59 (membrane inhibitor of reactive lysis) membrane proteins on red blood cells leads to an uncontrolled activation of complement. In turn, this unchecked, activated complement cascade results in intravascular lysis/destruction of RBCs. The presentation of PNH includes hemolytic anemia, pancytopenia, and venous thrombosis. Although hemolysis occurs throughout the day, the dramatic darkening in the color of urine in the evenings/early morning is due to the accumulation and concentration of the urine overnight. Diagnosis is confirmed by flow cytometry showing absence of CD55 and CD59.

Illustration A shows the darkening of the urine to a 'cola' or tea color seen in PNH.

Incorrect Answers:
Answer 1: Deficiency of C1 esterase-inhibitor is the cause of hereditary angioedema, which presents with episodic swelling.
Answer 2: Spectrin deficiency is characteristic of hereditary spherocytosis, an intrinsic hemolytic anemia that presents with jaundice, gallstones, and/or splenomegaly.
Answer 3: Paroxysmal cold hemoglobinuria (PCH) is due to the presence of an IgG autoantibody that is activated in cold temperatures and leads to a hemolytic anemia, with associated anemia and hemoglobinuria. PCH occurs mostly in children.
Answer 5: Autosomal recessive deficiency of platelet glycoprotein IIb/IIIa receptor describes the etiology of Glanzmann's thrombasthenia, a bleeding disorder.