A CBC shows anemia with burr-like red cells on smear and dark inclusions on supravital stain. Urine shows blood in the 3+ range and LDH is elevated. DAT is negative. Which condition is most likely?

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Multiple Choice

A CBC shows anemia with burr-like red cells on smear and dark inclusions on supravital stain. Urine shows blood in the 3+ range and LDH is elevated. DAT is negative. Which condition is most likely?

Paroxysmal nocturnal hemoglobinuria stems from an acquired defect in the PIGA gene in hematopoietic stem cells, leading to loss of GPI anchors and absence of CD55 (DAF) and CD59 on red cells. Without these protective proteins, red cells become highly susceptible to complement-mediated lysis, especially during sleep when mild acidosis can activate complement. This causes intravascular hemolysis with hemoglobin released into the bloodstream and then into the urine, hence a positive urine blood test due to hemoglobin (not intact red cells) and a high LDH from cell destruction. The direct antiglobulin (DAT) test is negative because the hemolysis is not driven by antibodies or complement bound to red cells, but by a membrane defect that makes cells vulnerable to complement. Smear findings like burr-like red cells reflect membrane abnormalities in affected cells, and supravital stains can reveal dark inclusions associated with this abnormal red cell population. The key clue tying this picture together is the combination of intravascular hemolysis with hemoglobinuria and a negative DAT, pointing toward PNH rather than an autoimmune or alloimmune hemolytic process. Confirmation is typically by flow cytometry showing loss of CD55/CD59 on red cells or by the Ham test (acidified serum test).

Paroxysmal nocturnal hemoglobinuria stems from an acquired defect in the PIGA gene in hematopoietic stem cells, leading to loss of GPI anchors and absence of CD55 (DAF) and CD59 on red cells. Without these protective proteins, red cells become highly susceptible to complement-mediated lysis, especially during sleep when mild acidosis can activate complement. This causes intravascular hemolysis with hemoglobin released into the bloodstream and then into the urine, hence a positive urine blood test due to hemoglobin (not intact red cells) and a high LDH from cell destruction. The direct antiglobulin (DAT) test is negative because the hemolysis is not driven by antibodies or complement bound to red cells, but by a membrane defect that makes cells vulnerable to complement.

Smear findings like burr-like red cells reflect membrane abnormalities in affected cells, and supravital stains can reveal dark inclusions associated with this abnormal red cell population. The key clue tying this picture together is the combination of intravascular hemolysis with hemoglobinuria and a negative DAT, pointing toward PNH rather than an autoimmune or alloimmune hemolytic process. Confirmation is typically by flow cytometry showing loss of CD55/CD59 on red cells or by the Ham test (acidified serum test).

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