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MKSAP Quiz: diagnosing hematologic abnormalities

This week's quiz asks readers to determine appropriate diagnostic testing for a 26-year-old woman admitted to the hospital with deep venous thrombosis.


A 26-year-old woman is admitted to the hospital for treatment of deep venous thrombosis of the right lower extremity confirmed by duplex Doppler ultrasonography. Medical history is noncontributory, and her only medication is an oral contraceptive.

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On physical examination, there is mild scleral icterus. Temperature is 37.2 ° C (99.9 °F), blood pressure is 110/67 mm Hg, pulse rate is 100/min, and respiration rate is 16/min. Abdominal examination discloses mild splenomegaly.

Laboratory studies:

Alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels are normal. A bone marrow biopsy reveals hypocellular bone marrow, absent iron stores, and signs of early myelodysplasia. The results of a direct and indirect antiglobulin (Coombs) test are negative.

Which of the following is the most appropriate diagnostic test to determine the cause of this patient's hematologic abnormalities?

A. Flow cytometry
B. Hemoglobin electrophoresis
C. Osmotic fragility study
D. Parvovirus B19 serology

Reveal the Answer

MKSAP Answer and Critique

The correct answer is A) Flow cytometry. This item is available to MKSAP 15 subscribers as item 12 in the Hematology and Oncology section. More information about MKSAP 15 is available online.

The coexistence of pancytopenia, hemolytic anemia, and thrombosis should raise the suspicion for paroxysmal nocturnal hemoglobinuria (PNH). PNH is caused by loss of glycosylphosphatidylinositol (GPI)–linked proteins on the cell surface. Two such proteins, CD55 and CD59, help reduce erythrocyte sensitivity to complement. Deficiency of CD55 and CD59 can be detected by flow cytometry. Because of the unopposed actions of complement, patients with PNH have direct antiglobulin (Coombs)–negative hemolysis. Iron deficiency is also a common finding in patients with PNH owing to iron loss in the urine. PNH is associated with thrombosis, perhaps secondary to loss of naturally occurring anticoagulants that are linked to membranes by GPI anchors. Finally, this disorder is associated with aplasia, myelodysplasia, and, rarely, acute leukemia. Recently, eculizumab, a monoclonal antibody to C5, has been reported to offer a sustained response to patients with PNH.

This patient does not have a history suggestive of a congenital hemoglobin disorder necessitating hemoglobin electrophoresis. A hemoglobinopathy would not explain the low leukocyte count or thrombocytopenia in this patient. Erythrocyte osmotic fragility is used to assess hereditary spherocytosis, but that disorder would not explain this patient's pancytopenia nor the deep venous thrombosis (DVT).

Parvovirus B19 may cause anemia or, especially in immunocompromised patients, pancytopenia, but the reticulocyte count should be less than 2%, and there is no association with DVT.

Key Point

  • Paroxysmal nocturnal hemoglobinuria is characterized by direct antiglobulin (Coombs)–negative hemolysis, pancytopenia, and thrombosis.