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MKSAP: 43-year-old man with severe abdominal pain

mksap
Conditions
March 8, 2014
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Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 43-year-old man is evaluated in the hospital for severe abdominal pain of 2 days’ duration. He is otherwise healthy except for the recent finding of pancytopenia. Family history is noncontributory. His only medication is a daily multivitamin. Following a physical exam and lab results, what test is most likely to establish the diagnosis?

On physical examination, temperature is 36.2 °C (97.2 °F), blood pressure is 143/69 mm Hg, pulse rate is 86/min, and respiration rate is 12/min. The patient appears jaundiced. There is no splenomegaly. The remainder of the examination is normal.

Laboratory studies were as follows:

Haptoglobin Undetectable
Hemoglobin 10.4 g/dL (104 g/L)
Leukocyte count 3400/µL (3.4 × 109/L)
Platelet count 89,000/µL (89 × 109/L)
Reticulocyte count 7%
Total bilirubin 2.8 mg/dL (48 µmol/L)
Direct bilirubin 0.4 mg/dL (7 µmol/L)
Lactate dehydrogenase 775 units/L

His complete blood count and liver chemistry values from 1 year ago were normal.

A CT scan of the abdomen shows mesenteric vein thrombosis but no lymphadenopathy or splenomegaly.

Which of the following tests is most likely to establish the diagnosis?

A: Direct Coombs (antiglobulin) test
B: Factor V Leiden assay
C: Flow cytometric analysis for CD55 and CD59
D: Lupus anticoagulant and anticardiolipin antibody assay

MKSAP Answer and Critique

The correct answer is C: Flow cytometric analysis for CD55 and CD5. This item is available to MKSAP 16 subscribers as item 60 in the Hematology and Oncology section.

The most appropriate test to establish a diagnosis is flow cytometric analysis for CD55 and CD59 on leukocytes or erythrocytes. This patient most likely has paroxysmal nocturnal hemoglobinuria (PNH), which is a primary acquired stem cell disorder characterized by a wide spectrum of clinical and laboratory findings, such as unprovoked venous thrombosis at an unusual location, hemolytic anemia, and mild to moderate pancytopenia. The diagnosis of PNH is made by flow cytometry, which can identify a subpopulation of erythrocytes or leukocytes lacking specific glycosylphosphatidylinositol-anchored surface proteins, such as CD55 or CD59.

The direct Coombs (antiglobulin) test is useful in the evaluation of autoimmune hemolysis. Autoimmune hemolytic anemia may be characterized by splenomegaly, spherocytic-shaped erythrocytes, reticulocytosis, elevated levels of unconjugated bilirubin and lactate dehydrogenase, and depressed levels of haptoglobin. Although this patient has some of these findings, he has no splenomegaly, and autoimmune hemolysis would not explain his pancytopenia or thrombosis.

Factor V Leiden is the most common inherited thrombophilic disorder and accounts for approximately half of the inherited thrombophilias in patients with venous thromboembolism. Although it may increase the risk for deep venous thrombosis, factor V Leiden would not explain this patient’s pancytopenia or hemolysis.

The antiphospholipid syndrome is associated with an increased risk for venous and arterial thromboembolism. Common sites of thrombosis include the lower extremities but may also include the visceral veins. There is also a strong correlation between this syndrome and pregnancy loss. Antiphospholipid syndrome could explain the patient’s unprovoked thrombosis but would not account for his pancytopenia or hemolysis.

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Key Point

  • The diagnosis of paroxysmal nocturnal hemoglobinuria is established by flow cytometric analysis of CD55 and CD59 on leukocytes and erythrocytes.

This content is excerpted from MKSAP 16 with permission from the American College of Physicians (ACP). Use is restricted in the same manner as that defined in the MKSAP 16 Digital license agreement. This material should never be used as a substitute for clinical judgment and does not represent an official position of ACP. All content is licensed to KevinMD.com on an “AS IS” basis without any warranty of any nature. The publisher, ACP, shall not be liable for any damage or loss of any kind arising out of or resulting from use of content, regardless of whether such liability is based in tort, contract or otherwise.

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