Examkin

Question

Difficulty: HardHematology and Oncology

A 32-year-old man comes to the emergency department due to severe right upper quadrant abdominal pain and progressive fatigue over the past week. He also reports that his urine has occasionally appeared unusually dark, particularly in the morning. He has no significant past medical history and takes no medications. His temperature is 37.2°C (99.0°F), blood pressure is 128/82 mm Hg, and pulse is 98/min. Physical examination reveals scleral icterus, pale conjunctivae, and right upper quadrant abdominal tenderness with hepatomegaly.

Laboratory studies show:

ParameterResult
Hemoglobin8.4 g/dL
Mean corpuscular volume94 fL
Platelets92,000/mm³
Leukocytes3,500/mm³
Total bilirubin3.8 mg/dL
Indirect bilirubin3.1 mg/dL
Lactate dehydrogenase1,450 U/L
Haptoglobin< 10 mg/dL

Doppler ultrasound of the abdomen demonstrates absent blood flow in the hepatic veins.

Which of the following is the most appropriate next step to confirm the underlying cause of this patient's findings?

  1. A
    Direct antiglobulin (Coombs) test
  2. B
    Bone marrow biopsy
  3. C
    JAK2 V617F mutation analysis
  4. Flow cytometry for CD55 and CD59Answer
  5. E
    Osmotic fragility test

Answer

Flow cytometry for CD55 and CD59
The correct answer is flow cytometry for CD55 and CD59. This patient's presentation of intravascular hemolysis (dark urine, elevated lactate dehydrogenase, low haptoglobin), pancytopenia, and atypical venous thrombosis (Budd-Chiari syndrome) is the classic triad for Paroxysmal Nocturnal Hemoglobinuria (PNH). PNH is an acquired hematopoietic stem cell disorder caused by a PIGA gene mutation, which leads to a deficiency of glycosylphosphatidylinositol (GPI) anchor proteins. This results in the absence of complement regulatory proteins, specifically CD55 (decay-accelerating factor) and CD59 (MAC-inhibitory protein), on cell surfaces. Without these proteins, red blood cells become highly susceptible to complement-mediated destruction. Flow cytometry of peripheral blood is the gold standard diagnostic test to confirm the absence of these specific proteins on the surface of red blood cells and leukocytes.

Step-by-Step Solution

1
Analyze the patient's clinical symptoms and initial physical examination findings.
The patient has fatigue, jaundice, dark morning urine, and abdominal pain with hepatomegaly.
To establish the primary clinical problems, which suggest hemolysis (jaundice, dark urine) and a hepatic issue (RUQ pain, hepatomegaly).
2
Interpret the laboratory and imaging results.
Labs show intravascular hemolysis (high LDH, high indirect bilirubin, low haptoglobin) and pancytopenia. Ultrasound confirms Budd-Chiari syndrome (hepatic vein thrombosis).
To objectively confirm the pathophysiologic processes occurring in the patient.
3
Synthesize the findings to form a unifying diagnosis.
The triad of intravascular hemolysis, pancytopenia, and atypical venous thrombosis is highly specific for Paroxysmal Nocturnal Hemoglobinuria (PNH).
To narrow down the differential diagnosis and select the appropriate confirmatory test.
4
Identify the gold standard diagnostic test for the suspected condition.
Flow cytometry for CD55 and CD59 confirms the diagnosis of PNH.
Because PNH is caused by an absence of the GPI anchor, which normally secures CD55 and CD59 to the cell surface, detecting their absence via flow cytometry is diagnostic.

Key Concept

Diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH)
Rate this question

Topics

Hematology and Oncology

More questions from this topic