Examkin

Question

Difficulty: HardOrdering Laboratory Tests

A 35-year-old man comes to the emergency department due to a 2-day history of severe, progressive right upper quadrant abdominal pain and abdominal swelling. He also reports worsening fatigue and passing dark-colored urine in the mornings over the past few months. His temperature is 37.2°C (99.0°F), blood pressure is 135/85 mm Hg, and pulse is 98/min. Physical examination reveals scleral icterus, tender hepatomegaly, and moderate ascites. A Doppler ultrasound of the abdomen demonstrates absent flow in the hepatic veins, consistent with Budd-Chiari syndrome.

Laboratory results are as follows:

Hemoglobin: 10.2 g/dL
Platelets: 125,000/mm³
Leukocytes: 3,800/mm³
Reticulocyte count: 5.5%
Lactate dehydrogenase: 950 U/L
Haptoglobin: <10 mg/dL (N: 41-165 mg/dL)
Total bilirubin: 3.2 mg/dL
Direct bilirubin: 0.5 mg/dL
Direct antiglobulin (Coombs) test: Negative
Urinalysis: Positive for hemoglobin and hemosiderin, negative for intact red blood cells.

Which of the following is the most appropriate next step in laboratory evaluation to establish the underlying diagnosis?

  1. Flow cytometry of peripheral blood cellsAnswer
  2. B
    Factor V Leiden and prothrombin G20210A gene mutation analysis
  3. C
    Bone marrow aspiration and biopsy
  4. D
    ADAMTS13 activity assay
  5. E
    Anticardiolipin and anti-beta-2-glycoprotein I antibodies

Answer

The most appropriate next step is flow cytometry of peripheral blood cells to evaluate for Paroxysmal Nocturnal Hemoglobinuria (PNH).
The correct answer targets the diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH). This patient presents with the classic triad of PNH: Coombs-negative intravascular hemolysis (elevated LDH, low haptoglobin, hemoglobinuria/hemosiderinuria), concurrent cytopenias (mild pancytopenia), and an atypical venous thrombosis (Budd-Chiari syndrome). PNH is an acquired clonal stem cell disorder caused by a mutation in the PIGA gene, resulting in impaired synthesis of the glycosylphosphatidylinositol (GPI) anchor. This leads to a deficiency of GPI-anchored complement regulatory proteins, specifically CD55 (decay-accelerating factor) and CD59 (MAC-inhibitory protein), on the surface of hematopoietic cells. Consequently, red blood cells are highly susceptible to complement-mediated lysis. The most appropriate and definitive next step in laboratory evaluation is flow cytometry of peripheral blood to demonstrate the absence or severe deficiency of these GPI-anchored proteins on erythrocytes and leukocytes.

Step-by-Step Solution

1
Analyze the patient's clinical presentation.
The patient has Budd-Chiari syndrome (hepatic vein thrombosis) accompanied by fatigue and morning dark urine.
Identifying the pattern of atypical large-vessel thrombosis combined with symptoms of episodic hemoglobinuria points toward a specific hematologic disorder.
2
Evaluate the laboratory findings.
Labs show Coombs-negative intravascular hemolysis (high LDH, low haptoglobin, indirect hyperbilirubinemia, hemoglobinuria) combined with mild pancytopenia (anemia, thrombocytopenia, leukopenia).
The combination of Coombs-negative intravascular hemolysis, cytopenias, and atypical venous thrombosis is the classic triad of Paroxysmal Nocturnal Hemoglobinuria (PNH).
3
Determine the diagnostic test of choice for the suspected condition.
Flow cytometry of peripheral blood cells.
PNH is caused by an acquired mutation in the PIGA gene, leading to a deficiency of GPI anchors that attach complement regulatory proteins (CD55, CD59) to cell membranes. Flow cytometry rapidly and non-invasively detects the absence of these proteins.

Key Concept

Paroxysmal Nocturnal Hemoglobinuria (PNH) classic triad (intravascular hemolysis, cytopenias, atypical venous thrombosis) and its diagnosis via flow cytometry.
Rate this question

Topics

Ordering Laboratory Tests

More questions from this topic