Haematology: paroxysmal nocturnal haemoglobinuria: practice question

A General Medicine question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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General Medicine · Haematology: paroxysmal nocturnal haemoglobinuria

Sample item

A 30-year-old woman has episodes of dark urine in the morning, a haemoglobin of 7.5 g/dL, raised LDH and a negative direct Coombs test. She also had a recent hepatic vein thrombosis, and her platelet and neutrophil counts are mildly reduced. Which test is the best confirmatory investigation?

AFlow cytometry for CD55 and CD59 on blood cellsBRepeat direct antiglobulin test with cold agglutinin titreCG6PD enzyme assayDOsmotic fragility test

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

A. Flow cytometry for CD55 and CD59 on blood cells

Paroxysmal nocturnal haemoglobinuria is an acquired clonal disorder from PIGA mutation in a stem cell, causing deficiency of GPI-anchored proteins CD55 and CD59 and complement-mediated intravascular haemolysis. Thrombosis at unusual sites such as hepatic veins is a leading cause of death. Flow cytometry for these proteins (or FLAER) is the diagnostic test, and complement inhibitors such as eculizumab are used for treatment.

Option by option

A. Flow cytometry for CD55 and CD59 on blood cells (correct)
Correct. Absent CD55 and CD59 on red cells and granulocytes confirm the diagnosis.
B. Repeat direct antiglobulin test with cold agglutinin titre
A cold agglutinin titre looks for autoimmune haemolysis, but the Coombs test is negative and thrombosis is unexplained.
C. G6PD enzyme assay
G6PD assay detects enzyme deficiency, which causes episodic haemolysis after oxidant exposure, with no thrombosis.
D. Osmotic fragility test
Osmotic fragility is raised in hereditary spherocytosis, which has a different clinical picture.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

Questions about this General Medicine question

What is the answer to this General Medicine question?

The best answer is A, Flow cytometry for CD55 and CD59 on blood cells. Paroxysmal nocturnal haemoglobinuria is an acquired clonal disorder from PIGA mutation in a stem cell, causing deficiency of GPI-anchored proteins CD55 and CD59 and complement-mediated intravascular haemolysis.

Why is "Repeat direct antiglobulin test with cold agglutinin titre" not the answer?

A cold agglutinin titre looks for autoimmune haemolysis, but the Coombs test is negative and thrombosis is unexplained.

Why is "G6PD enzyme assay" not the answer?

G6PD assay detects enzyme deficiency, which causes episodic haemolysis after oxidant exposure, with no thrombosis.

Why is "Osmotic fragility test" not the answer?

Osmotic fragility is raised in hereditary spherocytosis, which has a different clinical picture.

What concept does this question test?

It tests Haematology: paroxysmal nocturnal haemoglobinuria in General Medicine. Thrombosis at unusual sites such as hepatic veins is a leading cause of death. Flow cytometry for these proteins (or FLAER) is the diagnostic test, and complement inhibitors such as eculizumab are used for treatment.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Haematology: paroxysmal nocturnal haemoglobinuria?

For each disease know the classic presentation, the best test, and the first-line treatment. Then use the flashcards and the other General Medicine questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.