Bothered by an NBME 6 question

[norwegian wood]

---

Members don't see this ad.

This is one of the questions I got wrong on NBME 6:

A previously healthy 42-year-old woman has a 6-week history of fatigue, lightheadedness, and shortness of breath. Laboratory studies show:

Hematocrit 25%
Hemoglobin 8.3 g/dL
Leukocyte count 10,000/mm3
Platelet count 250,000/mm3
Reticulocyte count 4%
Total serum bilirubin 3 mg/dL
Direct serum bilirubin 0.3 mg/dL
Urine urobilinogen 2+

A peripheral blood smear shows microspherocytes. Which of the following is the most likely cause of the anemia?

A Acute hemorrhage
B Autoimmune hemolysis
C Hemolytic-uremic syndrome
D Hypersplenism
E Thrombotic thrombocytopenic purpura

I narrowed the choices down to B or D and in the end answered D (my diagnosis was hereditary spherocytosis) which was incorrect, so I guess the answer is B. I'm guessing their reasoning is a previously healthy 42-year-old woman would be more likely to get an autoimmune disorder. But here is the problem:

1. According to Robbins, hereditary spherocytosis has a variable presentation and the AD form can present acutely in adulthood only when a patient is decompensated by an aplastic/hemolytic crisis.

2. Comparing incidence rates, hereditary spherocytosis can be as common as 1:5000 according to Robbins and Harrison's. Autoimmune hemolysis on the other hand has only a 1:80000 incidence (The Autoimmune Diseases, Noel R. Rose, Ian R. Mackay, 1998)

So what do you guys think? Is the NBME answer correct?

 

[ScubaStarved]

The point you're missing is that she has an INTRAvascular hemolysis. Your choices then are TTP and HUS and cold, IgM-mediated AIHA.

She lacks the criteria for TTP and is not a kid with diarrhea, thus B.

Other causes of intravasc hemolysis: trauma, PNH, etc.

 

[norwegian wood]

The point you're missing is that she has an INTRAvascular hemolysis. Your choices then are TTP and HUS and cold, IgM-mediated AIHA.

She lacks the criteria for TTP and is not a kid with diarrhea, thus B.

Other causes of intravasc hemolysis: trauma, PNH, etc.

What points to an intravascular hemolysis here? Microspherocytes are seen in both autoimmune hemolysis and hereditary spherocytosis, and both can cause splenomegaly and hypersplenism.

And besides extravascular hemolysis is more common in autoimmune anemia (RBCs coated with IgG or IgM bodies are phagocytosed in the spleen) except when the complement system is activated by cold agglutinins, but this requires exposure to cold temperatures in the extremities which isn't found here.

 

[ScubaStarved]

What points to an intravascular hemolysis here? Microspherocytes are seen in both autoimmune hemolysis and hereditary spherocytosis, and both can cause splenomegaly and hypersplenism.

And besides extravascular hemolysis is more common in autoimmune anemia (RBCs coated with IgG or IgM bodies are phagocytosed in the spleen) except when the complement system is activated by cold agglutinins, but this requires exposure to cold temperatures in the extremities which isn't found here.

My bad, you are completely correct in this part. I misread the low direct bili as a low total. No posting at 5am anymore for me.

Nonetheless, you can still eliminate TTP/HUS and acute hemorrhage as you astutely did in the initial post.

Hypersplenism, though, has a more general meaning than HS. It implies only diffuse enlargement of the spleen with enhanced phagocytic function. Think of all causes of portal HTN, RA/SLE, HbSC disease, invasion, and so on. Though they do not give you an exam, they do not say that this lady has pleuritic chest/abdominal pain or splenomegaly or features of any other condition that could cause spleen enlargement. Finally, hypersplenic states often result in destruction of platelets as well (see PLT transfusions for cirrhotics). This is a topic uncovered by Goljan, but will be more relevant in a medicine rotation.

Perhaps someone else can provide you a more satisfying answer, but the points I see are female of autoimmune age, adult onset of symptoms, no Fam Hx, chronic course, and complete absence of information that would steer you to hypersplenism (both lab and physical).

 

[norwegian wood]

My bad, you are completely correct in this part. I misread the low direct bili as a low total. No posting at 5am anymore for me.

Nonetheless, you can still eliminate TTP/HUS and acute hemorrhage as you astutely did in the initial post.

Hypersplenism, though, has a more general meaning than HS. It implies only diffuse enlargement of the spleen with enhanced phagocytic function. Think of all causes of portal HTN, RA/SLE, HbSC disease, invasion, and so on. Though they do not give you an exam, they do not say that this lady has pleuritic chest/abdominal pain or splenomegaly or features of any other condition that could cause spleen enlargement. Finally, hypersplenic states often result in destruction of platelets as well (see PLT transfusions for cirrhotics). This is a topic uncovered by Goljan, but will be more relevant in a medicine rotation.

Perhaps someone else can provide you a more satisfying answer, but the points I see are female of autoimmune age, adult onset of symptoms, no Fam Hx, chronic course, and complete absence of information that would steer you to hypersplenism (both lab and physical).

Thanks. Yeah, that makes sense. I just wish they wrote the question better. In the real world you wouldn't be required to jump to an autoimmune diagnosis without at least doing a Coomb's test. Oh well.

 

[ArcGurren]

I think the fact that she's female and has a chronic hemolysis (indirect bilirubin increase, 2+ urobilinogen urine, low crit and low globin) with microspherocytes is more likely to be an autoimmune condition. It's not a great answer but it's the closest.

 

[What up doc]

This is one of the questions I got wrong on NBME 6:

A previously healthy 42-year-old woman has a 6-week history of fatigue, lightheadedness, and shortness of breath. Laboratory studies show:

Hematocrit 25%
Hemoglobin 8.3 g/dL
Leukocyte count 10,000/mm3
Platelet count 250,000/mm3
Reticulocyte count 4%
Total serum bilirubin 3 mg/dL
Direct serum bilirubin 0.3 mg/dL
Urine urobilinogen 2+

A peripheral blood smear shows microspherocytes. Which of the following is the most likely cause of the anemia?

A Acute hemorrhage
B Autoimmune hemolysis
C Hemolytic-uremic syndrome
D Hypersplenism
E Thrombotic thrombocytopenic purpura

I narrowed the choices down to B or D and in the end answered D (my diagnosis was hereditary spherocytosis) which was incorrect, so I guess the answer is B. I'm guessing their reasoning is a previously healthy 42-year-old woman would be more likely to get an autoimmune disorder. But here is the problem:

1. According to Robbins, hereditary spherocytosis has a variable presentation and the AD form can present acutely in adulthood only when a patient is decompensated by an aplastic/hemolytic crisis.

2. Comparing incidence rates, hereditary spherocytosis can be as common as 1:5000 according to Robbins and Harrison's. Autoimmune hemolysis on the other hand has only a 1:80000 incidence (The Autoimmune Diseases, Noel R. Rose, Ian R. Mackay, 1998)

So what do you guys think? Is the NBME answer correct?

Tuff question but hypersplenism would typically present w/ thrombocytopenia...also no mention of splenomegaly or any other consequences of hypersplenism....

 

[xlr8]

i think the elevated indirect bilirubin is really what clues you in to the intravascular hemolysis (since theres no sign of liver dysfunction).

scratch that: i think both intravascular and extravascular can cause elevated indirect bilirubin

 

[sadaca]

yea I agree this was a HORRIBLE question on nbme's part. I checked all books and everywhere says to differentiate between herdiarty spherocytosis and autoimmune hemolytic anemia they must say coombs test postive or negative. oh well