Extrinsic hemolytic normocytic anemia: Pathology review

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Extrinsic hemolytic normocytic anemia: Pathology review


Coagulation disorders


Vitamin K deficiency

Leukemoid reaction

Leukemoid reaction


Extrinsic hemolytic normocytic anemia: Pathology review

USMLE® Step 1 questions

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USMLE® Step 1 style questions USMLE

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A 7-year-old boy comes to the emergency department complaining of 2 days of fatigue, large purple spots on his legs, and bleeding in his mouth from the gums. He has no significant past medical history, and family history is unremarkable. His temperature is 37°C (98.6°F), pulse is 86/min, respirations are 20/min, and blood pressure is 108/66 mmHg. Upon physical exam, he is found to have pale skin, large purpura on his legs bilaterally, and bleeding mucosal petechiae. Laboratory tests are obtained and the results are shown below. Direct Coombs test is positive.    

Laboratory value  Result
 Hemoglobin  8.1 g/dL 
 Mean corpuscular volume (MCV)   86 fL 
 Platelet count  80,000/mm3  
 Reticulocyte count   4.6% 
 Haptoglobin  100 mg/dL (N = 50-220) 
Blood, plasma, serum  
 Lactate dehydrogenase (LDH)  1080 U/L 
Which of the following is the most likely diagnosis?


At the family medicine center, two people came in with progressive fatigue.

One of them is a 60 years old named Will whose past medical history included an aortic valve replacement with a mechanical valve due to severe aortic stenosis.

There’s Hanna, a 28 years old female of African descent.

She was diagnosed a year ago with systemic lupus erythematosus, or SLE. CBC is ordered for both people and it shows low hemoglobin with normal mean corpuscular volume, or MCV and reticulocyte count index over 2%.

They also have increased LDH. Now, Will has schistocytes on peripheral blood smear, while Hanna has spherocytes.

Both Will and Hannah are suffering from anemia, which is defined as lower than average levels of hemoglobin, typically below 13.5 g/dL in adult men and below 12.0 g/dL in adult women.

For children, this level varies based on the age. Now, anemias can be broadly grouped into 3 categories based on =MCV, which reflects the volume of an RBC.

So microcytic anemia is where the MCV is lower than 80 fL, normocytic, with an MCV between 80 and 100 fL, and macrocytic, with an MCV larger than 100 fL.

Normocytic anemias can be further classified as hemolytic when there’s increased destruction of RBCs, or hemolysis, and non-hemolytic when there’s decreased production of RBCs from the bone marrow.

When there’s hemolysis, the bone marrow revs up and starts pumping out immature RBCs called reticulocytes, but when there’s a bone marrow problem reticulocyte count is low.

So for your exams, it’s important to know that in hemolytic anemias there’s an increased reticulocyte production index of over 2%, while in non-hemolytic anemias it’s lower than 2%.

Alright, now hemolytic anemias can be classified as intrinsic or extrinsic hemolytic anemias.

In intrinsic hemolytic anemias, RBCs are destroyed because they’re defective, while in extrinsic hemolytic anemias, RBCs are normal but are later destroyed outside the bone marrow.

In this video, let’s focus on extrinsic hemolytic anemias that include autoimmune hemolytic anemia, microangiopathic hemolytic anemia, macroangiopathic hemolytic anemia and infections.


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  4. "Hemolytic Anemia: Evaluation and Differential Diagnosis" Am Fam Physician (2018)
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