Extrinsic hemolytic normocytic anemia: Pathology review


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Extrinsic hemolytic normocytic anemia: Pathology review

Hematological system


Iron deficiency anemia



Sideroblastic anemia

Anemia of chronic disease

Lead poisoning

Hemolytic disease of the newborn

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Autoimmune hemolytic anemia

Pyruvate kinase deficiency

Paroxysmal nocturnal hemoglobinuria

Sickle cell disease (NORD)

Hereditary spherocytosis

Anemia of chronic disease

Aplastic anemia

Fanconi anemia

Megaloblastic anemia

Folate (Vitamin B9) deficiency

Vitamin B12 deficiency

Fanconi anemia

Diamond-Blackfan anemia

Heme synthesis disorders

Acute intermittent porphyria

Porphyria cutanea tarda

Lead poisoning

Coagulation disorders


Vitamin K deficiency

Platelet disorders

Bernard-Soulier syndrome

Glanzmann's thrombasthenia

Hemolytic-uremic syndrome

Immune thrombocytopenic purpura

Thrombotic thrombocytopenic purpura

Mixed platelet and coagulation disorders

Von Willebrand disease

Disseminated intravascular coagulation

Heparin-induced thrombocytopenia

Thrombosis syndromes (hypercoagulability)

Antithrombin III deficiency

Factor V Leiden

Protein C deficiency

Protein S deficiency

Antiphospholipid syndrome


Hodgkin lymphoma

Non-Hodgkin lymphoma


Chronic leukemia

Acute leukemia

Leukemoid reaction

Leukemoid reaction

Dysplastic and proliferative disorders

Myelodysplastic syndromes

Polycythemia vera (NORD)

Myelofibrosis (NORD)

Essential thrombocythemia (NORD)

Langerhans cell histiocytosis

Mastocytosis (NORD)

Plasma cell dyscrasias

Multiple myeloma

Monoclonal gammopathy of undetermined significance

Waldenstrom macroglobulinemia

Hematological system pathology review

Microcytic anemia: Pathology review

Non-hemolytic normocytic anemia: Pathology review

Intrinsic hemolytic normocytic anemia: Pathology review

Extrinsic hemolytic normocytic anemia: Pathology review

Macrocytic anemia: Pathology review

Heme synthesis disorders: Pathology review

Coagulation disorders: Pathology review

Platelet disorders: Pathology review

Mixed platelet and coagulation disorders: Pathology review

Thrombosis syndromes (hypercoagulability): Pathology review

Lymphomas: Pathology review

Leukemias: Pathology review

Plasma cell disorders: Pathology review

Myeloproliferative disorders: Pathology review


Extrinsic hemolytic normocytic anemia: Pathology review

USMLE® Step 1 questions

0 / 8 complete


USMLE® Step 1 style questions USMLE

of complete

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?


Content Reviewers

Yifan Xiao, MD


Jung Hee Lee, MScBMC

Maria Emfietzoglou, MD

Kaylee Neff

Tanner Marshall, MS

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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  2. "Robbins Basic Pathology" Elsevier (2017)
  3. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
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  7. "Hemolytic uremic syndrome" Türk Pediatri Arşivi (2015)
  8. "Haemolytic uremic syndrome: diagnosis and management" F1000Research (2019)
  9. "Management of thrombotic thrombocytopenic purpura: current perspectives" Journal of Blood Medicine (2014)
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