Intrinsic hemolytic normocytic anemia: Pathology review

00:00 / 00:00



Intrinsic hemolytic normocytic anemia: Pathology review

Hematological system

Coagulation disorders


Vitamin K deficiency

Leukemoid reaction

Leukemoid reaction


Intrinsic hemolytic normocytic anemia: Pathology review

USMLE® Step 1 questions

0 / 7 complete


USMLE® Step 1 style questions USMLE

of complete

A 15-year-old boy with a history of sickle cell disease presents to his primary care physician for evaluation of bone pain in the right leg, fevers, and difficulty walking. The physician suspects osteomyelitis. Which of the following is the most likely causative pathogen?  


On the hematology ward, there’s a mother with her daughter, Kyra, a five -year old that has developed jaundice and complains of easy fatigability. She is an adopted child with an unknown family history. Clinical examination reveals a palpable spleen. Next to her, there’s a 35-year-old person of African descent, called Darnell, who started trimethoprim-sulfamethoxazole for treatment of acute prostatitis a few weeks ago. Recently, he developed jaundice, dark urine, back pain and fatigue. There’s also a father who brought Billy, his 13-year-old son, to the emergency department because of a painful and prolonged erection. CBC is ordered for all of them and it shows low hemoglobin with normal MCV and reticulocyte count index over 2%. They also have increased LDH. Now, Kyra also has an increased MCHC and spherocytes on peripheral blood smear, while Billy has sickled cells.

Although their symptoms are very different, they all suffer 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.This level varies based on the age for children. Now, anemias can be broadly grouped into 3 categories based on mean corpuscular volume, or MCV, which reflects the volume of a red blood cell. 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 and extrinsic hemolytic anemias. In intrinsic hemolytic anemias, the RBCs are destroyed due to RBC membrane defects, like in hereditary spherocytosis and paroxysmal nocturnal hemoglobinuria, or PNH; enzyme deficiencies, like in glucose 6 phosphate, or G6PD, deficiency and pyruvate kinase deficiency; and hemoglobin abnormalities, like in sickle cell anemia. Now, in extrinsic hemolytic anemias, the RBCs are normal but are later destroyed via extrinsic mechanisms such as autoantibodies directed against RBCs. In this video, let’s focus on intrinsic hemolytic anemias.


  1. "Kaplan USMLE Step 2 CK Lecture Notes Internal Medicine" Kaplan Medical (2017)
  2. "Robbins Basic Pathology" Elsevier (2017)
  3. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  4. "Hereditary Spherocytosis - Diagnosis, Surgical Treatment and Outcomes. A Literature Review" Chirurgia (2017)
  5. "Old and new insights into the diagnosis of hereditary spherocytosis" Annals of Translational Medicine (2018)
  6. "Pathophysiology, diagnosis, and treatment of paroxysmal nocturnal hemoglobinuria: a review" European Journal of Haematology (2015)
  7. "Diagnosis and management of PNH: Review and recommendations from a Belgian expert panel" European Journal of Haematology (2018)
  8. "Glucose-6-Phosphate Dehydrogenase Deficiency" Hematology/Oncology Clinics of North America (2016)
  9. "Sickle cell disease: a review. Immunohematology" Roseff SD (2009)
  10. "Management of Sickle Cell Disease: A Review for Physician Education in Nigeria (Sub-Saharan Africa)" Anemia (2015)
  11. "Diagnostic approach to hemolytic anemias in the adult" Revista Brasileira de Hematologia e Hemoterapia (2015)

Copyright © 2023 Elsevier, its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Cookies are used by this site.

USMLE® is a joint program of the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME). COMLEX-USA® is a registered trademark of The National Board of Osteopathic Medical Examiners, Inc. NCLEX-RN® is a registered trademark of the National Council of State Boards of Nursing, Inc. Test names and other trademarks are the property of the respective trademark holders. None of the trademark holders are endorsed by nor affiliated with Osmosis or this website.