Intrinsic hemolytic normocytic anemia: Pathology review


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Intrinsic hemolytic normocytic anemia: Pathology review

Hematology and oncology

Hematology and oncology

Anemia: Clinical (To be retired)

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

Leukemia: Clinical (To be retired)

Lymphoma: Clinical (To be retired)

Thrombocytopenia: Clinical (To be retired)

Bleeding disorders: Clinical (To be retired)

Thrombophilia: Clinical (To be retired)

Myeloproliferative neoplasms: Clinical (To be retired)

Plasma cell disorders: Clinical (To be retired)

Blood products and transfusion: Clinical (To be retired)


Anticoagulants: Heparin

Anticoagulants: Warfarin

Anticoagulants: Direct factor inhibitors

Antiplatelet medications


Hematopoietic medications

Ribonucleotide reductase inhibitors

Topoisomerase inhibitors

Platinum containing medications

Anti-tumor antibiotics

Microtubule inhibitors

DNA alkylating medications

Monoclonal antibodies

Antimetabolites for cancer treatment


Intrinsic hemolytic normocytic anemia: Pathology review

USMLE® Step 1 questions

0 / 6 complete


USMLE® Step 1 style questions USMLE

of complete

A 35-year-old man comes to the primary care office complaining of mild fatigue and shortness of breath. The patient has a past medical history significant for episodes of jaundice and intermittent right upper quadrant abdominal pain, which he has never been to the doctor for before. Temperature is 37.2°C (98.9°F), pulse is 72/min, respirations are 18/min, and blood pressure is 128/88 mmHg. Physical examination shows splenomegaly. Laboratory tests are obtained, and the results are shown below.  

Peripheral blood smear shows hexagonal crystals and target cells. This patient’s disease is most likely caused by a substitution of glutamic acid with which of the following amino acids?


Content Reviewers

Yifan Xiao, MD

Antonia Syrnioti, MD


Robyn Hughes, MScBMC

Maria Emfietzoglou, MD

Kaylee Neff

Jake Ryan

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.


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