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.