USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 58-year-old woman comes to the office for a follow-up visit. She was diagnosed with stage II adenocarcinoma of the colon following a colonoscopy two months ago. She subsequently underwent surgical resection of the tumor and was placed on adjuvant chemotherapy. Her regimen includes a drug whose activity is enhanced with the addition of leucovorin. Which of the following diagnostic tests or laboratory values are the most appropriate to monitor the patient for adverse reactions to the aforementioned drug?
Aplastic anemia is a pancytopenia, meaning all blood cell lines are decreased - so the term aplastic anemia, which just refers to low red blood cell count, is actually a misnomer.
So with aplastic anemia, there’s actually anemia, as well as leukocytopenia, or low white blood cells, as well as thrombocytopenia, or low platelet levels.
This condition takes many forms, ranging from mild to severe depending on the cause.
Now, blood cells are produced in the bones of the body, mainly in the bones of the pelvis, ribs and sternum, through a process called hematopoiesis.
This process starts in the bone marrow, the innermost portion of bone, where the hematopoietic stem cells reside.
These serve as progenitor cells for all the different cell types found in the blood.
First, hematopoietic stem cells, also called hemocytoblasts, can become lymphoid progenitors or myeloid progenitors.
The myeloid progenitors can differentiate into erythrocytes, or red blood cells, megakaryocytes, which eventually give rise to platelets, or myeloblasts, which can then become other white blood cells like monocytes, neutrophils, basophils, and eosinophils.
The most common cause of aplastic anemia is autoimmune destruction of hematopoietic stem cells.
The details of this mechanism are not fully understood, but research shows that there are alterations in the immunologic appearance of hematopoietic stem cells because of genetic disorders, or after exposure to environmental agents, like radiation or toxins.
This means that the hematopoietic stem cells start expressing non-self antigens and the immune system subsequently targets them for destruction.
As the immune system destroys hematopoietic stem cells a whole host of complications arise.
Due to the low red blood cell count tissues cannot properly oxygenate so the heart pumps harder to circulate the red blood cells leading to chest pain and shortness of breath.
Low platelet counts lead to an increased risk of bleeding from the most minor injuries and in mucosal areas. Low white blood cells counts lead to the body’s inability to fight off common infections that can lead to sepsis.
Now, there are many causes of aplastic anemia, but the disease is most often idiopathic, or without an identifiable cause.
Definable causes of aplastic anemia include radiation and toxins like insecticides or industrial agents that contain benzene.
Drugs that may cause aplastic anemia include chemotherapeutic agents, anti-seizure medications, antiinflammatory medications like indomethacin, antithyroid medications like propylthiouracil and methimazole, and antibiotics like chloramphenicol and sulfonamides.
- "Robbins Basic Pathology" Elsevier (2017)
- "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
- "Current concepts in the pathophysiology and treatment of aplastic anemia" Hematology (2013)
- "Aplastic anaemia" Hematology (2013)
- "Aplastic Anemia" New England Journal of Medicine (2018)
- "Harrison's Principles of Internal Medicine" McGraw-Hill (2004)
- "The complex pathophysiology of acquired aplastic anaemia" Clinical & Experimental Immunology (2015)