Hematopoietic medications

Hematopoietic medications

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Hematopoietic medications

Questions

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USMLE® Step 2 style questions USMLE

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A 60-year-old woman comes to the emergency department because of worsening shortness of breath for the past month. The patient states that she is unable to perform simple activities without getting short of breath. Today, the patient was unable to climb the stairs and decided to come to the emergency department. Past medical history is significant for hypertension, hyperlipidemia, and type 2 diabetes mellitus complicated by end-stage renal disease managed with dialysis. Current medications include insulin, metformin, lisinopril and atorvastatin. The patient is non-adherent to her medications. Temperature is 36.7°C (98.0°F), pulse is 65/min, respirations are 20/min and blood pressure is 134/83 mmHg. The EKG and chest x-ray are within normal limits. Laboratory results are shown below. There are no signs of active bleeding. The patient is given a unit of packed red blood cells with an appropriate response in her repeat hemoglobin. The physician is considering starting the patient on a medication commonly used to improve hemoglobin levels. Which of the following is a side-effect of this long-term therapy?  

Laboratory value  Result 
 Hemoglobin  6.8 g/dL 
 Hematocrit  21% 
 Leukocyte count  5,000/mm3 
 Platelet count    200,000/mm3 
 Mean corpuscular volume  81 μm3 
 Serum  
 Creatinine   2.5 g/dL 
 BUN  29 mg/dL 

Transcript

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Hematopoietic medications increase the amount of blood cells.

Ηema refers to blood and poiesis means to make.

Specifically, hematopoietic medications increase the production of erythrocytes or red blood cells, leukocytes or white blood cells, and platelets, which are small clot forming fragments of a larger cell called a megakaryocyte.

Now, before we discuss these medications in detail, let's take a step back and talk about the physiology of hematopoiesis, which can result in the production of over one hundred billion new cells every single day!

Hematopoiesis occurs in the bones of the body, but primarily in the bones of the pelvis, ribs, and sternum.

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 lymphoid progenitors can develop into lymphoblasts, which can then differentiate into T-lymphocytes, B-lymphocytes, or natural killer cells.

The myeloid progenitors can differentiate into erythrocytes, megakaryocytes, or myeloblasts, which can then become immune cells like monocytes, neutrophils, basophils, and eosinophils.

Now, in order for a hematopoietic stem cell to reach its final, mature form, the cell needs to receive the appropriate signals in the form of specific growth chemicals, called growth factors or stimulating factors.

While there are a multitude of these factors that cause differentiation of these cells, we’re only going to discuss the most important ones related to hematopoietic medications.

First, GM-CSF, or granulocyte macrophage colony stimulating factor, and G-CSF, or granulocyte colony stimulating factor, are glycoproteins released in response to infection by the endothelium, which is the inner lining of blood vessels, and immune cells such as macrophages, T-cells, and natural killer cells.

GM-CSF stimulates myeloid progenitors and causes them to divide and differentiate into all of its derivative cell types.

It also speeds up the maturation of monocytes (or macrophages), neutrophils, eosinophils, and basophils so they’ll be ready for action.

G-CSF, on the other hand, specifically induces myeloblasts to mature into neutrophils.

Next, thrombopoietin is a glycoprotein produced in the liver and kidneys.

It stimulates hematopoietic stem cells to differentiate into megakaryocytes, and also speeds up their maturation and fragmentation to generate platelets.

Finally, erythropoietin or EPO, which is produced in the kidneys, and to a lesser extent in the liver, stimulates hematopoietic stem cells and myeloid progenitors to differentiate into erythrocytes, or red blood cells.

Now, most hematopoietic medications act like analogues or synthetic versions of these growth factors.

Let’s start with sargramostim, which is a synthetic version of GM-CSF.

Sargramostim is often used to boost myeloid precursor production and maturation after a person undergoes a bone marrow transplant.

Other uses for sargramostim include increasing the myelocyte derived white blood cell count following chemotherapy or radiation therapy.

These therapies target rapidly dividing cells like cancer cells, but hematopoietic stem cells in the bone marrow are also dividing rapidly, so they almost always get affected too.

Sources

  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "Nomograms" D. Nicoll , C. Mark Lu, S.J. McPhee (Eds.), Guide to Diagnostic Tests, 7e. McGraw-Hill (2017)
  5. "Overview of hemostasis" J.C. Aster, H. Bunn (Eds.), Pathophysiology of Blood Disorders, 2e. McGraw-Hill. (2016)
  6. "Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis" Scientific Reports (2016)
  7. "The evolution of value with filgrastim in oncology" Future Oncology (2019)