hematopoiesis

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.

This is called bone marrow suppression.

In some people, sargramostim can cause life threatening allergic reactions, called anaphylaxis, where blood vessels dilate, leading to hypotension.

It can also cause a problem known as capillary leak syndrome, where fluids leak from the capillaries into the surrounding tissue, causing severe edema, or swelling.

Other problems associated with this medication include fever and arthralgias, or joint pain.

The medication filgrastim is a recombinant G-CSF and is used to correct neutropenia, or low neutrophil count.

So it’s used in diseases that decrease neutrophil production like leukemia, myelofibrosis, and chronic idiopathic neutropenia.

Another indication is for people undergoing treatments that inhibit neutrophil production, like chemotherapy or radiation therapy.

Unlike sargramostim, the toxicity associated with filgrastim is minimal.

The most commonly reported side effect is bone pain, which results from the high production of new neutrophils in the bone marrow.

Severe allergic reactions can also occur, but are very rare.

Now, romiplostim, and eltrombopag are medications that stimulate platelet production to treat thrombocytopenia, or low platelet count.

Romiplostim is recombinant thrombopoietin, whereas eltrombopag is a synthetic drug that acts as an agonist at the thrombopoietin receptor on myeloid progenitor cells to stimulate megakaryocyte production.

Both romiplostim and eltrombopag are used to treat disorders where the body starts breaking down platelets, like chronic immune thrombocytopenia.

These medications can exhibit serious side effects including increased risk of clot formation due to an increase in platelet production, and eltrombopag has been associated with liver toxicity and severe bleeding, limiting its use.

Lastly, the medication epoetin is a recombinant erythropoietin, or EPO, which stimulates the production of new red blood cells.

Epoetin is an incredibly powerful drug for the treatment of anemia, or low red blood cell count, especially when the anemia is due to chronic renal failure where the damaged kidneys can’t produce enough EPO.

It’s also useful for correcting anemias caused by other medications like the HIV drug zidovudine, as well as anemia caused by certain cancers like leukemia, and anemia in critically ill patients, called anemia of chronic disease.

It’s important to note that several weeks of therapy are required before erythrocyte counts rise, so it is not an alternative to transfusing blood.

In general, epoetin is a well tolerated medication, but it could cause hypertension and increase clot formation since there’s more red blood cells in the blood.

Summary

All right, as a quick recap, hematopoietic medications help to generate different types of blood cells including white blood cells, platelets and red blood cells.

They work by acting as analogues of the various physiological growth factors produced by the body.

They are used in disorders that decrease the levels of specific blood cells or platelets, but they are also used after treatments like chemotherapy or radiation therapy that suppresses the bone marrow.