Hematopoietic growth factors: Nursing pharmacology

Hematopoietic agents are medications used to increase the production of different types of blood cells including white blood cells, red blood cells, and platelets. They are mainly used in disorders that decrease the levels of specific blood cells, but they are also used after treatments like chemotherapy, or radiation therapy, that suppresses the bone marrow.

Now, hematopoietic growth factors act like analogs or synthetic versions of the various physiological growth factors produced by the body. These include granulocyte colony-stimulating factor or G-CSF, granulocyte-macrophage colony-stimulating factor or GM-CSF, thrombopoietin agents, and erythropoietin stimulating agents or ESAs.

Let’s start with G-CSF analogs, which include filgrastim and pegfilgrastim. These medications can be administered intravenously and subcutaneously and work by increasing the production of neutrophils in the bone marrow. So they’re used to reduce the risk of infections on account of low neutrophil counts, which can be associated with leukemia, myelofibrosis, or severe, chronic neutropenia.

Another indication is for clients undergoing treatments that inhibit neutrophil production, like chemotherapy or radiation therapy for solid tumors or hematologic malignancies, as well as those receiving bone marrow transplantation. Finally, G-CSF analogs can be used in hematopoietic stem cell transplantation, where progenitor cells are mobilized from the bone marrow by G-CSF, and then collected from the peripheral blood.

The most commonly reported side effects of G-CSF analogs are nausea and bone pain, resulting from the high production of new neutrophils in the bone marrow. Other side effects include fever, fatigue, skin rashes, coughing, dyspnea or chest pain. Less commonly, alopecia or hypertension can also occur, as well as diarrhea or severe hypersensitivity reactions. Very rarely, G-CSF analogs might cause the spleen to become enlarged and rupture. In clients with sickle cell disease, sickle cell crises have also been reported.

In terms of contraindications, filgrastim should not be administered to clients with hypersensitivity to Escherichia coli–derived proteins, while pegfilgrastim should not be given within 14 days before and 24 hours after the administration of cytotoxic chemotherapy.

Moving on to GM-CSF analogs, the most commonly used one is sargramostim which is given intravenously. Once administered, it stimulates myeloid progenitors for all types of white blood cells, and it causes them to divide and differentiate into monocytes or macrophages, neutrophils, basophils, and eosinophils.

Sargramostim is often used to boost myeloid precursor production and maturation after a client undergoes a bone marrow transplant or in case of failure or delayed engraftment of the bone marrow transplant. Other uses for sargramostim include increasing the myelocyte derived white blood cell count following chemotherapy or radiation therapy. And just like G-CSF analogs, sargramostim can be used to mobilize progenitor cells in the peripheral blood for hematopoietic stem cell transplantation.

Now, with sargramostim, a side effect called the “first dose effect” can occur, when the client can experience hypotension, tachycardia and flushing. Other most common side effects include fever, fatigue and bone pain, as well as dermatological reactions, like rashes and itching; cardiovascular reactions like hypertension; gastrointestinal reactions like diarrhea, nausea and vomiting; as well as various metabolic disturbances like hyperglycemia.

It can also cause a problem known as capillary leak syndrome, where fluids leak from the capillaries into the surrounding tissue, causing severe edema. More severe side effects associated with sargramostim are sepsis, arrhythmias, liver and kidney dysfunction.

Contraindications of sargramostim include known hypersensitivity to yeast products. It should also not be administered if there are excessive leukemia myeloid blast cells in the bone marrow or peripheral blood, as well as within 24 hours after the administration of chemotherapy or 12 hours after the last dose of radiation therapy. Sargramostim should also be used with caution during pregnancy and in clients with preexisting lung, heart, kidney, or liver disease.

Now let’s switch gears to look at thrombopoietin agents, which are medications that increase platelet count. Some examples include TPO receptor agonists, like romiplostim, avatrombopag and eltrombopag, which are used in the management of immune thrombocytopenic purpura, or ITP; myelodysplastic syndrome; or aplastic anemia. Romiplostim is administered subcutaneously, while avatrombopag and eltrombopag can be given orally. Once administered, they work by activating TPO receptors on the surface of megakaryocyte cells, which leads to increased platelet production.

Unfortunately, these medications do come with side effects. Romiplostim, for example, can cause headaches, respiratory infections and GI disturbances like nausea, vomiting and diarrhea; as well as rashes, joint pain, and fever.