Erythropoietin Stimulating Agents Can Prevent The Progression of Severe Anemia

By Urbanaveed
11 Min Read

Erythropoietin Stimulating Agents Can Prevent The Progression of Severe Anemia. Erythropoietin stimulating agents (ESAs) act as life saviors when it comes to the progression of severe anemic conditions. Severe anemic conditions arise when the blood hemoglobin drops down to critical levels (values are different depending upon age, and gender factors). Due to a major drop in the hemoglobin levels, erythrocyte precursor cells make less number of erythrocytes (red blood cells). Low red blood cell concentration in the blood has potential effects on the cardiovascular system.

In the context of erythropoietin-stimulating agents, these are the medicines that can boost the production of red blood cells in the bone marrow by stimulating directly their precursor cells. Normally, kidneys produce a hormone erythropoietin (EPO) that makes the bone marrow stem cells differentiate into red blood cells. Healthy kidneys hold the responsibility for the production of the erythropoietin (EPO) hormone. Kidney abnormalities upset the function of renal cells which produce erythropoietin, thus progressing towards anemia. In this informational blog about the importance of erythropoietin-stimulating agents (ESAs), we will discuss how they play a vital role in preventing the progression of anemia in the absence of erythropoietin hormone.

How Erythropoietin Stimulating Agents (ESAs) Work in The Body?

Erythropoietin stimulating agents (ESAs) medicines are almost similar in composition to erythropoietin (EPO) hormone. Both are glycoprotein in nature. They directly bind to the red blood precursor cells in the bone marrow whose maturation gives rise to the functional red blood cells. Red blood cell precursor cells (erythroid progenitor cells) have erythropoietin receptors at their surface. These receptors have binding sites for EPO and erythropoietin-stimulating agents (ESAs). When ESAs bind to these receptors, they bring about amplifications in the genetic expression of these cells. As a result, these precursor cells effectively mature and differentiate into red blood cells.

In this way, ESAs help prevent severe forms of anemia when there is a decline in naturally producing erythropoietin (EPO) hormone. Other than kidney diseases, some inflammatory diseases such as inflammatory bowel disease cause the malabsorption of iron into the blood, potentially leading to anemia. In such cases, erythropoietin-stimulating agents alone cannot produce enough RBCs to manage anemia. As iron is an important factor in the production of RBCs, the abnormalities that cause iron deficiency in the blood, also require iron-boosting treatments along erythropoietin stimulating agents.

Such conditions include iron deficiency anemia due to a drop in soluble ferrous ions, or the loss of absorptive surface in the intestines due to inflammation, infection, or surgical bypassing. Thus, in any such condition that interferes with iron absorption, erythropoietin-stimulating agents won’t alone provide effective treatment and would require the intake of iron also.

What Can Happen to Erythropoietin (EPO) Production in The Body That Stimulates the Need For ESAs?

The most striking urgency for taking erythropoietin-stimulating agents is the inability of kidneys to produce erythropoietin (EPO). As erythropoietin stimulating agents are just replenishing the absence of erythropoietin hormone, it’s necessary to know about the importance and working mechanism of erythropoietin hormone. But remember that patients do not always take erythropoietin stimulating agents to replenish the erythropoietin hormone, sometimes, this hormone is working perfectly. In some scenarios in which anemia persists due to inflammatory or nutritional reasons, anemia due to side effects of some medicines also creates a void for erythropoietin-stimulating agents.

CKD And ERSD Effect on EPO Production

In kidney abnormalities, such as Chronic Kidney Disease (CKD) and End Stage Renal Failure (ESRD), erythropoietin production is compromised. CKD and ERSD damage the kidney tissues including the tissues and cells responsible for producing erythropoietin. Fibrocytes are the cells in the renal cortex that are responsible for erythropoietin production. Any damage to these cells, especially in the CKD and ERSD, hinders their functional ability.

The most common complications of CKD and ERSD which damage the integrity of fibrocytes are inflammation, high oxidative stress, scarring, etc. In kidney diseases when kidneys are not filtering and clearing the waste products efficiently into the renal pelvis for excretion, the waste and toxic entities start accumulating in the kidneys. Such types of interferences cause inflammation in the renal cells. However, in the case of fibrocytes, scarring is preeminent.

Scarring Affects EPO Production

High blood pressure, diabetes, the presence of toxins, and activation of inflammatory pathways act as stimuli for scarring or fibrosis. High blood pressure damages the delicate structure of renal tubules. This damage activates the tissue-repairing mechanisms, including scar formation. Scar formation of fibrosis, itself is not destructive, rather it’s constructive to repair damaged tissues. But, in abnormal conditions such as CKD and ERSD, the balance between scar formation and degradation becomes upset. A comprehensive overview of how kidney damage causes scar formation in the renal cells, including fibrocytes, is as follows;

  • Kidney damage activates immune cells to release pro-inflammatory proteins (cytokines). One such factor is Transforming Growth Factor Beta (TGF-β) which induces fibrosis.
  • Damage to the kidney tissues activates scar formation cells (myofibroblasts) to fill the gap. Myofibroblasts create a favorable environment and encourage more fibroblasts to activate and take part in the scar formation.
  • These cells start accumulating collagen, fibronectin, and other components of an extracellular matrix (ECM) into the damaged renal tissues.
  • Inflammation and underlying kidney diseases create an imbalance between ECM degrading and producing enzymes, encouraging ECM-producing enzymes.
  • Scar formation works in a positive feedback loop, promoting more fibroblasts to convert into myofibroblasts for scar formation.
  • Excessive scar impedes the functional environment of renal cells, including fibrocytes that produce erythropoietin.
  • Thus, it is obvious that in the presence of serious kidney diseases, renal functions are sacrificed. Other than blood filtration and urine production, erythropoietin secretion is also an essential role of the kidneys. Erythropoietin is the linchpin for erythrocyte formation. To complete this void of erythropoietin, erythropoietin-stimulating agents play their role.

How does the Prolonged or Excessive Use of Erythropoietin Stimulating Agents Disturb Other Body Mechanisms?

Erythropoietin stimulating agents potentially raise the blood viscosity and in turn the blood pressure. The mechanisms are simple and easy to comprehend.

Increase in Blood Pressure

More red blood cells in the blood volume highlight its smoothness and make blood a thick liquid to flow. The heart has to work more to pump this thick blood. The left ventricle has to pump this restrictive blood to the all body and an increase in pumping demand leads to left ventricular hypertrophy. Moreover, thick blood faces more resistance in the blood vessels and activates baroreceptors in the blood vessels. Baroreceptors are present in certain blood vessels such as the carotid sinus and aortic arch. When these blood vessels face blood resistance, their stretch activates baroreceptors. Baroreceptors send signals to the brain, controlling the conditions of stress. As a result, it commands the sympathetic nervous system to release adrenal hormones. Adrenal hormones, adrenaline, binds to adrenergic receptors in the peripheral system and causes vasoconstriction.

Vasoconstricting Mechanisms and High Peripheral Blood Pressure

The purpose of rise in the peripheral blood resistance lies in the intelligence in maintaining perfusion. Blood perfuses oxygen and nutrients to the body cells and tissues and vasoconstriction can assist the perfusion and push the blood to tissues. However, another intelligent role of the sympathetic nervous system lies in its ability to cause vasoconstriction in peripheral blood vessels and not in the blood vessels that supply blood to the vital organs. This keeps the blood flow normal to vital organs and lets them not to be deprived of oxygen and nutrients. Well, coming back to the topic, erythropoietin stimulating agents can induce high blood pressure in cases of excessive or misuse.

Vasoconstricting Mechanisms By The Release of Renin

Similarly, when the renal environment senses high blood pressure in renal arteries, it activates the secretion of renin. Renin is a hormone that renal cells secrete to cause vasoconstriction and fluid retention. In this context, renin releases initiate an array of events to cause vasoconstriction. Activation of angiotensin ll causes a rise in blood pressure by causing vasoconstriction. Thus, compelling force on blood creates tension in blood vessels and the body takes this tension as a form of stress.

This is not a Medical Advice

This blog helps provide general information about erythropoietin stimulating agents, their mechanism of working, complications, and importance. It is advised to ask a professional medical advice before start using or terminating medicines.

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Student of BSc MLT at NUMS, and Content Writer in Health, Medicine, and Wellness. Finding soothe in writing and spreading knowledge.
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