Red Blood Cells

Bag of Red Blood Cells
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What are Packed Red Blood Cells?

Packed red blood cells (PRBCs) are a blood product obtained by separating red blood cells (RBCs) from whole blood. During this process, the plasma, platelets, and white blood cells are removed, leaving behind a concentrated solution of red blood cells suspended in a small amount of residual plasma. PRBCs are then stored in a preservative solution, allowing them to be stored for a longer period, usually up to 42 days. 

PRBC usage

Packed Red Blood cells account for the majority of blood components transfused in a given year at a transfusion center (which is usually based in a hospital). The American Red Cross estimates there are roughly 40,500 transfusions per day in the US. A whopping 72% of these transfusions consist of packed Red Blood Cells. Packed Red Blood Cells are units of Red Blood Cells manufactured by centrifuging/separating whole blood into it's respective parts (Red Blood Cells/Platelets/Plasma). You are unlikely to receive Red Blood Cells in any other form. Some transfusion centers provide units of whole blood for emergent trauma needs. 

RBC Characteristics

Red Blood Cells (also known as erythrocytes) are biconcave disk or doughnut shaped cells within our circulatory system that perform a vital function. RBCs pick up oxygen from the lungs and carry oxygen throughout the body, oxygenating the bodies organs and tissues, keeping them lively, healthy, and functioning. RBCs are able to perform this function due to the major protein comprising the cell, hemoglobin. Hemoglobin makes up most of the Red Blood Cell's 'dry weight' and is responsible for the distinct red hue of blood itself.

Interestingly, upon visual, oxygenated blood tends to look brighter red, whereas blood that has given up its oxygen to the tissues and is back on its way to transport more oxygen... is darker red. At the center of the hemoglobin molecular is an atom of Iron. This is why it's incredibly important to ensure adequate iron intake. Low iron intake (or absorption) means less iron is available to create these very necessary hemoglobin compounds.

RBC Formation

Red Blood Cells are formed in the bone marrow and pushed out into the peripheral blood after roughly one week of maturing in the bone marrow. Newly created fresh Red Blood Cells have an average lifespan of 120 days within circulation. There are multiple diseases that shorten this lifespan, resulting in anemia. 

Erythropoietin (EPO) is a hormone that in normal circumstances is constantly produced in low levels by the kidneys to help replenish old Red Blood cells that are constantly being removed from circulation. EPO tells the bone marrow to create more Red Blood cells. If the body senses low levels of oxygen reaching the tissues (hypoxia) it will produce more EPO to compensate and tell the bone marrow to create more Red Blood Cells. This can happen in situations such as sleep apnea or COPD, or can also happen in cases of anemia. Anemia is the lack of adequate Red Blood Cell counts, thus lower hemoglobin levels, thus lowered ability to oxygenate the bodies tissues as effectively.

Indications for Red Blood Cell Transfusion

Red Blood Cell transfusions, or more specifically, packed Red Blood Cell transfusions are used to correct anemia in a patient. Transfusions will not cure anemia, they are a treatment for anemia. Your doctor will need to figure out the underlying cause for anemia and create a curative plan from that information. Generally anemia is regarded as having a lack or decrease of the normal amount of Red Blood Cells in circulation. A lack of Red Blood Cells would then, as a result, mean a lessened amount of available hemoglobin, as well as a lower hematocrit percentage. 

Hematocrit / Hemoglobin

The hematocrit is a percentage of Red Blood Cells per entire blood volume. So, if a persons hematocrit is 45%, the rest of their blood is 55% plasma (with a small amount of this percentage including white blood cells and platelets as well) The reference ranges for these numbers differ between men and women. Men tend to have slightly higher RBCs/Hemoglobin(Hgb)/Hematocrit(Hct). Doctors generally focus on the "H&H" in regards to anemia, which is short for Hemoglobin and Hematocrit. The RBC value is not usually the most important factor when evaluating anemia. 

Normal Ranges

Men typically have anywhere from 14 - 17 g/dL (grams per deciliter) of hemoglobin and a hematocrit of 40.5-50.5%. 

Females typically range from 12 - 15 g/dL of hemoglobin and a hematocrit of 36%-44.5%.

Abnormal Results

Anything under these ranges would technically be considered anemia. It would be up to the physician evaluating to make that diagnostic decision. If anemia is suspected your doctor would likely order a Complete Blood Count which would include testing for the amount of RBCs, Hemoglobin, Hematocrit, and a few other parameter such as number of white blood cells/platelets, etc.  

In the US, the general trigger point for transfusion is when the hemoglobin reaches 7g/dL or lower. Certain populations may require a higher baseline number, such as cardiac patients and may be transfused when their hemoglobin reaches 8 or 9. Patients may also be transfused at a higher number simply if they are symptomatic and exhibiting signs that a transfusion is required. Patients with Sickle Cell Disease have lower than average baseline hemoglobin and may be transfused at different levels as well depending on their symptoms. 

Packed Red Blood Cells Specifics

How much does a unit of Red Blood Cells Raise Hemoglobin?

For an average sized adult, a unit of packed Red Blood Cells would be expected to raise the patients hemoglobin by 1g/dL (One gram per deciliter) and the patient's hematocrit by 3%.

 How much is in a unit of Packed Red Blood Cells?

A unit of packed Red Blood Cells is roughly 350mL, give or take.  A unit of packed Red Blood Cells has a hematocrit of anywhere from 55-80%. This is dependent on the donor's hematocrit as well as the type of unit additives that are used. 

Additive solution units will generally have lower hematocrits, whereas non-additive units will have higher hematocrits. This simply means there is a higher concentration of RBCs vs plasma and/or additive solution in the bag. Non-additive units like CPDA-1, will have roughly 100mL less volume than an additive unit containing additives such as AS-1,AS-3, etc and have roughly 250mL of volume.

Additive Vs Non-Additive PRBCs

Non-additive units are less common and are generally processed on donors who meet certain criteria to donate for neonatal and pediatric populations. Typically the most common criteria are being O negative and CMV (Cytomegalovirus) negative. O positive donors are sometimes also used for non additive units. Non-additive units are important for neonatal and pediatric populations as the additives used in additive units may not be tolerated well by the body in a neonatal or underdeveloped pediatric patient. Unit additives are perfectly safe for older pediatrics and adults. 

Additive units last longer in refrigerated storage as well. Units with additive solution such as AS-1 or AS-3 will be usable under refrigeration for up to 42 days post collection. Non-additive units treated only with anticoagulant solution CPDA-1 units last up to 35 days post collection under refrigeration.

Frozen Red Blood Cells

Packed Red Blood Cells are rarely frozen. Red Blood Cells will be frozen only for extreme cases in which the donor has an exceeding rare Blood Type phenomenon (such as Bombay Phenotype or an extremely rare antigen phenotype). Frozen Red Blood Cells must be treated with glycerol prior to freezing. Failure to treat with glycerol would destroy the Red Blood Cells. As the unit of Red Cells freezes, any of the liquid portion of the unit will begin to form ice crystals. These ice crystals will quite literally cause the Red Blood Cells to lyse or "pop". The addition of glycerol helps to prevent this from happening. Once thawed, the glycerol must be removed prior to transfusion. The entire process is lengthy, expensive, and seldom seen in transfusion centers but the option always exists for those in need!

Red Blood Cell Transfusions

Red Cell transfusions generally take the longest out of any of the types of blood components to transfuse. This is due to the relatively high viscosity (thickness of the solution) compared to platelets or plasma which is nearly liquid. A typical Red Cell transfusion can take one to four hours to complete. The speed depends on numerous factors such as whether it's a life-threatening need or routine transfusion, how well previous transfusions have been tolerated, patient's cardiac and overall health. Four hours is the MAXIMUM amount of the time for transfusion and is known as the Four Hour Rule. This is in place to ensure the safest possible transfusion. Beyond 4 hours, the unit has been spiked open and out of refrigeration for so long the risk of bacterial contamination and growth starts to increase.

Causes of Anemia Requiring Red Blood Cell Transfusion 

Anemia can be caused by many conditions. Typically anemias can be lumped into three different categories. Decreased production of Red Cells, Increased destruction of Red Cells, or acute Blood Loss from things like Trauma/Surgery/Childbirth/etc. 

Anemias caused by Decreased Production

Aplastic Anemia

Anemia caused by failure of the bone marrow to produce adequate numbers of Red Blood Cells. Can be caused by autoimmune antibodies directed towards the bone marrow, exposure to chemicals, etc. Some reasons are unknown as to why aplastic anemia forms. 

Iron Deficiency Anemia

Anemia associated with a deficiency of Iron. As mentioned before, Iron is required to form the compound hemoglobin within the Red Blood Cell. Patient's with IDA will have smaller than normal Red Blood Cells as well due to a direct result of have less hemoglobin capabilities per Red Blood Cell. 

Anemia of Chronic Disease

Anemia seen in those with chronic infections, inflammation, autoimmune issues, cancers. These situations can activate a chain of reactions that start with activating a pro-inflammatory cell signaling molecule called Interleukin-6 (IL-6). The end result is lower usable iron within circulation, and thus similar problems arise like that of Iron Deficiency Anemia. 

Leukemia and other Hematologic Malignancies

Leukemias, Multiple Myeloma, Myelodysplastic Syndrome, Lymphomas, etc. can cause anemia. One of many ways this happens is due to the leukemic or malignant cells overcrowding the bone marrow causing the cancerous cells to flourish rather than the normal healthy cells. 

Chronic Kidney Disease

Anemia can be seen in CKD, especially in later stages, due to the fact that the kidney is the organ that makes Erythropoietin, the hormone that tells the bone marrow to create Red Blood Cells at a normal rate (and under other certain conditions such as perceived hypoxia.). With impaired EPO production, your body lacks this important signaling hormone. 

Vitamin B12/Folate Deficiency

These vitamins are required for proper Red Blood Cell development. Vitamin B12 in particular is required for DNA synthesis. This impaired and delayed synthesis causes cells to grow large while waiting for synthesis to complete and also form in fewer numbers due to lack of substrate. These vitamin deficiencies could be caused to do poor diet, poor absorption, and/or alcoholism. 


patients on chemotherapy for hematological malignancies will often need continuous transfusion support throughout their time spent on chemo. The chemotherapeutic agents that affect cancerous cells can also cause normal healthy cells to be destroyed. These agents can also affect the bone marrow which affects blood cell production.

Anemias Caused by Increased Destruction

When Red Blood Cells have increased destruction, this is generally caused by hemolytic anemia. Hemolytic refers to hemolysis which means rupture of blood cells. Hemolytic anemia can be caused by many factors and causes anemia by destroying Red Blood Cells at a faster pace than the bone marrow can keep up. 

Hemoglobin defects

Defects in how hemoglobin in made within the cell can account for increased destruction of Red Blood Cells. Sickle Cell Anemia and Thalassemia are the two most common disorders involving hemoglobin defects.

Cellular defects

Hereditary disorders that cause the cell membrane of the Red Blood Cell to be altered resulting in a lesser lifespan and increased fragility and destruction exist. Diseases such as hereditary elliptocytosis and hereditary spherocytosis fit this definition. 

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

G6PD is essential for protection of Red Blood Cells from free radicals that can cause oxidative stress that could prematurely destroy the cell. With G6PD deficiency patients are more likely to experience shortened RBC lifespan due to the decreased ability to keep RBCs safe from these free radicals. 


Infections, especially from blood borne parasites such as Malaria and Babesia can cause increased destruction of Red Cells

Autoimmune Diseases

Autoimmune processes can cause increased destruction of red cells. Warm or Cold Auto-immune Hemolytic anemia exists in which the bodies immune system attacks its own Red Cells causing anemia. Warm or Cold simply refers to the temperature at which the autoantibody reacts (Warm=body temperature Cold=Room temperature or colder). Other autoimmune diseases such as Lupus or Cold Agglutinin Disease would fit this description. 


Cancers can cause autoimmune hemolytic anemia as well 


Certain prescription drugs can also cause a Drug Induced Hemolytic Anemia. Some of the most common include Methyldopa, Nitrofurantoin, Levodopa, NSAIDs, Cephalosporins, Pyridium, Levofloxacin, and Quinidine. 


The final cause of one's anemia can be attributed to simply bleeding. Trauma patients may bleed acutely from their initial injuries and continue to bleed slowly for some time until the body is fully healed. There could be bleeds related to childbirth, surgery, GI bleed, esophageal varices, ulcers, etc. 

PRBC Compatibility Testing 

Type and Screen

Prior to transfusion, the physician will order a Type and Screen. This is semi-short for Blood Type and Antibody Screen. This is to determine your Blood Type as well as if you have any antibodies directed towards "antigens" on your Red Blood Cells. The most common reason for someone to have made an antibody towards Red Cell antigens is if they've been pregnant or had a prior transfusion in the past.

In rare occasions, it is possible for someone to create an autoantibody towards their own red blood cells as well, without having history of transfusion or pregnancy. This is where the transfusion center Blood Bank comes in to play, and will be able to identify what these antibodies are in order to provide compatible blood. 

Patient's that do not have antibodies (the vast majority of people don't) will be able to receive crossmatched and type-specific blood in under an hour. The transfusion center Blood Bank will crossmatch a unit of blood that is compatible with with the patient's Blood Type.


Crossmatch simply means they take plasma of the recipient and mix it with the Red Blood Cells of the donor unit. If there is a clumping reaction, the unit is incompatible and should not be given. If there is no reaction observed, the unit is considered crossmatch compatible and is safe for transfusion from a serological perspective. Computerized systems have made this even easier. If the patient has a history of NO antibodies on file, and has at least two matching Blood Type's on file with the specific Transfusion Center Blood Bank, an "electronic crossmatch" can take place which allows for nearly instant availability of crossmatched RBCs. No physical testing of the units needs to take place. If the patient has an antibody or Blood Typing discrepancy, the Blood Bank will do a physical crossmatch at the lab bench.    

Despite best efforts, patients will still occasionally have side effects or other reactions to receive blood products. It is rare, but does happen. Reactions can range from mild to severe depending on the cause. See the transfusion reactions page for more information.