Transfusions

Transfusions of Whole Blood

Whole blood refers to human blood transfusion from a standard blood donation.

Learning Objectives

Describe whole blood in terms of transfusions

Key Takeaways

Key Points

  • Whole blood can be separated into its components: red blood cells, plasma, and platelets.
  • Blood can be transfused in either its relatively unprocessed form as whole blood, or through the administration of its processed and separated cellular or plasma componenets.
  • Plateletpheresis is a more efficient way to extract platelets than whole blood extraction, because plateletpheresis produces platelets that are more highly concentrated.
  • The blood is separated into distinct plasma and cellular layers by centrifugation, by sedimentation, or simply through gravity over a longer period of time.
  • Whole blood transfusion has similar risks to a transfusion of red blood cells and must be cross-matched based on blood type to avoid hemolytic transfusion reactions and other complications.

Key Terms

  • buffy coat: The fraction of an anticoagulated blood sample that contains most of the white blood cells and platelets following density gradient centrifugation of the blood.
  • centrifuge: A device in which a mixture of denser and lighter materials (normally dispersed in a liquid) is separated by rotation around a central axis at high speed.
  • plasma: The straw-colored/pale-yellow liquid component of blood that normally holds the blood cells of whole blood in suspension.

Blood transfusions are a key therapeutic component to treating those with excessive blood loss from severe injury or surgery. Whole blood refers to blood drawn directly from the body from which none of the components, such as plasma or platelets, have been removed. The blood is typically combined with an anticoagulant during the collection process, but is otherwise unprocessed. Whole blood may also be altered and processed for use in blood transfusion.

Blood Processing

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Centrifuged Blood: Whole blood is a term used in transfusion medicine for human blood from a standard blood donation.

Historically, blood was transfused as whole blood without further processing. Most blood banks now split the whole blood into two or more components, typically red blood cells and a plasma component such as fresh frozen plasma, which is extracted frozen plasma from the blood splitting process.

Platelets for transfusion can also be prepared from the buffy coat of whole blood, which has therapeutic benefits for those with platelet disorders or impaired clotting ability. Some blood banks have replaced this with platelets collected by plateletpheresis, a process in which platelets are extracted during initial blood collection. Plateletpheresis is more efficient because whole blood platelets typically aren’t concentrated enough to have a useful effect, while plateletpheresis platelets are highly packed and concentrated. It also minimizes the chance for platelet transplant rejection because a single donor will be able to contribute enough platelets via plateletpheresis.

The collected blood is generally separated into components by one of three laboratory methods:

  • Centrifuge quickly separates whole blood into plasma, buffy coat, and red cells by using centrifugal force to drop the cellular components to the bottom of a container.
  • Sedimentation, in which whole blood sits overnight, causing the red blood cells and plasma to settle and slowly separate by the force of normal gravity.

Practical Considerations

Whole blood transfusion has similar risks to those of transfusion of red blood cells. It must be cross-matched on the basis of blood type to avoid hemolytic transfusion reactions. Most of the indications for use are identical to those for red blood cells. Whole blood is not used because the extra plasma can contribute to transfusion associated circulatory overload (TACO), a potential complication that can dangerously increase blood pressure, causing pulmonary edema and acute respiratory distress.

Whole blood is sometimes “recreated” from stored red blood cells and fresh frozen plasma for neonatal transfusions. This provides a final product with a very specific hematocrit (percentage of red cells) with type O red cells and type AB plasma to minimize the chance of complications.

Whole blood is typically stored under the same conditions as red blood cells and can be kept up to 35 days if collected with CPDA-1 storage solution or 21 days with other common storage solutions such as CPD. If the blood will be used to make platelets, it is kept at room temperature until the process is complete. This must be done quickly to minimize the warm storage of RBCs in the unit.

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Blood Transfusions: Blood transfusions are common during surgeries.

Plasma and Blood Volume Expanders

A volume expander is a type of intravenous therapy that provides fluid replacement for the circulatory system.

Learning Objectives

Evaluate the use of blood volume expanders

Key Takeaways

Key Points

  • During blood loss, the amount of oxygen that can be delivered to the tissues is reduced due to lost red blood cells and decreased blood volume, which also causes a decrease in blood pressure.
  • Although they cannot replace lost red blood cells, blood volume expanders can help improve oxygen delivery in instances of blood loss by increasing blood volume and blood pressure so that blood can flow to the tissues.
  • Survival is possible with low red blood cell and hemoglobin levels as long as blood volume and blood pressure are maintained so blood continues to reach tissues.
  • Hypovolemic shock occurs when tissue oxygenation drops due to a decrease in blood volume.
  • Crystalloids volume expanders are aqueous solutions of mineral salts or other water-soluble molecules. Although they decrease the osmotic pressure by diluting the red blood cells, they increase both vascular and interstitial volume.
  • Colloids volume expanders contain larger insoluble molecules, such as gelatin or hydroxyethyl starch, and theoretically increase the intravascular volume but not interstitial and intracellular volumes.

Key Terms

  • crystalloid: Aqueous solutions of mineral salts or other water-soluble molecules, such as saline solution.
  • hypovolemic shock: Shock due to decreased blood volume, such as through severe bleeding or vomiting. It activates dangerous compensatory mechanisms that maintain blood flow to the brain while causing other organs to fail.
  • colloid: Blood volume expander containing larger insoluble molecules that exert osmotic pressure.

When blood is lost, the greatest immediate need is to stop further blood loss, then lost volume must be replaced. Blood volume is directly proportional to the blood pressure in the body, and when both decrease the flow of blood to important tissues may be inhibited. The remaining red blood cells can still oxygenate body tissue. A volume expander is a type of intravenous therapy that provides blood volume for the circulatory system. It may be used for fluid replacement.

Blood Volume and Oxygen Transport

Normal human blood has a significant excess oxygen transport capability because not all of the hemoglobin molecules are loaded with oxygen under normal conditions. As long as pulmonary function is sufficient for gas exchange and there is enough blood volume to have sufficient blood pressure, very low hemoglobin levels will be enough to sustain the patient. Those with low hemoglobin content will not be able to tolerate situations where a greater amount of oxygen is required (exercise, for example) until their hemoglobin levels are restored.

The body has compensatory feedback mechanisms to deal with lower hemoglobin levels. For instance, the heart pumps more blood with each beat, which increases blood pressure. Blood pressure is detected by the renal system, which increases blood volume and blood pressure by excreting less water during blood filtration. As a result of partial pressure gradient changes, more oxygen is released to the tissues. These adaptations are so effective that if only half of the red blood cells remain, oxygen delivery will still be around 75% of normal. A patient at rest only uses 25% of the oxygen available in their blood. In extreme cases, patients have survived with a hemoglobin level of about 1/7 the normal (i.e. 2 g/dl), although levels this low are very dangerous.

When blood loss is significant, the red blood cell level ultimately drops to a level that is too low for adequate tissue oxygenation. This is marked by hypoxia and hypovolemic shock, a condition in which tissue oxygenation drops from a lack of blood volume and harmful compensatory mechanisms activate, causing more damage. In these situations, the only alternatives are blood transfusion, packed red blood cells, or oxygen therapy.

Types of Volume Expanders

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Saline solution: A bag of saline. Saline can be used to increase blood volume when a blood transfusion is not possible.

There are two main types of volume expanders: crystalloids and colloids. Crystalloids are aqueous solutions of mineral salts or other water-soluble molecules. Colloids contain larger insoluble molecules, such as gelatin; blood itself is a colloid. There are also a few other volume expanders that may be used in certain situations:

  • Colloids: These solutions preserve a high-colloid osmotic pressure (protein-exerted pressure) in the blood, while this parameter is decreased by crystalloids due to hemodilution. The higher osmotic pressure from colloids draws fluids inward, preventing it from leaking out into the tissues as easily, which increases intravascular blood volume.
  • Crystalloids: The most commonly used crystalloid fluid is normal saline, a solution of sodium chloride at 0.9% concentration, which is close to the concentration in the blood (isotonic). Saline solution is administered intravenously (IV drips) and increases both intravascular and interstitial volume. They decrease osmotic pressure by diluting the blood.
  • Dextrose Water: This solution contains dextrose, a form of glucose. It is given to patients who have dangerously low blood sugar levels (important for cellular metabolism) as well as low blood volume.

Another common volume expander includes hydroxyethyl starch (HES/HAES, common trade names: Hespan, Voluven) which is considered a colloid. An intravenous solution of hydroxyethyl starch is used to prevent shock following severe blood loss caused by trauma, surgery, or another problem. It increases the blood volume, allowing red blood cells to continue to deliver oxygen to the body. When tissue blood perfusion is maintained, shock is averted as the dangerous compensatory mechanisms of shock aren’t activated.

Blood Groups and Blood Types

Red blood cells have surface-expressed proteins that define the self/not-self nature of the cells.

Learning Objectives

Evaluate the ABO and Rhesus blood groups in terms of donors and recipients

Key Takeaways

Key Points

  • Surface-expressed proteins called antigens on red blood cells determine an individual’s blood type. There are two types of antigen groups: the ABO system antigens and a Rhesus D antigen.
  • Exposure to a blood group antigen that is not recognized as self will cause the immune system to make specific antibodies to the new blood group antigen, often leading to destruction of the cells.
  • Knowing an individual’s antigen type is important to ensure compatibility if a transfusion is needed.
  • Blood type is inherited. O type is the most common despite being a recessive gene because it is more highly expressed in the gene pool, while type A and type B are dominant (and type AB is codominant) but are less common because they are less expressed in the gene pool.
  • Individuals may also be positive or negative for the rhesus D antigen in addition to their blood type. Rhesus D complications are common during fetal development if the parents differ in rhesus antigen expression.

Key Terms

  • antibodies: Also known as an immunoglobulin (Ig), a large Y-shaped protein produced by B-cells that is used by the immune system to identify and neutralize foreign objects such as bacteria and viruses.
  • antigen: A substance that induces an immune response, usually foreign.

Red blood cells have surface-expressed proteins that act as antigens, which are molecules that can illicit an immune system response. Red blood cells belong to different groups on the basis of the type of antigen that they express. Blood type determines compatibility for receiving blood transfusions from other people.

The ABO Blood Group System

If an individual is exposed to a blood group antigen (A or B) that is not recognized as self, the individual can become sensitized to that antigen. This will cause the immune system to make specific antibodies to a particular blood group antigen and form an immunological memory against that antigen. These antibodies can bind to antigens on the surface of transfused red blood cells (or other foreign tissue cells), often leading to destruction of the cells by recruitment of other components of the immune system.

Knowledge of an individual’s blood type is important to identify appropriate blood for transfusion or tissue for organ transplantation. There are four blood types that differ based on the antigen expressed by the red blood cell and by the type of associated antibody found in the plasma. The type of antigen determines which blood types that blood type may safely be donated to, while the type of antibody determines which types of antigen (and types of blood) will be rejected by the body.

This chart depicts blood type classification. Group A has a red blood cell type A, plasma antibody of anti-B, red blood cell antigen A. Group A has a red blood cell type B, plasma antibody of anti-A, red blood cell antigen B. Group AB has a red blood cell type AB, no plasma antibody, red blood cell antigens A and B. Group O has a red blood cell type ), plasma antibodies of anti-A and anti-B, no red blood cell antigen.

Blood type classification: Blood type (or blood group) is determined, in part, by the ABO blood group antigens present on red blood cell.

  • Blood group A individuals have the A antigen on the surface of their RBCs, and blood serum containing IgM antibodies against the B antigen. Therefore, a group A individual can only receive blood from individuals of groups A or O types, and can donate blood to individuals of groups A or AB.
  • Blood group B individuals have the B antigen on their surface of their RBCs, and blood serum containing IgM antibodies against the A antigen. Therefore, a group B individual can only receive blood from individuals of groups B or O, and can donate blood to individuals of groups B or AB.
  • Blood Group AB individuals have both A and B antigens on the surface of their RBCs, and their blood serum does not contain any antibodies against either A or B antigen. Therefore, an individual with type AB blood can receive blood from any group, but can only donate blood to another group AB individual. AB blood is also known as “universal receiver.”
  • Blood group O individuals do not have either A or B antigens on the surface of their RBCs, but their blood serum contains IgM antibodies against both A and B antigens. Therefore, a group O individual can only receive blood from a group O individual, but they can donate blood to individuals of any ABO blood group (i.e. A, B, O, or AB). O blood is also known as “universal donor.”

Blood types are inherited and represent genetic contributions from both parents. The gene that codes for blood type contains three alelles: IA and IB which give type A and B blood and are dominant, and i, which is recessive and codes type O. Children will have blood types similar to their parents based on inheritance. The i allele is far more commonly expressed in the gene pool than IA and IB, which is why type O blood is the most common type despite being a recessive phenotype. Type AB is the rarest because it is the combination of less commonly expressed alleles, and is the result of codominance between IA and IB alelles.

Rhesus Factor

Many people also have the rhesus D (Rh) antigen expressed by their red blood cells. Those that are have Rh antigens are positive for Rh, while those that don’t have it are Rh negative (ie. type O+ is type O with rhesus, type A- is type A without rhesus). Rh positive individuals do not have the antibodies for the Rh factor, but can make them if exposed to Rh. Besides being a consideration for blood transfusion, parents who differ based on Rh status must be cautious to ensure that maternal antibodies do not destroy their child’s red blood cells during fetal development, which can cause hemolytic anemia.

Typing and Cross-Matching for Transfusions

Blood banks test donor blood to ensure recipient compatibility, reducing the risk of hemolytic reaction, renal failure, and death.

Learning Objectives

Explain the purposes of typing and of cross-matching blood prior to transfusion

Key Takeaways

Key Points

  • Transfusion medicine is important to treat those with blood loss.
  • Given enough time, cross-matching is performed to ensure that donated blood will not cause a transfusion reaction.
  • Cross-matching involves mixing a sample of the recipient’s serum with a sample of the donor’s red blood cells and checking if the mixture agglutinates due to antibody reactivity.
  • If a transfusion with non-matched blood occurs, the patient risks red blood cell destruction, renal failure, shock, and death.

Key Terms

  • hemolysis: The destruction of red blood cells from pathological causes, such as infection or immune system mediated damage.
  • agglutinate: The act of red blood cells clumping together due to antibody reactivity.

Transfusion medicine is extremely effective at treating those with severe blood loss. Transfusions are often a required component of major surgeries. Due to the different antigen blood types, blood must be cross-matched during processing to avoid potential complications.

The Cross-Matching Process

Much of the routine work of a blood bank involves testing blood from both donors and recipients to ensure that every recipient is given blood that is compatible and is as safe as possible. Several laboratory tests allow cross-matching of compatible blood between donor and recipient. Patients should ideally receive their own blood or type-specific blood products to minimize the chance of a transfusion reaction. Risks can be further reduced by cross-matching blood, but this process isn’t always performed if time is short and the need for transfusion has not been anticipated.

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Agglutinated RBC: Red blood cells can agglutinate if the serum contains antibodies against the expressed proteins. In this image, the blood serum contains anti-A3 antibodies, which attack and agglutinate type A blood.

Cross-matching involves mixing a sample of the recipient’s serum with a sample of the donor’s red blood cells and checking if the mixture agglutinates, or forms clumps. These clumps are the result of antibodies binding the red blood cells together. If agglutination is not obvious by direct vision, blood bank technicians check for agglutination with a microscope. If agglutination occurs, that particular donor’s blood cannot be transfused to that particular recipient. In a blood bank, it is vital that all blood specimens are correctly identified, so labeling has been standardized using a barcode system known as ISBT 128. The blood group may be included on identification by military personnel in case they need an emergency blood transfusion.

Potential Transfusion Complications

If a patient receives blood during a transfusion that is not compatible with his or her blood type, severe problems can occur. Acute hemolytic transfusion reactions occur if donated blood cells are attacked by matching host antibodies. This can cause shock-like symptoms, such as fever, hypotension, and disseminated intravascular coagulation from immune system mediated endothelial damage. Transfusion reactions are also associated with acute renal failure. Lung injury is common as well, due to pulmonary edema from fluid overload if plasma volume becomes too high or neutrophil activation during a transfusion reaction. If the donated blood is contaminated with bacteria, it may induce septic shock in the patient.