Blood component therapy

Blood Component Therapy

Steven Podnos MD Slides from Dr. Su Yan MD

An adult human has about 4–6 liters of blood circulating in the body. Among other things, blood transports oxygen to various parts of the body. Blood consists of several types of cells floating around in a fluid called plasma.

1 Summarize

 1.1What is blood made up of?

 The red blood cells contain hemoglobin, a protein that binds oxygen. Red blood cells transport oxygen to, and remove carbon dioxide from, the body tissues.

The white blood cells fight infection.The platelets help the blood to clot, if you

get a wound for example.The plasma contains salts and various

kinds of proteins.

The first transfusion of blood in humans occurred in 1667. Progress was slow thereafter because of the complexities of transfusion, which we now recognize, particularly the incompatibility interspecies transfusions.

Landsteiner first described serologic differences between red cells of various individuals, allowing him to classify people into one of four groups depending on whether their red cells contained “agglutinogens” termed A or B.

Mixing blood from two individuals can lead to blood clumping or agglutination. The clumped red cells can crack and cause toxic reactions. This can have fatal consequences. Karl Landsteiner discovered that blood clumping was an immunological reaction which occurs when the receiver of a blood transfusion has antibodies against the donor blood cells.

This discovery led to a series of serologic, genetic, and immunochemical studies of red cell and other membranes.

Clinically, ABO is the most important of the red cell antigen systems identified to date.

Determination of ABO compatibility between donor and recipient is the basis of all of the pretransfusion testing.

The development of anticoagulants, blood preservatives, and sterile techniques allowed the collection and preservation of donor blood for later use.

More recently, component therapy has broadened the application of transfusion therapy from blood volume support to the specific replacement of most blood cells and many plasma proteins.

2 Red blood cell antigens

The differences in human blood are due to the presence or absence of certain protein molecules called antigens and antibodies.

The antigens are located on the surface of the red blood cells and the antibodies are in the blood plasma. Individuals have different types and combinations of these molecules.

The blood group you belong to depends on what you have inherited from your parents.

The antigenic composition of red blood cells is important in transfusion therapy. In man, 23 blood systems with 203 antigens have been identified thus far. A further 54 antigens have been identified, but not assigned to established systems.

Not all blood groups are compatible with each other.

In routine transfusion practice tests determine the compatibility of the clinically significant blood group antigens of the donor and recipient.

Antibodies reacting with red cell antigens can cause serious clinical problems.

Mixing incompatible blood groups leads to blood clumping or agglutination, which is dangerous for individuals.

Usually, same group in transfusion means ABO blood group of RBC is the same.

Determination of ABO and RH blood group is necessary before clinical transfusion.

Blood component transfusion reduces possibility of alloimmunization.

2.1 AB0 blood grouping system

According to the ABO blood typing system, there are four different kinds of blood types: A, B, AB or O .

Blood group AIf you belong to the blood group A, you have A antigens on the surface of your red blood cells and B antibodies in your blood plasma.

Blood group BIf you belong to the blood group B, you have B antigens on the surface of your red blood cells and A antibodies in your blood plasma.

Blood group ABIf you belong to the blood group AB, you have both A and B antigens on the surface of your red blood cells and no A or B antibodies at all in your blood plasma.

Blood group OIf you belong to the blood group O (null), you have neither A or B antigens on the surface of your red blood cells but you have both A and B antibodies in your blood plasma. 

Blood transfusions – who can receive blood from whom?

Of course you can always give A blood to persons with blood group A, B blood to a person with blood group B and so on. But in some cases you can receive blood with another type of blood group, or donate blood to a person with another kind of blood group.

The transfusion will work if a person who is going to receive blood has a blood group that doesn't have any antibodies against the donor blood's antigens. But if a person who is going to receive blood has antibodies matching the donor blood's antigens, the red blood cells in the donated blood will clump.

Blood-Type Genotypes Antigens Antibodies

A AA/AO A Anti-B

B BB/BO B Anti-A

O OO NoneAnti-A and

Anti-B

AB AB A and B None

The A antigen and the A antibodies can bind to each other in the same way that the B antigens can bind to the B antibodies. This is what would happen if, for instance, a B blood person receives blood from an A blood person. The red blood cells will be linked together, like bunches of grapes, by the antibodies. As mentioned earlier, this clumping could lead to death.

2.2 Rh factor blood grouping system

Many people also have a so called Rh factor on the red blood cell's surface. This is also an antigen and those who have it are called Rh+. Those who haven't are called Rh-. A person with Rh- blood does not have Rh antibodies naturally in the blood plasma (as one can have A or B antibodies, for instance).

But a person with Rh- blood can develop Rh antibodies in the blood plasma if he or she receives blood from a person with Rh+ blood, whose Rh antigens can trigger the production of Rh antibodies. A person with Rh+ blood can receive blood from a person with Rh- blood without any problems.

2.3 Blood group notation

According to above blood grouping systems, you can belong to either of following 8 blood groups:

A Rh+ B Rh+ AB Rh+ 0 Rh+

A Rh- B Rh- AB Rh- 0 Rh-

For a blood transfusion to be successful, AB0 and Rh blood groups must be compatible between the donor blood and the patient blood. If they are not, the red blood cells from the donated blood will clump or agglutinate.

The agglutinated red cells can clog blood vessels and stop the circulation of the blood to various parts of the body. The agglutinated red blood cells also crack and its contents leak out in the body. The red blood cells contain hemoglobin which becomes toxic when outside the cell. This can have fatal consequences for the patient.

The routine separation of donor blood into components and plasma fraction has made it possible for blood banks to provide the specialized blood products required for the support of patients through chemotherapy, complex surgical procedures and management of bleeding disorders such as hemophilia.

4 Blood component therapy

Blood transfusion is one of the oldest forms of therapy. Critical care frequently requires the urgent use of large numbers of blood component, often as a lifesaving supportive measure.

Actually, transfusion is a kind of transplantation of tissue cell, same as other organs ， transplantation, is all existing alloimmunization.

However, allogeneic blood may result in such permanent and severe complications as alloimmunization, viral infection, and graft-versus-host disease (GVHD), all potentially avoidable.

4.1 Red cell components

4.2 Platelet concentrate

4.3 Granulocyte transfusion

4.4 Modifications of cellular blood component

4.5 Plasma-derived blood components

4.1 Red Cell Components

4.1.1 Whole Blood:

Whole blood remains an excellent first choice for major trauma, for rapid GIB

(gastrointestinal bleeding), and for other clinical situations that benefit from simultaneous administration of red cells, volume replacement, and coagulation factors.

To supply normal hemostatic activity, whole blood would have to be less than 24h old. Although platelet and granulocyte function deteriorate within 24 h of refrigerated storage and the “labile” coagulation factors, and , Ⅴ Ⅷdecay substantially over the next 5 d, most of the functions of whole blood are well preserved during the storage interval.

A small number of cells are lost by hemolysis, and as many as 25 percent of red cells have diminished viability after 5 wk of refrigerated storage. Blood less than 5 d old or frozen deglycerolized red cells may be advantageous.

4.1.2 RBC:

After plasma is separated from red cells by centrifugation, the RBC component has a volume of about 200 ml and hematocrit (Hct) of about 80 percent.

Compared with whole blood, the major advantage of using red cells is decreased when volume is not required.

Additives not only increase storage to 42 d but also increase the volume to 300 ml and lower the Hct to 60 percent. These RBC units are standard in most facilities.

Indications for RBC transfusion: Hb concentration of 7g/dl is tolerated by

most patients with normal cardiac reserve and self-limited anemia, whereas an elderly intensive care unit (ICU) patient with cardiovascular and pulmonary compromise, sepsis, and metabolic disorders risks ischemia to the myocardium, brain, and other vital organs at the same level. In addition, such as tachycardia, tachypnia and oliguria, physiologic indicators of clinically important oxygen supply-demand balance are available during intensive care monitoring.

Each unit of RBC (or whole blood) is expected to raise Hb by 1 g/dl or the Hct by 3 percent in stable, nonbleed, average-sized adults.

4.1.3 Massive Transfusion:

Potentially exsanguinating hemorrhage

may require in excess of one blood volume in a 24h period or a transfusion rate exceeding 60 ml/min. This circumstance is defined as “massive transfusion”.

Massive transfusion may be

accomplished with either whole blood

or with a combination of RBC and

colloid or crystalloid solution.

Transfusion-related complications: hemorrhage

transient hyperkalemia

hypocalcemia

lower core body temperature

acute respiratory distress syndrome (ARDS)

hemorrhage

Hemorrhage may result from dilutional thrombocytopenia, or less often, from dilution of factors and , and from Ⅴ Ⅷconsumption coagulopathy related to hypotension and acidosis.

Measurement of fibrinogen concentrate and FDP( fibrin degradation products) should be used selectively.

transient hyperkalemia

Transient hyperkalemia from stored blood may adversely affect electrical and mechanical cardiac function in the acidotic, hypothermic and hypocalcemic patient.

hypocalcemia

Hypocalcemia may develop acutely as a result of the excess citrate chelating agent that anticoagulates stored blood.

lower core body temperature

Whole blood and RBC are stored at approximately 4 and require 30-45 ℃min to warm to room temperature. Massive transfusion of cold blood can lower core body temperature to 30 or ℃less with attendant bradycardia, decreased myocardial contractility, and impaired citrate metabolism.

★The major immediate risk of RBC transfusion in the ICU is accidental administration of blood to the wrong patient.

★The pretransfusion blood specimen must be labeled with the patient,s name and identification number.

Bag of packed red blood cells.

4.2 Platelet Concentrate

Platelet concentrates may be prepared from single (random) units of whole blood or from “single donors” by a cell seperator procedure known as plateletpheresis.

4.2.1 Indications for platelet transfusions:

Indications for theraputic platelet

transfusions must be individualized.

Patients with significant bleeding and either

thrombocytopenia or dysfunctional

platelets should be considered for platelet

transfusion.

Platelet transfusions should be considered for

bleeding patients with circulating counts less

than 50000/mm3 (50×109/L) and less than

80000/mm3 (80×109/L) when bleeding is life-

threatening or when minimal amounts or

bleeding may have catastrophic effects.

For patients with nonimmune platelet

destruction, such as those with

disseminated intravascular coagulation

(DIC) and thrombotic thrombocytopenic

purpura (TTP) , platelet transfusion may

be effective short-term supportive

therapy.

4.2.2 Dosage: The therapeutic dose of platelets depends on

several factors. As a guide, each unit of platelets should increase the platelet count by

about 12,000/ mm3 (12×109/L) for an adult.

Bleeding, fever, infection, splenomegaly, alloimmunization, and intravascular consumption, each decreases the expected increment. Response to platelet infusions should be continually monitored as essential elements of patient management.

4.3 Granulocyte Transfusions

Granulocyte concentrates are collected from single donors by use of a blood cell separator. Each concentrate contains approximately 1010 granulocytes which are about one tenth of the normal adult,s daily production and that is far fewer than that of an infected patient. Granulocytes are fragile and may be stored no longer than 24 h. The usual concentrate contains about 250 ml of plasma and has a Hct of 15 to 20 percent. ABO compatibility is necessary.

4.3.1 Indications of granulocyte transfusions

There is however ample evidence that granulocyte transfusions can benefit a selected group of patients: those with gram-negative sepsis or progressive localized infections, severe granulocytopenia, and temporary suppression of leukocyte production.

4.3.2 Adverse effectsGranulocyte transfusions result in febrile

reactions in as many as 40 percent of recipients. More serious are the pulmonary reactions, especially the rare allergic-type reaction associated with leukoagglutinins and the refractory pulmonary edema linked to the simultaneous infusion of granulocytes and the antifungal agent, amphotericin B.

4.4 Modifications of cellular blood component About 70% of the blood products are

filtered to remove leukocytes (white blood cell) that fight foreign material such as bacteria, viruses and abnormal cells that may cause disease. When leukocytes are present in donated blood, they may not be tolerated by the person receiving the blood and cause some types of transfusion complications

Three modifications of blood components are worth considering: irradiation, leukocyte reduction and resuspension, or “washing”.

4.4.1 irradiation

Gamma irradiation inactivates immunocompetent lymphocytes, that contaminate cellular blood component. It can prevent GVHD after transfusion. Patients with acquired immunodeficiency syndrome (AIDS) have not required irradiated cells.

4.4.2 Leukocyte reduction and resuspension

Leukocyte reduction can be used in several different circumstances. Because many febrile reactions are a result of leukocytes present in the blood component, filters that reduce the number of leukocytes to less than 5*108 per transfusion can prevent some of these reactions.

4.4.3 “Washing” Cellular components can be washed free of

plasma with saline or saline-anticoagulant solution. 10-20% of cells may be lost during the washing and resedimentation process. Washing cellular components do not prevent viral infection, alloimmunization, or GVHD.

4.5 Plasma-Derived Blood Components

4.5.1 Plasma: Plasma separated from a unit of whole blood

and frozen within 8 h of collection is designated fresh frozen plasma (FFP) . The usual volume of FFP is about 225 ml. FFP supplies all of the constituents of fresh plasma, including the labile coagulation factors, albumin and globulin.

Broad-spectrum factor replacement is

used for patients with severe liver

disease, especially in the presence of

bleeding or before invasive procedures.

FFP may be used for more specific coagulation factor therapy. FFP is the only source of labile factor Ⅴ

and is commonly used as a source of factors , , , and .ⅡⅦ Ⅹ Ⅺ

Infusions of FFP rapidly replace vitamin K-dependent coagulation factors in bleeding patients receiving sodium warfarin anticoagulation.

4.5.2 Cryoprecipitate:

This “bag” of cryoprecipitate contains approximately 100 u of factor VIII and von Willebrand factor, 75 u of factor XIII, and 250mg of fibrinogen in a volume of 20 ml.

In the critical care setting, cryoprecipitate is used most often as a source of fibrinogen.

The usual dose of cryoprecipitate in treating hypofibrinogenemia is an initial infusion of 10 bags, followed by 10 to 20 bags q8h or as necessary to keep the fibrinogen level above 100 mg/dl. The half-life of fibrinogen is about 4d.

4.5.3 Human serum albumin (HSA)HSA is comprised of 96 percent albumin

and 4 percent α-and β –globulin. Clinical indications for colloid solutions include hypovolemic shock, hypotension associated with hypovolemia in liver failure or protein-losing conditions, and inadequate diuresis in fluid overloaded hypoproteinemic patients.

4 Blood component therapy

4.1 Red cell components

4.2 Platelet concentrate

4.3 Granulocyte transfusion

4.4 Modifications of cellular blood component

4.5 Plasma-derived blood components

5 Adverse effects of blood transfusion

5.1 Hemolysis

5.2 Febrile nonhemolytic reactions

5.3 Transfusion-transmitted infection

5.1 Hemolysis The most feared acute reaction, intravascular

hemolysis, is caused by the recipient,s

complement-fixing antibodies interacting with donor red cells; ABO incompatibility is most often implicated in these occurrences and hemolysis may be accompanied by shock, acute renal failure (ARF), and DIC. Delayed hemolysis is often subclinical, detected by the presence of fever, jaundice, and a falling Hct about a week after transfusion.

5.2 Febrile nonhemolytic reactions: They are of little clinical importance and

share many signs and symptoms with acute hemolytic reactions. Bacterial contamination of blood components, is being recognized increasingly as an acute complication of transfusion that is first manifested by chills and fever.

5.3 Transfusion-transmitted infection:

Transfusion-transmitted infection includes human immunodeficiency virus (HIV) and hepatitis and may increase the frequency of postoperative infection and possibly of cancer recurrence.

Alloimmunization: Allogeneic blood transfusion is a form of

temporary transplantation. This procedure introduces a multitude of foreign antigens and living cells into the recipient that will persist for a variable amount of time. A recipient who is immunocompetent often will mount an immune response to the donor antigens, resulting in a variety of clinical consequences depending on the blood cells and specific antigens involved.

Transfusion-Associated GVHD:

GVHD occurs when transfused lymphocytes are not rejected and react with tissues of the recipient. With some exceptions, this disease can only occur in immunosuppressed patients. Transfusion-associated GVHD (TAGVHD) can be transmitted by whole blood, red cell concerntrates, and plantelet concentrates. Most cases of TAGVHD in the past occurred after organ transplantation.

The major clinical sign of TAGVHD is a progressive pancytopenia. In addition, these patients develop a skin rash and increase in liver enzymes.

An irradiation inactivates all immunoreactive lymphoid cells and prevents TAGVHD. Leukocyte filtration is not sufficient to prevent TAGVHD.

Transfusion-Related Acute Lung Injury: This reaction is rare and occurs within

minutes or hours after a transfusion. The patients develop fever, tachycardia, and have shortness of breath.

The pathophysiology of this reaction is thought to be immune mediated.

Allergic Reaction:

Allergic reaction occur in 1-2% of all transfusions. The symptoms are urticaria and itch within minutes of the transfusion. The symptoms usually subside if the transfusion is slowed and antihistamine is given. The transfusion may be continued if there is no progression after 20-30 min.

Every unit of blood is tested for

– Antibodies to HIV-1 and HIV-2 (AIDS). An antibody is protein in the blood produced by the body in response to a foreign protein (antigen) such as the AIDS virus

– Antibodies to HBc produced during and after infection with Hepatitis B Virus

– Antibodies to HCV produced after infection with the Hepatitis C virus

– Antibodies to HTLV-I/II produced after infection with Human T-Lymphotropic Virus (HTLV-I and HTLV-II)

– Antibodies to HBsAg produced after infection with Hepatitis B

– HIV-1 p24, a test for the HIV (AIDS) antigen

– For blood type (ABO) and Rh factor

– Tp, the agent that causes syphilis

– ALT, an elevated ALT may indicate liver inflammation, which may be caused by a hepatitis virus

– The presence of unexpected antibodies that may cause reactions after the transfusion

– CMV, a test for the cytomegalovirus (performed on physician request)

– NAT (Nucleic Acid Testing) - a new technology that can detect the genetic material of Hepatitis C and HIV. This test, which is still under investigation, has the potential to identify these viruses faster and more accurately