Fresh frozen plasma
Encyclopedia
The term fresh frozen plasma (FFP) refers to the liquid portion of human blood that has been frozen and preserved after a blood donation
and will be used for blood transfusion
. The capitalized term Fresh Frozen Plasma in United States
can refer to the fluid portion of one unit of human blood that has been centrifuged, separated, and frozen solid at -18 °C or colder within eight hours of collection. The term "FFP" is often used to mean any transfused plasma product. The other commonly transfused plasma, PF24
, has similar indications as those for FFP with the exception of heat-sensitive proteins in the plasma such as factor V.
The use of plasma and its products has evolved over a period of four decades. The use of FFP has increased tenfold from between the years 2000-2010 and has reached almost 2 million units annually in the United States. This trend may be attributable to multiple factors, possibly including decreased availability of whole blood due to widespread acceptance of the concept of component therapy. FFP contains the labile as well as stable components of the coagulation
, fibrinolytic
and complement system
s; the protein
s that maintain oncotic pressure
and modulate immunity; and other proteins that have diverse activities. In addition, fat
s, carbohydrate
s and mineral
s are present in concentrations similar to those in circulation. Although well-defined indications exist for the use of FFP in single or multiple coagulation deficiencies, indications for many of its other uses may be empiric.
to stop massive hemorrhage.
In addition, circumstances exist in which FFP has been employed and is believed to be of therapeutic value, but data supporting its efficacy are limited or unavailable (e.g., multiple coagulation protein deficiencies in the uncontrollably bleeding patient). Because such patients are often critically ill and satisfactory alternative therapy may not be at hand, FFP may be appropriate.
Indications for the use of FFP include the following:
and are easily treated with FFP.
are deficient in the functional vitamin K
dependent coagulation factors II, VII, IX, and X, as well as proteins C and S. These functional deficiencies can be reversed by the administration of vitamin K. However, for anticoagulated patients who are actively bleeding or who require emergency surgery, FFDP (or single-donor plasma) can be used to achieve immediate hemostasis
It is however exceedingly common for patients to have documented blood clotting abnormalities (Prolonged APTT, INR) after large blood loss requiring for example 4 units or more of packed red blood cells. FFP is commonly recommended in these settings. In urgent situations it may be unacceptable to wait hours for lab test results before blood products are given. Though unlikely to be done, a clinical trial to prove efficacy and lack of adverse effects of giving empiric FFP compared to placebo would not be unethical, since the true risks and benefits of this currently intuitive practice is unknown.
for treatment of thrombosis
.
.
) is transmitted by blood transfusions and possibly by FFP. Allergic or anaphylactoid reactions can occur in response to FFP administration and may vary from hives to fatal noncardiogenic pulmonary edema
.
FFP should be blood type
-matched to ensure compatibility, as agglutination
reactions are possible, though rare. The potential for alloimmunization is present, as demonstrated by the infrequent formation of anti-Rh
antibodies. For this reason, plasma containing anti-D antibodies (from an RhD-negative donor) is preferably not given to an RhD-positive recipient, and RhD-positive plasma is avoided in RhD-negative women of child-bearing age. As with any intravenously administered fluid, excessive amounts of FFP may result in hypervolemia
and cardiac failure.
Safe and effective alternative treatment often exists so that FFP is no longer the therapy of choice in many conditions. Cryoprecipitate
should be used when fibrinogen
or von Willebrand factor
is needed. For treatment of hemophilia A, cryoprecipitate or factor VIII concentrates, heated or unheated, are available. For treatment of severe hemophilia B, factor IX complex is preferable. Both of these concentrates are prepared from pooled plasma, and the risk of virus transmission is negligible as there hasn't been an infection since 1985 when techniques were developed to kill of viruses including HIV. The factor IX concentrate carries the additional hazard of thrombogenicity.
Crystalloid, colloid solutions containing human serum albumin
or plasma protein fraction, hydroxyethyl starch
, and dextran
are preferable to FFP for volume replacement. The practice of administering both packed red cells and FFP to the same patient should be discouraged, as this adds to the cost and doubles the infection rate. When conditions are appropriate, whole blood should be given.
For nutritional support, amino acid
solutions and dextrose are available.
The most important alternative to the use of FFP is a comprehensive program of blood conservation. This includes measures such as autologous donation before elective surgery, the infusion of shed blood, and the realization that in many patients normovolemic anemia is not an indication for transfusion.
Nevertheless, in augmenting replacement of whole blood lost in catastrophic haemorrhage, FFP replacement must be considered along with replacement of packed red blood cells.
Blood donation
A blood donation occurs when a person voluntarily has blood drawn and used for transfusions or made into medications by a process called fractionation....
and will be used for blood transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
. The capitalized term Fresh Frozen Plasma in United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
can refer to the fluid portion of one unit of human blood that has been centrifuged, separated, and frozen solid at -18 °C or colder within eight hours of collection. The term "FFP" is often used to mean any transfused plasma product. The other commonly transfused plasma, PF24
PF24
Plasma Frozen Within 24 Hours After Phlebotomy, commonly called FP24, PF-24, or similar names is a frozen human blood plasma product used in transfusion medicine. It differs from fresh-frozen plasma in that it is frozen within 24 hours of blood collection, whereas FFP is frozen within 8 hours...
, has similar indications as those for FFP with the exception of heat-sensitive proteins in the plasma such as factor V.
The use of plasma and its products has evolved over a period of four decades. The use of FFP has increased tenfold from between the years 2000-2010 and has reached almost 2 million units annually in the United States. This trend may be attributable to multiple factors, possibly including decreased availability of whole blood due to widespread acceptance of the concept of component therapy. FFP contains the labile as well as stable components of the coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
, fibrinolytic
Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
and complement system
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
s; the protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s that maintain oncotic pressure
Oncotic pressure
Oncotic pressure, or colloid osmotic pressure, is a form of osmotic pressure exerted by proteins in blood plasma that usually tends to pull water into the circulatory system.Throughout the body, dissolved compounds have an osmotic pressure...
and modulate immunity; and other proteins that have diverse activities. In addition, fat
Fat
Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
s, carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
s and mineral
Mineral
A mineral is a naturally occurring solid chemical substance formed through biogeochemical processes, having characteristic chemical composition, highly ordered atomic structure, and specific physical properties. By comparison, a rock is an aggregate of minerals and/or mineraloids and does not...
s are present in concentrations similar to those in circulation. Although well-defined indications exist for the use of FFP in single or multiple coagulation deficiencies, indications for many of its other uses may be empiric.
Indications
Few specific indications for the use of FFP exist. These indications generally are limited to the treatment of deficiencies of coagulation proteins for which specific factor concentrates are unavailable or undesirable. In many clinical practices, fresh and frozen plasma contains proteins with two important coagulation factors in it - the V and the VIII. Other documentations indicate FFP has no enough beneficial effect when it's used as a transfusionBlood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
to stop massive hemorrhage.
In addition, circumstances exist in which FFP has been employed and is believed to be of therapeutic value, but data supporting its efficacy are limited or unavailable (e.g., multiple coagulation protein deficiencies in the uncontrollably bleeding patient). Because such patients are often critically ill and satisfactory alternative therapy may not be at hand, FFP may be appropriate.
Indications for the use of FFP include the following:
Replacement of isolated factor deficiencies
FFP is efficacious for treatment of deficiencies of factors II, V, VII, IX, X, and XI when specific component therapy is neither available nor appropriate. Requirements for FFP vary with the specific factor being replaced. For example, hemostatic levels of factor IX in a patient with severe deficiency are difficult to achieve with FFP alone, whereas patients with severe factor X deficiency require factor levels of about 10 percent to achieve hemostasisHemostasis
Hemostasis or haemostasis is a process which causes bleeding to stop, meaning to keep blood within a damaged blood vessel . Most of the time this includes blood changing from a liquid to a solid state. Intact blood vessels are central to moderating blood's tendency to clot...
and are easily treated with FFP.
Reversal of warfarin effect
Patients who are anticoagulated with warfarinWarfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
are deficient in the functional vitamin K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
dependent coagulation factors II, VII, IX, and X, as well as proteins C and S. These functional deficiencies can be reversed by the administration of vitamin K. However, for anticoagulated patients who are actively bleeding or who require emergency surgery, FFDP (or single-donor plasma) can be used to achieve immediate hemostasis
Massive blood transfusion (>1 blood volume within several hours)
Use of FFP in massive blood transfusion, for which there is less credible evidence of efficacy, appears to have increased in frequency in the past decade, possibly due in part to the relative unavailability of whole blood. Pathological hemorrhage in the massively transfused patient is caused more frequently by thrombocytopenia than by depletion of coagulation factors. The empiric use of FFP to reverse hemostatic disorders should be confined to those patients in whom factor deficiencies are presumed to be the sole or principal derangement. There is no evidence that the prophylactic administration of FFP decreases transfusion requirements in multiply transfused patients who do not have documented coagulation defects.It is however exceedingly common for patients to have documented blood clotting abnormalities (Prolonged APTT, INR) after large blood loss requiring for example 4 units or more of packed red blood cells. FFP is commonly recommended in these settings. In urgent situations it may be unacceptable to wait hours for lab test results before blood products are given. Though unlikely to be done, a clinical trial to prove efficacy and lack of adverse effects of giving empiric FFP compared to placebo would not be unethical, since the true risks and benefits of this currently intuitive practice is unknown.
Use in antithrombin III deficiency
FFP can be used as a source of antithrombin III in patients who are deficient of this inhibitor and are undergoing surgery or who require heparinHeparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
for treatment of thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
.
Treatment of immunodeficiencies
FFP is useful in infants with secondary immunodeficiency associated with severe protein-losing enteropathy and in whom total parenteral nutrition is ineffectual. FFP also can be used as a source of immunoglobulin for children and adults with humoral immunodeficiency. However, the development of a purified immune globulin for intravenous use largely has replaced FFP.Treatment of thrombotic thrombocytopenic purpura
FFP may be beneficial for the treatment of thrombotic thrombocytopenic purpuraThrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura is a rare disorder of the blood-coagulation system, causing extensive microscopic thromboses to form in small blood vessels throughout the body...
.
Risks
The risks of FFP include disease transmission, anaphylactoid reactions, alloimmunization, and excessive intravascular volume, as well as Transfusion Related Acute Lung Injury (TRALI) and an increase in infections (including surgical wound infections). The potential viral infectivity of FFP probably is similar to that of whole blood and red blood cells. The rate of posttransfusion hepatitis depends on many factors, including donor selection. In rare instances, human immunodeficiency virus (HIVHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
) is transmitted by blood transfusions and possibly by FFP. Allergic or anaphylactoid reactions can occur in response to FFP administration and may vary from hives to fatal noncardiogenic pulmonary edema
Pulmonary edema
Pulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...
.
FFP should be blood type
Blood type
A blood type is a classification of blood based on the presence or absence of inherited antigenic substances on the surface of red blood cells . These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system...
-matched to ensure compatibility, as agglutination
Agglutination
In contemporary linguistics, agglutination usually refers to the kind of morphological derivation in which there is a one-to-one correspondence between affixes and syntactical categories. Languages that use agglutination widely are called agglutinative languages...
reactions are possible, though rare. The potential for alloimmunization is present, as demonstrated by the infrequent formation of anti-Rh
Rh blood group system
The Rh blood group system is one of thirty current human blood group systems. Clinically, it is the most important blood group system after ABO. At Present, the Rh blood group system consists of 50 defined blood-group antigens, among which the 5 antigens D, C, c, E, and e are the most important...
antibodies. For this reason, plasma containing anti-D antibodies (from an RhD-negative donor) is preferably not given to an RhD-positive recipient, and RhD-positive plasma is avoided in RhD-negative women of child-bearing age. As with any intravenously administered fluid, excessive amounts of FFP may result in hypervolemia
Hypervolemia
Hypervolemia, or fluid overload, is the medical condition where there is too much fluid in the blood.The opposite condition is hypovolemia, which is too little fluid volume in the blood.-Causes:Excessive sodium or fluid intake:* IV therapy...
and cardiac failure.
Alternatives
Evidence indicates that other plasma components (e.g., single-donor plasma) that do not meet the criteria of FFP may have adequate levels of coagulation factors and are suitable for patients in whom FFP is indicated. Single-donor plasma is efficacious in the treatment of mild deficiencies of stable clotting factors. It also is of value in treatment of multiple deficiencies as in reversal of warfarin effects or in liver disease.Safe and effective alternative treatment often exists so that FFP is no longer the therapy of choice in many conditions. Cryoprecipitate
Cryoprecipitate
Cryoprecipitate, also called "Cryoprecipitated Antihemophilic Factor", "Cryoprecipitated AHF", and most commonly just "cryo", is a frozen blood product prepared from plasma.It is often transfused as a four to six unit pool instead of as a single product...
should be used when fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
or von Willebrand factor
Von Willebrand factor
von Willebrand factor is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome...
is needed. For treatment of hemophilia A, cryoprecipitate or factor VIII concentrates, heated or unheated, are available. For treatment of severe hemophilia B, factor IX complex is preferable. Both of these concentrates are prepared from pooled plasma, and the risk of virus transmission is negligible as there hasn't been an infection since 1985 when techniques were developed to kill of viruses including HIV. The factor IX concentrate carries the additional hazard of thrombogenicity.
Crystalloid, colloid solutions containing human serum albumin
Human serum albumin
Human serum albumin is the most abundant protein in human blood plasma. It is produced in the liver. Albumin constitutes about half of the blood serum protein...
or plasma protein fraction, hydroxyethyl starch
Hydroxyethyl starch
Hydroxyethyl starch is a nonionic starch derivative. It is one of the most frequently used volume expander under the trade names Hespan by B. Braun Medical Inc...
, and dextran
Dextran
Dextran is a complex, branched glucan composed of chains of varying lengths...
are preferable to FFP for volume replacement. The practice of administering both packed red cells and FFP to the same patient should be discouraged, as this adds to the cost and doubles the infection rate. When conditions are appropriate, whole blood should be given.
For nutritional support, amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
solutions and dextrose are available.
The most important alternative to the use of FFP is a comprehensive program of blood conservation. This includes measures such as autologous donation before elective surgery, the infusion of shed blood, and the realization that in many patients normovolemic anemia is not an indication for transfusion.
Effectiveness
There is little scientific evidence to support the increasing use of FFP in clinical medicine purely for volume expansion. While FFP is a reliable solution for intravascular volume replacement in acute blood loss, alternative therapies are equally satisfactory and considerably safer. There is no documentation that FFP has a beneficial effect when used as part of the transfusion management of patients with massive hemorrhage. FFP contains the major plasma proteins, including the labile coagulation factors (V and VIII), but in clinical practice other blood components or derivatives usually provide greater efficacy.Nevertheless, in augmenting replacement of whole blood lost in catastrophic haemorrhage, FFP replacement must be considered along with replacement of packed red blood cells.