Fresh frozen plasma (FFP) is a blood product made from the liquid portion of

whole blood Whole blood (WB) is human blood from a standard blood donation. It is used in the treatment of massive bleeding, in exchange transfusion, and when people donate blood to themselves (autologous transfusion). One unit of whole blood (approxima ...

. It is used to treat conditions in which there are low

blood clotting factors Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of coagulation ...

(INR > 1.5) or low levels of other

blood proteins Plasma proteins, sometimes referred to as blood proteins, are proteins present in blood plasma. They perform many different functions, including transport of hormones, vitamins and minerals in activity and functioning of the immune system. Other ...

. It may also be used as the replacement fluid in plasma exchange. Using

ABO compatible A blood type (also known as a blood group) is based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glycoli ...

plasma, while not required, may be recommended. Use as a

volume expander A volume expander is a type of intravenous therapy that has the function of providing volume for the circulatory system. It may be used for fluid replacement or during surgery to prevent nausea and vomiting after surgery. Physiology When blood is ...

is not recommended. It is administered by slow injection into a vein. Side effects include nausea and itchiness. Rarely there may be

allergic reactions Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, alle ...

blood clots A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulati ...

, or

infections An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

. It is unclear if use during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

is safe for the baby. Greater care should be taken in people with

protein S deficiency Protein S deficiency is a disorder associated with increased risk of venous thrombosis. Protein S, a vitamin K-dependent physiological anticoagulant, acts as a nonenzymatic cofactor to activate protein C in the degradation of factor Va and factor V ...

IgA deficiency Selective immunoglobulin A (IgA) deficiency (SIgAD) is a kind of immunodeficiency, a type of hypogammaglobulinemia. People with this deficiency lack immunoglobulin A (IgA), a type of antibody that protects against infections of the mucous membr ...

, or

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

. Fresh frozen plasma is made up of a complex mixture of water,

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

carbohydrate A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ...

s, fats, and

vitamin Vitamins are Organic compound, organic molecules (or a set of closely related molecules called vitamer, vitamers) that are essential to an organism in small quantities for proper metabolism, metabolic function. Nutrient#Essential nutrients, ...

s. When frozen it lasts about a year. Plasma first came into medical use during the

Second World War World War II or the Second World War (1 September 1939 – 2 September 1945) was a World war, global conflict between two coalitions: the Allies of World War II, Allies and the Axis powers. World War II by country, Nearly all of the wo ...

. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. In the United Kingdom it costs about £30 per unit. A number of other versions also exist including plasma frozen within 24 hours after phlebotomy, cryoprecipitate reduced plasma, thawed plasma, and solvent detergent plasma.

Definition

In the United States it refers to the fluid portion of one unit of

that has been centrifuged, separated, and frozen solid at or colder within eight hours of collection from whole blood donation or was otherwise collected via apheresis device. The phrase "FFP" is often used to mean any transfused plasma product. The other commonly transfused plasma, plasma frozen within 24 hours after phlebotomy ( PF24), has similar indications as those for FFP. PF24 has slightly lower levels of Factors V and VIII than FFP. PF24 is more commonly used than FFP in the United States.

Medical uses

There are few specific indications for FFP. These generally are limited to the treatment of deficiencies of coagulation proteins for which specific factor concentrates are unavailable or undesirable. A usual dose of plasma is 10–20 mL/kg recipient weight. Indications for the use of FFP include the following: *Replacement of isolated factor deficiencies: FFP is used to treat rare bleeding disorders when specific factor concentrates are not available. FFP is the usual treatment for factor V deficiency. *Reversal of warfarin effect:

Patients who are anticoagulated with

warfarin Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...

are deficient in the functional

vitamin K Vitamin K is a family of structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-translational modification, post-synthesis modification of certain proteins ...

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. For anticoagulated patients who are actively bleeding or who require emergency surgery, prothrombin complex concentrate (ideally, four factor PCCs) should be used if available. FFP/PF24/thawed plasma should only be used if more effective alternative treatments are not available. The ASA task force recommends starting with 5–8 mL/kg of FFP for warfarin reversal and rechecking laboratory values. *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

heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Heparin is a blood anticoagulant that increases the activity of antithrombin. It is used in the treatment of myocardial infarction, ...

for treatment of

thrombosis Thrombosis () is the formation of a Thrombus, blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fib ...

. There are purified, human derived, as well as recombinant forms of antithrombin III available in the US. *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 (i.e., IVIG) has largely replaced fresh frozen plasma *Treatment of thrombotic thrombocytopenic purpura: Therapeutic plasma exchange with FFP/PF24 or thawed plasma as the replacement fluid is considered the treatment of choice for patients with proven or suspected

thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that results in thrombi, blood clots forming in small blood vessels throughout the body. This results in a thrombocytopenia, low platelet count, hemolytic anemia, low red blood cells d ...

(TTP). FFP is not recommended unless there is ongoing bleeding or there is a significant blood clotting problem. That is, FFP is not used in people to reverse warfarin if there is no bleeding, even for an INR > 9 unless they need urgent surgery. It is also not used in elective surgery, or non-emergency surgery. Thawed plasma is made from FFP or PF24 and kept refrigerated (at 1–6 °C) after thawing can be stored for 5 days post thaw. Prophylactic plasma transfusions might have an effect for people with a blood clotting disorder and receive an invasive procedure. For people with a blood clotting disorder and receive a planned invasive non-cardiac procedure it is not certain if prophylactic plasma transfusions improve all-cause mortality up to 30 days, major bleeding within 24 hours, number of transfusions per participants within one week, number of individuals requiring a transfusion within one week and serious adverse events measured by plasma-related complications within 24 hours. Different triggers for fresh frozen plasma may have little to no effect on major bleeding within 24 hours and serious adverse events measured by plasma transfusion-related complications within 24 hours. Furthermore, different triggers for fresh frozen plasma may reduce the number of individuals requiring a transfusion within 7 days.

Risks

The risks of FFP include disease transmission, anaphylactoid reactions, and excessive intravascular volume (transfusion associated circulatory overload (TACO)), as well as

transfusion related acute lung injury Transfusion-related acute lung injury (TRALI) is the serious complication of transfusion of blood products that is characterized by the rapid onset of excess fluid in the lungs. It can cause dangerous drops in the supply of oxygen to body tissu ...

(TRALI). Risks of transfusion transmitted infections are similar to that of whole blood and red blood cells.

Chemistry

FFP is made by

centrifugation Centrifugation is a mechanical process which involves the use of the centrifugal force to separate particles from a solution according to their size, shape, density, medium viscosity and rotor speed. The denser components of the mixture migrate ...

of whole blood or apheresis device followed by freezing and preservation.

Frequency of use

The use of plasma and its products has evolved over a period of four decades. The use of FFP has increased tenfold in the United States between the years 2000 and 2010 and has reached almost 2 million units annually. 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.

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, also called cryo for short, or Cryoprecipitate Antihemophilic factor (AHF), is a frozen blood product prepared from blood plasma. To create cryoprecipitate, plasma is slowly thawed to 1–6 °C. A cold-insoluble precipita ...

or fibrinogen concentrates should be used when fibrinogen is needed. For treatment of

hemophilia A Haemophilia A (or hemophilia A) is a blood clotting disorder caused by a genetic deficiency in clotting factor VIII, thereby resulting in significant susceptibility to bleeding, both internally and externally. This condition occurs almost exclu ...

, recombinant factor VIII concentrates are available. For treatment of severe

hemophilia B Haemophilia B, also spelled hemophilia B, is a blood clotting disorder causing easy bruising and bleeding due to an inherited mutation of the gene for factor IX, and resulting in a deficiency of factor IX. It is less common than factor VIII defic ...

, recombinant factor IX concentrates are available. Crystalloid or colloid solutions such as

human serum albumin Human serum albumin is the serum albumin found in human blood. It is the most abundant protein in human blood plasma; it constitutes about half of serum protein. It is produced in the liver. It is soluble in water, and it is monomeric. Albumin ...

or plasma protein fraction, are preferable to FFP for volume replacement. For nutritional support,

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

solutions and

dextrose Glucose is a sugar with the molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae during photosynthesis from water an ...

are available. The most important alternative to the use of FFP is a comprehensive program of blood conservation. This includes measures such as intraoperative cell salvage and the realization that in many patients normovolemic anemia is not an indication for transfusion.

References

External links

NIH Consensus Development Program: Fresh Frozen Plasma: Indications and Risks (public domain)

Circular of Information describing intended uses of transfusion products in the United States
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