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Clinical use of plasma components

Clinical use of plasma components
Author:
Lynne Uhl, MD
Section Editor:
Steven Kleinman, MD
Deputy Editor:
Jennifer S Tirnauer, MD
Literature review current through: Feb 2022. | This topic last updated: Feb 14, 2022.

INTRODUCTION — Products prepared from human plasma can be lifesaving in some conditions (eg, trauma, massive transfusion, disseminated intravascular coagulation [DIC], bleeding due to a factor deficiency when a specific clotting factor is not available, bleeding due to a vitamin K antagonist when a prothrombin complex concentrate is not available). At the same time, plasma products carry infectious and other risks. Thus, it is important to use the appropriate plasma product in the appropriate clinical setting.

This topic review will discuss available plasma products, indications and dosing for these products, and potential complications of plasma transfusion.

The use of other products, including Cryoprecipitate, coronavirus disease (COVID-19) convalescent plasma, and plasma derivatives such as prothrombin complex concentrates (PCCs) and individual coagulation factor concentrates, are discussed in separate topic reviews.

Cryoprecipitate – (See "Clinical use of Cryoprecipitate".)

Convalescent plasma – (See "COVID-19: Convalescent plasma and hyperimmune globulin".)

Platelet-rich plasma – (See "Investigational approaches to the management of osteoarthritis", section on 'Platelet-rich plasma' and "Elbow tendinopathy (tennis and golf elbow)", section on 'Platelet-rich plasma and other biologic injections'.)

PCCs – (See "Plasma derivatives and recombinant DNA-produced coagulation factors", section on 'Individual procoagulant factors' and "Management of warfarin-associated bleeding or supratherapeutic INR" and "Reversal of anticoagulation in intracranial hemorrhage".)

Coagulation factor concentrates – (See "Treatment of bleeding and perioperative management in hemophilia A and B" and "Factor XI (eleven) deficiency" and "Rare inherited coagulation disorders".)

Collection of plasma by apheresis, separation of plasma from donated blood, and manufacture of plasma derivatives (albumin, immune globulins, coagulation factor concentrates) are discussed separately. (See "Plasma derivatives and recombinant DNA-produced coagulation factors".)

Therapeutic plasma exchange (removal of patient plasma and replacement with another fluid, sometimes donor plasma) is also discussed separately. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology" and "Therapeutic apheresis (plasma exchange or cytapheresis): Complications".)

PLASMA PRODUCTS

Overview of products — Most clinicians are familiar with transfusion of Fresh Frozen Plasma (FFP); however, there are several other plasma products that are also used in transfusion medicine. Some of these products may be substituted by the transfusion service if FFP has been ordered.

FFP is a licensed plasma product that must be prepared from whole blood or apheresis and frozen within eight hours of collection. Additional products include the following:

Plasma Frozen Within 24 Hours After Phlebotomy (PF24) – Plasma Frozen Within 24 Hours After Phlebotomy (PF24) is plasma that is frozen more than eight hours but less than 24 hours after collection. This product is also referred to as Frozen Plasma.

Thawed Plasma – Thawed Plasma is plasma that was frozen (ie, FFP or PF24), thawed, and kept at refrigerator temperature for up to five days.

Liquid Plasma – Liquid Plasma is plasma that has never been frozen.

Solvent/Detergent Plasma (S/D Plasma) – Solvent/Detergent (S/D) Plasma is plasma treated with viral inactivating agents (eg, solvents and detergents) prior to freezing.

Plasma Cryoprecipitate Reduced – Plasma Cryoprecipitate Reduced is plasma from which Cryoprecipitate has been removed. This product is also referred to as Cryo-Poor Plasma.

Dried Plasma – Dried Plasma, also called Freeze-Dried Plasma, is a liquid-free preparation that can be stored at room temperature prior to reconstitution.

Convalescent Plasma – Convalescent Plasma is plasma prepared from individuals who have recovered from infection with a specific pathogen. (See "COVID-19: Convalescent plasma and hyperimmune globulin".)

In addition to S/D plasma, other methods for pathogen inactivation of plasma, such as psoralen/ultraviolet (UV) light, are available. These systems are discussed separately. (See "Pathogen inactivation of blood products".)

In clinical practice, physicians in most hospitals who wish to transfuse plasma will place an order either for FFP or for "plasma" without further specification. The transfusion service will fill that order using FFP, PF24, or Thawed Plasma according to inventory management practices, without notifying the physician of which specific product is used. Most plasma transfused in the United States is PF24, not FFP.

FFP, PF24, and Thawed Plasma are generally considered clinically interchangeable (ie, of equivalent efficacy) because they contain essentially the same amounts of coagulation factors [1]. However, none of these products have been directly compared with each other in randomized trials. Ideally, the policy concerning which of these products can be used (or substituted) will have been previously established by appropriate hospital committees.

Units of FFP, PF24, and Thawed Plasma are also comparable in volume, since each is prepared from a unit of whole blood. However, there is some inherent variability in volume among plasma units based on differences in hematocrit between donors. In some hospitals, larger volume plasma units prepared by apheresis may also be available.

FFP — Fresh Frozen Plasma (FFP) is prepared from single units of whole blood or from plasma collected by apheresis techniques. It is frozen at -18 to -30°C within eight hours of collection and, when appropriately stored, is usable for one year from the date of collection. Standard FFP units derived from a single unit of whole blood have a volume of approximately 200 to 250 mL; "jumbo" units prepared by apheresis may be as large as 600 mL.

FFP contains all of the coagulation factors and other proteins present in the original unit of blood, slightly diluted by the citrate-containing anticoagulant solution used to collect the blood.

Plasma Frozen Within 24 Hours After Phlebotomy (PF24) — Plasma frozen within 24 hours of collection (rather than eight hours for FFP) is a licensed product called PF24, or Frozen Plasma. PF24 maintains all the clotting factors at approximately the same levels as in FFP, except that factor VIII levels are in the range of 65 to 80 percent of normal and protein C is decreased [2-4]. While other factor levels may also be slightly reduced, these levels are perfectly acceptable for normal coagulation, especially in light of the fact that the "normal" range of factor VIII is roughly 50 to 150 percent of normal [2,3,5-7].

Of note, PF24 was previously called FP24.

Thawed Plasma — In the 1996 edition of Standards for Blood Banks and Transfusion Services, the transfusion expiration time for FFP was extended from no more than 24 hours after thawing to up to five days when stored at refrigerator temperature (ie, 1 to 6°C), when used to treat coagulopathies other than factor VIII deficiency [8]. This component, which after 24 hours of storage must be relabeled as "Thawed Plasma," and which, as a non-US Food and Drug Administration (FDA) licensed product, cannot be shipped across state lines, is a valuable and versatile product. Studies have confirmed earlier observations regarding the stability of clotting factors other than factors V and VIII in Thawed Plasma that has been stored at refrigerator temperatures for up to five days [2,5,9-13].

Thawed Plasma has the advantage of being available for immediate use; this is particularly important in both emergency department and operating room settings. (See "Initial management of moderate to severe hemorrhage in the adult trauma patient".)

However, Thawed Plasma should not be used as a predominant source of either factor V or factor VIII, and its usefulness in neonates is not yet known. In one study, levels of plasticizers (eg, di(2-ethylhexyl) phthalate, DEHP) leached from the plastic storage bags increased from 22 ppm at the time of thawing to 66 ppm on day 5, suggesting that such long storage of Thawed Plasma may not be safe for neonates and infants [13].

The use of Thawed Plasma as an alternative to FFP or PF24 simplifies the logistics of managing bleeding patients in complex settings, and also provides the additional benefit of a substantial reduction in the wastage of FFP or PF24 thawed for use and discarded when not transfused within the first 24 hours [14]. This is a particularly valuable benefit to minimize the wastage of group AB plasma, which is often in short supply.

Liquid Plasma — Liquid Plasma is plasma that has never been frozen. It is separated and infused no later than five days after the expiration date of the whole blood from which it is prepared; it is stored at 1 to 6°C. Some trauma surgeons use liquid plasma in early trauma management based on the potential role of an "endotheliopathy" associated with severe trauma that responds better to plasma that has never been frozen; improved outcomes with this have not been demonstrated by a randomized controlled trial.

Pathogen-inactivated plasma (S/D Plasma, others) — Because plasma is essentially acellular, it can be virally inactivated using agents that would otherwise lyse cellular blood components. Treatment of pooled plasma prior to freezing with a solvent and a nonionic detergent inactivates a number of viruses with lipid envelopes, including HIV, hepatitis B virus, and hepatitis C virus [15]. Non-lipid-enveloped viruses (eg, hepatitis A virus, parvovirus B19) are not inactivated by this process, nor are prions. The Solvent/Detergent (S/D) method is similar to that used to inactivate viruses in immune globulin and coagulation factors. (See "Pathogen inactivation of blood products", section on 'Plasma/FFP'.)

S/D Plasma has similar levels of most clotting factors and similar hemostatic properties as standard FFP [16]. Because it is prepared from a very large pool of donors, it might decrease the risk of allergic reactions in individuals who receive large amounts of plasma, such as in thrombotic thrombocytopenic purpura (TTP) [17]. (See "Immunologic transfusion reactions", section on 'Treatment and prevention of anaphylactic reactions' and "Immunologic transfusion reactions".)

Other pathogen inactivation methods that use DNA-binding compounds and ultraviolet (UV) or visible light are also safe and effective to various degrees in eliminating pathogens from plasma. These include:

Amotosalen plus UVA light (Intercept System)

Riboflavin plus UV light (Mirasol PRT System)

Methylene blue plus visible light (THERAFLEX MB Plasma System)

Specific products and their availability in different jurisdictions are discussed separately. (See "Pathogen inactivation of blood products", section on 'Plasma/FFP'.)

Plasma Cryoprecipitate Reduced — Plasma Cryoprecipitate Reduced is the plasma remaining after Cryoprecipitate has been removed. This product is also referred to as "Cryo-Poor Plasma." It has been employed as plasma replacement in some patients with thrombotic thrombocytopenic purpura. This subject is discussed separately. (See "Immune TTP: Initial treatment", section on 'Overview of procedure and plasma products'.)

Cryo-Poor Plasma is suitable for use in patients with vitamin K deficiency or correction of major bleeding in the setting of warfarin anticoagulation because the removal of Cryoprecipitate from plasma does not deplete the vitamin K-dependent clotting factors (table 1). (See "Overview of vitamin K", section on 'Vitamin K deficiency' and "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Treatment of bleeding'.)

Dried Plasma — Dried Plasma or Freeze-Dried Plasma (FDP) is a product in which the liquid component of plasma is removed, to make a powdered preparation that can be reconstituted on-site at the time of infusion. Methods of preparation include lyophilization (removal of liquid under vacuum pressure) and spray-drying (exposure of a stream of plasma to high temperature gas for less than a second to remove liquid without denaturing proteins).

Various products have been developed for military use, and some of these are available from French and German manufacturers, including lyophilized plasma treated with pathogen inactivation technologies and single donor plasma [18,19]. The major advantage of these products is that they can be stored at room temperature, making them potentially available in settings that lack on-site equipment for freezing, refrigerating, and thawing. Products using these and other technologies are under development in the United States [18,20].

INDICATIONS

Overview of indications — There is a general consensus that plasma transfusions are often misused. The use of plasma products is thought to be unnecessarily high in the United States [21,22], as well as in other countries [23-25], despite the presence of guidelines concerning their use [26,27]. Many experts believe that the use of plasma for transfusion should be closely monitored and curtailed wherever possible, both because plasma products carry infectious and other risks, and because plasma serves as a limited resource for the further manufacture of plasma derivatives (eg, albumin, gamma globulin, purified coagulation factors) [28,29]. (See 'Settings in which plasma is not appropriate' below.)

A plasma product is generally indicated in the management of bleeding when multiple coagulation factors are deficient or when a specific factor concentrate is not available.

Examples are summarized in the table (table 1) and include [30]:

Massive transfusion – A dilutional coagulopathy occurs during massive transfusion protocols if plasma is not also transfused. (See "Massive blood transfusion".)

Severe liver disease or DIC – Individuals with severe liver disease may have bleeding due to globally decreased coagulation factor production. Individuals with disseminated intravascular coagulation (DIC) may have bleeding due to massive coagulation factor consumption. In both of these cases, treatment of the underlying disease is paramount. If factor replacement is needed, a plasma product may be the best source of multiple clotting factors. (See "Hemostatic abnormalities in patients with liver disease", section on 'Bleeding' and "Evaluation and management of disseminated intravascular coagulation (DIC) in adults", section on 'Prevention/treatment of bleeding'.)

Rare clotting factor deficiencies – In general, treatment of bleeding due to deficiency of a single coagulation factor is ideally treated with a specific coagulation factor concentrate. However, there may be cases where a specific factor concentrate is not available; in these cases, a plasma product can be used as a source of the deficient factor. Factor deficiencies for which plasma is most likely to be used to treat bleeding include factor V and factor II (table 2). (See "Rare inherited coagulation disorders", section on 'Management of specific deficiencies'.)

COVID-19 – Convalescent plasma for individuals with coronavirus disease 2019 (COVID-19) is discussed separately. (See "COVID-19: Convalescent plasma and hyperimmune globulin" and "COVID-19: Management in hospitalized adults", section on 'Antibody-based therapies (anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma)'.)

Plasma products generally should not be used to correct excessive anticoagulation with a vitamin K antagonist, other anticoagulants, or other causes of a prolonged international normalized ratio (INR). This is especially true in the absence of bleeding. However, when the INR is substantially elevated (eg, >2.0) due to a vitamin K antagonist and a prothrombin complex concentrate (PCC) is not available, plasma transfusion can be considered to treat bleeding or prevent surgical bleeding. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Treatment of bleeding' and "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Urgent surgery/procedure'.)

The indications for plasma products in the management of thrombotic thrombocytopenic purpura (TTP), including plasma infusion for hereditary TTP (Upshaw-Schulman syndrome) and therapeutic plasma exchange for immune TTP due to an ADAMTS13 inhibitor (autoantibody) are discussed separately. (See "Hereditary thrombotic thrombocytopenic purpura (TTP)" and "Immune TTP: Initial treatment".)

When plasma is indicated, most products are considered clinically interchangeable, including Fresh Frozen Plasma (FFP), Thawed Plasma, Plasma Frozen Within 24 Hours After Phlebotomy (PF24), and pathogen-inactivated plasma products. The only indication for Liquid Plasma is the initial treatment of patients who are undergoing massive transfusion because of life-threatening trauma/hemorrhages. (See "Massive blood transfusion", section on 'Trauma'.)

Risks and benefits of pathogen-inactivated plasma products are presented separately. (See "Pathogen inactivation of blood products", section on 'Plasma/FFP'.)

Multiple coagulation factor replacement — FFP, PF24, and Thawed Plasma can be used to treat or prevent major bleeding with deficiency of multiple coagulation factors, such as in massive transfusion, severe liver disease, or DIC. In contrast, these products are not used to correct a minimally elevated INR in the absence of bleeding. (See 'Settings in which plasma is not appropriate' below.)

The specific conditions, along with other components of their management (eg, vitamin K administration), are discussed in detail separately:

Massive transfusion protocols – (See "Massive blood transfusion" and "Use of blood products in the critically ill".)

Bleeding due to the coagulopathy of liver disease – (See "Hemostatic abnormalities in patients with liver disease" and "Assessing surgical risk in patients with liver disease".)

Bleeding in DIC – (See "Evaluation and management of disseminated intravascular coagulation (DIC) in adults", section on 'Treatment'.)

Bleeding associated with vitamin K antagonist anticoagulation if a PCC is not available – (See 'Settings in which plasma is not appropriate' below and "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Treatment of bleeding'.)

Replacement of specific coagulation factors — FFP, PF24, and Thawed Plasma are not concentrates of any of the specific circulating plasma proteins and, in general, should not be used as primary therapy for a specific coagulation factor defect (eg, hemophilia A, hemophilia B, factor VII deficiency, factor XIII deficiency) when specific coagulation factor concentrates are available.

Exceptions include the following:

FFP may be used in some cases for the management of inherited factor XI deficiency. (See "Factor XI (eleven) deficiency".)

FFP and PF24 may be used as a source of factor V in severe cases of DIC with persistent bleeding when the persistent bleeding is thought to be a result of factor V deficiency rather than a global decrease in coagulation factors, or for inherited factor V deficiency. Thawed Plasma, depending upon its length of storage, may have reduced levels of factor V and would not be appropriate for factor V replacement in this setting. (See "Evaluation and management of disseminated intravascular coagulation (DIC) in adults" and "Rare inherited coagulation disorders", section on 'Factor V deficiency (F5D)'.)

FFP, PF24, or Thawed Plasma can be used as a source of factor replacement for some of the other rare inherited coagulation factor deficiencies (eg, X, VII, II). (See "Rare inherited coagulation disorders", section on 'Management of specific deficiencies'.)

FFP may be used in the (unlikely) circumstance that a specific factor concentrate or recombinant product is not available for managing bleeding in a patient with a coagulation factor deficiency (eg VIII, IX, XIII). (See "Rare inherited coagulation disorders", section on 'Management of specific deficiencies' and "Treatment of bleeding and perioperative management in hemophilia A and B", section on 'Acute therapy for bleeding'.)

The use of Cryoprecipitate in the treatment of specific coagulation factor deficiencies (eg, fibrinogen, factor XIII) is discussed separately. (See "Clinical use of Cryoprecipitate".)

Plasma exchange — The use of plasma during therapeutic plasma exchange is discussed in detail separately. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology" and "Therapeutic apheresis (plasma exchange or cytapheresis): Complications" and "Immune TTP: Initial treatment".)

Settings in which plasma is not appropriate — Plasma should not be used in settings in which there is no evidence for benefit and/or if a safer alternative is available. Examples include the following:

Minimally elevated INR – We do not use plasma to treat bleeding or as prophylaxis for invasive procedures in patients with an INR <1.85 (or <2.0), due to lack of high-quality data that support its efficacy in this setting and the known risks of complications from plasma transfusion [31]. (See 'Risks' below.)

The INR of plasma products collected and prepared from healthy individuals can be as high as 1.3 [32]. Therefore, even large-volume transfusion of plasma (eg, half the individual's plasma volume) would only reduce a minimally elevated INR by a small amount, if at all.

In individuals with liver disease, the INR does not accurately reflect bleeding risk; hemostasis is considered to be rebalanced, and often thrombosis risk is increased. (See "Hemostatic abnormalities in patients with liver disease", section on 'Physiologic effects of hepatic dysfunction'.)

Existing guidelines suggest that plasma be considered for lowering the INR only when the patient's INR is ≥1.6, and published studies suggest that plasma is unlikely to fully or even partially correct an INR ≤1.85 or to reduce the risk of clinical bleeding [32-37]. Examples of available evidence include:

A trial that randomly assigned 57 hospitalized adults who were undergoing procedures outside the operating room and had an INR of 1.5 to 2.5 to receive or not receive plasma transfusion found little to no difference in hemoglobin concentration after the procedures [38]. Approximately 60 percent of the participants had cirrhosis. The likelihood of INR <1.5 was higher in the plasma group but occurred in only 39 percent. The mean decrease in hemoglobin (a measure of bleeding) was 0.6 g/dL in the plasma arm and 0.4 g/dL in the control arm. Only one individual had a major bleed (hemoglobin decrease 2 g/dL); that individual was in the plasma arm but did not receive the full plasma dose of 10 mL/kg. There were no differences in hospital length of stay or adverse events.

A study of administration of FFP to 121 patients with an INR in the range of 1.1 to 1.85 noted correction of the INR to normal in only one patient (0.8 percent) and partial correction of the INR in only 15 percent [35]. The median decrease in the PT and INR was 0.2 seconds and 0.07, respectively, and was independent of the number of units of FFP infused (median 2 units; range 1 to 20).

Volume expansion – Plasma products should not be used as a source of protein or nutrients or as a volume expander because other plasma derivatives (eg, albumin, intravenous immune globulin) and/or solutions (eg, crystalloid) can provide the needed components with a lower risk of plasma-related complications such as transfusion-related acute lung injury (TRALI), infection, immunologic reaction, or volume overload [30]. (See "Intraoperative fluid management" and "Treatment of severe hypovolemia or hypovolemic shock in adults".)

Anticoagulants – Plasma should not be used to reverse the effect of an anticoagulant when a more specific product is available (eg, four-factor prothrombin complex concentrate [PCC] for reversing warfarin; specific antidotes for direct oral anticoagulants). (See "Management of warfarin-associated bleeding or supratherapeutic INR" and "Management of bleeding in patients receiving direct oral anticoagulants".)

Neurologic or psychiatric conditions – There is no evidence that plasma from young donors has any benefits in slowing the aging process or treating neurologic or psychiatric conditions. The US Food and Drug Administration has issued a cautionary statement that such treatments are unproven and should not be assumed to be safe or effective [39,40].

DOSE AND INFUSION RATE — The typical dose of plasma is approximately 10 to 15 mL/kg (ie, approximately three to five units) in most adults. This calculation is based on the following:

As a general rule, hemostasis can be achieved when the activity of coagulation factors is at least 25 to 30 percent of normal, in the absence of an inhibitor such as heparin, and when the level of fibrinogen is at least 75 to 100 mg/dL (table 1) [41]. Thus, approximately one-third to one-quarter of an individual's plasma volume should be infused.

The plasma volume in adults is approximately 40 mL/kg (eg, 2400 mL, 2800 mL, 3200 mL for a 60, 70, or 80 kg individual, respectively).

Standard units of plasma (FFP, PF24, Thawed Plasma) have a volume of approximately 200 to 250 mL.

This dose (ie, 750 to 1250 mL of plasma) represents a significant volume challenge [32].

Infusion rates depend on the volume load that can be tolerated by the patient. The following general guidelines apply:

Healthy individual – 2 to 3 mL/kg/hour (ie, approximately one unit in 1.5 hours).

Individual with volume overload or heart failure – 1 mL/kg/hour (ie, approximately one unit in approximately four hours). (See 'Volume overload (TACO)' below.)

Individual undergoing plasma exchange – 60 mL/minute; this can be raised to 100 mL/minute if the situation warrants and this rate is tolerated by the patient's veins. The rate can be this high because fluid is simultaneously being removed during the infusion.

The dose may have to be repeated in critically ill patients or in those with massive bleeding, depending upon the patient's clinical response, presence or absence of appropriate shortening of previously abnormal coagulation times, and the half-life and plasma level of the missing or reduced coagulation factor(s) (table 3) [42,43]. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Serious/life-threatening bleeding'.)

ABO MATCHING — Plasma contains antibodies, including antibodies to red blood cell (RBC) antigens. All units of blood collected are subjected to an antibody screen (ie, the donor's serum is tested against a red cell pool known to contain virtually all relevant antigens). If the screen is positive (ie, the donor has at least one antibody to an RBC antigen) plasma will not be made from that unit. Therefore, if a unit of plasma is prepared for transfusion, the only red cell alloantibodies that it can have are ABO antibodies.

Due to the normal presence of A and/or B alloantibodies in patients with blood types A, B, and O, donor plasma must be either ABO-identical or ABO-compatible with the recipient. (See "Red blood cell antigens and antibodies", section on 'ABO blood group system'.)

Thus:

A patient with type A blood can accept plasma from donors who are type A (identical) or type AB (compatible).

A patient with type B blood can accept plasma from donors who are type B (identical) or type AB (compatible).

A patient with type O blood can accept plasma from donors who are type O (identical) or types A, B, or AB (compatible).

A patient with type AB blood can only accept plasma from donors who are type AB (identical).

Few studies have addressed the clinical impact of using ABO-compatible plasma rather than ABO-identical plasma:

In a matched, retrospective study of trauma patients, the overall complication rate was significantly higher for the 284 subjects receiving ABO-compatible plasma than for the 284 receiving ABO-identical plasma (53.5 versus 40.5 percent) [44]. As the volume of ABO-compatible plasma infused increased, a stepwise increase in complications was seen, reaching 70 percent for those receiving more than six units of ABO-compatible plasma.

In a retrospective cohort study of 86,082 Swedish patients who received their first plasma transfusion between 1990 and 2002, there was an increased mortality associated with exposure to ABO-compatible plasma compared with ABO-identical plasma, with the excess risk mostly confined to those receiving five or more units (RR 1.15; 95% CI 1.02-1.29) [45].

It is difficult to interpret the significance of these retrospective studies since results could be confounded by many factors, including the relative efficacy of fresher versus thawed plasma. While these data suggest that ABO-identical plasma may result in somewhat better outcomes, the logistical difficulty in providing such components is considerable. Specifically, the need for ABO-identical components would appear to be secondary to the need to rapidly supply adequate amounts of plasma for trauma patients.

RISKS — Potential risks of plasma exposure include infection, volume overload, and other transfusion reactions. The relative frequency of different types of reactions and an approach to evaluating a suspected transfusion reaction are presented in detail separately. (See "Approach to the patient with a suspected acute transfusion reaction", section on 'Frequency of reactions' and "Approach to the patient with a suspected acute transfusion reaction", section on 'Initial patient assessment'.)

The following sections summarize selected risks, ordered from more common to less common.

Febrile and allergic reactions — Infusion of plasma can be associated with allergic reactions, fever, and chills. Urticaria is common (1 to 3 percent), and febrile nonhemolytic reactions affect 0.1 to 1 percent. These reactions should be treated symptomatically. Despite the fact that antihistamines and/or acetaminophen are frequently ordered prior to transfusion, there is no evidence to support their effectiveness for the prevention of such reactions. (See "Immunologic transfusion reactions", section on 'Febrile nonhemolytic reactions'.)

Volume overload (TACO) — Transfusion-associated circulatory overload (TACO) is a form of volume overload that can occur with infusion of large volumes of plasma (or other blood products). Pulmonary edema can develop, especially in older adults, small children, and those with preexisting cardiac disease. TACO is relatively common (>1 percent), although the true incidence may be challenging to determine since not all cases are reported.

Volume overload can be avoided by reducing the rate of infusion to 1 mL/kg per hour in susceptible patients. (See "Transfusion-associated circulatory overload (TACO)", section on 'Prevention'.)

Transfusion-related acute lung injury (TRALI) — Transfusion-related acute lung injury (TRALI) is a relatively common (<0.01 percent) and potentially fatal complication of blood product transfusion. It is characterized by new acute respiratory distress (eg, hypoxemia, infiltrates on chest radiography) within six hours of transfusion. (See "Transfusion-related acute lung injury (TRALI)".)

Since one of the mechanisms of TRALI is transfusion of donor antibodies directed against recipient HLA or neutrophil antigens, a worldwide approach to TRALI prevention involves preparing plasma components for transfusion from either male donors, never pregnant female donors, or female donors who have been screened and found not to have antibodies to HLA antigens. This action has resulted in a substantial drop in reported TRALI cases after plasma transfusion. Another approach involves using solvent/detergent treated plasma product (S/D plasma); these products are pooled from multiple donors and appear to have a negligible risk for TRALI. (See "Transfusion-related acute lung injury (TRALI)", section on 'Prevention'.)

Anaphylactic reactions — Anaphylactic reactions following transfusion of plasma may occur in patients with IgA deficiency and antibodies to IgA [46]. These are relatively rare (1 in 20,000 to 1 in 50,000). For such patients, IgA-deficient plasma from donors in the national registry is available [47,48]. Very rarely, passive transfer of an allergic phenotype (eg, acquired peanut anaphylaxis from donor IgE antibodies) can occur [49]. (See "Immunologic transfusion reactions", section on 'Anaphylactic transfusion reactions' and "Selective IgA deficiency: Management and prognosis", section on 'Safe administration of blood products'.)

Infection — Plasma is derived from human blood and therefore carries an infectious risk. The risk of most transfusion-transmitted infections is very low (<1 in 1 million for most viruses) and approximately equivalent for a transfusion of a unit of plasma (eg, FFP, PF24, Thawed Plasma) as it is for a unit of red blood cells, with the exception of a lower risk of transmitting intracellular viruses such as CMV and HTLV. Risk for individual organisms is summarized in the table (table 4).

Because plasma is basically an acellular blood component, pathogen reduction of plasma components has been successfully achieved, and approved systems to accomplish this are available. This subject is discussed separately. (See "Pathogen inactivation of blood products".)

The literature contains conflicting reports on whether the infusion of plasma increases the risk of infection through a potential immunomodulatory effect [50,51].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acquired bleeding disorders" and "Society guideline links: Rare inherited bleeding disorders" and "Society guideline links: Transfusion and patient blood management" and "Society guideline links: COVID-19 – Index of guideline topics".)

SUMMARY AND RECOMMENDATIONS

Preparation and products – Plasma is prepared from whole blood or apheresis in a blood center or hospital laboratory. The major plasma components used in transfusion medicine include the following (see 'Plasma products' above):

FFP – Fresh Frozen Plasma (FFP) is plasma frozen within eight hours of collection. (See 'FFP' above.)

PF24 – Plasma Frozen Within 24 Hours After Phlebotomy (PF24) is frozen within 24 hours of collection; this is also called Frozen Plasma. (See 'Plasma Frozen Within 24 Hours After Phlebotomy (PF24)' above.)

Thawed Plasma – Thawed Plasma has been frozen (ie, FFP or PF24), thawed, and kept at refrigerator temperature for up to five days.

Liquid Plasma – Liquid Plasma has never been frozen. (See 'Liquid Plasma' above.)

S/D PlasmaSolvent/Detergent Plasma (S/D Plasma) has been treated with viral inactivating agents prior to freezing. Other pathogen-inactivation methods are also available. (See 'Pathogen-inactivated plasma (S/D Plasma, others)' above and "Pathogen inactivation of blood products", section on 'Plasma/FFP'.)

Plasma Cryoprecipitate Reduced – Plasma from which Cryoprecipitate has been removed; also referred to as Cryo-Poor Plasma. (See 'Plasma Cryoprecipitate Reduced' above.)

Convalescent Plasma – Convalescent Plasma is obtained an individual who has recovered from an infectious disease, which can provide passive immunity to individuals who are ill from that disease or at high risk of developing disease following exposure. (See "COVID-19: Convalescent plasma and hyperimmune globulin".)

Indications – Plasma is often misused. FFP, PF24, and Thawed Plasma are indicated for treatment or prevention of major bleeding with deficiency of multiple coagulation factors, such as with massive blood transfusion, bleeding in a patient with liver disease, or disseminated intravascular coagulation (DIC) (table 1). Rarely, plasma may be used to treat bleeding due to a factor deficiency when a specific factor concentrate is not available (table 2). Plasma is used as the replacement fluid for therapeutic plasma exchange for thrombotic thrombocytopenic purpura (TTP). Plasma products should not be used as a source of albumin or nutrients, as a volume expander, or to "correct" a minimally elevated INR (<1.85 or <2 in a nonbleeding or preoperative patient) or to reverse warfarin effect in the absence of bleeding. (See 'Indications' above.)

Dose – Plasma generally is administered intravenously at a dose of 10 to 15 mL/kg of body weight. (See 'Dose and infusion rate' above and "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Serious/life-threatening bleeding'.)

ABO type – Due to the normal presence of A and/or B alloantibodies in patients with blood types A, B, and O, donor plasma must be either ABO-identical or ABO-compatible with the recipient. (See 'ABO matching' above.)

Risks – Risks of plasma transfusion include febrile and allergic reactions; volume overload; transfusion-related acute lung injury (TRALI); anaphylaxis, and infection. (See 'Risks' above and "Approach to the patient with a suspected acute transfusion reaction".)

Other products – The uses of Cryoprecipitate and plasma derivatives are discussed separately. (See "Clinical use of Cryoprecipitate" and "Plasma derivatives and recombinant DNA-produced coagulation factors".)

Plasma exchange – The use of plasma products for therapeutic plasma exchange is discussed separately. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology" and "Therapeutic apheresis (plasma exchange or cytapheresis): Complications" and "Immune TTP: Initial treatment".)

ACKNOWLEDGMENT — The UpToDate editors gratefully acknowledge the extensive contributions of Arthur J. Silvergleid, MD, to earlier versions of this and many other UpToDate topics.

REFERENCES

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  6. Cardigan R, Lawrie AS, Mackie IJ, Williamson LM. The quality of fresh-frozen plasma produced from whole blood stored at 4 degrees C overnight. Transfusion 2005; 45:1342.
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  8. Klein HG. Standards for Blood Banks and Transfusion Services, 17th ed, AABB, Bethesda 1996.
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  13. Sheffield WP, Bhakta V, Mastronardi C, et al. Changes in coagulation factor activity and content of di(2-ethylhexyl)phthalate in frozen plasma units during refrigerated storage for up to five days after thawing. Transfusion 2012; 52:493.
  14. Wehrli G, Taylor NE, Haines AL, et al. Instituting a thawed plasma procedure: it just makes sense and saves cents. Transfusion 2009; 49:2625.
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  16. Inbal A, Epstein O, Blickstein D, et al. Evaluation of solvent/detergent treated plasma in the management of patients with hereditary and acquired coagulation disorders. Blood Coagul Fibrinolysis 1993; 4:599.
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  21. Consensus conference. Fresh-frozen plasma. Indications and risks. JAMA 1985; 253:551.
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  26. Lauzier F, Cook D, Griffith L, et al. Fresh frozen plasma transfusion in critically ill patients. Crit Care Med 2007; 35:1655.
  27. Roback JD, Caldwell S, Carson J, et al. Evidence-based practice guidelines for plasma transfusion. Transfusion 2010; 50:1227.
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  29. Sarode R, Refaai MA, Matevosyan K, et al. Prospective monitoring of plasma and platelet transfusions in a large teaching hospital results in significant cost reduction. Transfusion 2010; 50:487.
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Topic 7920 Version 70.0

References

1 : The bioequivalence of frozen plasma prepared from whole blood held overnight at room temperature compared to fresh-frozen plasma prepared within eight hours of collection.

2 : Evaluation and comparison of coagulation factor activity in fresh-frozen plasma and 24-hour plasma at thaw and after 120 hours of 1 to 6°C storage.

3 : Stability of coagulation factors in plasma prepared after a 24-hour room temperature hold.

4 : Coagulation factor content of plasma produced from whole blood stored for 24 hours at ambient temperature: results from an international multicenter BEST Collaborative study.

5 : Coagulation factor levels in plasma frozen within 24 hours of phlebotomy over 5 days of storage at 1 to 6 degrees C.

6 : The quality of fresh-frozen plasma produced from whole blood stored at 4 degrees C overnight.

7 : Plasma for transfusion in the era of transfusion-related acute lung injury mitigation.

8 : Plasma for transfusion in the era of transfusion-related acute lung injury mitigation.

9 : Serial measurement of clotting factors in thawed plasma stored for 5 days.

10 : Effect of 24-hour whole-blood storage on plasma clotting factors.

11 : Coagulation parameters of CPD fresh-frozen plasma and CPD cryoprecipitate-poor plasma after storage at 4 degrees C for 28 days.

12 : Activity of clotting factors in fresh-frozen plasma during storage at 4 degrees C over 6 days.

13 : Changes in coagulation factor activity and content of di(2-ethylhexyl)phthalate in frozen plasma units during refrigerated storage for up to five days after thawing.

14 : Instituting a thawed plasma procedure: it just makes sense and saves cents.

15 : Solvent/detergent treatment of human plasma--a very robust method for virus inactivation. Validated virus safety of OCTAPLAS.

16 : Evaluation of solvent/detergent treated plasma in the management of patients with hereditary and acquired coagulation disorders.

17 : Solvent detergent treated pooled plasma and reduction of allergic transfusion reactions.

18 : Dried plasma: state of the science and recent developments.

19 : Comprehensive US government program for dried plasma development.

20 : Characterization and first-in-human clinical dose-escalation safety evaluation of a next-gen human freeze-dried plasma.

21 : Consensus conference. Fresh-frozen plasma. Indications and risks.

22 : Why do physicians request fresh frozen plasma?

23 : Why do physicians request fresh frozen plasma?

24 : Population-based audit of fresh-frozen plasma transfusion practices.

25 : A national study of plasma use in critical care: clinical indications, dose and effect on prothrombin time.

26 : Fresh frozen plasma transfusion in critically ill patients.

27 : Evidence-based practice guidelines for plasma transfusion.

28 : Reduction in plasma transfusion after enforcement of transfusion guidelines.

29 : Prospective monitoring of plasma and platelet transfusions in a large teaching hospital results in significant cost reduction.

30 : Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant.

31 : The art of plasma transfusion therapy.

32 : Fresh frozen plasma is ineffective for correcting minimally elevated international normalized ratios.

33 : Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review.

34 : Is fresh frozen plasma clinically effective? A systematic review of randomized controlled trials.

35 : Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities.

36 : Toward rational fresh frozen plasma transfusion: The effect of plasma transfusion on coagulation test results.

37 : Fresh-frozen plasma transfusion in patients with mild coagulation abnormalities at a large Canadian transfusion center.

38 : Plasma trial: Pilot randomized clinical trial to determine safety and efficacy of plasma transfusions.

39 : Plasma trial: Pilot randomized clinical trial to determine safety and efficacy of plasma transfusions.

40 : Plasma trial: Pilot randomized clinical trial to determine safety and efficacy of plasma transfusions.

41 : Plasma trial: Pilot randomized clinical trial to determine safety and efficacy of plasma transfusions.

42 : Indications for plasma in massive transfusion.

43 : Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients.

44 : Impact of ABO-identical vs ABO-compatible nonidentical plasma transfusion in trauma patients.

45 : Post-transfusion mortality among recipients of ABO-compatible but non-identical plasma.

46 : Transfusion reactions associated with anti-IgA antibodies: report of four cases and review of the literature.

47 : The transfusion needs of an autologous bone marrow transplant patient with IgA deficiency.

48 : Transfusion management of an IgA deficient patient with anti-IgA and incidental correction of IgA deficiency after allogeneic bone marrow transplantation.

49 : Passive transfer of peanut hypersensitivity by fresh frozen plasma.

50 : Exposure to allogeneic plasma and risk of postoperative pneumonia and/or wound infection in coronary artery bypass graft surgery.

51 : Transfusion of fresh frozen plasma in critically ill surgical patients is associated with an increased risk of infection.