Transfusion medicine
Transfusion therapy
Other therapy
Plasma use
Authors: Abdulaziz Al Mana, M.D., M.Sc., Crystal Yan, M.D., M.B.A., Yamac Akgun, M.D., YanYun Wu, M.D. Ph.D.
Editorial Board Member: Kyle Annen, D.O.
Deputy Editor-in-Chief: Patricia Tsang, M.D., M.B.A.
Last author update: 8 September 2021
Last staff update: 8 September 2021
Copyright: 2021, PathologyOutlines.com, Inc.
PubMed Search: Plasma use [TI]
Table of Contents
Definition / general | Essential features | Terminology | Characteristics | Pathophysiology | Clinical features | Blood donor screening | Blood donor testing | Treatment | Sample assessment & plan | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Al Mana A, Yan C, Akgun Y, Wu Y. Plasma use. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedplasma.html. Accessed April 24th, 2024.
Definition / general
- Plasma is the aqueous part of blood and contains albumin, coagulation factors including fibrinogen, immunoglobulins and other proteins (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021], Cohn: Technical Manual, 20th Edition, 2020)
- Used directly for transfusion purposes or indirectly for preparation of specific plasma protein products through different fractionation processes (Cohn: Technical Manual, 20th Edition, 2020, ISBT Science Series 2008;3:148)
- Derived from whole blood or apheresis collection (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021], Cohn: Technical Manual, 20th Edition, 2020, ISBT Science Series 2008;3:148)
Essential features
- Plasma used for transfusion purposes is either frozen (< -18 °C), refrigerated (1 - 6 °C), kept at room temperature (20 - 24 °C) or thawed after freezing (30 - 37 °C) (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021], Cohn: Technical Manual, 20th Edition, 2020)
- Different plasma types (see below) are considered equivalent for transfusion purposes, although minor differences in some labile coagulation factors do exist
- Plasma transfusions are generally indicated in coagulopathic patients with active bleeding; all units should contain coagulation factors, natural anticoagulants and ADAMTS13 at acceptable levels but lower levels of heat labile Factors V and VIII can result if freezing of fresh plasma is delayed (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021])
- Volume: whole blood derived units contain 200 - 250 mL on average but apheresis derived units may contain 400 - 600 mL (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021])
Terminology
- Fresh frozen plasma (FFP): plasma frozen within 8 hours of collection (Transfusion Medicine and Hemostasis 2009:1;161)
- Plasma frozen within 24 hours after phlebotomy (PF24): plasma refrigerated within 8 hours of collection and frozen within 24 hours of collection (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021])
- Plasma frozen within 24 hours after phlebotomy held at room temperature up to 24 hours after phlebotomy (PF24RT24): plasma stored at room temperature for up to 24 hours after collection and frozen within 24 hours of collection (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021])
- Plasma, cryoprecipitate reduced: plasma prepared from thawed whole blood derived FFP with cryoprecipitate removed by centrifugation (FFP - cryoprecipitate) and refrozen within 24 hours of thawing (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021])
- Thawed plasma: frozen plasma (FFP, PF24 or PF24RT24) that has been thawed and refrigerated for up to 4 days after the initial 24 hour post thaw period (maintained in a closed system) (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021])
- Thawed plasma, cryoprecipitate reduced: frozen plasma (plasma, cryoprecipitate reduced) that has been thawed and refrigerated for up to 4 days after the initial 24 hour post thaw period (maintained in a closed system) (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021])
- Liquid plasma: plasma that has been prepared from whole blood and only refrigerated (never frozen) and can be transfused up to 5 days after the expiration date of the whole blood (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021])
| Product | Postcollection temporary hold | Frozen postcollection |
| FFP | Within 8 hours | |
| PF24 | Refrigerated within 8 hours | Within 24 hours |
| PF24RT24 | Room temperature for up to 24 hours | Within 24 hours |
| Post thaw 0 - 24 hours | Post thaw 24 - 120 hours |
| FFP | Thawed plasma |
| PF24 | Thawed plasma |
| PF24RT24 | Thawed plasma |
| Plasma, cryoprecipitate reduced | Thawed plasma, cryoprecipitate reduced |
Characteristics
- All types of plasma should contain coagulation factors, natural anticoagulants and ADAMTS13 at acceptable levels but lower levels of heat labile Factors V and VIII can result if freezing of fresh plasma is delayed
- All frozen plasma products should be infused immediately after thawing or refrigerated for up to 24 hours
- After 24 hours, the product must be relabeled as thawed plasma and can be stored in the refrigerator for an additional 4 days
- Thawed plasma has reduced levels of mainly Factors V, VII and VIII
- PF24 and PF24RT24 are prepared when whole blood or plasma cannot be transported, processed and frozen in time after phlebotomy due to geographic or logistical constraints
- Both have reduced levels of Factor VIII compared with FFP
- PF24 also has reduced levels of protein C while PF24RT24 furthermore has reduced levels of Factor V and protein S
- Plasma, cryoprecipitate reduced is deficient in fibrinogen, Factor VIII, Factor XIII and von Willebrand factor (vWF) due to removal of the cryoprecipitate
- Liquid plasma has variable levels of coagulation factors and other proteins
- Reference: AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021]
| Product | Compared with FFP, reduced levels of |
| PF24 | Factor VIII and protein C |
| PF24RT24 | Factors V and VIII and protein S |
| Thawed plasma | Factors V, VII and VIII |
| Liquid plasma | Variable; depends upon storage condition |
| Product | Shelf life |
| FFP | 12 months frozen 7 years at -65 °C (with FDA approval) |
| Thawed plasma | 4 days after the initial 24 hour post thaw period |
| Liquid plasma | 26 days (from anticoagulant citrate dextrose (ACD) / citrate phosphate dextrose (CPD) or citrate phosphate double dextrose (CP2D) whole blood units) 40 days (from citrate phosphate dextrose adenine (CPDA-1) whole blood units) |
Pathophysiology
- Transfusion reactions that are strongly associated with plasma transfusion include allergic / anaphylactic reactions, transfusion related acute lung injury (TRALI) and transfusion associated circulatory overload (TACO); although less common, other types of transfusion reaction may occur (Transfusion 2012;52:65S, Blood 2019;133:1840)
- TRALI is one of the leading causes of transfusion related mortality
- Characterized by acute hypoxemia and noncardiogenic pulmonary edema occurring within 6 hours of transfusion
- Most patients recover within 96 hours with respiratory support
- Higher risk from plasma containing blood products due to the presence of antibodies against human leukocyte antigens (HLA) or human neutrophil antigens (HNA)
- Current mitigation strategies to minimize the exposure risk to HLA alloantibodies include collection from men, never pregnant women or parous women who test negative for HLA antibodies
- Transfusion associated circulatory overload (TACO) has a similar presentation and should be included in the differential diagnosis for TRALI
- TACO is typically involved with large volume plasma transfusions in susceptible individuals with evidence of cardiogenic pulmonary edema and volume overload (increased brain natriuretic peptide [BNP] or N terminal pro B type natriuretic peptide [NT proBNP])
- References: Cohn: Technical Manual, 20th Edition, 2020, Hematology Am Soc Hematol Educ Program 2018;2018:585
Clinical features
- Plasma contains antibodies, including antibodies to red blood cell antigens (Transfusion Medicine and Hemostasis 2009:1;161)
- All units undergo antibody screen for non ABO antibodies; if the screen is positive, plasma will not be made from that unit (Transfusion Medicine and Hemostasis 2009:1;161)
- If a unit of plasma is prepared for transfusion, the only red cell alloantibodies (if present) are ABO antibodies (Transfusion Medicine and Hemostasis 2009:1;161)
- AB blood group is the universal plasma donor because it lacks anti-A and anti-B (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021])
- Group A plasma is readily available compared with AB; therefore, it has potential to relieve current pressure on the AB plasma inventory, especially in the trauma or other emergency settings (Transfusion 2014;54:1751)
- In comparison with restricting transfusions to ABO compatible plasma, evidence has shown that group B and AB patients transfused with group A plasma benefited without greater incidence in morbidity or mortality (Transfusion 2014;54:1751)
- Liquid plasma is increasingly used in emergencies and early trauma management to avoid delays in thawing with comparable results to frozen plasma products (Transfusion Medicine and Hemostasis 2009:1;161)
- Thawed plasma is also used in emergencies due to availability and can help reduce the wastage from frozen plasma products when not transfused within the first 24 hours after thawing (Transfusion Medicine and Hemostasis 2009:1;161, Transfusion 2009;49:2625)
- Plasma, cryoprecipitate reduced is almost exclusively used in patients with thrombotic thrombocytopenic purpura (TTP) as regular infusions or exchange transfusions (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021], Cohn: Technical Manual, 20th Edition, 2020)
- It should never be used for repletion of coagulation factors (fibrinogen, Factor VIII, Factor XIII and vWF) or as a substitute for FFP, PF24 or thawed plasma (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021], Cohn: Technical Manual, 20th Edition, 2020)
- Solvent / detergent treated plasma (SD plasma): pooled from many donor units, the major advantage is an extra safety measure and lower likelihood of allergic reactions, TRALI and transfusion transmitted infections (Shock 2016;46:468)
- Pathogen reduced / inactivated plasma (PRT plasma): new technology utilizing various methods (e.g amotosalen, UV light, etc.), as an additional safety measure against transfusion transmitted infections (Hematol Oncol Clin North Am 2019;33:749)
- Dried plasma: in military / trauma settings where conventional plasma storage is logistically difficult or unavailable; since 2018, FDA emergency authorization for pathogen reduced leukocyte depleted freeze dried plasma has been granted to the U.S. Department of Defense (U.S. FDA: FDA News Release [Accessed 14 July 2021], Transfusion 2016;56:S128)
Blood donor screening
- Per FDA requirements, all donors must be screened via donor history questionnaire (DHQ) for risk factors of transfusion transmitted infections and other conditions that may adversely affect the health of the donor or the safety, purity or potency of the blood or blood component (U.S. FDA: Implementation of Acceptable Full-Length and Abbreviated Donor History Questionnaires and Accompanying Materials for Use in Screening Donors of Source Plasma [Accessed 14 July 2021])
Blood donor testing
- Per FDA requirements, all donors must be tested for infectious disease markers (IDM) using FDA licensed donor screening tests (U.S. FDA: Testing Human Cells, Tissues, and Cellular and Tissue Based Product (HCT/P) Donors for Relevant Communicable Disease Agents and Diseases [Accessed 14 July 2021])
Treatment
- Actively bleeding patients with multiple coagulation factor deficiencies / defects
- Rapid vitamin K antagonist reversal in cases of Coumadin (warfarin) overdose, that results in bleeding or in patient undergoing an invasive procedure requiring prompt coagulation factor replacement when factor concentrates, such as 4 factor prothrombin complex concentrates, are not available or contraindicated
- During massive transfusions associated with significant coagulation factor deficiencies / defects
- Specific plasma protein factor deficiencies / defects, either congenital or acquired, when licensed factor concentrate is not available
- Transfusion or replacement fluid for therapeutic plasma exchange (TPE) in patients with TTP (first line treatment) or in conjunction with albumin as replacement fluid in patients with underlying coagulopathy, requiring therapeutic plasma exchange for other indications
- TPE is the mainstay treatment for TTP (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021], Cohn: Technical Manual, 20th Edition, 2020)
- Patients with clinical and laboratory evidence of TTP (low levels or reduced ADAMTS13 activity) are treated with TPE to remove antibodies to ADAMTS13 and replete ADAMTS13 until their platelet counts recover (AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021], Cohn: Technical Manual, 20th Edition, 2020)
- Perioperative management of coagulopathy (see note below)
- Dosing: typical dose of plasma is around 10 - 15 mL/kg
- Hemostasis is usually achieved when the coagulation factor activity is at least 25 - 30% of normal
- Infusion: infusion rates depend on the volume load that can be tolerated by the patient
- Suggested rates:
- Healthy individual: 2 - 4 mL/kg per hour
- Individual with volume overload or heart failure: 1 mL/kg per hour or less
- Note: other approaches should be explored whenever possible before transfusing with plasma to avoid the risks of an adverse event, which includes various types of blood product related transfusion reaction, transfusion transmitted infections, etc.
- References: AABB: Circular of Information for the Use of Human Blood and Blood Components [Accessed 2 June 2021], Cohn: Technical Manual, 20th Edition, 2020
Sample assessment & plan
- Assessment: 37 year old female with prior history of chronic relapsing thrombotic thrombocytopenic purpura (TTP) treated with multiple FFP transfusions / plasma exchanges. She presented to the emergency room directly from hematology clinic due to an acute drop in platelet count (28 x 10³/mcL), with undetectable ADAMTS 13 activity and elevated inhibitor level indicating relapsed TTP. The patient had history of bruises with prior episodes but currently denies bleeding, fever or neurological symptoms.
- Plan: The patient will start daily plasma exchange sessions using plasma as replacement fluid (1 - 1.5 plasma volume) until platelet counts recover (> 150 x 10³/mcL) and lactate dehydrogenase (LDH) is near normal for 2 - 3 consecutive days. An order for stat central venous catheter placement is placed. The patient will be premedicated with diphenhydramine before starting the procedure. Please report any transfusion reaction to blood bank.
- Reference: J Clin Apher 2019;34:171
Board review style question #1
Which of the following is a correct statement?
- Fresh frozen plasma (FFP) has a shelf life of 5 days
- Liquid plasma has a shelf life of 26 days if derived from citrate phosphate double dextrose (CP2D) whole blood
- Plasma frozen within 24 hours after phlebotomy (PF24) has a shelf life of 24 hours
- Thawed plasma has a shelf life of 3 days
Board review style answer #1
B. Liquid plasma has a shelf life of 26 days if derived from citrate phosphate double dextrose (CP2D) whole blood
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Board review style question #2
Which of the following is a correct statement?
- Group A plasma may be given to any patients during a bleeding emergency
- Group A plasma should never be given to a group AB patient
- Group O plasma is the universal plasma
- Liquid plasma should not be used for bleeding emergency, as it has decreased levels of Factor V and VIII
Board review style answer #2
A. Group A plasma may be given to any patients during a bleeding emergency
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