• Transfusion of fresh frozen plasma (FFP) is mainly indicated for the treatment of complex coagulopathies in which multiple coagulation factors and inhibitors are depleted. Some common indications include the following (1,2):
  • Massive bleeding in trauma, cardiovascular surgery, or organ transplantation with prolonged prothrombin time and/or activated partial thromboplastin time
  • Active bleeding during or prior to invasive procedures/surgery in patients with congenital or acquired factor deficiency when no alternative therapies (factor concentrates) are available.
  • Acute reversal of vitamin K antagonist therapy
  • Disseminated intravascular coagulation
  • Thrombotic thrombocytopenia purpura
• A cross matching is not required, but ABO compatibility should be considered before transfusion (Table 1).

• Normal plasma volume is about 50 mL/kg or 3,500 mL in a 70-kg man.
• Normal coagulation factor levels are in the range of 50–150% (0.5–1.5 IU/mL).
• Plasma proteins exert an oncotic pressure of 25–30 mm Hg (60–70% derived from albumin). Normal plasma albumin levels are 3.5–5.0 g/dL.
• Plasma preparation:
  • Whole blood centrifuge: Donor whole blood is centrifuged and the top plasma fluid layer is separated from red blood cells and platelets.
  • Plasmapheresis donations: Allows for a single donor and reduces recipient exposure to infection and HLA antibodies. It is an extracorporeal therapy technique that involves removal of whole blood, sequestration of plasma via a cell separator, and return of nonplasma components.
• Freezing:
  • FFP is frozen within 8 hours of collection to –18°C to help prevent inactivation of labile coagulation factors V and VIII.
  • FP24 is the plasma that is frozen within 24 hours of phlebotomy (3). It is being used increasingly as a substitute for FFP because it allows for selection for male-only donors in an attempt to reduce the risk of transfusion-related acute lung injury (TRALI). It contains slightly lower levels of factors V and VIII, but their replacements are not typically indicated.
  • Although they are technically different products, they are considered therapeutically equivalent. Both are stored, thawed, and infused similarly.
• Storage:
  • <–18°C: products can be stored for up to 12 months
  • <–65°C: products can be stored up to 7 years
• Contents:
  • 1 donor unit of FFP = 250 mL (~220 mL plasma, ~30 mL anticoagulant)
  • In theory, 1 mL of plasma = 1 unit of coagulation factors; thus 1 plasma unit contains 220 units. Actual coagulation factors vary significantly among different plasma units. Freezing and thawing may reduce factor levels.
  • Contains coagulation factors, anticoagulant proteins, albumin, and immunoglobulins
  • Devoid of red cells, leukocytes, and platelets. (The lack of leukocytes makes the risk of CMV transmission a nonissue.)
• Thawed FFP
  • After thawing, FFP contains near normal levels of many plasma proteins (procoagulant and inhibitory components of the coagulation cascades, acute phase proteins, immunoglobulins, and albumin), fats, carbohydrates, and minerals in circulation.
  • Coagulation factors are reasonably well maintained with some decreases of factor V and VIII in thawed plasma kept at 1–6°C for up to 5 days.
• ABO compatibility:
  • Antigenic red blood cells are removed during processing; however, small amounts may still be present in donor FFP. Additionally, ABO antigens may be present in the donor FFP. To that extent, although ABO compatibility is preferred whenever possible, in emergencies, it is not necessary.
  • Type AB is considered the universal FFP donor, as it has no antibodies in the plasma to Type A, B, AB or O erythrocytes (Table 1).

• Complications of FFP administration:
  • TRALI is caused by anti-HLA antibodies present in donor plasma. It is the leading cause of morbidity and mortality after plasma transfusion. Female donor units are more likely to be associated with TRALI. In some countries, male donors are specifically chosen, with a demonstrated decrease in incidence. More commonly, male donor FP24 is being utilized.
  • Allergic reactions are the most common complication with a 1–3% incidence.
  • Patients with IgA deficiency may develop an anaphylactic reaction when transfused with IgA-containing blood products including FFP. IgA is a serum immunoglobulin and antibody found at mucosal surfaces. IgA deficiency results from an intrinsic B cell defect.
  • Fluid or circulatory overload can result from large volume administration, particularly in patients with limited cardiovascular reserve.
• Infection transmission:
  • The risks of viral transmission, particularly hepatitis C and human immunodeficiency virus, have been significantly reduced by the nucleic acid testing of donor blood.
  • Treatment of FFP with methylene blue or solvent-detergent further reduces virus transmission risks.
  • Prion disease transmission (Creutzfeldt-Jakob disease) should be reduced by avoiding plasma collections from an endemic area.
  • Hypocalcemia from citrate overload can occur with massive plasma transfusion.

• In adults, 1 unit of plasma increases most factors by ~2.5%; 4 plasma units by ~10%. A 10% increase in factor levels is typically necessary to make a significant change in coagulation status. However, this will vary depending on the patient's size and clotting factor levels.
• Pediatric dosing: 10–15 mL/kg gives a 15–20% rise in factor levels.
• Little evidence exists to inform the best therapeutic plasma transfusion practice. Current indications include the following (2,3):
  • Abnormal coagulation screening tests in the face of bleeding or prophylactically in nonbleeding subjects prior to invasive procedures or surgery.
  • Microvascular bleeding in the presence of PT or PTT > 1.5 times normal. This is believed to correspond to factor levels <30% of normal. However, the relationship among coagulation tests, the extent of coagulopathy, and the need for FFP remains unclear.
  • Urgent reversal of warfarin; consider vitamin K if time permits and prothrombin complex concentrate if available.
  • Massive transfusion may require coagulation factor replacement with FFP without waiting for laboratory results. Abnormalities of PT/PTT are often seen after a rapid infusion >4 units of packed RBCs. The main advantage of "damage control resuscitation" with a fixed ratio (1:1) transfusion of RBC and FFP is the prevention of severe dilution and early correction of coagulopathy.
  • Isolated factor deficiency (factors II, V, VII, IX, X, XI) replacement II, V, VII, IX, X, XI) when specific component therapy is unavailable
  • Hereditary antithrombin or protein C deficiency; however, purified lyophilized antithrombin or protein C concentrate is available and preferable to FFP.
  • Disseminated intravascular coagulation
  • Plasmapheresis for thrombotic thrombocytopenic purpura
  • Infants with protein-losing enteropathy
  • Cell salvage processing can result in depletion of plasma fractions. FFP may be needed after several units have been administered
• Plasma is not as viscous as packed RBCs and does not need to be diluted with crystalloid.

• Transfusion-Related Lung Injury
• Red Blood Cell Transfusion
• Infectious Risk of Transfusion

Kenichi A. Tanaka , MD, MSc

Satoru Ogawa , MD