Human plasma continues to be the major source of coagulation factor replacement therapy for patients with clotting factor deficiency. Originally plasma was provided as part of a unit of whole blood and more recently as a specific component, fresh frozen plasma (FFP). The emergence of several new alternatives to FFP requires the review of the relative merits of each product.

Each unit of FFP is derived from a single unit of whole blood. The volume is 220-300ml and it is frozen within 8 hours of collection to maintain normal levels of all coagulation factors. FFP can be stored frozen for up to one year at £ -18° C. When ordered for transfusion it is thawed in a 37° C water bath (takes approximately 25-30 minutes) and can be kept up to 24 hours in a refrigerator (1-6° C). Only ABO identical or compatible FFP can be transfused.

FFP therapy is indicated for patients who are bleeding or undergoing an invasive procedure and have a documented coagulopathy. (i.e. prolonged prothrombin [PT] time or activated partial thromboplastin time [APTT]). Multiple studies have shown that patients with mild prologations of the PT (i.e. <3-4 seconds) are NOT at increased risk for bleeding.^1-8 The most common inappropriate use of FFP is to correct minor prolongations of the PT or APTT.

For patients with significant coagulation factor deficiency the dose of FFP should be 10-20 ml/kg. Thus in a 70 kg patient at least 3-4 units of FFP are required to provide sufficient factors to improve hemostasis.⁹

Each unit of liquid plasma is derived from a single unit of whole blood. The plasma is removed from the whole blood and is stored refrigerated, not frozen like FFP. The volume is 220-300ml and it can be stored refrigerated for up to 26 days. LP differs from FFP in that it contains normal levels of all coagulation factors except factor VIII and factor V. Factor VIII declines to <10% of normal levels, however factor VIII levels in most patients with coagulopathy (i.e. liver disease) are typically normal or elevated since it is an acute phase reactant. Factor V levels decline to 35% of normal which is above the hemostatic level of factor V which is 20-25%. When ordered for transfusion it can be issued immediately since thawing is not required. Only ABO identical or compatible LP can be transfused.

The indications for LP are nearly identical to FFP except for patients with consumptive coagulopathy, such as DIC, in which factor VIII levels may be low and FFP is preferred.

SD plasma is a new plasma product which is expected to be approved by the FDA imminently. SD plasma has undergone treatment with the solvent tri-N-butyl phosphate (TNBP) and the detergent Triton X-100 to destroy any lipid bound viruses including: HIV, HCV, HBV and HTLVI,II. The process does not destroy non-enveloped viruses such as parvovirus, hepatitis A virus, and prion particles. The SD process includes pooling approximately 2000 units of thawed FFP, treating it with the solvent and detergent, and then refreezing the treated plasma into 200 ml aliquots. SD plasma can be stored for up to one year frozen at £ -18° C. When ordered for transfusion it is thawed in a 37° C water bath (takes approximately 25-30 minutes) and can be kept up to 24 hours in a refrigerator (1-6° C). Only ABO identical or compatible SD plasma can be transfused.

Same as FFP

Same as FFP

Delayed release plasma is otherwise handled exactly the same and used clinically in a manner identical to FFP.

The introduction of these plasma alternatives comes at a time when the risks of transfusion have declined dramatically and, for the major viruses, have become very small. Thus the increments of increased safety associated with these alternatives is very small.

The risk profile for FFP and liquid plasma is the same and is summarized in Table 1.

The risk of HIV1,2, HBV, HCV and HTLV I,II transmission have essentially been eliminated by the solvent detergent treatment. The pooled nature of SD plasma however may increase the risk of non enveloped viruses such as parvovirus. The presence of neutralizing antibody to parvovirus and hepatitis A virus in the pooled SD plasma is felt to prevent their transmission however insufficient clinical data are available at this time to estimate the risk of transmission. Theoretically there is also the risk that a new virus entering the blood supply which is not inactivated by SD treatment would be spread more rapidly because of the pooled nature of SD plasma.

The risk of HIV1,2, HBV, HCV and HTLV I,II is greatly decreased by holding the plasma until the donor can be retested beyond the window period for these viruses. The risk reduction would be at least one log less than the risks noted in Table 1. Delayed release plasma does not require pooling and thus is not associated with the concerns noted above for SD plasma.

The decisions regarding use of plasma alternatives also includes cost considerations. Approximate comparative costs are noted in Table 2. SD plasma has not yet been offered commercially however indications are that is will cost $ 20-60 more than FFP.