Fresh frozen plasma

Fresh frozen plasma (FFP) is defined as the fluid portion of one unit of human blood that has been centrifuged, separated, and frozen solid at -18° C (or colder) within 6 hours of collection. Other single-donor plasma units, either frozen or liquid, may be substituted for FFP. Indications for these products are interchangeable with those for FFP except for coagulation factor V deficiency. For that reason, the term FFP in this article otherwise applies to all single-donor plasma units.

The use of plasma and its products has evolved over a period of four decades. The use of FFP has increased tenfold within the past 10 years and reached almost 2 million units annually in the United States. 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. FFP contains the labile as well as the stable components of the coagulation, fibrinolytic and complement systems; the proteins that maintain oncotic pressure and modulate immunity; and other proteins that have diverse activities. In addition, fats, carbohydrates and minerals are present in concentrations similar to those in circulation. Although well-defined indications exist for the use of FFP in single or multiple coagulation deficiencies, indications for many of its other uses may be empiric.

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Indications

Few specific indications for the use of FFP exist. These indications generally are limited to the treatment of deficiencies of coagulation proteins for which specific factor concentrates are unavailable or undesirable. In addition, circumstances exist in which FFP has been employed and is believed to be of therapeutic value, but data supporting its efficacy are limited or unavailable (e.g., multiple coagulation protein deficiencies in the uncontrollably bleeding patient). Because such patients are often critically ill and satisfactory alternative therapy may not be at hand, FFP may be appropriate.

Indications for the use of FFP include the following:

Replacement of isolated factor deficiencies

FFP is efficacious for treatment of deficiencies of factors II, V, VII, IX, X, and XI when specific component therapy is neither available nor appropriate. Requirements for FFP vary with the specific factor being replaced. For example, hemostatic levels of factor IX in a patient with severe deficiency are difficult to achieve with FFP alone, whereas patients with severe factor X deficiency require factor levels of about 10 percent to achieve hemostasis and are easily treated with FFP.

Reversal of warfarin effect

Patients who are anticoagulated with warfarin are deficient in the functional vitamin K 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. However, for anticoagulated patients who are actively bleeding or who require emergency surgery, FFDP (or single-donor plasma) can be used to achieve immediate hemostasis.

Massive blood transfusion (>1 blood volume within several hours)

Use of FFP in massive blood transfusion, for which there is less credible evidence of efficacy, appears to have increased in frequency in the past decade, possibly due in part to the relative unavailability of whole blood. Pathological hemorrhage in the massively transfused patient is caused more frequently by thrombocytopenia than by depletion of coagulation factors. The empiric use of FFP to reverse hemostatic disorders should be confined to those patients in whom factor deficiencies are presumed to be the sole or principal derangement. There is no evidence that the prophylactic administration of FFP decreases transfusion requirements in multiply transfused patients who do not have documented coagulation defects.

Use in antithrombin III deficiency

FFP can be used as a source of antithrombin III in patients who are deficient in this inhibitor and are undergoing surgery or who require heparin for treatment of thrombosis.

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 largely has replaced FFP.

Treatment of thrombotic thrombocytopenic purpura

FFP may be beneficial for the treatment of thrombotic thrombocytopenic purpura.

Risks

The risks of FFP include disease transmission, anaphylactoid reactions, alloimmunization, and excessive intravascular volume. The potential viral infectivity of FFP probably is similar to that of whole blood and red blood cells. The rate of posttransfusion hepatitis depends on many factors, including donor selection. In rare instances, human immunodeficiency virus (HIV) is transmitted by blood transfusions and possibly by FFP. Allergic or anaphylactoid reactions can occur in response to FFP administration and may vary from hives to fatal noncardiac pulmonary edema. The potential for alloimmunization is present, as demonstrated by the infrequent formation of Rh antibodies. As with any intravenously administered fluid, excessive amounts of FFP may result in hypervolemia and cardiac failure.

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 should be used when fibrinogen or von Willebrand factor is needed. For treatment of hemophilia A, cryoprecipitate or factor VIII concentrates, heated or unheated, are available. For treatment of severe hemophilia B, factor IX complex is preferable. Both of these concentrates are prepared from pooled plasma, and the risk of virus transmission is high. The factor IX concentrate carries the additional hazard of thrombogenicity.

Crystalloid, colloid solutions containing human serum albumin or plasma protein fraction, hydroxyethyl starch, and dextran are preferable to FFP for volume replacement. The practice of administering both packed red cells and FFP to the same patient should be discouraged, as this adds to the cost and doubles the infection rate. When conditions are appropriate, whole blood should be given.

For nutritional support, amino acid solutions and dextrose are available.

The most important alternative to the use of FFP is a comprehensive program of blood conservation. This includes measures such as autologous donation before elective surgery, the infusion of shed blood, and the realization that in many patients normovolemic anemia is not an indication for transfusion.

Effectiveness

There is little scientific evidence to support the increasing use of FFP in clinical medicine. While FFP is a reliable solution for intravascular volume replacement in acute blood loss, alternative therapies are equally satisfactory and considerably safer. There is no documentation that FFP has a beneficial effect when used as part of the transfusion management of patients with massive hemorrhage. FFP contains the major plasma proteins, including the labile coagulation factors (V and VIII), but in clinical practice other blood components or derivatives usually provide greater efficacy.

Sources

• NIH Consensus Development Program: Fresh Frozen Plasma: Indications and Risks (public domain)
• Circular of Information for Blood Products