Use and Abuse of Fresh Frozen Plasma
Darrell J. Triulzi. M.D.
Fresh frozen plasma (FFP) is the primary source of coagulation factors for patients with coagulation factor deficiencies. It is also the most common blood component to be used inappropriately in clinical practice. Both overtransfusion, and less commonly undertransfusion have been observed. This review can serve as a guide to better FFP transfusion practice.
Each unit of FFP contains approximately 225ml of plasma derived from a single unit of whole blood. It is stored frozen at -18° C or colder to preserve all factors at hemostatic levels including the labile factors V and VIII. FFP is thawed in a 37° C waterbath upon request (20-30 minutes) and can be stored after thawing for up to 24 hours at 1-6° C. FFP must be ABO compatible or identical. Crossmatching is not required.
The major indication for FFP is replacement therapy for documented coagulation factor deficiency in a bleeding patient or patient undergoing an invasive procedure. The primary method for documenting a coagulation factor deficiency is by measuring the prothrombin time (PT) or activated partial thromboplastin time (aPTT). The INR has only been studied in the setting of Coumadin dosing and should not be used to assess the risk of bleeding in other settings (i.e. bleeding patients not on Coumadin). Several studies and clinical experience have shown that minor prolongations of the PT or aPTT are NOT associated with increased risk of bleeding.1-5 Only 15% - 35% of normal levels of factors are required to maintain normal hemostasis. Conservatively, this corresponds to a PT or aPTT prolonged 3 seconds above the upper limit of normal.4 FFP transfusions for patients with minor (<3 seconds) prolongations of PT/aPTT are the most common reason for unnecessary transfusion.
Other indications for FFP include emergency reversal of Coumadin, and replacement fluid in plasma exchange for thrombotic thrombocytopenic purpura (TTP).
FFP should not be used as a volume expander or a protein supplement. FFP does not reverse the effects of heparin and is not indicated in patients with prolongations of their aPTT or PT due to lupus anticoagulants. FFP should not be used prophylactically for expected massive transfusion or following cardiac bypass.
Each unit of FFP raises the factor levels in an adult by 3-5%. As a result, 1-2 unit transfusions are an insufficient dose in adult patients with a significant coagulopathy. The recommended dose is 10-20 ml/kg body weight which corresponds to 4-6 units in a 70 kg adult.
As with any blood component, FFP must be administered through a standard blood administration set to remove debris or small clots. FFP may be rapidly transfused over 20-30 minutes. The rate is mainly limited by the patients ability to tolerate the volume.
Allergic reactions occur in approximately 1% of patients receiving FFP. The reactions are usually mild consisting of an urticarial rash (hives) and pruritus, although more serious reactions have been reported. Occasionally patients given large volumes of FFP rapidly, may develop citrate toxicity due to a transient decrease in ionized calcium. These reactions are typically characterized by perioral numbness and tingling, rarely progressing to neuromuscular excitability, arrhythmias, or hypotension.
The risk of viral transmission of FFP is similar to that for red cells and platelets. However, FFP has not been associated with transmission of CMV or HTLV-I,II since these viruses are exclusively white cell associated and plasma is virtually acellular.
RISK ESTIMATES FOR TRANSFUSION TRANSMITTED VIRUSES
PITTSBURGH VS U.S.
Risk per tested unit -1996/1997
* U.S. risks from Schreiber GB et al. NEJM 1996;334:1685
** Risks based on Central Blood Bank donor prevalence statistics
A virally inactivated alternative to FFP (solvent-detergent treated plasma), is likely to be approved by the FDA soon. This product will provide a small increment of increased safety, but may be substantially more expensive. Controversy regarding the cost effectiveness of solvent-detergent treated plasma makes it difficult to predict how this product will be used in clinical practice.
McVay PA, et al. Lack of increased bleeding after liver biopsy in patients with mild hemostatic abnormalities. Am J Clin Pat. 1990; 94:747-753.
Zins M, et al. U.S.-guided percutaneous liver biopsy with plugging of the needle track: a prospective study in 72 high-risk patients. Radiology. 1992; 184:841-843.
McVay PA, et al. Lack of increased bleeding after paracentesis and thoracentesis in patients with mild coagulation abnormalities. Transfusion 1991;31:164-171.
Wachtel S, et al. The relationship of prothrombin time (PT) to clotting factor levels and the "transfusion trigger" for fresh frozen plasma (abstract). Blood. 1994; 84:Suppl:682a.
Squillante CE, et al. Fine-needle liver biopsy in patients with severely impaired coagulation. Liver. 1993; 13:270-273.
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