Fresh frozen plasma is being widely overused as a therapeutic agent,and “innovative educational efforts” aimed at physicians areneeded to stem the sharply increased risk of spreading infectiousdisease through this blood product’s unwarranted use.
Medical and blood banking specialists attending a recent three-dayconsensus conference offered those conclusions in a draft report andpress briefing immediately following the meeting. The NationalInstitutes of Health and the Food and Drug Administration convened thegathering expressly to examine issues surrounding the growingprofessional concerns about FFP indications, effectiveness, and safety. The 11-member panel that authored the post-conference statement andconclusions was emphatic. FFP administration, it said, has increaseddramatically in recent years “despite the paucity of definitiveindications for its use” and “in the presence of mountingevidence of its potential risks,” including viral hepatitis andpossibly AIDS. Many patients who receive FFP can be managed “more effectivelyand safely with alternative modalities,” the panel said, notingthat FFP use “must be justified on clinical grounds until betterevidence is available.” The panel also pointedly criticized one practice. “There isno justification for the use of FFP as a volume expander. Saferalternative therapy exists.
” The most appropriate indications for FFP, the panel said, are: * some documented protein deficiencies; * selected patients who require massive transfusions; * patients with multiple coagulation defects as in liver disease; * in conjunction with therapeutic plasma exchange for thromboticthrombocytopenic purpura; * infants with protein-losing enteropathy; and * selected patients with other immune deficiencies. “Its use in most other cases should be discouraged,” thereport concluded. Translated to percentages, the picture is more graphic. Harvardmedical school professor emeritus Dr. James Tullis, the panel chairman,estimated that 90 per cent of current FFP use is inappropriate.
Figuressupplied by researchers at the conference indicate that some 700,000patients a year are receiving 1.8 million units of FFP–a tenfoldincrease over the last five years. During the same period, while little apparently was done to definespecifications for therapeutic applications, blood product specialistscame to realize that risk of disease transmission through FFP had become”significant.” Panel members referred to one estimate thatperhaps 20,000 to 70,000 cases of viral hepatitis are transmitted eachyear through FFP.
They also cited studies indicating that the incidenceof non-icteric and icteric hepatitis following multiple transfusions ofwhole blood or red blood cells is between 3 and 10 per cent. Theybelieve the range for transfusions with FFP is likely the same. The panelists said most of the misuse probably occurs in replacingblood lost during cardiac surgery, while a second troublesome practiceis combining plasma with red blood cells when other combining fluidscould be used with less risk. Dr.
Scott Swisher, a Michigan State University medical professorwho addressed the conference, reported that American Red Cross recordsshowed that FFP went largely to tertiary care, high-technologyhospitals. University medical centers, university-affiliated hospitals, and VAfacilities represent 4.31 per cent of the hospitals served by the RedCross, yet received 25.8 per cent of the FFP distributed, he said. Incontrast, general and speciality hospitals ordered FFP in “directproportion” to their representation: 69.
4 per cent of FFP to 72.8per cent of facilities served. And investor-owned, military, and PublicHealth Service hospitals received less FFP than their representation onthe roster. What accounts for this blood product’s popularity if, as thereport noted, little in the literature supports its increased use inclinical medicine? “The trend may be attributable, in part, to a decreasedavailability of whole blood due to widespread acceptance of the conceptof component therapy,” the panel’s statement said. Other contributing factors mentioned during the conference but notincluded in the summary document included the high cost of somealternatives, limited knowledge among clinicians about scientificallysound transfusion practices, and inadequate instruction of medicalschool students and residents. Some questioned whether clinical laboratory directors, hospitaltransfusion service chiefs, and blood bank directors always have accessto or comply with the latest scientific opinion, or whether they attimes promote FFP use because the product is a revenue generator. Alsocited: the accepted medical practice of administering component-loadedplasma rather than determining and ordering the specific components apatient needs.
As for alternatives, the panel said the most important is acomprehensive program of blood conservation. This includes measuressuch as autologous donations before elective surgery, the use of cellsavers, reinfusion of shed blood, “and the realization that in manypatients normovolemic anemia is not life-threatening.” Added the panel: “Single-donor plasma is efficacious intreating mild deficiencies of stable clotting factors” and “ofvalue for multiple deficiencies, as in reversal of warfarin effects orin liver disease …. Cryoprecipitate should be used when fibrinogen orvon Willebrand factor is needed.
For treatment of hemophilia A,cryoprecipitate of factor VIII concentrates, heated or unheated, areavailable. For hemophilia B, factor IX complex is preferable ….Albumin, plasma protein fraction, crystalloid solutions, hydroxyethylstarch, or dextran are preferable to FFP for volume replacement. Wholeblood or blood modified by removal of the platelets and cryoprecipitateshould be used if available, rather than the combined administration ofplasma and red blood cells.
” The panel noted that FFP use is controlled locally and determinedlargely by existing practice. “Attempts to alter FFP usefrequencly have been ineffective,” it pointed out. But wheresuccessful, a “strong local proponent of modern transfusionpractices” is usually found. “Ongoing collaborative efforts, including component therapyworkshops involving clinicians and blood bank directors, can do much toalter existing practices,” it advised. “Increased attentionto the risks and benefits of component therapy in the medical schoolsand teaching hospitals also may change FFP use.” When appropriate, information regarding FFP’s potential risksand benefits, as well as those for other blood products, should be madeavailable to patients who receive them, the panel said. The report also provided a lengthy list of recommended futureresearch goals, including: * A national prospective epidemiologic study to identify thecurrent usage patterns of FFP and related products.
* Defining the etiology of uncontrollable hemorrhage in themassively transfused patient. * Clinical investigations to identify the factor(s) in fresh frozenplasma that appears to cause beneficial effects in patients who areundergoing apheresis for treatment of syndromes such as thromboticthrombocytopenic purpura. * Blood salvage during operative procedures to allow a morejudicious use of FFP and other blood products. * Production of the safest possible FFP or substitutes. * Technology involving membrane-separation techniques to separatecellular products more effectively.
* Development of an efficient system by which a larger volume ofFFP can be collected from a single donation, thus lessening the numberof donor exposures. At this writing, panel participants were reviewing the draftdocument, and a final version was to have been published late lastmonth. Some close to the working group expected only minor wordingchanges, while others anticipated considerable rewriting. No one,however, predicted major substantive changes since no major riftsemerged among the specialists during the conference.
Meanwhile, a Red Cross spokesman said the ARC fully supported thedraft. Officials at the American Association of Blood Banks elected towithhold comment until the final version was available.