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Consensus Development Conference Statement September 24-26, 1984
This statement is more than five years old and is provided solely for historical purposes. Due to the cumulative nature of medical research, new knowledge has inevitably accumulated in this subject area in the time since the statement was initially prepared. Thus some of the material is likely to be out of date, and at worst simply wrong. For reliable, current information on this and other health topics, we recommend consulting the National Institutes of Health's MedlinePlus http://www.nlm.nih.gov/medlineplus/. This statement was originally published as: Fresh Frozen Plasma: Indications and Risks. NIH Consens Statement 1984 Sept 24-26; 5(5):1-12. For making bibliographic reference to the statement in the electronic form displayed here, it is recommended that the following format be used: Fresh Frozen Plasma: Indications and Risks. NIH Consens Statement Online 1984 Sept 24-26 [cited year month day]; 5(5):1-12. Introduction and ConclusionsFresh 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 statement 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. 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. In an effort to resolve some of the questions surrounding the steadily increasing use of FFP, the National Heart, Lung, and Blood Institute, the Center for Drugs and Biologics of the Food and Drug Administration, and the Office of Medical Applications of Research convened a Consensus Development Conference on FFP on September 24-26, 1984. After a day and a half of presentations by experts in the field, a consensus panel drawn from the medical professions, blood banking organizations, and the general public considered the evidence and agreed on answers to the following key questions:
Panel's ConclusionsThe administration of FFP has increased dramatically in recent years despite the paucity of definitive indications for its use. This increase has occurred in the presence of mounting evidence of its potential risks, which include viral hepatitis and possibly AIDS. Many patients who receive FFP can be managed more effectively and safely with alternative modalities. Appropriate use of FFP must be justified on clinical grounds until better evidence is available. Research to develop safer FFP and alternative therapies is encouraged. There is no justification for the use of FFP as a volume expander or as a nutritional source. Safer alternative therapies exists. FFP is indicated for some documented coagulation protein deficiencies as well as for selected patients who require massive transfusions. It is indicated for patients with multiple coagulation defects as in liver disease, in conjunction with therapeutic plasma exchange for thrombotic thrombocytopenic purpura, for infants with protein-losing enteropathy, and for selected patients with other immune deficiencies. Its use in most other cases should be discouraged. Innovative educational efforts are needed
to encourage appropriate use. What Are the Currently Recommended Clinical Indications for FFP?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 DeficienciesFFP 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 EffectPatients 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 DeficiencyFFP 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 ImmunodeficienciesFFP 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 PurpuraFFP may be beneficial for the treatment of
thrombotic thrombocytopenic purpura. What Are the Risks of FFP?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--predominantly non A, non B-depends on many
factors, including donor selection. The incidence of nonicteric and
icteric hepatitis following multiple transfusions probably ranges between
3 and 10 percent. In rare instances, acquired immunodeficiency syndrome
(AIDS) 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. What Alternative Therapies Exist?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 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. Because of the special nature of neonatal
requirements for blood and blood products, these issues were not addressed
specifically in this report. Nonetheless, efforts should be exerted to
continue to avoid undue exposure to multiple donor sources. What Is the Current Scientific Knowledge Regarding the Effectiveness of FFP?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. What Directions for Future Research Are Indicated?Research aims should be directed toward:*
*No priorities are implied in this sequence The use of FFP is controlled locally and
determined largely by existing practice. Attempts to alter FFP use
frequently have been ineffective. The most successful attempts can be
attributed to a strong local proponent of modern transfusion practices.
Ongoing collaborative efforts, including component therapy workshops
involving clinicians and blood bank directors, can do much to alter
existing practices. Increased attention to the risks and benefits of
component therapy in the medical schools and teaching hospitals also may
change the use of FFP. When appropriate, information regarding potential
risks and benefits of FFP and other blood products should be made
available to patients who receive those products. Consensus Development Panel
Panel Chairman Professor of Medicine Emeritus Harvard University Medical School New England Deaconess Hospital Boston, Massachusetts
Chief, Coagulation Laboratory Walter Reed Army Institute of Research Associate Professor of Medicine Uniformed Services University of the Health Sciences Washington, D.C.
Professor of Laboratory Medicine Yale University School of Medicine New Haven, Connecticut
Board of Directors The National Hemophilia Foundation Stow, Ohio
Professor of Mathematics and Statistics Boston University Boston, Massachusetts
Professor of Medicine University of Pittsburgh School of Medicine Vice President, Research/Coagulation Central Blood Bank of Pittsburgh Pittsburgh, Pennsylvania
Professor and Chairman of Anesthesia Professor of Pharmacology University of California School of Medicine San Francisco, California
Professor of Surgery Washington University School of Medicine Director, Barnes Hospital Burn Center St. Louis, Missouri
Cardiac Surgeon-in-Charge Johns Hopkins Hospital Professor of Surgery Johns Hopkins University School of Medicine Baltimore, Maryland
Clinical Professor of Surgery Harvard Medical School Massachusetts General Hospital Boston, Massachusetts
Associate Minister Cedar Lane Unitarian Church Bethesda, Maryland Speakers
"Epidemiology of AIDS in the United States: Cases Associated with Transfusions" Chief, Surveillance Section Centers for Disease Control Atlanta, Georgia
"Fresh Frozen Plasma as a Nutritional Supplement" Director Nutritional Support Service Assistant Professor of Surgery University of Cincinnati Cincinnati, Ohio
"Postcardiac Pulmonary Bypass" Staff Surgeon Department of Thoracic and Cardiovascular Surgery The Cleveland Clinic Foundation Cleveland, Ohio
"Modified Whole Blood and Cryoprecipitate" Managing Director Puget Sound Blood Center Associate Professor of Medicine University of Washington Seattle, Washington
"Clinical Significance of Decreased Oncotic Pressure" Associate Professor of Surgery Harvard Medical School Boston, Massachusetts
"Coagulopathy of Acquired Factor Deficiency in Liver Disease and Deranged Hemostasis of Uremia" Chief, Medical Service Boston Veterans Administration Medical Center Boston, Massachusetts
"Immune Globulin" Director, Plasma Proteins Branch Center for Drugs and Biologics Food and Drug Administration Bethesda, Maryland
"Risk of Disease Transmission" Director, State Laboratory Institute Massachusetts Department of Public Health Professor of Medicine Tufts University School of Medicine Boston, Massachusetts
"Physiology of Clotting Factors" Associate Member Scripps Clinic and Research Foundation La Jolla, California
"Hemostasis in Massively Transfused Trauma Patients" Professor of Surgery University of Washington Director, Burn Unit Harbor View Medical Center Seattle, Washington
"Plasma Fractions as Alternative to Fresh Frozen Plasma" Director of Research and Development Blood Derivatives Program New York Blood Center, Inc. New York, New York
"Salt and Water Versus Protein-Containing Solutions" Chairman Department of Surgery Michael Reese Hospital and Medical Center Chicago, Illinois
"Plasma Fibronectin: Its Potential Therapeutic Value" Professor and Chairman Department of Physiology Albany Medical College of Union University Albany, New York
"Evaluation of Fresh Frozen Plasma, Plasma Protein Fraction, Albumin, Whole Blood, and Crystalloids" Professor of Surgery Department of Surgery University of California, Los Angeles School of Medicine Harbor-UCLA Medical Center Torrance, California
"Overview of Fresh Frozen Plasma" Professor of Medicine College of Human Medicine Michigan State University East Lansing, Michigan
"Coagulopathy of Apheresis or Exchange" Regional Director North-East Scotland Blood Transfusion Service Royal Infirmary Foresterhill, Aberdeen SCOTLAND Planning Committee
Assistant to the Director Center for Drugs and Biologics Food and Drug Administration Bethesda, Maryland
Chief, Blood Resources Branch Division of Blood Diseases and Resources National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, Maryland
Director of Communications Office of Medical Applications of Research National Institutes of Health Bethesda, Maryland
Social Science Analyst Office of Medical Applications of Research National Institutes of Health Bethesda, Maryland
Managing Director Puget Sound Blood Center Associate Professor of Medicine University of Washington Seattle, Washington
Information Specialist Public Inquiries and Reports Branch National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, Maryland
Professor of Anesthesia Harvard Medical School Anesthetist Massachusetts General Hospital Boston, Massachusetts
Professor of Surgery Wayne State University Detroit, Michigan
Chairman Department of Surgery Michael Reese Hospital and Medical Center Professor of Surgery Pritzker School of Medicine University of Chicago Chicago, Illinois
Executive Vice President for Medical Affairs Blood Systems, Inc. Scottsdale, Arizona
Professor of Medicine Emeritus Harvard University Medical School New England Deaconess Hospital Boston, Massachusetts Conference Sponsors
Claude Lenfant, M.D. Director
Itzhak Jacoby, Ph.D. Acting Director
Harry M. Meyer, M.D. Director Supplemental Information for NIH Consensus Statement on Fresh Frozen Plasma: Indications and RisksSince the NIH Consensus Statement on Fresh Frozen Plasma: Indications and Risks was issued, additional information has become available that supplements the original statement. Recommendations included in the statement
continue to be valid. However, it should be noted that the current
frequencies of infectious virus transmission by single units of blood or
blood components are lower than reported in the statement. For more recent
information, see Schreiber GB. The risk of transfusion-transmitted viral
infections. NEJM 1996;334:1685-1690. Also, "non-A, non-B
hepatitis" is now known to be almost exclusively caused by the
hepatitis C virus (HCV). A test for HCV antibodies was developed several
years ago, and a recently improved version is in universal use in the
United States. |
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