TATM 2003;5(3):363-367

Fresh Frozen Plasma: Clinical Guidelines and Use

SUMMARY
Fresh frozen plasma (FFP) is the liquid portion of one unit of human blood that contains the labile and stable components of the coagulation, fibrinolytic and complement systems, as well as the proteins that maintain oncotic pressure and
AND

S YLVAIN B LISLE , MD , FRCPC , J EAN -F RANOIS H ARDY, MD , FRCPC

DEPARTMENT OF ANESTHESIOLOGY UNIVERSITY OF MONTREAL MONTREAL, QUEBEC, CANADA

modulate immunity.The clinician must remember that a unit of single-donor allogeneic plasma is a heterogeneous solution of proteins. Infusion of FFP normalizes abnormal tests efficaciously in patients with hereditary coagulopathies. However, its benefit in the treatment of excessive bleeding remains unclear and variable. In clinical practice, indication to transfuse FFP is based on a double threshold: a combination of abnormal coagulation tests plus excessive bleedings. FFP is not the first-line option in the prevention of hemorrhage and in emergency reversal of oral anticoagulation for life-threatening complications.

Fresh frozen plasma Indications Guidelines

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It was during the 19th century that the liquid part of blood was first designated as plasma, the Greek word for modeling. Allogeneic plasma is now considered the source of many circulating proteins, particularly coagulation factors. Fresh frozen plasma (FFP) is the liquid portion of one unit of human blood that has been centrifuged, separated and frozen solid at -18C (or colder) within six hours of collection. It contains the labile and stable components of the coagulation, fibrinolytic and complement systems, as well as the proteins that maintain oncotic pressure and modulate immunity. The clinician must remember that a unit of single-donor allogeneic plasma is a heterogeneous solution of proteins.1 The normal concentration of coagulation factors ranges from 0.5 to 1.5 U/mL. However, a significant number of units may present as an isolated factor deficiency, particularly factors VII and IX.1 The variable mean content of coagulation factors is influenced by individual variations, the ABO blood group, and conditions during the preparation and storage of plasma. Viral inactivation even further decreases the concentration of components in the plasma. For example, it decreases the concentration of factor VIII and protein S, respectively, by 20% and 50%, and the concentration of 2-antiplasmin by as much as 75% of its initial concentration. Under such conditions, the clinician should not expect a homogeneous response to the transfusion of plasma. The use of FFP has increased dramatically in recent years. Its administration is based on two assumptions: an inadequate concentration of coagulation factors will increase the risk of an adverse outcome; and (2) replenishment with allogeneic plasma can correct, decrease or prevent these risks. Does the recent scientific literature validate this rationale and the increasing use of FFP in clinical medicine? Do clinicians need to reconsider transfusion practice guidelines? This paper will review the guidelines for the use of fresh frozen plasma based on the level of evidence in the literature on the indications and benefits of plasma transfusion.

Since 1997, new published studies continue to refine our standards of good transfusion practice. Indications for the use of FFP are confined to the following conditions.

Replacement of Isolated Factor Deficiencies

FFP is indicated for the replacement of isolated factor deficiencies (II, V, VII, IX, X, and XI) only when specific component therapy is neither available nor appropriate. In fact, only factor V, protein S and plasminogen are not available as a purified concentrate. Plasma should be used only when bleeding has occurred or is reasonably expected to occur from surgery or other invasive procedures. Under such conditions, the transfusion of allogeneic plasma is effective to increase the concentration of one factor above 0.5 U/mL.4 Furthermore, requirements for FFP (dosage, frequency and length of administration) vary with the specific factor being replaced.

Reversal of Warfarin Effect

Anti-vitamin K drug use is becoming increasingly more prevalent. Major hemorrhagic complications occur at a rate of 2.7 per 100 treatments a year. Even in patients assigned to less intense therapy (international normalized ratio [INR] 2.0 to 3.0), the annual incidence of major bleeding averaged 1.3%.5 These complications increase significantly with age and are associated with an escalating INR. An INR > 4.0 carries an absolute risk of intracranial hemorrhage of 2% per year with a mortality rate of 76%. Prompt, effective and reliable normalization of the anticoagulant effect produced by these drugs is the primary goal of the treatment. Traditionally, in anticoagulated patients with active bleeding or requiring emergency surgical or invasive procedures, FFP has been used to achieve immediate hemostasis. The American Society of Anesthesiology recommends a dose of 5 to 8 mL/kg. Guidelines from the Canadian Medical Association make no recommendation regarding the volume of FFP to be administered considering the lack of systematic assessments of this therapy. A number of trials with limited numbers of patients compare FFP to other treatment options. In contrast with FFP, the reversal of anticoagulation with prothrombin complex concentrates (PCC) is faster (within 5 hours) and more effective, but is of short duration. FFP has an intermediate effectiveness (fewer patients achieve an INR < 1.5) and its action is delayed (within 7 to 8 hours). In two recent studies designed to compare the efficacy of allogeneic plasma with PCC (reported in factor IX unit) and factor VII concentrate, the transfusion of 4 units of allogeneic plasma (5-8 mL/kg) was insufficient to reach the lower limit of 0.2 U/mL for vitamin K-dependent factors (II, VII, IX, X) and to normalize the INR.1,6 Even after the infusion of a mean volume of FFP of more than 2.7 liters, more than 8 hours were needed to observe the correction of the INR ( 1.3).6 PCC antagonized the INR more rapidly and completely than plasma. Moreover, in comparison with FFP-treated patients presenting intracerebral hemorrhage, the administration of PCC has been associated with less deterioration on the Reaction Level Scale. However, this higher efficacy also entails some risk. Thrombosis and DIC have been associated with this product, particularly in liver disease. Recombinant activated factor VII (rFVIIa) is able to normalize experimentally prolonged INR in healthy volunteers.7 For many clinicians, FFP is, therefore, no longer the first choice of treatment for the immediate reversal of effects of warfarin.

Practice Guidelines
Standard transfusion practice has traditionally been based on a consensus of expert opinions. The most rigorous practice guidelines were formulated by the American Society of Anesthesiologists (ASA) in 19962 and the Canadian Medical Association (CMA) in 1997.3 The American task force reviewed the literature published until mid-1994 in order to develop evidence-based guidelines on the proper indications for perioperative administration of allogeneic blood products (ABP). The Canadian guidelines were based on a systematic review of the literature published between January 1966 and July 1996 and an assessment of the level of evidence. The bibliographic search included articles on the transfusion of red blood cells and plasma in both adults and children. The American and Canadian experts make six recommendations each. These recommendations are summarized in Table 1. The CMA bases its guidelines and recommendations on a double transfusion threshold where clinical appreciation of bleeding is an essential element needing consideration in the transfusion of plasma. Based on this double threshold, excessive bleeding unrelated to hypothermia, anemia, acidosis, hypocalcemia or a surgically treatable source must be active and an abnormal hemostatic profile must be identified.
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Disseminated Intravascular Coagulation (DIC)

Infusion of allogeneic plasma is recommended in patients with acute disseminated intravascular coagulation who have active bleeding associated with increased PT, INR or aPTT (activated partial thromboplastin time), provided that the triggering condition can also be treated effectively. Forty-one per cent (41%) of patients with brain injury develop an early profile (1 to 4 hours) of DIC.8 The development of a laboratory coagulopathy is significantly associated with a higher mortality rate in adults8,9 and children.10 In non-survivors, severe brain edema, rather than intracranial hemorrhagic complications, is the most frequent image seen on cerebral axial tomography. Early prophylactic administration of plasma cannot prevent the development of a coagulopathy in these patients.11 Plasma transfusion is not indicated in DIC without bleeding or in chronic DIC. In decompensate DIC with bleeding, transfusion of FFP, along with other blood components and especially rapid resolution of the initial trigger, may be useful.

prophylactic plasma transfusion is not indicated for percutaneous liver biopsy, paracentesis and thoracentesis if the INR is 2.0.3 Other options may be available in a near future if current investigations are conclusive. Among them, rFVIIa induces a dose-dependent reduction of prolonged PT in cirrhotic patients.15,16

Plasma Exchange Therapy

Indications for the use of FFP depend on the initial diagnosis. In GuillainBarr syndrome, for example, exchange with albumin as opposed to FFP has been associated with a lower morbidity rate.17 In contrast, the administration of FFP during plasma exchange improves outcome in patients presenting with either thrombotic thrombocytopenic purpura (TTP) or adult hemolytic-uremic syndrome (HUS).18 Plasma transfusion is not, however, recommended in the classic form of pediatric HUS.

Cardiopulmonary Bypass/Cardiac Surgery

Abnormal coagulation test values are commonly used to justify the administration of plasma in patients presenting with excessive bleeding although spontaneous recovery of these parameters is observed over a few hours. The reduction of plasma factor levels is too modest to be the sole factor involved in most cases of excessive bleeding,19 and there is no proven correlation between the various laboratory test abnormalities and patients presenting with excessive bleeding or an anticipated blood loss. Furthermore, although bleeders tend to receive more blood components, there is surprisingly little effect on the coagulation factor levels measured. Preventive use of plasma after cardiopulmonary bypass cannot reduce the mediastinal drainage and increases exposure to allogeneic blood products.20,21 A recent study evaluates the benefit of allogeneic plasma (either FFP or solvent/detergent plasma [SDP], volume infused of 8.5 mL/kg) in 67 patients undergoing cardiac surgery and requiring massive transfusion.22 Effective control of bleeding was defined as a reduction in blood loss of more than 50%. This beneficial response was observed in approximately 40% of the cohort, without significant difference between FFP and SDP . However, the treatment was totally ineffective in about 25% of patients. The mortality rate was significantly higher in the group of patients infused with FFP (FFP: 32% versus SDP: 11%, p = 0.04). The positive impact of allogeneic plasma transfusion on the control of the hemorrhage, therefore, remains variable, necessitating a balance between the benefits of a spontaneous recovery and a potential risk of thrombosis.

Massive Blood Transfusion/Microvascular Bleeding

Abnormal hemostasis can occur in association with massive transfusion. In order of appearance, fibrinogen concentration < 0.5 g/L, clotting factor levels < 20%, and platelet count < 50 x 109/L are the abnormal hemostatic parameters associated with microvascular bleeding in massively transfused patients.12,13 A significant decrease in clotting factor levels usually translates into a prolonged PT and aPTT (> 1.8 times the normal).12 In 45 patients with acquired coagulation deficits (with active bleeding, surgical prophylaxis, or warfarin overdose), the infusion of 8 mL/kg of FFP was associated with an appropriate bleeding control in up to 27 % of cases.14 Interestingly, the active bleeding was contained more frequently than the correction of the PT by three times. In the context of massive transfusion (more than one blood volume), FFP should be administered if there is microvascular bleeding associated with a significantly increased PT, INR or aPTT (double threshold). If PT, INR or aPTT cannot be measured quickly, allogeneic plasma may be transfused in an attempt to stop diffuse non-surgical bleeding. FFP is ineffective in controlling persistent bleeding from a surgically correctable cause or related to hypothermia, vascular hypertension, ionized hypocalcemia, acidosis, anemia and no significant abnormalities of coagulation tests. There is no evidence that the prophylactic administration of FFP is effective or decreases transfusion requirements in massively transfused patients who do not have documented coagulation defects.

Liver Disease
Liver disease impairs the hemostatic system by different mechanisms, such as dysfunction of clotting and restriction factors, increasing fibrinolysis and thrombocytopenia. Risks of excessive bleeding in patients with liver disease include gastrointestinal hemorrhage, bleeding during routine procedures (liver biopsy), or during major surgery. In patients with liver disease, infusion of FFP is recommended when there is actual bleeding or to prepare for surgery or liver biopsy when PT or INR are moderately abnormal (INR > 2.0). The efficacy of allogeneic plasma to prevent excessive bleeding during surgery or liver biopsy remains speculative, and

Improper Use
There is no justification for the use of FFP as a volume expander or as a nutritional source. Prophylactic transfusion of plasma before paracentesis or thoracocentesis in patients with moderate coagulation abnormalities (PT or PTT up to twice the midpoint normal value) secondary to liver disease is not required. As already stated, FFP should not be used prophylactically with massive blood transfusion since there is no documentation that it has a beneficial effect when used as part of the transfusion management of patients with massive hemorrhage. Nor should it be used prophylactically after cardiopulmonary bypass.

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population or condition does not account for this large variation. Medical management and other institutional factors must, therefore, be considered as independent risk factors for plasma transfusion. Financial cost, too, is Normal plasma volume is 30 to 40 mL/kg. In theory, plasma should be a strong modulator of the use of FFP. given in doses calculated to achieve a minimum of 30% the normal plasma Even more disquieting is the lack of adherence to the guidelines on the factor concentration (10 to15 mL/kg). In cases of urgent reversal of warfarin use of allogeneic plasma. The majority of clinicians would agree with the anticoagulation, 5 to 8 mL/kg may be inadequate in many patients. recommendations and guidelines. Yet bedside adherence to these guidelines These recommended dosages are not derived from systematic is poor, in part because of the difficulty in translating a synthetic algorithm assessments of therapy. Ongoing clinical and laboratory evaluations are and a fear of complications. Many authors have, in fact, observed an necessary to measure the response and to determine subsequent action. extrapolation of these guidelines resulting in a high rate of transfusion. Indeed, of all allogeneic blood products, the transfusion of plasma continues to show the highest rate of inappropriate use. Reported inappropriateness rates for Variability of Transfusion Practice transfusion episodes range from 18% to 96%,26-29 with the rate being twice that observed for red blood cell transfusions in one particular study.30 The use of FFP is controlled locally and varies not only from country Better compliance is paramount and can be improved by institutional to country but also from one institution to the next. Institutional exposure measures, such as the creation of education programs, the implementation to plasma is reported to range from 0% to as high as 97% in primary of audit practices, and the introduction of an algorithm based on a double elective coronary artery bypass surgery.23-25 The diversity of the patient threshold (excessive bleeding plus abnormal coagulation). Plasma transfusion diagnostic algorithms Table 1. reduce unwarranted plasma requests by 64%, Guidelines on the Indications for Plasma Transfusion mediastinal drainage by 52%, the relative risk of surgical American Society re-exploration for hemorrhage by 74%, and exposure Level of evidence of Anesthesiologists Canadian Medical Association to allogeneic plasma by 83%.31-34 Expert opinion For known factor deficiencies for Plasma should be used only when

Dose

which specific concentrates are unavailable

For urgent reversal of warfarin therapy

bleeding has occurred or is reasonably expected to occur from surgery or other invasive procedures When serious bleeding has occurred or is expected in patients with vitamin K deficiency For bleeding in patients with liver disease or to prepare for surgery or liver biopsy when PT or INR are sufficiently abnormal Prophylactic use is not indicated if the INR is 2.0 Massive transfusion if there is microvascular bleeding with significant increased PT, INR or aPTT

Expert opinion

Conclusion
Allogeneic plasma is a heterogeneous biological product. The perception of the efficacy of FFP is generally overestimated. Infusion of FFP normalizes abnormal tests efficaciously in patients with hereditary coagulopathies. Its benefit in the treatment of excessive bleeding remains unclear and variable. In clinical practice, FFP is recommended in situations of excessive bleeding and abnormal coagulation tests (double threshold). FFP is not the first-line option in the prevention of hemorrhage and in emergency reversal of oral anticoagulation for life-threatening complications. The rate of inappropriate transfusion of FFP remains high. Clinical practice must be based on the benefit, risk and efficiency of treatment, including cost. This assures an optimal and efficient use of FFP . Also, this approach offers a framework for the evaluation of new therapeutic agents (PCC, factor VII concentrates and rFVIIa). Indications for therapeutic plasma transfusion are decreasing rapidly as new alternatives will be proven beneficial. Through the establishment of a transfusion committee to monitor the use of blood products and the implementation of an appropriate plasma transfusion protocol and guidelines, hospitals can effectively reduce exposure to allogeneic blood products and promote good clinical practice.

Weak (no randomized controlled study available)

For correction of microvascular bleeding with elevated PT or aPTT (> 1.5 times normal) With transfusion of > one blood volume and when PT and aPTT cannot be obtained in a timely fashion

Weak (no randomized controlled study available)

For acute disseminated intravascular coagulation with active bleeding associated with increased PT, INR or aPTT, provided that the triggering condition can also be treated effectively Plasma should be used in the treatment of TTP or adult HUS Dosage Plasma should be given in doses calculated to achieve a minimum of 30% the normal plasma factor concentration (10 to 15 mL/kg), except for urgent reversal of warfarin anticoagulation (5 to 8 mL/kg) These values are not derived from systematic assessments of therapy No recommendation regarding volume of plasma to be administered

Weak (no randomized controlled study available)

Strong (at least one randomized controlled study) Expert opinion

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K e y

P o i n t s

1. A unit of single donor plasma is a heterogeneous solution of proteins and the clinicians should not expect a homogeneous response to the transfusion of plasma. 2. FFP is indicated for the replacement of isolated factor deficiencies only when specific components therapy is neither available nor appropriate. Only factor V, protein S and plasminogen are not available as a purified concentrate. 3. FFP is no longer the first choice of treatment for the immediate reversal of effects of warfarin. 4. Plasma transfusion is not indicated in DIC without bleeding or in chronic DIC. In decompensate DIC with bleeding, transfusion of FFP , along with other blood components and especially rapid resolution of the initial trigger, may be useful. 5. In the context of massive transfusion, FFP should be administered if there is microvascular bleeding and a significantly increased PT, INR or aPTT (double threshold). If PT, INR or aPTT cannot be measured quickly, allogeneic plasma may be transfused in an attempt to stop diffuse non-surgical bleeding. 6. In patients with liver disease, infusion of FFP is recommended when there is actual bleeding or to prepare for surgery of liver biopsy when PT or INR are moderately abnormal (INR > 2) 7. FFP should not be used prophylactically after cardiopulmonary bypass. 8. Indications for therapeutic plasma are decreasing rapidly as new alternatives such as prothrombin complex concentrates, factor VII concentrates and rFVIIa will be proven beneficial. 9. Of all allogeneic blood products, the transfusion of plasma continues to show the highest rate of inappropriate use. Reported inappropriateness rates for transfusion episodes range from 18% to 96%. 10. The establishment of a transfusion committee to monitor the use of blood products and the implementation of appropriate protocols and guidelines can effectively reduce exposure to allogeneic blood products and promote good clinical practice.

R E F E R E N C E S 1. Makris M, Greaves M, Phillips WS, Kitchen S, Rosendaal FR, Preston EF. Emergency oral anticoagulant reversal: the relative efficacy of infusions of fresh frozen plasma and clotting factor concentrate on correction of the coagulopathy. Thromb Haemost 1997;77:477-80. 2. Practice Guidelines for blood component therapy: A report by the American Society of Anesthesiologists Task Force on Blood Component Therapy. Anesthesiology 1996;84:732-47. 3. Expert Working Group. Guidelines for red blood cell and plasma transfusions for adults and children. CMAJ 1997;156(11 Suppl):S1-24. 4. Inbal A, Epstein O, Blickstein D, Kornbrot N, Brenner B, Martinowitz U. Evaluation of solvent/detergent treated plasma in the management of patients with hereditary and acquired coagulation disorders. Blood Coagul Fibrinolysis 1993;4:599-604. 5. Levine MN, Raskob G, Landefeld S, Kearon C. Hemorrhagic complications of anticoagulant treatment. Chest 2001;119(1 Suppl):108S-121S. 6. Boulis NM, Bobek MP, Schmaier A, Hoff JT. Use of factor IX complex in warfarin-related intracranial hemorrhage. Neurosurgery 1999;45:1113-9. 7. Erhardtsen E, Nony P, Dechavanne M, Ffrench P, Boissel JP, Hedner U. The effect of recombinant factor VIIa (NovoSeven) in healthy volunteers receiving acenocoumarol to an International Normalized Ratio above 2.0. Blood Coagul Fibrinolysis 1998;9:741-8. 8. Hulka F, Mullins RJ, Frank EH. Blunt brain injury activates the coagulation process. Arch Surg 1996;131:923-8. 9. Olson JD, Kaufman HH, Moake J, et al. The incidence and significance of hemostatic abnormalities in patients with head injuries. Neurosurgery 1989;24:825-32. 10. Chiaretti A, Pezzotti P, Mestrovic J, et al. The influence of hemocoagulative disorders on the outcome of children with head injury. Pediatr Neurosurg 2001;34:131-7. 11. Winter JP, Plummer D, Bottini A, Rockswold GR, Ray D. Early fresh frozen plasma prophylaxis of abnormal coagulation parameters in the severely head-injured patient is not effective. Ann Emerg Med 1989;18:553-5. 12. Ciavarella D, Reed RL, Counts RB, et al. Clotting factor levels and the risk of diffuse microvascular bleeding in the massively transfused patient. Br J Haematol 1987;67:365-8. 13. Hiippala S. Replacement of massive blood loss. Vox Sang 1998;74 Suppl 2:399-407. 14. Lerner RG, Nelson J, Sorcia E, et al. Evaluation of solvent/detergent-treated plasma in patients with a prolonged prothrombin time. Vox Sang 2000;79:161-7. 15. Bernstein DE, Jeffers L, Erhardtsen E, et al. Recombinant factor VIIa corrects prothrombin time in cirrhotic patients: a preliminary study. Gastroenterology 1997;113:1930-7. 16. Jeffers L, Chalasani N, Balart L, Pyrsopoulos N, Erhardtsen E. Safety and efficacy of recombinant factor VIIa in patients with liver disease undergoing laparoscopic liver biopsy. Gastroenterology 2002;123:118-26. 17. Raphael JC, Chevret S, Hughes RA, Annane D. Plasma exchange for Guillain-Barre syndrome. Cochrane Database Syst Rev 2001:CD001798. 18. Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med 1991;325:393-7. 19. Bick RL. Alterations of hemostasis associated with cardiopulmonary bypass: pathophysiology, prevention, diagnosis, and management. Semin Thromb Hemost 1976;3:59-82. 20. Trimble AS, Osborn JJ, Kerth GW, Gerbode F. The prophylactic use of fresh frozen plasma after extracorporeal circulation. J Thorac Cardiovasc Surg 1964;48:314-6. 21. Kasper SM, Giesecke T, Limpers P, Sabatowski R, Mehlhorn U, Diefenbach C. Failure of autologous fresh frozen plasma to reduce blood loss and transfusion requirements in coronary artery bypass surgery. Anesthesiology 2001;95:81-6. 22. Haubelt H, Blome M, Kiessling AH. Effects of solvent/detergent-treated plasma and fresh-frozen plasma on haemostasis and fibrinolysis in complex coagulopathy following open-heart surgery. Vox Sang 2002;82:9-14. 23. Goodnough LT, Johnston MF, Toy PT. The variability of transfusion practice in coronary artery bypass surgery. Transfusion Medicine Academic Award Group. JAMA 1991;265(1):86-90. 24. Stover EP, Siegel LC, Parks R, et al. Variability in transfusion practice for coronary artery bypass surgery persists despite national consensus guidelines: a 24institution study. Institutions of the Multicenter Study of Perioperative Ischemia Research Group. Anesthesiology 1998;88:327-33. 25. Kytola L, Nuutinen L, Myllyla G. Transfusion policies in coronary artery bypassa nationwide survey in Finland. Acta Anaesthesiol Scand 1998;42:178-83. 26. Venema D, Schut M, van Oers MH. [Lack of adherence to the guidelines on the use of fresh frozen plasma]. Ned Tijdschr Geneeskd 1998;142:1999-2002. 27. Thomson A, Contreras M, Knowles S. Blood component treatment: a retrospective audit in five major London hospitals. J Clin Pathol 1991;44:734-7. 28. Beloeil H, Brosseau M, Benhamou D. [Transfusion of fresh frozen plasma (FFP): audit of prescriptions]. Ann Fr Anesth Reanim 2001;20:686-92. 29. Pita-Ramirez L, Cabrera Carbajal BE, Ortega Zavala C. [Reasons for fresh frozen plasma transfusion in a general hospital]. Rev Invest Clin 1999;51:89-92. 30. Metz J, McGrath KM, Copperchini ML, et al. Appropriateness of transfusions of red cells, platelets and fresh frozen plasma. An audit in a tertiary care teaching hospital. Med J Aust 1995;162:572-3, 576-7. 31. Spiess BD, Gillies BS, Chandler W, Verrier E. Changes in transfusion therapy and reexploration rate after institution of a blood management program in cardiac surgical patients. J Cardiothorac Vasc Anesth 1995;9:168-73. 32. Despotis GJ, Grishaber JE, Goodnough LT. The effect of an intraoperative treatment algorithm on physicians' transfusion practice in cardiac surgery. Transfusion 1994;34:290-6. 33. Nuttall GA, Oliver WC, Santrach PJ, et al. Efficacy of a simple intraoperative transfusion algorithm for nonerythrocyte component utilization after cardiopulmonary bypass. Anesthesiology 2001;94:773-81. 34. Marconi M, Almini D, Pizzi MN, et al. Quality assurance of clinical transfusion practice by implementation of the privilege of blood prescription and computerized prospective audit of blood requests. Transfus Med 1996;6:11-9.

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