Volume 167 Issue 9

Evaluation of the ThinPrep Pap test as an adjunct to the conventional Pap smear Jennifer M Roberts, A Marion Gurley, Julia K Thurloe, Ronald Bowditch and Colin R A Laverty For editorial comment, see Wain Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - ©MJA1997 Abstract Objective: To evaluate the ThinPrep Pap test as an adjunct to the conventional Pap smear. Design and setting: Prospectively collected cervical samples were split for independent screening at a large specialised private gynaecological pathology practice in Sydney. Main outcome measures: Detection of additional significant abnormalities (cervical intraepithelial neoplasia 1, or more severe); changed management recommendations from "repeat smear in 12 months" or "...six months" to "colposcopy"; a reduction in unsatisfactory reports. Results: 35 560 paired (split-sample) conventional and ThinPrep slides were prepared. Significant abnormalities were detected in 724 conventional smears (2%). Additional significant abnormalities were found in 85 ThinPrep slides whose corresponding conventional smear was negative or unsatisfactory even after review, representing a 12% increase in the detection of significant abnormalities. As a result of the addition of ThinPrep, management recommendations were changed from "repeat smear in 12 months" or "...six months" to "colposcopy" for 89 of 1669 women whose conventional Pap smears showed minor non-specific changes or papillomavirus. There were 1258 conventional smears (3.5%) that were unsatisfactory compared with 235 ThinPrep slides (0.7%); for only 74 samples (0.2%) were both slides unsatisfactory. Conclusions: The addition of the ThinPrep Pap test improves detection and clinical management of cervical abnormalities, and reduces the number of unsatisfactory samples which would otherwise require repeat tests. MJA 1997; 167: 466-469 Introduction The conventional Pap smear has been the mainstay of screening for cervical precancer for approximately 50 years, without major changes in techniques relating to preparation and interpretation. In recent years there has been increasing pressure to improve Pap smear standards to reduce the occurrence of false negative results, with their associated morbidity and mortality for the women involved, and legal consequences for health professionals.1,2 Many false negative cases are the result of problems of sample transfer and smear quality.3,4 The conventional Pap smear represents only a small subsample of the cellular material collected on the sampling implement,5,6 with the remainder traditionally being discarded. Importantly, this small subsample is a non-random fraction of the material collected and is not necessarily representative of the whole. The traditional smearing technique also produces slides which vary greatly in quality, making it sometimes difficult to find and interpret abnormal cells. Improvements in both subsample selection and slide quality should therefore reduce the number of false negative cases. The ThinPrep Pap test is an automated technique developed with the aim of producing better quality slides.7 Each cervical sample is rinsed into a vial of fixative fluid. In the laboratory the sample is homogenised, and a representative subsample is collected on a single-use filter, transferred to a glass slide, and stained in the routine fashion. This technique results in a better quality preparation, as the problems of poor fixation, uneven thickness of the cellular spread, and obscuring of cells by blood and inflammatory exudate are overcome. We aimed to evaluate the impact of this technology on detection rates of significant abnormalities, accuracy in reporting, and numbers of unsatis - fact ory preparations when it was used in addition to the conventional Pap smear. Methods In a pilot study in the first half of 1996, we evaluated 1051 samples to test the performance of the ThinPrep 2000 machine (Cytyc Corporation, Boxborough, Mass., USA), as previous experience with an earlier model had highlighted some technical problems.8 The pilot study showed slides of uniformly high quality and so, in July 1996, the test was offered to all referring practitioners at a charge to patients of $20.30. For this study, we analysed paired samples collected between 1 July 1996 and 30 May 1997 by practitioners who chose to offer ThinPrep (TP) to their patients as an adjunct test. We used a split-sample protocol in which routine samples of the transformation zone (squamo-columnar junction) -- the area of the cervix where abnormalities are most likely to occur -- were taken with a broom-like device, the Cervex brush (Rovers BV, Netherlands). We insisted on the use of this implement as our earlier study8 had shown that sampling with a spatula was more likely to result in a TP slide with insufficient cells. For postmenopausal women and those who had had previous cervical surgery or ablation, an endocervical brush sample was added. After a conventional Pap smear was made, the sampling implement was vigorously rinsed in a vial of PreservCyt fixative fluid (Cytyc Corporation, Boxborough, Mass., USA). TP slides were prepared from the vial by the ThinPrep 2000 machine and both slides were stained routinely. A duplicate of each request form was made, and the conventional smear and the TP slide were examined independently by different cytotechnologists. Nineteen of our 28 cytotechnologists were involved in reading the TP slides; all 28 read conventional smears. Any slide showing minor abnormalities was reviewed by a second experienced cytotechnologist. If cervical intraepithelial neoplasia (CIN) of any grade was detected, or if a high grade lesion was suspected, the case was referred to a cytopathologist for review. Slide pairs (conventional Pap smear and TP) displaying a significant discrepancy were also reviewed. The final report issued to the referring doctor was structured according to the National Health and Medical Research Council (NHMRC) reporting terminology9 (see Box 1) and contained any relevant information obtained from both slides, together with the relevant management recommendations. For the purposes of analysis, separate final results of the two slides were also recorded. A significant abnormality was defined as one for which the management recom mendation is "colposcopy" (see Box 1). This includes any grade of CIN, adenocarcinoma in situ (AIS), invasive carcinoma or the suspicion of a high grade abnormality ("inconclusive" in NHMRC terminology). Results Approximately 500 referring practitioners chose to offer TP to their patients as an adjunct test. Some of these doctors offered the TP test to all women, and others only to selected women. Thirty-five per cent of women having non-screening cytological tests had TP, whereas only 24% of women having routine cytological tests had TP. Currently, about 30% of all smears received in this laboratory are accompanied by a TP sample. We received 35 560 paired split-sample conventional Pap smear slides and TP samples for analysis in this study. Box 1 presents a comparison of final (i.e., reviewed) results for TP and conventional Pap smear slides. Of the 34 141 paired results that were satisfactory for both slides, 32 195 (94.3%) showed total agreement and 1946 (5.7%) did not. Of the latter group, the TP slide showed a more severe abnormality than the conventional slide in 1194 (61.4%), and the opposite was true in 752 (38.6%; chi-squared = 100.4; df = 1; P < 0.001). For the 1946 paired slides which did not show total agreement, 271 had substantial discrepancies in which colposcopy would have been recommended based on the result of one test, but not the other. Of these, colposcopy would have been recommended on the basis of the TP result alone for 167 (61.6%), and on the basis of the conventional Pap smear result alone for 104 (38.4%; chi-squared = 14.6; df = 1; P < 0.001). Significant abnormalities were detected in 724 conventional smears. An additional 85 significant abnormalities were detected on TP slides for which the corresponding conventional slides, even after review, were either negative (78) or unsatisfactory (7). This represents a 12% increase in the detection of significant abnormalities. There were 14 TP slides that predicted high-grade epithelial abnormality (HGEA), while the corresponding conventional smears were either negative or unsatisfactory. Histological follow-up of 11 of these confirmed HGEA in eight, and low-grade epithelial abnormality (LGEA) in three. There were also 27 TP slides reported as inconclusive, while the corresponding conventional smears were either negative or unsatisfactory. Histological follow-up of 17 of these showed HGEA in seven, LGEA in eight, and inflammation in only two. Further, 15 conventional smears originally reported as negative, and reviewed because their TP counterparts showed an abnormality, were subsequently reported as HGEA or inconclusive. These "screening" false negatives are not represented in Box 1, which shows only final results (i.e., after review). ThinPrep slides not only increased detection of abnormalities, but also influenced management recommendations. On the basis of conventional smear tests, the recommendations for 1669 women (4.7%) with minor non-specific changes or features of human papillomavirus (HPV) effect were "repeat smear in 12 months" or "...six months", respectively. For 89 of these women (5.3%), this recommendation was changed to "colposcopy" as a result of a higher grade abnormality being detected on the TP slide. Histological follow-up concentrated on the predicted HGEA and inconclusive categories. Findings are shown in Box 2 (below). Of conventional smears, 1258 (3.5%) were found to be unsatisfactory, but only 74 (0.2%) were unsatisfactory by both methods, representing a 94% reduction in unsatisfactory reports. TP predicted HGEA in four smears reported as unsatisfactory on the conventional smear; all four have been histologically confirmed to be HGEA. Minor abnormalities (minor non- specific changes/HPV) were detected in 1669 (4.7%) of the conventional smears and 2027 (5.7%) of the TP slides. An endocervical component was absent in 8.3% of the conventional smears and in 20.0% of the TP slides. In 6.4% of cases, neither slide displayed an endocervical component. With respect to glandular abnormalities, 13 cases of adenocarcinoma in situ (AIS) or adenocarcinoma were detected by both methods. There was one histologically confirmed case of adenocarcinoma in which the conventional smear was reported as inconclusive (suspicious of AIS) and the corresponding TP slide was negative. Further TP slides were made from the remaining sample in the vial but none of these contained abnormal cells. Discussion Overall, we found that diagnostic agreement between the conventional Pap smear and the TP Pap test was high. Where there was disagreement, a higher grade abnormality was predicted significantly more often by TP than by the conventional smear. The addition of the TP test resulted in detection of additional histologically confirmed HGEA, leading to a reduction in the number of false negatives and a corresponding increase in sensitivity. The fact that the same proportion of HGEA (83%) was histologically confirmed for both conventional Pap smear and TP shows that TP does not result in undue overreporting, and that, although sensitivity has been increased, the positive predictive value of the test has been maintained. The extra significant abnormalities detected on TP and the increased accur acy of reporting are mainly attributable to improved subsampling of the cervical specimens, resulting in fewer "subsampling" false negatives. Computer-assisted rescreening of conventional smears would have no impact on this area. "Screening" false negatives (although few in this study) will also be reduced by the addition of a slide of much higher quality, and by the independent screening of additional material. That there were cases in which an abnormality detected on conventional smear was not detected on TP is not surprising, as the split-sample protocol favours the conventional smear. In these cases it appears that all abnormal cells in the sample were transferred to the conventional smear, leaving none in the TP vial. A "direct-to-vial" protocol in which 100% of the material collected is rinsed into the fluid fixative should eliminate this problem. However, if only a very small number of abnormal cells are present in the vial, then they may not be represented on any single TP slide. The addition of the TP test resulted in a large reduction in reporting of unsatisfactory preparations. This is a direct result of removal of the many variables associated with the conventional Pap smear technique (poor fixation, uneven thickness of the cellular spread, and obscuring of cells by blood and inflammatory exudate), and represents significant time and cost savings, as the need for a repeat smear is avoided. Significantly, there were four women with histologically confirmed HGEA which was predicted by TP, but whose conventional smears were reported as unsatisfactory. These abnormalities may have been detected by the recommended repeat smear three months later, but there is always a risk that women will not return for follow-up. A very small percentage of TP slides were unsatisfactory and this was always the result of there being insufficient cells in the specimen. In these cases the machine reported a dilute specimen. We believe that a number of these cases were the result of the use of incorrect sampling implements, contrary to the recommended protocol. Of some surprise to us was the increase in reporting of minor non-specific changes. While some of this no doubt represents a genuine increase in detection of minor abnormalities, we feel that other factors must be contributing. In particular, we believe that the improved nuclear morphology obtained in the TP process requires cytotechnologists and cytopathologists to "relearn" subtle criteria used at this end of the diagnostic spectrum. We noted this trend early in the study period and have been addressing it with numerous educational sessions. We continue to monitor reporting in this category. The addition of TP tests resulted in a decreased proportion of combined reports lacking an endocervical compon ent. However, TP alone had a higher rate of absent endocervical compon ent. The reason for this is unclear, but may relate to TP slides being prepared from left-over cellular material. We can only speculate that the "endocervical component present" rate may improve in a direct-to-vial situation. Even though there were more TP slides lacking an endocervical component, there was only one case in which there was a significant glandular abnormality present in the conventional smear and not in the TP slide. As further slides prepared from the TP vial also failed to show abnormal cells, we assume that no abnormal cells were present in the vial. An important advantage of the TP process is the presence of further cellular material in the fluid fixative which can be used to prepare more slides, or for HPV typing which may have clinical relevance in the triage of patients with low grade abnormalities.10 In the United States, the Food and Drug Administration has approved the TP Pap test as a replacement for the conventional Pap smear.11 This decision was based on analysis of data on 7360 paired samples derived from six different centres (Data on file, Cytyc Corporation, Boxborough, Mass., USA). Our data, on a larger sample from a single practice, support the assertion that the TP Pap test performs substantially better than the conventional smear on analysis of significant parameters. While we continue to offer the TP Pap test as an additional proced ure, we anticipate that the machine-made slide may replace the conventional smear in the future. Acknowledgements We thank Tabatha Lovelace, Lisa Wong, Rozanne Van Gramberg and Samira Bounassif for technical assistance. Statement of potential conflict of interest: The Cytyc Corporation (Boxborough, Mass., USA) lent us one of the Thinprep 2000 machines used in this study. The company was not involved in the design of the study, collection of data, analysis of results or preparation of the manuscript. References DeMay RM. To err is human -- to sue American. Diagn Cytopathol 1996; 15: iii-vi. Skoumal SM, Florell SR, Bydalek MK, Hunter WJ. Malpractice protection: communication of diagnostic uncertainty. Diagn Cytopathol 1996; 14: 385-389. Gay JD, Donaldson LD, Goellner JR. False-negative results in cervical cytologic studies. Acta Cytol 1985; 29: 1043-1046. Joseph MG, Cragg F, Wright VC, et al. Cyto-histological correlates in a colposcopic clinic: a 1 year prospective study. Diagn Cytopathol 1991; 7: 477-481. Hutchinson ML, Isenstein LM, Goodman A, et al. Homogeneous sampling accounts for the increased diagnostic accuracy using the ThinPrep Processor. Am J Clin Pathol 1994; 101: 215-219. Goodman A, Hutchinson ML. Cell surplus on sampling devices after routine cervical cytologic smears. A study of residual cell populations. J Reprod Med 1996; 41: 239-241. Zahniser DJ, Hurley AA. Automated slide preparation system for the clinical laboratory. Cytometry 1996; 26: 60-64. Laverty CRA, Thurloe JK, Redman NL, Farnsworth A. An Australian trial of ThinPrep: a new cytopreparatory technique. Cytopathology 1995; 6: 140-148. National Pathology Accreditation Advisory Council, Commonwealth Department of Health and Family Services. Requirements for gynaecological (cervical) cytology. Canberra: AGPS, 1997. Sherman ME, Schiffman MH, Lorincz AT, et al. Cervical specimens collected in liquid buffer are suitable for both cytological screening and ancillary Human Papilloma virus testing. Cancer 1997; 81; 89-97. Communication, 20 May 1996. Rockville, Md.: Center for Devices and Radiological Health, Food and Drug Administration, 1996. (Received 3 Feb, accepted 14 July 1997) Authors' details Dr Colin Laverty & Associates, Pathologists, Eastwood, NSW. Jennifer M Roberts, MB BS, FRCPA, Pathologist; A Marion Gurley, MB ChB, FIAC, Pathologist; Julia K Thurloe, BSc, MEc, Statistician; Ronald Bowditch, BScAg CT(ASC), Senior Cytotechnologist; Colin R A Laverty, MB BS, FRCPA, Principal Pathologist. Reprints: Dr C R A Laverty, Dr Colin Laverty & Associates, Pathologists, 18 Glen Street, Eastwood, NSW 2122. ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Reduction of inappropriate use of blood products by prospective monitoring of transfusion request forms Annabel Tuckfield, Michael N Haeusler, Andrew P Grigg and Jack Metz For editorial comment, see Allain & Williamson Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Methods - Results - Discussion - References - Authors' details - - ©MJA1997 Abstract Objective: To determine the effect of prospective monitoring on appropriateness of transfusions of red cells, platelets and fresh frozen plasma (FFP). Design: Prospective interventional study. Setting: Royal Melbourne Hospital (a tertiary teaching hospital), Melbourne, Victoria, March-May 1996. Intervention: The blood product request form was modified to incorporate indications for transfusion and clinical and laboratory data. Requests were monitored by blood bank laboratory staff for conformation with hospital transfusion guidelines; non-conforming requests were discussed with the requesting medical practitioner by the Haematology Registrar before blood products were issued. In cases of disagreement, blood products were always issued. Subjects: 200 consecutive transfusion episodes for each product (red cells, platelets and FFP). Outcome measures: Appropriateness of transfusion, assessed by a Consultant Haematologist according to hospital guidelines. Rates of inappropriate transfusion episodes after intervention were compared with rates in a previous study. Results: After intervention, rates of inappropriate transfusion episodes fell significantly (red cells, 16% to 3% [P=0.004]; platelets, 13% to 2.5% [P=0.02]; and FFP, 31% to 15% [P=0.02]). Almost all inappropriate FFP transfusion episodes post-intervention were due to failure to demonstrate prolongation of prothrombin or activated partial thromboplastin times more than 1.5 times the control value. Conclusion: Prospective monitoring of request forms can reduce rates of inappropriate transfusions. High rates of inapproriate FFP transfusions possibly reflect uncertainty about appropriate laboratory criteria for FFP transfusion. While results of large prospective randomised controlled clinical trials of FFP transfusions are awaited, current laboratory criteria can be retained, but should be applied with flexibility. MJA 1997; 167: 473-476 Introduction In 1995, we reported results of an audit of blood product use at a tertiary teaching hospital (Royal Melbourne Hospital, Victoria).1 Indications for transfusion were analysed, mainly by retrospective review of medical records. We found that blood product use was inappropriate for 16% of red cell, 13% of platelet and 31% of fresh frozen plasma (FFP) transfusion episodes. In a significant number of episodes, the specific indication for transfusion was not documented in the medical record. Blood products must be used appropriately to minimise patient exposure to potential hazards, to conserve a limited resource and to contain costs. Measures to reduce inappropriate use of blood products have had varying results. While retrospective audit and education do not produce consistent and continuing improvements,2-8 prospective monitoring (monitoring of requests for blood products before issue) has usually been more successful.9-15 Consequently, in March 1996, the Royal Melbourne Hospital introduced prospective monitoring of transfusion requests with the aim of reducing inappropriate use of blood products. We present the results of the first three months of this intervention. Methods Intervention Blood products request form: The blood products request form was redesigned to incorporate the indication for transfusion and relevant clinical and laboratory data. These included: For red cells: haemoglobin level and clinical parameters (pulse rate and blood pressure); For platelets: platelet count and presence or absence of bleeding; For FFP: results of coagulation tests (prothrombin time [PT] or international normalised ratio [INR] and activated partial thromboplastin time [APTT]); and For all blood products: reasons for transfusion and operation (if applicable). In addition, the redesigned request form stipulates that the indication for transfusion must conform with the hospital's transfusion guidelines, which are printed on the reverse of the form (Box 1). Criteria for appropriate transfusions: The criteria were the same as those used in the audit.1 For FFP use, the requirement for coagulation times to be prolonged by more than 50% translated to PT >20 seconds or APTT >40 seconds. For massive blood transfusion (10 or more units of red cells in less than 24 hours), blood products were issued before laboratory results were available, and these transfusions were accepted as appropriate. In view of the potentially devastating effects of minor haemorrhage associated with neurosurgical procedures, these were exempted from the criteria for FFP use.1 Monitoring: On receiving a completed blood product request form, the senior medical laboratory scientist determined that the necessary information had been provided, and telephoned the requesting doctor to obtain any missing information. The scientist then checked that the indications conformed with transfusion guidelines, and if so, blood products were issued. If clinical or laboratory indications did not conform, the request was referred to the Haematology Registrar who consulted the requesting doctor. There were three possible outcomes: they agreed (i) either that the transfusion was not indicated and the blood products were not issued or (ii) that it was indicated and the products were issued or (iii) they disagreed and the products were issued. The consultation was never confrontational, and the blood product was always issued when there was disagreement. However, for the study these cases were subsequently referred to the Consultant Haematologist who reviewed the haematological data, transfusion request and medical record to decide if the transfusion was indeed inappropriate. Analysis of outcomes For each type of blood product (red cells, platelets and FFP), we analysed 200 consecutive transfusion episodes between March and May 1996. As in the initial audit, we excluded FFP transfusions for patients with thrombotic thrombocytopenic purpura, because of the different rationales for FFP use in this condition and in coagulation factor depletion. Rates of inappropriate blood product use after introduction of prospective monitoring were compared with those found during the previous audit (pre-intervention) with two-sided Fisher's exact tests. Results Indications for transfusion of red cells, platelets and FFP after introduction of prospective monitoring are shown in Box 2 (below). They were the same as in the pre-intervention audit.1 Numbers of transfusions referred to the Consultant Haematologist for review were: red cells, eight; platelets, 12; and FFP, 41. Final numbers of transfusion episodes deemed inappropriate were: red cells, six (3%); platelets, five (2.5%); and FFP, 30 (15%). Compared with the pre-intervention audit, rates of inappropriate transfusion episodes were significantly reduced, from 16% to 3% for red cells (P= 0.004), 13% to 2.5% for platelets (P=0.02) and 31% to 15% for FFP (P= 0.02). Of the six patients in whom red cell use was deemed inappropriate, five had a pretransfusion haemoglobin concentration greater than 100 g/L, the threshold for appropriate transfusion (range in these patients, 104-114 g/L). The sixth patient had a haemoglobin concentration of 98 g/L, but no clinical indications to warrant transfusion. In four of the five inappropriate platelet transfusion episodes, the platelet count was greater than 63x109/L (range, 63x109-159x109/L), a level at which platelets are not indicated except in the case of excessive bleeding with cardiac bypass surgery. Although three of these four transfusions were given in association with cardiac bypass surgery, there was no evidence of excessive bleeding. In 30 patients, FFP transfusion was deemed inappropriate as coagulation test results did not meet the criterion of a 50% prolongation of coagulation times. In one of these 30, this was because no coagulation tests had been performed. Discussion We found that the rate of inappropriate transfusion episodes fell significantly after introduction of prospective monitoring, from 16% to 3% for red cells, from 13% to 2.5% for platelets and from 31% to 15% for FFP. The success of prospective monitoring in reducing rates of inappropriate transfusions for red cells and platelets was not matched for FFP. This agrees with results of three previous studies, which have found persistently high rates of FFP transfusions despite monitoring (>40%,8 33%13 and 27%,15 respectively). As in these studies, we found the reason for deeming FFP use inappropriate was almost invariably failure to show sufficient abnormality in coagulation test results. The need to document abnormal coagulation with a PT or APTT greater than 1.5 x the control value, before FFP transfusion is deemed appropriate, rests on the assumptions that abnormal bleeding is unlikely if coagulation times are shorter than this but likely if they are longer, and that, when coagulation times are greater than 1.5 x the control value, FFP transfusion is likely to prevent or control bleeding. Detailed analysis of published data suggests that these assumptions are questionable.16-23 It is of interest that we found that lowering the cut-off for appropriate FFP transfusions from PT >20 seconds (1.5 times the control value) to PT >17 seconds would have lowered the rate of inappropriate transfusions from 15% to 3%, comparable to the rate found for red cell and platelet transfusions. A PT of 17 seconds is still 3.5 seconds longer than the median control value. Further investigation is needed to establish the clinical guidelines for FFP transfusion. Two publications24,25 have pointed to the need for a large multicentre prospective randomised controlled clinical trial to provide a definitive answer for the role of FFP in patients with acquired multiple coagulation defects. In the interim, it would seem reasonable to require docu mentation of abnormal coagulation as a criterion for appropriate FFP use, but the available evidence does not warrant rigid application of a cut-off level, such as 50% prolongation of PT or APTT. Other issues that must be addressed before a system of prospective monitoring can be introduced include exemption criteria. Some protocols exempt operating room patients,6 "desperate situations"14 and haematology and oncology patients.13 Emergency situations are also usually exempted from the requirement for laboratory data if the laboratory cannot provide urgent results at all times. If the criteria are to be applied to emergency situations, laboratory facilit ies must be available to provide the data quickly. In some programs of prospective monitoring, blood products are never withheld, but apparently inappropriate transfusions are later reviewed.11,14 Refusal to issue blood products leads to an adversarial relationship between clinicians and laboratory staff, which may compromise patient care. Refusal might also have medicolegal implications if subsequent patient morbidity or death could be attributed to withholding of the transfusion. For sustained improvement in practice, prospective monitoring must be continued indefinitely.11 This is both time consuming and demanding of staff. The demand might be lessened by computerised audit of transfusion requests; clinical and laboratory data could be entered into a program which flags non-compliant requests for review by blood bank staff.26 In conclusion, prospective monitoring was successful in reducing inappropriate use of red cells and platelets, but only partly successful for FFP. This probably reflects uncertainty about the appropriate clinical guidelines for FFP use, and although current laboratory criteria for FFP use should probably be retained, they should be applied with flexibility. References Metz J, McGrath KM, Copperchini ML, et al. Appropriateness of transfusions of red celIs, platelets and fresh frozen plasma. An audit in a tertiary care teaching hospital. Med J Aust 1995; 162: 572-577. Lam HTC, Schweitzer SO, Petz L, et al. Are retrospective peer-review transfusion monitoring systems effective in reducing red blood cell utilization? Arch Pathol Lab Med 1996; 120: 810-816. Toy PTCY. Audit and education in transfusion medicine. Vox Sang 1996; 70: 1-5. Bamerte RE, Fish DJ, Eisenstaedt RS. Modification of fresh frozen plasma transfusion practices through educational intervention. Transfusion 1990; 30: 253-257. Soumerai SB, Salem-Schatz S, Avorn J, et al. A controlled trial of educational outreach to improve blood transfusion practice. JAMA 1993; 270: 961-966. Solomon RR, Clifford JS, Gutman SI. The use of laboratory intervention to stem the flow of fresh frozen plasma. Am J Clin Pathol 1988; 89: 518-521. Brien WF, Buttier RJ, Inwood MJ. An audit of blood component therapy in a Canadian general teaching hospital. Can Med Assoc J 1989; 140: 812-815. Shanberge JN, Quattrochiocchi-Longe T. Analysis of fresh frozen plasma administration with suggestions for ways to reduce usage. Transfus Med 1992; 2: 189-194. Simpson MB. Prospective concurrent audits and medical consultation for platelet transfusions. Transfusion 1987; 27: 192-195. McCullough J, Steeper TA, Connelly DP, et al. Platelet utilization in a university hospital. JAMA 1988; 259: 2414-2418. Silver H, Tahhan HR, Anderson J, et al. A non- computer dependent prospective review of blood and blood component utilization. Transfusion 1992; 32: 260-265. Brandis K, Richards B, Ghent A, et al. A strategy to reduce inappropriate red blood cell transfusion. Med J Aust 1994; 160: 721-722. Hawkins TE, Carter JM, Hunter PM. Can mandatory pretransfusion approval programmes be improved? Transfus Med 1994; 4: 45-50 Cheng G, Wong HF, Chan A, et al. The effects of a self-educating blood component request form and enforcements of transfusion guidelines on FFP and platelet usage. Clin Lab Haem 1996; 18: 83-87. 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: 11-19. Counts RB, Haisch C, Simon TL, et al. Hemostasis in massively transfused trauma patients. Ann Surgery 1979; 190: 91-99. Braunstein AH, Oberman HA. Transfusion of plasma components. Transfusion 1984; 24: 281-286. 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: 365-368. Harvey MP, Greenfield TP, Sugrue ME, et al. Massive blood transfusion in a tertiary referral hospital. Clinical outcomes and haemostatic complications. Med J Aust 1995; 163: 356-359. Houry S, Georgeac C, Hay J, et al. A prospective multicentre evaluation of preoperative hemostatic screening tests. Am J Surg 1995; 170: 19-23. Gelb AB, Roth RI, Levid J, et al. Changes in blood coagulation during and following cardiopulmonary bypass. Lack of correlation with clinical bleeding. Am J Clin Pathol 1996; 106: 87-99. Murray DJ, Olson JD, Strauss AR, et al. Coagulation changes during packed red cell replacement of major blood loss. Anesthesiology 1988; 69: 839-845. Murray DJ, Pennell BJ, Weinstein SL, et al. Packed red cells in acute blood loss: dilutional coagulopathy as a cause of surgical bleeding. Anesth Analg 1995; 80: 336-342. McVay PA, Toy PTCY. Lack of increased bleeding after liver biopsy in patients with mild hemostatic abnormalities. Am J Clin Pathol 1990; 94: 747-753. Cohen H. Avoiding the misuse of fresh frozen plasma. BMJ 1992; 307: 395-396. Gardner RM, Golubjatnikov OK, Laub RM, et al. Computer critiqued blood ordering using the HELP system. Comput Biomed Res 1990; 23: 514-528. (Received 20 Mar, accepted 1 Jul 1997) Authors' details Department of Diagnostic Haematology, Royal Melbourne Hospital, Melbourne, VIC. Annabel Tuckfield, FRACP, FRCPA, Registrar; Michael N Haeusler, FAIMS, Senior Scientist, Blood Bank; Andrew P Grigg, FRACP, FRCPA, Haematologist; Jack Metz, MD, FRCPA, Head. Reprints will not be available from the authors. Correspondence: Dr A Tuckfield, Diagnostic Haematology, Post Office, Royal Melbourne Hospital, Parkville, VIC 3050. E-mail: depATmis.medrmh.unimelb.edu.au ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.