Executive committee
	Head of department
	Business manager
	Consultant haematologist
	Principal scientific officer
Safety officer
Quality control officer
Computer and data processing supervisor
Sectional scientific/technical heads
	Cytometry
	Blood film morphology
	Immunohaematology
	Haemostasis
	Blood transfusion
	Special investigations (haemolytic anaemias, haemoglobinopathies, cytochemistry, molecular techniques, etc.)
Clerical supervisor

The activities of the various members of staff clearly overlap and there must be adequate effective communication between them. There should be regular briefings at meetings of technical heads, with their section staff. The only way to avoid unauthorized ‘leakage’ of information from policy-making committees is to ensure that all members of staff are kept fully informed of any plans which might have a bearing on their careers, working practices and wellbeing.

In many countries, there are now requirements established by regulatory agencies for accreditation of laboratories and audit of their performance, as well as documents on laboratory management and practice from standards-setting authorities; there is also a plethora of guidelines from national and international professional bodies. These may indicate a need for a special sub-committee of the executive committee, whose duty it is to keep abreast of these matters, to be responsible for developing standard operating procedures (SOPs) and to inter-relate with the different sections in the same way as the safety officer.

Staff Appraisal

All members of staff should receive training to enhance their skills and to develop their careers. This requires setting of goals and regular appraisal of progress for both managerial and technical ability. The appraisal process should cascade down from the head of department and appropriate training must be given to those who undertake appraisals at successive levels. The appraiser should provide a short list of topics to the person to be interviewed, who should be encouraged to add to the list, so that each understands the items to be covered. Topics to be considered should include: quality of performance and accurate completion of assignments; productivity and dependability; ability to work in a team; and ability to relate to patients, clinicians and co-workers. It is not appropriate to include considerations relating to pay. An appraisal interview should be a constructive dialogue of the present state of development and the progress made to date; it should be open-ended and should identify future training requirements. Ideally, the staff members should leave the interviews with the knowledge that their personal development and future progress are of importance to the department; that priorities have been identified; that an action plan with milestones and a time scale has been agreed; and that progress will be monitored. Formal appraisal interviews (annually for senior staff and more often for others) should be complemented by less formal follow-up discussions to monitor progress and to check that suboptimal performance has been modified. Documentation of formal interviews can be limited to a short list of agreed objectives. Performance appraisal can have lasting value in the personal development of individuals, but the process can easily be mishandled and should not be started without training in how to hold an appraisal interview.²

Continuing Professional Development

Continuing professional development is a process of continuous systematic learning which enables health workers to be constantly brought up to date on developments in their professional work and thus ensure their competence to practice throughout their professional careers. Policies and programmes have been established in a number of countries and, in some, participation is a mandatory requirement for the right to practice.³

In the UK, clinical haematologists and clinical scientists who have the relevant qualifications awarded by the Royal College of Pathologists (RCPath) and are licenced to practice by the General Medical Council, are required to participate in a scheme organized by the College. This involves maintenance of a portfolio showing their participation in relevant educational and academic affairs and demonstrations of their professional skills.

The Institute for Biomedical Science undertakes a similar scheme for scientists/technologists working in the laboratory, which is mandatory for registration to practice by the UK Health Professions Council. The procedure is based on obtaining ‘credits’ for various activities that qualify, such as: attendance at specified lectures, workshops and conferences; giving lectures; writing books or journal articles; using computer or journal-based programmes; and taking part in peer review discussions.

Strategic and Business Planning

The head of department is responsible for determining the long-term (usually up to 5 years) strategic direction of the department. Strategic planning requires awareness of any national and local legislation that may affect the laboratory and of changes in local clinical practice that may alter workload. Expansion of a major clinical service, such as organ transplantation, or the opportunity to compete for the laboratory service of other hospitals and clinics, may pose an external opportunity, but may also be a threat to the laboratory, depending on its ability to respond to the consequential increase in workload. Technical or scientific expertise would be a strength, whereas a heavy workload, without adequate staffing or lack of automation for routine tests, is likely to preclude any additional developmental work and would, thus, be a weakness.

Increasingly, laboratories must meet financial challenges and the need for greater cost-effectiveness. This may require rationalization by eliminating unused laboratory capacity, avoiding unnecessary tests and ensuring more efficient use of skilled staff and expensive equipment. This may require centralization of multiple laboratory sites or, conversely, there may be advantages in establishing satellite centres for the benefit of patients and clinicians if these can be shown to be cost-effective. Account must also be taken of the role of the laboratory in supervision of the extra-laboratory point-of-care procedures that have become increasingly popular.

A business plan is primarily concerned with determining short-term objectives that will allow the strategy to be implemented over the next financial year or so. It requires prediction of future work level and expansion. Planning of these objectives should involve all staff because this will heighten awareness of the issues and will develop personal concern in the strategy. In all but the smallest laboratory, a business manager is required to coordinate such planning and to liaise with the equivalent business managers in other clinical and laboratory areas.

Workload Assessment and Costing of Tests

Laboratories should maintain accurate records of workload, overall costs and the cost per test in order to apportion resources to each section. Computerization of laboratories has greatly facilitated this process. In assessing workload, account must be taken of the entire cycle from test receipt to issue of a report, whether the test is by a manual or semi-automated method or by a high-volume multiple-analyte automated analyser. Apportioning of resources should also take account of the roles of biomedical scientists/senior technologists and junior technicians, supervised laboratory assistants, clerical staff and medical personnel responsible for reviewing the report. Out of hours service requires a different calculation of costs.

Methods were developed for determining the workload and costs for various laboratory tests taking account of test complexity, total number of tests performed, quality control procedures, cost of reagent and use of material standards so that laboratories could compare their operational productivity with a peer group of participating laboratories. A good example is given on the website Standards for Management Information Systems in the Canadian Health Service Organizations.

A similar workload recording method was published by the College of American Pathologists,⁴ and the Welcan system was established in the UK.⁵ However, more recently, benchmarking schemes have been established that take account of productivity, cost-effectiveness and utilization compared with a peer group. The College of American Pathologists created their Laboratory Management Index Program in which participants submit their laboratories operating data on a quarterly basis and receive peer comparison reports from similar laboratories around the country by which their own cost-effectiveness can be evaluated.

Financial Control

Full costing of tests includes all aspects of laboratory function (Table 24.2).

Table 24.2 Factors contributing to cost of laboratory tests

Direct costs
	Staff salaries
	Laboratory equipment purchases
	Reagents and other consumables
	Equipment maintenance
	Standardization and quality control
	Specific technical training on equipment
Indirect costs
	Capital costs and mortgage factor
	Depreciation
	Building repairs and routine maintenance
	Lighting, heating and waste disposal
	Personnel services
	Cleaning services
	Transport, messengers and porters
	Laundry services
	Computers and information technology
	Telephone and fax
	Postage
	Journals and textbooks

The amount allocated for staff salaries should include the cost of training and should take into account absences for annual leave or sickness. It needs also to take into account the extent to which staff of various levels, as described earlier, are involved. Indirect costs may be apportioned to different sections of a department who share common overhead costs.

Calculation of Test Costs

When preparing a budget, the following formula provides a reasonably reliable estimate of the total annual costs:

where

L = Labour costs for each test from estimate of time taken and the salary rate of the staff member(s) performing the tests

N = Number of tests in the year

C = Cost of consumables per test (including controls)

E = Annual equipment cost based on initial cost divided by expected life of the item or the annual cost of hire (see below)

M = Annual maintenance and servicing of equipment

O = Laboratory overheads (Table 24.2)

S = Supervision

T = Transport and communication

A = Laboratory administration, including salaries of clerical and other non-technical staff.

Efficient budgeting requires regular monitoring, at least monthly. Computer spreadsheets provide an easily comprehended view of the financial state and the likely responses in the running of the laboratory.

In general, staff cost is by far the largest component of the total costs of running a laboratory. Furthermore, many of the other costs are obligations outside the direct control of the laboratory. If financial savings become necessary, they can be achieved in a variety of ways, but large savings usually necessitate a reduction in staff because employment costs can account for three-quarters of total expenditure. Possible initiatives include the following:

• Rationalization of service with other local hospitals to eliminate duplication

• Restructuring within a hospital laboratory for cross-discipline working (usually between haematology and clinical chemistry)

• Subcontracting of labour-intensive tests to a specialist laboratory

• Greater use of automated instruments/methods

• Employment of part-time contract staff (e.g. for overnight and weekend emergency service or for the phlebotomy service) and sharing of emergency service between local hospitals

• Review of price setting on the basis of workload and calculated cost per test.

Increasingly, use of automated systems for routine screening tests allows the laboratory to consider staff reduction, although an estimate of savings must take account of capital, maintenance contracts and running costs of the equipment, especially the high cost of some reagents, and whether the system can be used to high capacity and throughout a 24 h service.

Purchasing expensive equipment outright adds to the capital assets of the laboratory, with the consequential cost of depreciation (usually 8–10% per annum). Leasing equipment can be a better alternative and, in many countries, most equipment is obtained in this way. Careful calculation of the lease cost is required because this can be up to 20% higher than outright purchase. An advantage of leasing is flexibility to upgrade equipment should workload increase or technology change. If maintenance and consumable costs are included in the same agreement, it may be possible to negotiate a reduction in charge for the consumables, but it is important to neither underestimate nor overestimate the annual requirements that will be included in the contract.

When automation is coupled with centralization of the service to another site, care must be taken to maintain service quality.⁶ Failure to do so will encourage clinicians to establish independent satellite laboratories. Loss of contact between clinical users and laboratory staff may compromise the pre-analytical phase of the test process and may lead to inappropriate requests, excessive requests and test samples that are of inadequate volume or are poorly identified. When services are centralized, attention must be paid to all phases (pre-analytical, analytical and post-analytical) of the test process, including the need for packaging the specimens and the cost of their transport to the laboratory.⁶

Test reliability

The reliability of a quantitative test is defined in terms of the uncertainty of measurement of the analyte (sometimes referred to in documents as ‘measurand’). This is based on its accuracy and precision.⁷

Accuracy is the closeness of agreement between the measurement that is obtained and the true value; the extent of discrepancy is the systematic error or bias. The most important causes of systematic error are listed in Table 24.3. The error can be eliminated or at least greatly reduced by using a reference standard with the test, together with internal quality control and regular checking by external quality assessment (see Chapter 25, p. 594).

Table 24.3 Systematic errors in analyses

Analyser calibration uncertain (no reference standard available)

Bias in instrument, equipment or glassware

Faulty dilution

Faults in the measuring steps (e.g. reagents, spectrometry, calculations)

Sampling not representative of specimen

Specimens not representative of in vivo status (Ch. 1, p. 3)

Incomplete definition of analyte or lack of critical resolution of analyser

Approximations and arbitrary assumptions inherent in analyser’s function

Environmental effects on analyser

Pre-analytical deterioration of specimens

Precision is the closeness of agreement when a test is repeated a number of times. Imprecision is the result of random errors; it is expressed as standard deviation (SD) and coefficient of variation (CV%). When the data are spread normally (Gaussian distribution), for clinical purposes, there is a 95% probability that results that fall within a range of +2SD to −2SD of the target value are correct and a 99% probably if within the range of +3SD to −3SD (see also Fig. 2.1).

Some of the other factors listed in Table 24.3 can be quantified to calculate the combined uncertainty of measurement. Thus, for example, when a calibration preparation is used, its uncertainty is usually stated on the label or accompanying certificate. The standard uncertainty is then calculated from the sum of the quantified uncertainties as follows:

Expanded uncertainty of measurement takes account of non-quantifiable items by multiplying the previous amount by a ‘coverage factor’ (k), which is usually taken to be ×2 for 95% level of confidence.^7,⁸

It may be necessary to decide by statistical analysis whether two sets of data differ significantly. The t-test is used to assess the likelihood of significant difference at various levels of probability by comparing the means or individually paired results. The F-ratio is useful to assess the influence of random errors in two sets of test results (see Appendix, p. 625).

Of particular importance are reports with ‘critical laboratory values’ that may be indicative of life-threatening conditions requiring rapid clinical intervention. Haemoglobin concentration, platelet count and activated partial thromboplastin time have been included in this category.⁹ The development of critical values should involve consultation with clinical services.

Test selection

It is important for the laboratory to be aware of the limits of accuracy that it achieves in its routine performance each day as well as day-to-day.¹⁰ Clinicians should be made aware of the level of uncertainty of results for any test and the potential effect of this on their diagnosis and interpretation of response to treatment (see below).

To evaluate the diagnostic reliability and predictive value of an individual laboratory test, it is necessary to calculate test sensitivity and specificity.¹¹ Sensitivity is the fraction of true positive results when a test is applied to patients known to have the relevant disease or when results have been obtained by a reference method. Specificity is the fraction of true negative results when the test is applied to normals.

where TP = true positive; TN = true negative; FP = false positive; FN = false negative.

Overall reliability can be calculated as:

Sensitivity and specificity should be near 1.0 (100%) if the test is unique for a particular diagnosis. A lower level of sensitivity or specificity may still be acceptable if the results are interpreted in conjunction with other tests as part of an overall pattern. It is not usually possible to have both 100% sensitivity and 100% specificity. Whether sensitivity or specificity is more important depends on the particular purpose of the test. Thus, for example, if haemoglobinometry is required in a clinic for identifying patients with anaemia, sensitivity is important, whereas in blood donor selection, for selecting individuals who are not anaemic, specificity is more important.

Likelihood Ratio

The ratio of positive results in disease to the frequency of false-positive results in healthy individuals gives a statistical measure of the discrimination by the test between disease and normality. It can be calculated as follows:¹²

The higher the ratio, the greater is the probability of disease, whereas a ratio <1 makes the possibility of the disease being correctly diagnosed by the test much less likely. Conversely, the likelihood of normality can be calculated as:

An alternative method is that of Youden, which is obtained by calculating Specificity/(1 − Sensitivity).¹³ Values range between −1 and +1. With a positive ratio rising above zero towards +1 there is an increasing probability that the test will discriminate the presence of the specified disease and there is decreasing likelihood that the test is valid when the ratio falls from 0 to −1.

Receiver–Operator Characteristic Analysis

The relative usefulness of different methods for the same test or of a new method against a reference method can also be assessed by analysing the receiver–operator characteristics (ROC).¹² This is demonstrated on a graph by plotting the true-positive rates (sensitivity) on the vertical axis against false-positive rates (1 − specificity) on the horizontal axis for a series of paired measurements (Fig. 24.1). Obviously, the ideal test would show high sensitivity (i.e. 100% on vertical axis), with no false positives (i.e. 0% on horizontal axis). Realistically, there would be a compromise between the two criteria, with test selection depending on its purpose, i.e. whether as a screening to exclude the disease in question or to confirm a clinical suspicion that the disease is present. In the illustrated case Test A is more reliable than Test B for both circumstances.

Figure 24.1 Receiver–operator characteristic (ROC) analysis. Graph shows curves relating true-positive rates (sensitivity) to false-positive rates (1 − specificity) for two tests A and B making the same measurements.

Test Utility

To ensure reliability of the laboratory service, tests with no proven value should be eliminated and new tests should be introduced only when there is independent evidence of technical reliability as well as cost-effectiveness.

For assessing cost-effectiveness of a particular test, account must be taken of (1) cost per test as compared with other tests that provide similar clinical information; (2) diagnostic reliability; and (3) clinical usefulness as assessed by the extent with which the test is relied on in clinical decisions, whether the results are likely to change the physician’s diagnostic opinion and the clinical management of the patient, taking account of disease prevalence and a specified clinical or public health situation. This requires audit by an independent assessor to judge what proportion of the requests for a particular test are actually used intelligently and what percentage are unnecessary or wasted tests.^14,¹⁵ Information on the utility of various tests can also be obtained from benchmarking (see p. 579) and published guidelines. Examples of the latter are the documents published by the British Committee for Standards in Haematology (www.BCSHGuidelines.com). The realistic cost-effectiveness of any test may be assessed by the formula:

A/(B × C), where A = cost/test, as described on p. 566

B = diagnostic reliability, as described on p. 567

C = clinical usefulness, as described above.

Economic aspects should also be considered when providing an automated total screening programme for every patient, in contrast to specifically selected tests. Thus, while many clinicians may not be familiar with all of the 12 or more parameters included in the blood count as reported routinely by modern automated analysers and in most cases, some of these measurements are unlikely to be clinically useful, nevertheless the ‘not-requested’ information may be provided at no extra cost and even significant saving of time in the laboratory.

Instrumentation

Equipment Evaluation

Assessment of the clinical utility and cost-effectiveness of equipment to match the nature and volume of laboratory workload is a very important exercise. Guidelines for evaluation of blood cell analysers and other haematology instruments have been published by the International Council for Standardization in Haematology.¹⁶ In the UK, appraisal of various items of laboratory equipment was formerly undertaken by selected laboratories at the request of the Department of Health’s Medical Devices Agency, subsequently renamed Medicines and Healthcare products Regulatory Agency (MHRA) and now replaced by the Centre for Evidence-based Purchasing (CEP). (Their reports can be accessed from the website: www.pasa.nhs.uk/ceppublications.)

Principles of Evaluation

The following aspects are usually included in evaluations:

1. Verification of instrument requirements for space and services

2. Extent of technical training required to operate the instrument

3. Clarity and usefulness of instruction manual

4. Assessment of safety (mechanical, electrical, microbiological and chemical)

6. Throughput time and number of specimens that can be processed within a normal working day

7. Reliability of the instrument when in routine use and adequacy of service and maintenance provided

8. Cost per test, including operating time, reagents, daily start-up procedure and regular (usually weekly) maintenance procedures

9. Staff acceptability, impact on laboratory organization and level of technical expertise required to operate the instrument

10. Any relevant authority label, e.g. CE mark on a device indicates that it conforms to defined specifications of the EU directive 98/79 for in vitro diagnostic medical devices (IVDD), as described in the Official Journal (OJ) of the EC: 7.12.98.

After an instrument has been purchased and installed, it is useful to undertake regular less extensive checks of performance with regard to precision, linearity, carryover and comparability.

where l₁ and l₃ are the results of the first and third measurements of the samples with a low concentration and h₃ is the third measurement of the sample with a high concentration.

Accuracy and Comparability

Accuracy and comparability test whether the new instrument (or method) gives results that agree satisfactorily with those obtained with an established procedure and with a reference method. Test specimens should be measured alternately, or in batches, by the two procedures. If results by the two methods are analysed by correlation coefficient (r), a high correlation does not mean that the two methods agree. Correlation coefficient is a measure of relation and not agreement. It is better to use the limits of agreement method.¹² For this, plot the differences between paired results on the vertical axis of linear graph paper against the means of the pairs on the horizontal axis (Fig. 24.2); differences between the methods are then readily apparent over the range from low to high values. If the scatter of differences increases at high values, logarithmic transformed data should be plotted.

Figure 24.2 Limits of agreement method. Shows mean values for paired results by two methods A plus B (horizontal axis) plotted against the differences (A minus B) between the paired results (vertical axis). Horizontal lines represent equality with range of ±10 units (mean ±SD). Upper figure shows no bias between methods A and B, whereas lower figure shows false high results (negative values) for method B.

It is also useful to check for bias by including the instrument or method under test in the laboratory’s participation in an external quality assessment scheme (see p. 594). Bias is expressed by:

where R = measurement by the device/method being tested and M = target result.

Another method to check for bias is by means of the variance index. For this, the coefficient of variation is established at an optimal chosen value (CCV) to ensure a reliable method and the variation index (VI%) is calculated as:

Maintenance logs

All laboratory equipment should be inspected regularly and specific maintenance procedures should be carried out. Each item of laboratory equipment should have a maintenance log to document what maintenance is required, the desired frequency and when it was last carried out. The log includes servicing and repairs by the manufacturer. Equipment used to test biological specimens must be cleaned thoroughly before a maintenance procedure is carried out to reduce the biohazard. The procedure for such cleaning must be documented (as a standard operating procedure), together with the name of the responsible worker and the date.

Data processing

It is essential that accurate records of laboratory results are kept for whatever period is stipulated by national legislation. Computer-assisted data handling is essential for all but the smallest laboratory. For long-term storage of data, possibilities include a printed (hard) copy, a memory stick and external hard drive or a local server. Laboratory results are usually issued as numeric data with abnormal results highlighted for the clinician. Report forms should be reader friendly. Serial data are particularly useful to illustrate any trend with time and may be in the form of a cumulative tabulation or a graph. For the latter, an arithmetic scale should be used for haemoglobin concentration, red cell count and reticulocytes, whereas platelet and leucocyte counts are best displayed on a logarithmic scale (Fig. 24.3). A graph is particularly useful for displaying results in relation to target intervals because this facilitates adjustment of dosage of drugs that are likely to affect the blood. Furthermore, this method of archiving reduces the number of pages of laboratory reports in the patient’s file.¹⁷

Figure 24.3 Haematological chart for plotting blood count data on a time-related graph. This illustrates the course in a patient with chronic lymphocytic leukaemia. Haemoglobin is recorded arithmetically; the other components are on a logarithmic scale. If reticulocytes are included, they should be recorded arithmetically.

Laboratory Computers

Developments in computer technology have made available powerful microcomputers and sophisticated computer software at moderate prices. Such computers may be an integral part of an analytical instrument or interfaced to it by cable. A modem is required to link the computer to the telephone or broadband for access to the internet and electronic mail and also to interconnect within a local area network, so as to provide for data interchange and to enable multiple workers to use a common database. Such computers may be an integral part of an analytical instrument or interfaced to it. Because computers are developing at such a rate, it is essential to seek expert advice to ensure that the instrument being purchased is fit for purpose. Helpful advice on the applications of the internet for health professions is given in a monograph by Kiley.¹⁸ Programmes that provide access to a vast amount of information include Google Scholar and the US National Library of Medicine PubMed and Medline, the latter being the primary component of PubMed especially on biomedical topics. Publishers of journals also provide internet access to citations and abstracts of articles, both current and archived, for a large number of medical journals. Access to the full journal articles usually requires a subscription fee for the full articles that can be read directly on the computer or printed out, conveniently as a pdf file but in a scheme known as Health Inter-Network Access to Research Initiatives, an agreement was made between the World Health Organization and the world’s leading publishers, whereby in more than 100 developing countries this access is available free of charge or at greatly reduced prices to staff and students of teaching hospitals, research and public health institutes, universities and professional colleges.

A comprehensive overview of various topics relating to life sciences is provided by the Encyclopedia of Life Sciences (ELS) published on the internet by Wiley-Blackwell. Many individual experts have their own websites for presenting dissertations and comments in their specialties, while manufacturers provide up-to-date information on their products.

It is impractical to provide a comprehensive index of all relevant websites; however, Table 24.5 lists some that are of particular interest for the haematology laboratory, including some that are also noted in the text. In any event, entering a key word or phrase is likely to provide access to a vast amount of information on virtually any topic as well as links to related items.

Table 24.5 Selected www. internet sites of haematological interest

scholar.google.com	Access to an extensive bibliography on scientific and medical topics
who.int	World Health Organization^a
international council for standardization in haematology	Lists publications from International Council for Standardization in Haematology – The acronym ICSH is inadequate – recent activities are also reported on www.islh (see below)
ish-world.org	Home page of International Society of Haematology
ifbls.org	International Federation of Biomedical Laboratory Science; arranges international congresses and educational resources
isth.org	International Society of Thrombosis and Haemostasis; includes bibliography and full reports of official communications from their scientific and standardization committees
islh.org	International Society for Laboratory Hematology; includes details of annual symposium and activities of the International Council for Standardization in Haematology
isbt-web.org	Home page of International Society of Blood Transfusion
rcpath.org.uk	General information from Royal College of Pathologists
ibms.org	General information from Institute of Biomedical Science, including various aspects of CPD
ifbls	International Federation of Biomedical Laboratory Science
ukneqas.org.uk	Home page of UK NEQAS; click onto Haematology for information on the various tests included in their surveys
ukas/cpa.co.uk	Clinical Pathology Accreditation, as authorized by UKAS, with details of its functions and the procedures for a laboratory applying for accreditation
pubmed.com	National Library of Medicine with access to MEDLINE
mhra.gov.uk	MDA reports of instrument and kits evaluations
bcshguidelines.com	Home page of the British Committee for Standards in Haematology, providing the full text of all current and past guidelines, whether published in book or journal format
transfusionguidelines	UK blood transfusion guideline documents
rph.wa.gov.au/labs	Malaria training programme from Royal Perth Hospital, Australia. For other sites on this topic: see www.Malariatraining.com
westgard.com	JO Westgard’s ‘Lesson of the Month’ and other tutorials on quality assurance

a There are various items on the WHO website of particular interest for laboratory practice. Note especially: /Essential health technology (EHT); /Diagnostics and laboratory technology (DLT); /Quality Management in Transfusion Medicine; /Medical devices.

Pre-analytical and post-analytical stages of testing

The haematology laboratory should be involved in the pre-analytical alstage (test requesting, blood sample collection and transport to the laboratory) as well as the post-analytical stage (return of results to the clinician). Account must also be taken of physiological variables (see Chapter 2) and endogenous variables, such as medicines and other substances taken by the patient.¹⁹ Both variables have a significant impact on test reliability, laboratory performance and client satisfaction.

Test Requesting

There is considerable variation between clinicians in their test ordering patterns, and laboratory staff have historically exerted little influence on test request patterns, although sustained educational programmes may achieve more selective testing. Unnecessary requests often result from inappropriate request forms, such as those that permit clinicians to tick from a list instead of requesting specific tests. Modification of the requesting pattern might focus on specific needs, included use of problem-orientated request forms ²⁰ and a computer-based ordering of tests using protocols written by specialist clinical teams.²¹

Specimen Collection and Delivery

It is essential to have positive identification of the patient as well as reliable sample identification and thus patient-sample and inter-sample identification must be checked at all times. Failure to do so can result in delayed diagnosis, even misdiagnosis, resulting in incorrect treatment of the patient, and it may be a serious cause of error in blood transfusion. In one inter-laboratory Q-probe analysis in the USA (see p. 579), 0.1–5% of specimens were unacceptable due to mislabelling, incomplete label, illegible label and even specimens without any label.^22,²³ Methods have been developed for electronic ordering of tests using the hospital’s patient identification barcode for checking the patient’s identity at the time of phlebotomy, printing the barcode onto the specimen containers and checking this by means of a hand-held scanner at all stages during processing in the laboratory until the report is issued.

After the blood has been collected, every effort must be made to ensure its delivery to the laboratory without delay. If this is not coordinated, samples may remain in clinical areas awaiting collection by porters who then follow a fixed circuit of other hospital areas before eventually reaching the laboratory. However, if responsibility for blood collection and transport is held by the laboratory, these separate activities can be coordinated. Alternative and faster means of specimen delivery to laboratories, with no significant effect of the specimens, include pneumatic tube conveyor or rail-track conveyor systems,^24,²⁵ although there has been a report of lysed specimens due to a defect in the system.²⁶ Specimen transport from remote clinics to a central laboratories is referred to in Chapter 26 (see p. 614).

Pre-Analytical Phase

The time of receipt of the specimens in the laboratory should be registered.¹⁹ The specimens must be checked to ensure that they are appropriate for the tests that are requested and that there has been no contamination by leakage on the outside of the tubes and/or the request forms. Requests should be registered and the specimens should be separated into ‘routine’ and ‘urgent’, the latter being handed directly to the appropriate staff member.

Post-Analytical Phase

After the tests have been carried out, the following procedures are required to ensure proficiency in the post-analytical phase:

1. Processing of results for transcription onto report forms

2. Immediate scrutiny of urgent results with issue of provisional report and its delivery to the requesting clinician

3. Assessment of the significance of results in the context of established reference values and decision for further tests. ‘Critical laboratory values’ for adults and for children should be established for life-threatening conditions requiring rapid clinical intervention (e.g. haemoglobin concentration, platelet count, activated partial thromboplastin time)²⁷

4. Transmission of final report without unreasonable delay to the location indicated on the request form. Computer-assisted reporting of results to linked monitors and printers located in clinical areas is very helpful,²⁸ but in some countries most hospitals rely on manual transport of result sheets and this can significantly prolong request completion times. Pneumatic tube and rail-track conveyor systems used for the pre-analytical stage can also be used for rapid return of results to wards and clinics.

Return of results is, of course, no guarantee that ward or clinic staff will react in a timely way to change a patient’s treatment or even file report forms in the patient’s medical record. It is the responsibility of the clinician to ensure that the reports of tests requested by them are received, noted and acted on. However, good laboratory practice includes speedy notification to the responsible clinical staff of a result that shows an apparently unexpected serious abnormality. A recent development has been the use of mobile cameraphones to transmit test results to the relevant clinician or even images (e.g. a stained blood film, from the laboratory) in order to obtain rapid authoritative support from an expert at a remote location.²⁹ In these situations, it may be necessary to comply with local or national regulations concerning confidentiality of patients records, including the use of encrypted memory sticks to store the information.

5. As an audit of utility of the laboratory, there should be regular contact with users to ensure that the reports arrive in due time for optimal use during clinical management and that the clinicians are satisfied that results are presented in a clear and unambiguous form; there should also be discussions on test selection, taking account of the clinical relevance of the tests that are undertaken, the introduction of new tests and evaluation of benefit versus cost, as discussed earlier.

Test Turnaround Time

As described above, it is essential to ensure that tests are carried out and results reported to clinicians as rapidly as possible. The usual measure of this is the test turnaround time, which takes account of work scheduling, selection of equipment and training.³⁰ It is most easily measured as the time lapse between arrival of a blood specimen in the laboratory and issue of the validated result. In a small unit, this can be undertaken manually, albeit tediously. In a computerized laboratory, however, it is relatively easy to record these times and then to calculate the median time, the 95th percentile for completing each test and the percentage of tests completed within a pre-selected time.³¹ While this information is based on the performance of an individual laboratory, it should be possible to make comparisons with a peer group in benchmarking studies (see page 000).

It should, however, be noted that turnaround time as described above usually refers only to the analytical stage of testing and excludes the time delay of the pre-analytical and post-analytical stages of testing. When the laboratory has responsibility for all three stages, it becomes possible to extend the measurement of analytical turnaround time to the more meaningful parameter of request completion time (total time from initiation of the request to delivery of the result). The speed with which modern systems perform reduces the need for interrupting the routine specimens for urgent tests, but the laboratory should also have an efficient way to convey urgent results to the requesting clinician.³² In critically ill patients, it is especially important to avoid any delay between receipt of the test results by the ward staff and its relay to the relevant clinician for an active response. A report on this specific point by a College of American Pathologists Q-probe survey showed that while reports on tests from critically ill patients were generally received in the ward by computer link within less than 5 min, there was often a significant, and thus potentially serious, delay before they reached the relevant clinician.³³ The use of mobile camera phones as described above to transmit test results directly to the appropriate clinician could provide a solution, especially in an after-hours service.²⁹

Point-of-Care Testing

Point-of-care testing (POCT), also known as near-patient testing, functions at two levels: either within a hospital as an adjunct to the laboratory or for primary healthcare outside the hospital.

Specialist clinical areas within hospitals have an increasing need for a customized laboratory service to meet their particular requirements. When rapid results are especially important, laboratory testing within the clinical area may be the best arrangement. Intensive care units have a long established need for near-patient monitoring of blood gases, but other clinicians use laboratory tests for monitoring ill patients and for making rapid decisions on treatment (e.g. in oncology outpatient clinics) and this has increased demand for a rapid results service. POCT may also be necessary when a test is performed on capillary (not anti-coagulated) blood (e.g. for patients attending an anticoagulant control clinic).

Diagnostic laboratories are often located in areas of the hospital that are remote from critical care and outpatient areas. Rapid transit systems, including pneumatic tubes (see earlier), may be the preferred alternative to multiple satellite testing areas, particularly when the main laboratory already offers a rapid results service. Knowledge of test turnaround time in the laboratory (see above) is required in order to make an informed decision on the need for near-patient testing in satellite areas. When POCT equipment is the preferred option, the running of the satellite laboratory and maintenance of its equipment should be the responsibility of the appropriate pathology discipline. This is essential for quality control, safety and accreditation, whether the satellite is staffed by laboratory staff, as in busy locations or used by medical staff or nurses as a marginal activity. A designated member of laboratory staff should supervise this service, visiting each test location daily and ensuring that all results and quality control data are integrated into the main laboratory computer system. Some instruments designed for POCT will store quality-control data on a computer with a memory stick from which the data can subsequently be transferred to the main laboratory. Guidelines on the organization of a POCT service have been published by the British Committee for Standards in Haematology ³⁴ and the UK Medical Devices Agency,³⁵ in the USA by the Clinical and Laboratory Standards Institute³⁶ and internationally by the International Council for Standardization in Haematology³⁷ and the International Standard Organization.³⁸

Point-of-Care Testing Beyond the Laboratory

POCT beyond the laboratory is increasingly popular in some countries and it is particularly useful when patients live a distance away from a hospital laboratory. Instrument manufacturers are now producing tabletop or hand-held devices that are simple to use, autocalibrated and require minimum maintenance. The haematology tests that are usually undertaken include haemoglobin concentration, blood cell counting by simple analysers, erythrocyte sedimentation rate and prothrombin time for oral anticoagulation control.

Although this use of POCT is independent, the local hospital laboratory should encourage the doctors and clinics to seek advice and help with selection of appropriate instruments, their standardization/calibration and quality control, including a link into the external quality assessment scheme in which the laboratory participates. Harmonization of reports with laboratory records is helpful when a patient is referred to the hospital. Studies on the management of anti-coagulation control have shown that with appropriate training and cooperation from the laboratory, pharmacists are able to provide as reliable a service as the hospital-based one and, in general, with more convenience for the patient.³⁹

A major source of error in POCT outside the hospital is faulty specimen collection, whether for venous or finger-prick samples. Clinic staff who undertake this procedure should be given supervised training (see Chapter 1, p. 3).

Patient Self-Testing

There is an increasing trend toward self-testing by patients, and simple portable pre-calibrated coagulometers, which use capillary blood to measure prothrombin time and the International Normalized Ratio, are now available. It has been shown that patients are able to use these instruments correctly and, once their treatment has been established, the individual patients can be relied on to maintain their anti-coagulation within the therapeutic range ⁴⁰ (see also Chapter 20, p. 471). It is important that the selected instruments conform to national, European (CEN) or international (ISO) standards to ensure that they are reliable and that the instructions for their use are clear, unambiguous and written for the users.

Laboratory Services for General Practitioners

The customers of a haematology laboratory include not only hospital clinicians but also general practitioners/family doctors who have different priorities from hospital practitioners. They may have simple point-of-care screening tests on site, but appropriate service beyond that is outlined in the following sections.

Pre-Analytical Service

Provision of adequate information to the general practitioner is important. This may include a users’ handbook or an encyclopedia listing all available tests, their utility and normal reference ranges, together with a wall chart to show the correct specimen container and volume of blood required, requirements for patient preparation (e.g. fasting), the timing of any medication that may affect the test result and the turnaround time for each test. The latter is important so that patients can be given a follow-up appointment to be told the result. Handbooks should be of loose-leaf format to facilitate updating. Education should cover safety aspects, such as how to deal with blood spillage or a needle-stick injury. A specimen transport system at an agreed time of day is particularly important so that patients can be given a suitable appointment for blood collection.

Post-Analytical Service

The general practitioner needs a fast report service for abnormal test results. Ideally, there should be an interfaced computer connection to the laboratory and to the duty haematologist or at least a direct e-mail address, telephone or fax number at the health centre. With transmission of results by fax or e-mail, confidentiality must be ensured by secure identification of the recipient and, when internet access is available, a secure password entry is essential. When there is no electronic link to the laboratory, it may prove economical to use the specimen transport service to return test results to general practitioners.

Standard Operating Procedures

Standard operating procedures are written instructions that are intended to maintain optimal consistent quality of performance in the laboratory. They should cover all aspects of work, with some relating to test procedures and others relating to specimen collection, laboratory safety, handling of urgent requests, data storage, telephone reporting policy, and so on. They may be based on standard textbook descriptions or an instrument manufacturer’s instruction manual, but they should reflect daily practice and each laboratory must prepare its own individual set of SOPs. They should be reviewed regularly and any revisions must be highlighted with the date. Older versions must be archived and numbered copies of the new version must be distributed to authorized locations. A suggested format for an SOP is given in Table 24.6.

Table 24.6 Format for a standard operating procedure (SOP)

Cover page
	Title, reference number, date of preparation, name of author, name of authorizer, distribution of the SOP and its availability
Scope
	Purpose of the SOP; principles of procedure or test; grade(s) of staff permitted to undertake the task(s), responsibility for implementation of SOP, training requirement file
Specimen requirements
	Type and amount; delivery arrangements; storage conditions, any time or temperature restrictions
Specimen reception
	Registration and check of request form; criteria for rejecting a specimen
Health and safety precautions
	Obligatory protection requirements
	Handling and disposal of ‘high-risk’ samples, broken specimen containers and blood spillage
Equipment, materials and reagents
	Lists of equipment, apparatus, reagents, controls, calibrators, forms and other stationery
Test procedure
	Step-by-step details of sample processing, test procedure, quality control checks and use of standards, calculation of results
Reporting
	Procedure for reporting results for routine and urgent requests; printed instructions to patient when relevant
Clinical significance
	An understanding of the clinical reason for the test and significance of abnormal results
	Reference range and confidence limits for healthy normal men, women and children
Test limitations
	How to recognize errors and steps to avoid or correct them
Maintenance of equipment
	List of schedule for routine in-house maintenance (daily, weekly) and servicing
Specimen storage post-test
	Period of retention and conditions for storage: instructions for disposal of specimens and diluted subsamples
List of relevant literature
Date when SOP is due to be reviewed

Laboratory audit and accreditation

Audit

Laboratory audit is the systematic and critical analysis of the quality of the laboratory service. The essence of audit is that it should be continuous and designed to achieve incremental improvement in quality of the day-to-day service. It should encompass the pre-analytical, analytical and post-analytical stages of laboratory practice; and should take account of five components:⁴¹

1. Solving problems associated with process or outcome

2. Monitoring workload in the context of demand control

3. Monitoring introduction of new tests or changes in practice

4. Monitoring adherence to guidelines and best practice

5. Monitoring of analytical quality.

Examples of specific aspects of laboratory practice requiring audit are given in Table 24.7.

Table 24.7 Examples of laboratory audit

Understanding of laboratory functions by users

Request forms: patient identity, clear indications of test(s) and relevant clinical information

Specimen labels with unambiguous identification of the patient

Appropriateness of test requests

Test menu in response to clinical needs

Appropriateness of blood samples (e.g. adequate volume, choice of anticoagulant)

Storage of reagents and specimens

Reference ranges and interpretation of abnormal results

Timeliness of reports

Internal quality control results

External quality assessment scheme performance

Cost-effectiveness of specialist tests

Precise and clear laboratory reports, especially highlighting abnormal results

Reporting methods (e.g. personal contact, computer, telephone, fax, camera phone)

Compliance with safety policies

Use of blood and blood products

Frequency and cause of transfusion reactions

Turnaround time for emergency requests

Satisfaction of outpatients undergoing venepuncture

Satisfaction of laboratory users on laboratory competence

The first stage of audit is to define the standard to be achieved; this may be in the form of a standard operating procedure for an analytical procedure, a protocol for test ordering, pre-surgery blood transfusion order schedule or a target turnaround time. These standards will have been agreed within the laboratory and, whenever possible, in conjunction with relevant users of the laboratory. Clinical input is invaluable in relation to the clinical significance of analyser-generated results, test utility (see p. 568), appropriate laboratory utilization,¹² and the advantages and disadvantages of point-of-care tests (see p. 574). To monitor performance against the agreed standards, each laboratory section should form its own audit group or, if there is an audit group for the whole department, it should be open to all grades of staff to allow peer review and to take advantage of the educational value of audit. Laboratory staff should lead the audit process rather than having it imposed on them. It is good practice to make a short report of each audit meeting, recording attendance, the items identified for improvement and an action list.

In the UK, a national steering group monitors serious hazards of transfusion (‘SHOT’). A large proportion of the incidents that have occurred have been the result of incorrect identification of patient–specimen link, with the wrong blood being collected from the hospital blood bank or satellite refrigerator, or failure in bedside checking procedures (see p. 519).

The audit process improves quality simply by examining and questioning established standards and guidelines. The ever-increasing need for cost-effectiveness is likely to forge closer working relationships between the different pathology disciplines, as well as between laboratories within the same discipline. This changing laboratory environment highlights the need for continuous training of haematology staff in good laboratory management and in the importance of audit.

Accreditation

The purpose of laboratory accreditation schemes is to allow external audit of a laboratory’s organization, staffing, direction and management performance in an appropriate quality assurance programme and level of user satisfaction. The advantage to the accredited laboratory is that this indicates to clinical users that it has a demonstrable standard of practice with competence, impartiality and capability that has been independently confirmed by external peer review. Such review should include assessment of basic functional structure (laboratory facilities such as staff and equipment), processes (test analyses), outcome (quality of test results including timeliness and interpretation), interaction with clinical users and optimal use of resources.

In the UK, this proficiency testing function is undertaken by an independent organization, the UK Accreditation Service (www.ukas.com), which is the sole national body recognized by the UK Government and by the EU, with authority to validate specified tests that are undertaken by a laboratory, certifying that these tests are up to date, recognized as standard practice and comply with ISO and CEN standards (see p. 587). Previously, the majority of clinical laboratories in the UK were accredited by Clinical Pathology Accreditation Ltd (CPA), a body established by the Royal College of Pathologists and working in association with UKAS; however, as CPA has more recently been considered not to be independent of its participating laboratories, its function has been assumed directly by UKAS. For any specific test, reliability is judged by performance in the relevant surveys of the UK National External Quality Assurance Scheme (see Chapter 25).

In other countries, certification for accreditation may also be undertaken by government-authorized bodies. Thus, in the USA, control is undertaken mainly by the CAP Accreditation and Laboratory Improvement scheme in accordance with the Clinical Laboratories Improvement Amendments (CLIA 1988) regulations.^42,⁴³ In Australia, control is maintained by a government authority, the National Pathology Accreditation Advisory Council (NPAAC), which sets the standards for accreditation of laboratories. Descriptions of the requirements for national accreditation programmes are available on their websites.

An important component of all accreditation programmes is participation in proficiency testing/external quality assessment schemes (see Chapter 25). These schemes are expected to conform to standards that are specified by the International Laboratory Accreditation Cooperation (ILAC) and are described in ISO/IEC Guide 43. ISO 17043 (see Table 24.8) is an updated version of ISO Guide 43. Another useful document is ILAC G22 (‘Use of proficiency testing as a tool for accreditation in testing’).

Table 24.8 ISO and European (EN) standards relating to medical laboratory practice

ISO 9000	A series of standards and guidelines on selection and use of quality management systems and quality assurance (complementary aspects are specified in ISO 9001–9004)
ISO 22869	Guidance document on implementation of ISO 15189 (formerly ISO Guide 25)
ISO 15194	In vitro diagnostic medical devices: measurement of quantities in samples of biological origin; description of reference materials
EN 12286	In vitro diagnostic medical devices: presentation of reference measurement procedures
EN 13612	Performance evaluation of in vitro diagnostic medical devices
ISO 15198	Validation of manufacturers’ recommendations for user quality control
ISO 25680	Calculation and expression of measurement uncertainty
ISO 22870	Point-of-care testing (POCT) – requirements for quality and competence
ISO/IEC 17043	Conformity assessment – general requirements for proficiency testing. This is update of ISO Guide 43–1 & 2
ISO/EN 17025	Competence of Testing and Calibration Laboratories; formerly ISO Guide 25 and EN45001
EN 375	Information supplied by manufacturers with in vitro diagnostic reagents
EN 591	Instructions for use of in vitro diagnostic instruments
EN 592	Instructions for use of in vitro diagnostic instruments for self-testing
EN 13532	General requirements for in vitro diagnostic medical devices for self-testing
ISO 17593	Requirements for in vitro monitoring systems for self-testing of oral anticoagulation therapy
EN 14136	Use of external quality assessment schemes in assessment of performance of in vitro diagnostic procedures
ISO 6710	Single-use containers for venous blood specimen collection
ISO 15190	Safety management for medical laboratories
ISO/EN 14971	Medical devices – application of risk management to medical devices

ISO, International Organization for Standardization; EN, Comité Européen de Normalization.

Some national schemes have established formal links with each other, such as the Western European Laboratory Accreditation Cooperation. The website of the European Proficiency Testing Information Service (EPTIS) lists a wide range of schemes worldwide in various sciences, including laboratory medicine.

International standards of practice

The International Standards Organization (ISO) has established guidelines for laboratory practice. Of special importance are ISO 15189: ‘Medical laboratories – particular requirements for quality and competence’, which sets out the rules for laboratory management; ISO 9000 series: ‘Quality management and quality systems’ and ISO 17025: ‘Competence of testing and calibration laboratories’. These and other relevant standards from ISO and the European authority CEN are listed in Table 24.8.

Benchmarking

Benchmarking is now recognized as an essential technique for achieving continuous improvement in laboratory performance to ensure that it is effective and efficient with elimination of waste. It functions by providing a reference point for laboratories to assess their performance by comparison with their peers and the leaders in the field.⁴⁴ Departments are divided into several categories on the basis of their size, whether academic or non-teaching and whether responsible for special activities. Their responses to a lengthy annual questionnaire permit evaluation of various aspects of laboratory practice. By standardizing definitions of tests and requests, it is possible to establish an agreed method for estimating workload in a standard way and to provide the optimal criteria for staffing levels, skill-mix, productivity, reliability and cost-effectiveness, taking account of clinical needs and local patient population (‘case-mix’). Thus, benchmarking judges the quality of service of a laboratory, by assessing whether it can be run more efficiently with improved cost-effectiveness and clinical effectiveness. It provides an assessment of the adequacy of staffing with realistic measure of workload parameters, how test throughput and reporting time might be improved, taking account of how variation in clinical practice might affect the laboratory service and whether cost-effectiveness and clinical benefit might be improved by decentralizing some components or conversely by eliminated satellite units. This has become an essential method for achieving continuous sustainable improvement based on evidence rather than intuition.

In the USA, the scheme known as ‘Q-probe’ was established in 1989 by the College of American Pathologists Laboratory Improvement Program, to facilitate implementation of CLIA ‘88 requirements by providing laboratories with continuing peer review and education with periodic on-site audit. Reports of various Q-probe studies are published regularly in the Archives of Pathology and Laboratory Medicine. In the UK, a similar scheme has been developed in keeping with the requirements of the Commission for Health Improvement (CHI). It is undertaken by the Clinical Benchmarking Company, which is a partnership established by the Clinical Management Unit of the Centre for Health Planning at Keele University with Tribal Newchurch Limited (www.newchurch.co.uk/consulting), an informatics service company specializing in working with healthcare organizations. For its laboratory services, it operates with a team of advisers appointed by the Royal College of Pathologists. Assessment of performance of an individual laboratory is based on comparison with best performance in a comparable peer cluster and performance in the UK National External Quality Assessment Scheme (see Chapter 25). Another organization with similar function is DAWN Benchmarking.

Laboratory Safety

Principles of Safety Policy

Every laboratory worker should receive instructions on the potential hazards in their workplace, from specimen collection to waste disposal, and including sites where point-of-care tests are carried out, reagent stores and satellite storage refrigerators that hold blood and blood products. There should be a procedure to protect the health and wellbeing of all members of the staff and legitimate visitors, taking account of mandatory rules and regulations as well as local practices.

There should be a designated safety officer of sufficient seniority, with authority to implement departmental safety policy in all sections of the laboratory. The safety officer should be responsible for day-to-day management of safety issues and should be directly accountable to the head of department. There must be an established protocol for handling needle-stick injury to a member of staff, with immediate referral to the appropriate hospital department of occupational health, which should provide a 24 h advisory service. All incidents must be recorded, safety protocol reviewed and measures taken to prevent recurrence.

The safety officer must have the training and time to do the job well and provide ongoing training for other staff who must not be allowed to handle potentially hazardous materials until they have completed training in accordance with the safety requirements. The safety officer should represent the laboratory on relevant safety committees and work closely with hospital occupational health, control of infection and radiation protection officers. Within the department, a safety committee should be established as a useful forum for safety audit.

Departmental safety policy should be documented as a booklet which is readily accessible in each section of the laboratory. A loose-leaf format facilitates updating. It must provide a comprehensive account of departmental safety policy (Table 24.9). Attention must be drawn to known and potential hazards in relation to infection, toxic substances, fire, radiation and mechanical injury. Where a hazard cannot be eliminated, the risk should be reduced so far as is reasonably practicable (e.g. by reducing the frequency and period of exposure). The safety booklet should refer to relevant local, national and international safety legislation.

Table 24.9 Items to be included in laboratory safety policy document

Blood collection

Labelling, transport and reception of specimens

Handling of specimens and containment of high-risk specimens

Location of protective equipment

Managing and reporting needle-stick injury

Management of eye-splash

Disposal of used needles, syringes and lancets

Procedure for blood spillage

Hazard risk assessment for all substances in the laboratory

Safety in near-patient testing

Protective clothing

Health records of staff, including immunization

Laboratory security, out-of hours working and visitors to the department

Waste disposal

Electrical equipment testing

Recording of accidents

Safety cabinet monitoring

Laboratory cleaning policies

Policy for receiving and sending postal specimens

Radiation protection

Fire precautions

Staff training programmes

Safety inspections

Schedule for safety committee meeting

In addition to the safety booklet which sets out laboratory safety policy, SOPs should also include information on handling reagents which are classified by relevant authorities as hazardous to health (see below), together with relevant safety and decontamination protocols (see p. 582).

The standard for safety management in medical laboratories has been established by the International Organization for Standardization (ISO 14971 and 15190; Table 24.8). This provides rules for a safe working environment in the laboratory and includes a comprehensive list of items to be checked when auditing safety practice. A similar document on safety of electrical equipment used in the laboratories has been established by the International Electrotechnical Commission (IEC).⁴⁵

WHO has also published comprehensive manuals on safety in healthcare laboratories,^46,⁴⁷ and there is a WHO website linked to the Safe Injection Global Network (www.who.int/injection_safety), which describes strategies for safe handling of blood intended for transfusion. This includes (a) selection of blood donors, testing of blood units, appropriate clinical use of blood and, when applicable, viral inactivation of human material for therapeutic use; (b) safe and appropriate use of injections, sharps waste management and prevention of cross-infection; and (c) procedures conducted according to universal precautions. Proposals for best practices and global activities are reviewed at: www.who.int/sign.

At a national level, in many countries there are mandatory requirements for safety at work and these include hospitals and clinical laboratories. In the UK, the authority for this is the Health and Safety Executive, which has established procedures for prevention of infections in clinical laboratories.⁴⁸ The toxicity of all chemical reagents used in the laboratory, including those incorporated into kits, is governed by the Health and Safety Executive (HSE), which is responsible for the Control of Substances Hazardous to Health (COSHH) regulations and requires that any substances hazardous to health should be categorized and certified by COSHH with regard to degree of physical and biological hazard, safety measure for use, handling of spillage and waste disposal (see www.hse.gov.uk/pubns/chindex.htm).

Other essential sets of regulations for the laboratory concern the use of radioactive materials. These are described in the Ionizing Radiations Regulations 1999 (No. 3232). The management of these various regulations and methods for investigation of accidents are described by Holt.⁴⁹

The specific safety requirements to be considered in laboratory practice are described below. They include design of premises, electrical and radiation safety, fire hazard, toxic and carcinogenic reagents, handling of biohazardous material and waste disposal.

Design of Laboratory

The area where work is carried out should be sufficiently large to easily accommodate items of equipment, all of which should be installed on fixed surfaces or stable trolleys. If possible, equipment which produces excessive noise should be kept separate from the general working area. Optimal lighting should be ensured and there should be adequate ventilation with protection from dust as well as a comfortable ambient temperature for workers and for optimal functioning of equipment. There should be appropriate storage facilities for chemicals (see below). Fire extinguishers and first-aid cabinets should be placed in easily accessible sites. The laboratory working area must meet design standards for ‘level 2 containment’ and there should be restricted access, which should be enforced where possible.

Electrical and Radiation Safety

All electrical equipment used should be certified by its manufacturer to comply with the national or international safety standards. Electrical equipment should not interfere electrically with in vivo medical devices (e.g. pacemakers) unless clearly marked with an appropriate caution. Before installation, all electrical devices should be inspected by someone trained in portable appliance testing, who must ensure that all plugs, fuses and electrical cables are appropriate and functional and that the plugs and cables are not adjacent to water taps. There should be a planned programme of preventive maintenance for each item of electrical equipment. All equipment should be decontaminated before inspection or repair.

Protection when handling radioactive material and using equipment for measuring radioactivity is described in Chapter 17, p. 374.

Fire Hazard

Most fires result from accidents with flammable substances such as alcohol and solvents. All manipulations of such substances must be carried out away from naked flames. Bulk stocks should be kept in flame-protected bins in a storage area separated from the laboratory and clearly marked as ‘FIRE RISK’. Not more than 400 ml should be kept on an open bench or shelf. In many countries, gas burners are no longer available, but where they are used, they must never be left unattended and pilot lights must never be left on overnight. The burners should be as close as possible to the gas source and lengthy connecting tubes must be avoided.

Fire blankets and fire extinguishers, especially those suitable for dealing with electrical and chemical fires, should be placed near to doors of rooms and at strategic points in corridors. They should be inspected regularly.

Chemical Safety

Dangerous chemicals such as strong acids and alkalis must be stored at floor level; chemicals which are likely to react with each other must be stored well apart; poisons should be stored in locked cabinets. Manufacturers’ product safety data sheets must be checked for advice on safe handling of any potentially toxic or carcinogenic substances. Such reagents must be stored in a secure place with restricted access; they should be handled only by experienced staff wearing protective clothing and weighing should be carried out in an air-flow cabinet at face velocity of around 0.8 m/s.

Eyewash Facilities

An eyewash station should be conveniently located where hazardous chemicals or biological materials are handled. This should consist of a spray device attached to the water supply by a flexible hose. If access to plumbing is not available, the alternative is an ample supply of easy-to-open containers of water.

Biohazardous Specimens

When handling blood, the most commonly encountered pathogens are HIV and hepatitis viruses. All specimens of human origin should be regarded as potentially infectious and must be handled appropriately by means of universal precautions in order to minimize exposure of skin and mucous membranes to the hazard. Special precautions are necessary with highly infectious specimens (see below).

Universal Precautions

1. Personal hygiene precautions to be adopted in areas where blood is collected, specimens are handled and analytical work is carried out:

a. Eating, drinking and the application of cosmetics are absolutely forbidden.

b. Staff should not wear jewellery and ideally, watches and rings should be removed.

c. Disposable latex rubber or plastic gloves should be worn during sample handling and analytical work.*

d. An outer protective gown or coat should be worn and personal clothing should not be allowed to protrude beyond the sleeves of the protective clothing.

e. Any exposed cuts or abrasions must be kept covered with waterproof dressings.

f. Hands must be washed when leaving analytical areas.

2. Venepuncture should be performed wearing disposable thin plastic or rubber latex gloves. Care must be taken to prevent injuries when handling syringes and disposing of the needles. Do not recap used needles by hand; do not detach the needle from the syringe or break, bend or otherwise manipulate used needles by hand. Used disposable syringes and needles, lancets and other sharp items such as glass slides, must be placed in a puncture-resistant plastic ‘sharps’ container for disposal. Care must be taken to avoid blood contamination of tourniquets as a potential cause of cross-infection. If necessary, they should be washed with soap and water.

3. As far as possible, only disposable syringes, needles and lancets should be used. Disposable syringes and lancets must never be reused on a different person.

4. Specimens should be sent to the laboratory in individual closed plastic bags, separated from the request forms to prevent their contamination should there be any leakage from the specimens. Ideally, the plastic bag should be placed inside another container. Tubes which minimize the risk of leakage are available.

5. Mouth pipetting is absolutely prohibited.

6. Centrifugation must be performed in sealed centrifuge buckets.

7. Blood and bone marrow slides must be handled in the same way as blood samples until they are fixed in methanol, stained and covered with a cover glass.

8. Used material must be placed in designated biohazard plastic bags awaiting disposal (see below).

9. Protective laboratory clothing (e.g. white coats) must never be worn outside the laboratory.

10. Additional precautions with infectious or potentially infectious material:

a. Only experienced staff should perform procedures.

b. Specimens should be handled in a microbiological safety cabinet (if the procedure involves generation of an aerosol) or in a clearly segregated and designated area of the laboratory.

c. Specimens should be handled using protective clothing (close-fitting disposable gloves, disposable plastic apron, glasses or goggles, face mask).

d. Disposable plastic should be used instead of glassware; sharp-pointed instruments (e.g. scissors) should not be used.

e. There should be special arrangements for waste disposal (see p. 583).

Disinfectants

There are several types of chemical which have been used as germicides, including aldehydes, phenols, halogens, alcohols and hypochlorites. However, some of these are no longer available in laboratories. Those that are now used are indicated in Table 24.10. No single disinfectant is effective against all pathogens and their effectiveness depends on the nature of the organism.^47,⁵⁰

Table 24.10 Properties of common disinfectants

Sodium hypochlorite (chlorine)

This is the most commonly used disinfectant in the laboratory as it is very active against all microorganisms, although less active against fungi. Its disadvantage is that it is corrosive to metal. As hypochlorite solutions gradually lose their strength, fresh dilutions must be made daily. For general use, a concentration of 1 g/l (1000 ppm) as available chlorine is required; a stronger solution containing 5 g/l (5000 ppm) is necessary for dealing with blood spillage.

Household bleaches usually contain 50 g/l as available chlorine and should thus be diluted 1:50 for general use and 1:10 for blood contamination. Other chlorine-containing compounds which can be used are prepared as follows:

Calcium hypochlorite. (70% available chlorine) 1.4 g/l; 7 g/l for blood contamination.

Sodium dichloroisocyanurate (NaDCC). (60% available chlorine) 1.7 g/l; 20 g/l for blood contamination

Chloramine. (25% available chlorine) 20 g/l in all conditions.

Alcohols

Ethanol and isopropyl alcohol have similar disinfectant properties at a concentration of 70–80% in water; higher or lower concentrations reduce their germicidal effectiveness. They are active against vegetative bacteria and lipid viruses but not against spores or fungi. Their effect on non-lipid viruses is variable. Alcohol is especially effective when mixed with other agents (e.g. 80% alcohol with 100 g/l of formaldehyde or with 2 g/l (2000 ppm) available chlorine).

Applications of Disinfectants

Routinely, on completion of the day’s work, the working area should be wiped with a freshly prepared 1% w/v sodium hypochlorite solution (chlorine bleach). Reusable pipettes should be soaked in a 2.5% solution for 30 min or longer. A 10% solution must be used for cleaning up blood spillage. The diluted sodium hypochlorite solution should be freshly made each day. It is helpful to add detergent to the solution as disinfectants are most active on clean surfaces. A stabilized blend of peroxide with surfactant and organic acids in a buffer system is available as a commercial product, ‘Virkon’ (Antec-DuPont). It appears to be effective as a general disinfectant for all hard surfaces, plastic and stainless steel laboratory equipment, medical instruments and laundry and also for absorbing spilled blood or other body fluids.

Automated equipment

Some automated equipment can be disinfected by flushing several times with 10% w/v sodium hypochlorite, followed by several flushes with water. Hypochlorite causes corrosion of metal surfaces. Other instruments have special requirements for decontamination; always refer to the manufacturer’s instructions.

Centrifuges

Laboratory centrifuges require particular attention. They should never be cleaned using hypochlorite solution or other metal corrosives. Any spillage of blood should be dealt with immediately and the bowl, head and buckets (including rubber pads) should be disinfected regularly (e.g. with 2% Virkon) and then rinsed with a detergent (e.g. Decon 90) or 70% ethanol. Special care is required when a glass or plastic tube breaks in a centrifuge (Table 24.11).

Table 24.11 Procedure for decontaminating a centrifuge after breakage of a tube

1.	Switch off centrifuge motor and do not open lid for 1 h to allow aerosols to settle. Inform the safety officer.
2.	When breakage involves a known high-risk specimen in a sealed bucket, strong gloves, goggles and a protective apron must be worn and the bucket opened in a safety cabinet.
3.	If the leakage was confined to a sealed bucket, manually open the centrifuge and, using forceps to remove broken tubes and any solid debris, discard the contents of the bucket into 2% Virkon.
4.	Decontaminate the inside of the lid, bowl and external surfaces of the buckets with 2% Virkon, rinse with Microsol 3+ (Analis, Belgium) or a detergent such as Decon 90 or 70% ethanol and leave to dry.
5.	Buckets, rotors and other small centrifuge items may be autoclaved where appropriate. Alternatively, more delicate items (e.g. whole microfuges) may be fumigated within a safety cabinet.
6.	All contaminated disposable material must be placed in appropriate bags for autoclaving.