The ACL TOP TM Hemostasis Testing System: Features and Technical Description

Transcription

1 COAGULATION 15 The ACL TOP TM Hemostasis Testing System: Features and Technical Description

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3 The ACL TOP TM Hemostasis Testing System: Features and Technical Description

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5 Table of Contents I. Overview Page 5 II. Technical Description Page 8 III. Main System Features Page 16 IV. Specification Table Page 22 V. Hemostasis Assays Page 23 VI. IL Monographs Page 24

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7 I. Overview 5 What It Is The new ACL TOP hemostasis system from Instrumentation Laboratory is a fully automated, benchtop, random-access analyzer, designed specifically for in vitro coagulation and fibrinolysis diagnostic testing in the assessment of thrombosis and hemostasis. As the new standard in hemostasis, the ACL TOP works harder and smarter to meet the increasing demands of the highvolume test lab, offering more capabilities while reducing time-consuming QC and maintenance tasks. What It Does The ACL TOP combines flexibility, intelligence, ease-of-use and speed to deliver complete Testing Process Automation for the demanding hemostasis laboratory. The ACL TOP system: Consolidates testing capabilities into one system Provides a complete solution for both routine and specialty assays (clotting, chromogenic and immunoassays) Offers high throughput with up to 360 PT results per hour, 24 hours a day, 7 days a week Operates quickly and easily, with an expandable and versatile platform that can be tailored to the needs of each laboratory Automates QC and maintenance, increasing productivity while reducing workload Developed by the leaders in intelligent automation, the ACL TOP offers high performance for the high-volume lab. How It Works The ACL TOP system provides results for both direct hemostasis measurements and calculated parameters. The ACL TOP performs the following types of tests: Coagulometric (Turbidimetric) Tests Chromogenic (Absorbance) Tests Immunological Tests The following describes the operating principles for each of the three types of tests. (For additional detail, please see the ACL TOP Operator s Manual.) Coagulometric (Turbimetric) Measurements The principle of coagulometric clot detection is used to measure and record the amount of time required for a plasma specimen to clot. The technique assesses coagulation endpoints by measuring change in optical density. Chromogenic (Absorbance) Measurements Chromogenic tests use the colorimetric principle of measuring absorbance of light by the solution in a cuvette. The amount of light that reaches the photodector is converted into an electrical signal that is proportional to enzyme activity.

8 6 Why It Works (Better, Faster, and Easier) Immunological Measurements The principle of immunological measurement is used to directly measure and record the concentration of an analyte in a sample (and not its activity) by measuring change in optical density. Although similar to the turbimetric method, the immunological method relies on the formation of antigen-antibody complexes to affect light transmission. The ACL TOP testing process is fully automated, with on-board QC and maintenance, enhancing performance and productivity. Please see below for more on system features and benefits. The ACL TOP was developed based on feedback from the people who use the instruments. Created by Instrumentation Laboratory (IL), who has been at the forefront of diagnostic innovation for over 40 years, the ACL TOP delivers what users asked for and more. Highly automated for high-throughput screening, the ACL TOP works harder and does more, offering the following features for a total solution: Optimal Sample Management Parallel loading of racks; no sample queuing Continuous loading 120 samples on-board Simultaneous loading of different sample containers Closed-Tube Sampling (CTS) with cap-piercing module Barcode identification Sample presence detection Automatic sample predilution Factor parallelism testing with automatic multiple solutions Automatic Checks and Validation Sample liquid level sensing Automatic rerun testing with possibility of extra sample predilution for enhanced test linearity Automatic reflex testing Automatic results validation Optimal Reagent Management Parallel loading of racks for reagents, calibrators, controls, deficient plasma, and any required material Continuous loading Up to 60 materials on-board Barcoded vials for random loading and automatic identification, including vial size, expiration date and lot Vial presence detection for non-barcoded materials Handling of multiple vials of the same material Automatic Sensing and Tracking Reagent liquid level sensing Volume tracking Expiration date tracking Calibration stability tracking Real-Time STAT Capability STAT samples loaded on any rack, in any position, at any time System ready to run 24 hours a day Expiration date tracking PT result in less than three minutes when processing one sample from idle system status

9 7 In addition to automation of the testing process, the ACL TOP takes care of itself so users can minimize time performing QC and maintenance. QC software allows for set-up of automatic QC analysis utilizing Westgard Rules. Minimal maintenance is needed (less than five minutes daily), ordered by the user, but performed by the system. Fully automatic maintenance is provided for all other daily activities. Last, the system s user-friendly interface and intuitive controls make operation fast and easy. The result is more capabilities, greater assurance of high performance, with less effort. ACL TOP Benefits Here s why the ACL TOP is the optimal choice for high throughput testing: Complete Broad test menu and large capacity of materials on-board Consolidated workstation for routine and specialty assays: clotting, chromogenic and immunoassays Specialty assays as easy as routine Fast Continuous operation High throughput (up to 360 PT results per hour) Optical units capable of simultaneous reading of clotting and chromogenic assays allows optimal throughput, independent of test mix Real-time processing of STAT samples Friendly Powerful and intuitive Windows 2000 software and touch-screen Automated reagent management, automated QC and automated maintenance On-line help Safe Transparent, locked covers for samples and reagents CTS-configuration option minimizes exposure to biohazards Barcoded vials for all materials Password-controlled user access and automatic logging of significant events Reliable 24 hours/7 days continuous operation State-of-the-art technology Extensive company history in instrument and reagent development and manufacturing Versatile Base configuration (Open-Tube Sampling) CTS configuration with cap-piercing module Laboratory Automation System (LAS) configuration offering direct off-board sampling without mechanical interfaces

10 8 II. Technical Description Hardware The ACL TOP hardware was designed for efficiency and effectiveness in the high-throughput hemostasis laboratory. IL s innovative development team limited the number of moving components without compromising the throughput of the system. The end result is a reliable system, requiring minimal maintenance, which meets the needs of the high-volume laboratory. The hardware on the ACL TOP is divided into two modules: 1. Control module (CM) Pentium-based processor used by the operator to interact with the system. 2. Analytical module (AM) This module is composed of seven areas: cuvette loading, sample area, cuvette shuttle, reagent area, optical reading units, cuvette waste and the external clean solutions. These components are highlighted below. Analytical Module Control Module Sample Area Reagent Area Cuvette Loading Area Cuvette Waste Drawer External Rinse and Clean

11 9 Cuvette Loading The cuvette loading area is on the left side of the analyzer. The cuvette, composed of polystyrene, is uniquely designed. Four individual cuvettes are molded together to form a cuvette strip. Ten strips are linked together to form a cuvette clip. Ten clips are packaged together as a cuvette block. The block is packaged to facilitate ease of entry into the cuvette loading area. The area will accommodate two blocks at one time for a total of 800 on-board cuvettes. The cuvette clips are loaded vertically. When the clip advances to the front, it is moved to a horizontal position. The cuvette shuttle then grips one strip from the clip and transports it for use. The cuvettes are used for either sample predilutions or analysis. The cuvette loading area is accessible at all times to the operator. This allows for cuvette loading at any time while the system is idle or operating. The system will alert the user when the cuvettes are running low and when the loader is empty. Cuvette Clip Cuvette Strip Cuvette Block

12 10 Sample Area The sample area is located to the right of the cuvette loading area. This area contains the heated sample probe with a dedicated rinse bath, rack positions for samples and diluents, and cuvette strip holders for dilutions and incubation. It is visible through the tinted-glass safety panel on the front of the analyzer and is maintained at ambient temperature. The safety panel is monitored and locked for safety during sample processing, yet it provides visible access to the area. This area accommodates the sample racks and two diluent racks. The samples are loaded in racks on-board the system. Each rack will hold ten samples. The sample area will accommodate 12 racks, for a total of 120 samples. The racks contain barcode identification. The system alerts the user if a specimen in a rack position cannot be identified. The racks also contain spring clips that allow usage of sample tubes of varying sizes. In addition to direct tubes, samples may be processed in cups or pour-off tubes. To process in pour-off tubes, adapters are available for use. The diluent racks in this area are located to the right of the 12 samples racks. Each rack can hold: sample diluent, control, calibrator, quality control or clean material. This area can accommodate two racks for a total of 16 materials. Cuvette Hold Area (room temperature) Sample Probe Cuvette Incubator Area Clean / Rinse Wells Cuvette Load Area Sample Rack Area Diluent Rack Area Sample Area (ACL TOP Base Model)

13 11 Sample Rack Any of the sample or diluent positions can be accessed by pressing a button below the desired location on the analyzer. This activates the barcode reader to position itself respectively. The barcode reader traverses the front of the system along with a rigid curtain. The curtain ensures safety and maintains the area at the optimal temperature during analysis. When the reader is positioned, a rack can be inserted while the sample barcodes are read. Positioning the reader beside the rack minimizes stray light from impacting the barcode reading. Once a rack is latched into position, the LED for the location turns green. During analysis, it turns orange and the rack is locked and non-removable. Upon completion of the analysis for all samples on the rack, the LED returns to green. The rack can then be removed and replaced with a new rack of samples to be processed. Samples and materials in the sample area are aspirated using the sample probe. The probe incorporates a sensor that recognizes the presence of liquids and stops at the optimized liquid level. During aspiration and transport, the probe heats the liquid to 37 C +/- 1 C. A Teflon tube connects the probe to a syringe pump that is capable of delivering 4 to 250 µl. The samples and materials are aspirated and dispensed into a cuvette. The cuvette strips are held in the sample area in two regions; one at ambient air temperature and the other heated to 37 C. The ambient temperature area can hold 14 cuvette strips and the incubated area can hold eight strips. In these areas, dilutions and incubations of sample occur. Cuvette Shuttle The cuvette shuttle has a unique, highly efficient design for moving cuvette strips throughout the system. The shuttle runs along the back of the analyzer behind the sample and reagent areas. The shuttle grips the desired cuvette strip, retracts it into its 37 C heated chamber, moves to the next desired position and places the cuvette strip. The shuttle has access to all cuvette areas at all times and can, therefore, move cuvettes to any position. The system utilizes one shuttle for all cuvette transportation needs.

14 12 Reagent Area The reagent area is located to the right of the sample area. This area has two heated reagent probes, along with a corresponding rinse bath, rack positions for reagents and diluents, eight cuvette strip incubators and four Optical Read Units (ORU). It is visible through the tinted-glass safety panel on the front. The reagent cooling area is maintained at approximately 15 C. The safety panel is monitored and locked for safety during reagent aspiration, yet it provides visible access to the area. This area accommodates the reagent racks and a diluent rack. The reagents are loaded in racks on-board the system. Each rack can hold six reagent vials and the reagent area can accommodate six racks for a total of 36 reagents. The racks contain barcode identification. The system alerts the user if a specimen cannot be identified. The first two positions within each rack have stirring capability; therefore, the system can accommodate 12 vials requiring reagent stirring. These positions can also be utilized for non-stirred reagents. The reagent rack area is divided into two regions. One region is for intermediate reagents and the other is for starter reagents. The intermediate reagents are those that are added first to the sample in the cuvette. They can then be mixed and incubated with the sample. The reagent area contains eight incubator positions to hold cuvette strips for dispensation and incubation of intermediate reagents. The starter reagents are those that initiate the final reaction. The starter reagents are dispensed when the cuvette strip is loaded into one of the four ORUs. Incubators and ORUs are maintained at 37 C. As an example, in the APTT test, the intermediate reagent is cephalin and the starter reagent is calcium chloride. Reagent rack positions 1-4 are utilized for the intermediate reagents and 3-6 for the starter. Positions 3-4 are crossover positions that can be utilized for either. Separation of the reagents into two types allows for both probes to be active simultaneously. Reagent Area

15 13 The diluent rack in this area is located to the left of the six reagent racks. The rack can hold eight materials including: a reagent diluent, deficient plasma or an intermediate reagent. This area, like the reagent rack area, is maintained at approximately 15 C. Any of the reagent or diluent positions can be accessed by pressing a button below the desired location on the analyzer. This activates the barcode reader to position itself respectively. The barcode reader traverses the front of the system along with a rigid curtain. The curtain mantains the area at the optimal temperature during analysis. Once the reader is positioned, a rack can be inserted while the barcodes are read. Positioning the reader beside the rack minimizes stray light from impacting the barcode reading. Once a rack is latched into position, the LED for the location turns green. During analysis, it turns orange and the rack is locked and non-removable. After the barcode homes itself or is positioned in another location, the appropriate reagent probe for the rack location checks the volume within each vial in the rack. Following the reagent aspiration of the vials in a rack, the LED returns to green. The reagent rack can then be removed and the reagents refilled or changed. Reagents and materials in the reagent area are aspirated using the appropriate reagent probe. The probe incorporates a sensor that recognizes the presence of liquid and stops at the optimized liquid level. During aspiration and transport, the probes heat the liquid to 37 C +/- 1 C. A Teflon tube connects the probe to a syringe pump that is capable of delivering µl. Reagent Rack Loading

16 14 Optical Read Unit (ORU) The uniquely designed ORU contributes significantly to the system throughput speed. The system has four ORUs. Each ORU accommodates one cuvette strip; thus, 16 reactions can be read simultaneously. The design of the fiber optics in the ORU allows each cuvette to be read at two wavelengths: 671 nm and 405 nm. The sophisticated software then determines which reading to utilize, based on the contents of the cuvette. Simultaneous readings allow a mix of assays to be processed within a cuvette strip, utilizing different wavelengths. This results in minimal cuvette wastage and enhances throughput. Waste Systems The used cuvettes are deposited into the cuvette waste bin (a drawer located on the right side of the analyzer), containing a disposable liner that holds up to 800 cuvette strips. The drawer is monitored for volume. The operator is alerted visually and audibly when the drawer is nearly full. The drawer can be removed and emptied at any time during operation without affecting test processing. The liquid waste collects within an internal accumulator that collects waste from the sample and reagent rinse baths. The fluid collected is periodically pumped out of the system. The fluid pumped out can be collected in an external waste container or pumped directly to a drain. The external waste container contains a level sensor. The operator is alerted visually and audibly when the container is nearly full. The operator can empty the container at any time during operation without affecting test processing. Cuvette Waste Drawer

17 15 System Rinse and Clean The right side of the analyzer holds the bottle for the system rinse and clean. The rinse is used for cleaning the probes between aspirations and is packaged in a 4 L bottle. The clean solution is an acid cleaner used to prevent carryover between reagent aspirations for particular tests. The clean is automatically aspirated and utilized, based upon the testing in process. It is packaged in a 500 ml bottle. Sensors monitor the level of liquid in the bottles. The operator is alerted visually and audibly when the containers are running low, allowing for the appropriate system actions. System Rinse and Clean

18 16 III. Main System Features The ACL TOP software was designed to compliment the Analytical Module hardware. The program operates under a MS Windows 2000 platform. The universality of MS Windows simplifies training and integration of the analyzer into the laboratory. Included in the software are several key features that separate the ACL TOP from other systems. They are described below. Reagent Management The ACL TOP provides a completely automated reagent tracking system. When the reagents are loaded on-board and the barcode is read, the system takes complete control over management of the vial. First, it performs an initial volume measurement. If the measurement increases by 30% over the previous reading, the vial is considered to be new and the onboard stability is reset. The system then counts down stability time from that point. When the stability time is approaching zero, the operator is alerted, allowing time to prepare a new vial. If the time reaches zero, an alarm is sounded and all testing of that vial is flagged with a onboard stability flag. The system provides the operator the ability to manually reset the stability time at any point. This is useful if a vial is removed from the system, refrigerated and later returned. In addition, the system will also monitor lot number expiration via the barcode. When a lot is expired, the operator is warned. In certain situations, reagent lot expirations may be extended by Instrumentation Laboratory, after testing. In this case, through the system software, the operator can extend the expiration date, thereby eliminating the warning when the reagent barcode is read. The system also allows multiple vials of the same reagent on-board to be entered. When this occurs, the vials are aspirated in a first in-first out fashion. Reagent Rack Status Display

19 17 Reagent Rack Detailed Display Calibration Calibration on the ACL TOP can be performed any time, including when the system is running patient samples or calibrations for other tests. The user has the option to set up each individual test for automatic calibration in either hourly or test-count intervals. If this option is not used, the operator can calibrate the tests as needed. The system stores the last five calibrations for each test handled in a first infirst out order. Once a calibration is complete, the system can auto-validate the curve based upon user-selectable criteria. If the auto-validation option is not used, the operator can manually validate the curve prior to use. The system allows validation of any of the available five stored calibrations. Prior to validation of any curve, the operator can view the clot curves. Calibration Curve Details Display

20 18 Quality Control (QC) The QC program on the system makes extensive use of automation and implementation of Westgard Rules. The automated functions of QC are similar to those for the calibration features, allowing QC to be performed at any time or automatically on the system at set intervals. For automatic QC, the operator can set the frequency in either hourly or test-count intervals. For both manual and automatic QC, the bar-coded QC vials can be placed on the system, eliminating the need to pour the QC material into sample cups. QC can be set-up and run for both an active lot and an alternate lot of material. The data generated for QC can be displayed in either a table or a Levey- Jennings format. The user can select to view the data for a particular date range or number of points. The QC review screen allows the operator to review data for the active and alternate lot. QC Graph Display Sample Management The powerful result database enhances the system s ease of operation. The database will hold 20,000 sample IDs. Each of these IDs can have 30 tests associated with them. The database will, therefore, maintain 600,000 results. The IDs can be entered into the database either manually or, more commonly, via the bi-directional host interface. The host interface can function either using host query or dynamic download. The host query operates without operator intervention. When a rack is introduced and the barcodes are read, the host is automatically queried for the requests. STAT samples are always given priority over routine samples onboard. STAT samples can be placed in any rack and in any position within the rack and do not need to be segregated. Even if they are mixed among routine samples, the system can track them and process them with priority. STAT PT results are available in as little as two and a half minutes. Upon completion of the results, they are available for viewing, printing or host-transmitting. The database on the system can be customized with four views by the operator, providing flexibility to laboratory staff. For example, the main database screen can be customized to meet the varying needs of each shift. Results in the database can be filtered using multiple criteria to

21 19 select specific samples or results. In addition, samples can be selected and the results recalculated to reflect calibration updates on the system. For longterm off-line result storage, the system provides the ability to export results into data files in various formats (e.g., pdf). These files can then be viewed using commonly available database programs on a separate computer system. Factor Parallelism Factor assays on the system can be processed using multiple dilutions. The dilutions are automatically prepared by the system and the results are checked for integrity and plotted against the calibration curve. If a sample is void of factor inhibitors, the sample dilution curve and the calibration curve will parallel each other. If a sample contains an inhibitor, the two curves often intersect one another. In addition to the visual representation, the ACL TOP utilizes algorithmic data checks to flag potential samples with potential inhibitors. Parallelism Display with No Inhibitor Parallelism Display with Inhibitor

22 20 Clot Curves The ACL TOP provides the ability to view clot signature curves for patients, QC and calibrations. Clot curves visually demonstrate the reaction readings that occur within a cuvette. They are a valuable aid to assess result concerns. The system will maintain the last 100,000 clot curves in its database, managed in a first in-first out fashion. Sample Result Clot Curve Auto-Validation of Results The ACL TOP is ideally suited for high-volume, hemostasis laboratories which process hundreds of samples each day. Generally, the results of these samples fall within the normal range without any system flags. The ACL TOP can be set-up to automatically validate these results. The results can then be automatically transmitted to the host system. This feature eliminates manual validation of results by an operator and decreases result turn-around time. The criteria used for auto-validation can be customized.the user selects from a list of errors and conditions for which results should not be automatically validated. In addition to routine patient sample results, auto-validation can also be set-up for factor parallelism and calibration curves. Parallel Lot Testing In the hemostasis laboratory, changes in lot numbers for controls and reagents necessitate a cross-over study in which a result comparison is run on the original and new lots. The ACL TOP facilitates this process by providing an automated system to track the original and a new lot of material for reagents and quality control liquids. The reagent alternate lot allows calibration and sample processing for result evaluation. The quality control liquids allow a new control range to be established, while the original material is processed. Once a sufficient number of control determinations have been performed, the alternate lot can be activated and thus becomes the primary lot.

23 21 Reflex Testing Reflex testing is an automated method for evaluation of an initial set of results and the triggering of additional testing, based upon evaluations of rules. The reflex-testing program on the ACL TOP provides extensive flexibility and options for setting up reflex testing. The system permits 100 reflex logic definitions. Each of these definitions can have up to ten rules, which can utilize numeric limits or error conditions. If rules are met, additional tests can be added to the sample. Since each sample can have a maximum of 30 tests, up to 29 can be added if the sample initially had one test ordered. Security The ACL TOP security program allows each laboratory to define 100 unique users for the system. Each user can then be assigned one of four access levels: Administrator, Supervisor, Senior Operator or Operator. At the Administrator level, the operator can define which level has access to each submenu on the system. When a user logs onto the system, they are required to enter a unique username and password. A user can only enter submenus if their access level is equal to or greater than the level assigned for the submenu. This flexible program allows each lab to customize the security system. Actions performed on the ACL TOP are tracked by user, and therefore, provide an audit trail for laboratory management. Log File All system modifications, warnings and errors on the ACL TOP are tracked in the system log book. This provides an automated method for the laboratory to maintain an audit trail for the analyzer and is also useful for trouble-shooting. The log book lists the date and time, user and a description for the last 10,000 entries. The log file is managed in a first in-first out fashion. When the log book file is opened on the system, the user can easily sort, using multiple sorting criteria. This makes it simple for the operator to monitor the system for a certain action or time interval.

24 22 IV. Specification Table Feature Description Test menu Clotting, chromogenic and immunological assays Continuous sample loading YES Continuous reagent loading YES Continuous operation YES Samples transport system Racks Samples on-board 120 (10 samples/rack) Reagents transport system Racks Reagents on-board 60 (44 refrigerated + 16 room temperature) Reagents barcode reader YES (integrated) Barcoded reagents YES (barcode includes lot, exp. date and vial size) Cuvettes on-board 800 Total number of materials (calibrators, QC, reagents) 1000 IL materials 500 User-programmable materials 500 Total number of applications 500 IL applications 250 User-programmable applications 250 Tests per sample 30 Profiles 100 Tests in a single profile 15 Throughput (Base model) PT tests/hour 360 (360 samples/hour) APTT tests/hour 320 (320 samples/hour) PT and APTT tests/hour 330 (165 samples/hour) Sample predilution YES Calibration curve predilution YES Stored calibrations for each test 5 Factor parallelism YES STAT capability YES (at any time in any position) Rerun testing YES (configurable) Reflex testing YES (configurable) Reflex rules 100 Criteria in each single reflex rule 10 Tests generated by each single reflex rule 29

25 23 Feature Description Quality Control program YES (with configurable multi-rules) QC results in each statistic file Unlimited Reaction curves in QC database 10,000 Displayable QC results 20,000 Results autovalidation YES Patient samples results database 20,000 samples Reportable units per test 4 Reaction curves in patient database 100,000 Results in AR database 5/test Reaction curves in AR database 5/test Results in NPP database 5/test Reaction curves in NPP database 5/test Security system YES (configurable) Operators 100 Events log system YES Messages in logbook 10,000 Bi-directional interface YES Host query function YES PC External Operating system Windows 2000 Monitor 17 color LCD touch-screen (external) Keyboard YES (external) Mouse YES (external) Printer YES (external) User interface Windows-based, powerful, easy to use Environmental conditions C (59-89 F) with a relative humidity of 5-85% (non-condensing) Electrical requirements Voltage V AC ±10% Current 5-10 A Frequency Hz Noise Emission 70 dba Dimensions (analyzer) W x D x H 151 cm x 76 cm x 73 cm Weight (analyzer) 150 Kg

26 24 V. Hemostasis Assays IL offers a broad and comprehensive panel of hemostasis assays. PT APTT Fibrinogen Thrombin Time Intrinsic Factors Extrinsic Factors D-Dimer Antithrombin Protein C Protein S Factor V Leiden (APC-R) Lupus Anticoagulant von Willebrand Factor Plasminogen Plasmin Inhibitor Heparin (UF and LMW) HS-CRP Please contact your local IL representative for information about the availability of specific products and applications on the ACL TOP, in your area.

27 VI. IL Monographs 25 A series of monographs devoted to relevant topics in the field of hemostasis are available from your local IL representative. 1. Monitoring of the Anticoagulant Therapy with Vitamin K Antagonists. F. D Agostino, G Cambiè, D. Fugazza, M. Nardella, L. Bevilacqua, A. Lombardi, L. Preda. 2. Multicentre Assessment of a New High Sensitivity Thromboplastin for Analysis of Patients Receiving Oral Anticoagulant Therapy. A. Buggiani, N. Erba, B. Morelli, M. Spagnotto. 3. Protein C Activity Measurement. Evaluation of a New Snake Venom-Activated Method (ProClot) in Comparison with a Thrombin-Activated Method. A. Tripodi, F. Franchi, P.M. Mannucci. 4. A New Thromboplastin Based Method (IL Test Protein S) for the Determination of Functional Protein S. R.G. Malia, P.C. Cooper. 5. The Anticoagulants: Protein C And Protein S. M.R. Ledford. 6. Coagulation Glossary. E. Finotto, A. Lombardi, L. Preda, G. Semprini. 7. Algorithms for Diagnosis of Disorders in Hemostasis. 8. Quality Control. Practical Applications for the Clinical Laboratory. D. Delucia. 9. APC Resistance. F. Axelsson, S. Rosén. 10. D-Dimer. J. Serra. 11. Design of a New Synthetic Phospholipid APTT Reagent: APTT-SP (liquid). M. Rose. 12. Clot Signature Curves and the ACL Futura. K. Doubleday, S. Kumnick. 13. IL Test vwf: Ag, A Diagnostic Tool for von Willebrand Disease. M. Piñol, J. Serra, E. Botta. 14. IL Test Free Protein S, A Diagnostic Tool for Protein S Deficiency. M. Sales, B. Arza, S. Rosén.

28 26 Instrumentation Laboratory - A History of Innovation IL has been at the forefront of discovery in diagnostics for over 40 years. From critical care testing sites to high-volume laboratories, you can count on IL for advanced technology and superior performance. For more information about the ACL TOP, please contact your local IL representative or visit us at ACL TOP is a trademark of Instrumentation Laboratory. Windows is a registered trademark of Microsoft Corporation. Teflon is a registered trademark of E.I. du Pont de Nemours and Company.

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30 28 Notes All rights reserved - Printed in Italy - Grafica Briantea - 07/04

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