Newsletter from All Eights

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1 Guide to Newsletter from All Eights Focus Thrombophilia in Asian Countries: Myth or Reality? First Local Paper APCR test in the investigation of thrombophilic state Application System validation & correlation protocols Announcing the Haemostasis Symposium & Workshop 2009, of June, Shangri-La Hotel, KL

2 Dear readers, Editor s messages Welcome to the second edition of the Guide to Haemostasis Newsletter from All Eights. In this issue, we are proud to cover some of the topics presented at the Stago Symposium at the 5 th Congress of the Asian Pacific Society on Thrombosis and Haemostasis, Singapore, 18 September Stago together with professionals from various countries focused on Thrombophilia in Asian Countries from introduction of Thrombophilia to comparison between Thrombophilia in Western countries versus Asian countries. They also explored the genetic risk factors for deep vein thrombosis among Japanese, hereditary thrombophilia in Korea, normal ranges and estimated deficiency prevalence of antithrombin, protein C and protein S in the general Chinese population. All Eights is also proud to publish our first local paper submitted by Dr Wan Zaidah from HUSM. We are extremely grateful for her contribution and hope to hear more from her as well as the local community. We encourage our readers to submit their experiences either in technical or clinical aspects to share to the community. If the article or paper is published, there will be a RM100 gift voucher for the contributor. In the section on application, we focus on system validation and correlation protocols. These topics are really relevant as users apply them frequently. We also take this opportunity to announce that All Eights will organize a 2009 Haemostasis Symposium & Workshop in Kuala Lumpur, under the auspices of Haemophilia Society of Malaysia and co-sponsored by Diagnostica Stago. All Eights would like to extend a very warm welcome to all accepted to attend and participate in this grand event. Due to logistics, limited seats are available. We would like to thank all individuals who have contributed to the newsletter. We look forward to continually provide you with future editions and welcome comments and input on the newsletter. Please send to: Marketing Department ALL EIGHTS (M) SDN BHD 45, Jalan TS 6/10A, Subang Industrial Park, Subang Jaya, Selangor Darul Ehsan, Malaysia. Tel: Fax: marketing@alleights.com.my Website: Best wishes, Editorial team

3 CONTENTS FOCUS Stago Symposium at the 5 th Asian-Pacific Society on Thrombosis and Haemostasis 2 Thrombophilia in Asian countries: Myth or Reality? 3 Thrombophilia in Western countries versus Asian countries 3 Hereditary Thrombophilia in Korea: What we learned from population and patients 4 Genetic risk factors for deep vein thrombosis among Japanese 4 Normal ranges and estimated deficiency prevalence of antithrombin, protein C and protein S in the general Chinese population 5 APC-R test in the inverstigation of thrombophilic state 7 APPLICATION Installation & Validation Guidelines for Coagulation Analyzers 9 The Selection Process 9 Method Validation 9 Precision 9 Linearity, Sensitivity and Reportable Range 10 Accuracy 12 System Correlation 12 Reference Range Study 12 INFORMATION UPDATES Stago User Group Meeting 2009 Haemostasis Symposium & Workshop 16 Pool Norm 18 STA-QCE International Haemostasis Proficiency Programme 19

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5 Focus 2 STAGO SYMPOSIUM AT THE 5 TH ASIAN- PACIFIC SOCIETY ON THROMBOSIS AND HAEMOSTASIS The symposium sponsored by Stago at the 5 th Congress of the Asian-Pacific Society on Thrombosis and Haemostasis held on 18 th September 2008 in Grand Copthorne Waterfront Hotel, Singapore. The symposium was chaired by Changgeng RAUN, MD, PhD from Suzhou University Medical College, Suzhou, China and Nicole SCHLEGEL from Robert Debré Hospital and Paris7-Denis Diderot University, Paris, France. The topic for this symposium was about Thrombophilia in Asian Countries: Myth or Reality? This symposium provided a great opportunity for everyone to exchange ideas and experiences in this field. Professor Changgeng RUAN opened the symposium by stating This symposium provided an advanced overview of data on genetic risk factors for VTE from large series of subjects from three countries of the Asia Pacific Area. These data should be helpful for the prevention and management of VTE patients in this large geographic area. This is followed by Doctor Nicole Schlegel s comparison of the genetic risk factors of VTE between western and eastern populations. Three other speakers presented their cases as well. Professor Yongqiang Zhao, from Peking Union Medical College Hospital, Beijing, China, presented the results of the largest prospective multicentric survey establishing the normal ranges and genetically determined deficiencies of the three major natural anticoagulants in the general Chinese population of Han origin. Assistant Professor Hee Jin Kim, from Samsung Medical Center and Sungkyunkwan University School of Medicine, Seoul, Korea, discussed the results of her research on hereditary thrombophilia in Korea, comparing VTE patients to a large cohort of healthy Korean people. Professor Toshiyuki Miyata, from the National Cardiovascular Center Research Institute, Osaka, Japan, gave his speech on the genetic risk factors for DVT among a very large series of Japanese and gives a special light on several aspects of protein S deficiency in Japan. The following pages contain brief abstracts of each topic mentioned above. Venous thromboembolism (VTE) deep vein thrombosis (DVT) and pulmonary embolism (PE) is a severe process which can be triggered by a number of factors either acquired or genetic. VTE is a major cause of mortality and morbidity in western populations but is considered to be less frequent in eastern populations. Geographic differences about the genetic risk factors of VTE have been progressively established, showing that two mutations, Factor V Leiden and G20210A mutation in Factor II gene are frequent in VTE western patients but quite absent in VTE eastern patients. By Changgeng Ruan, Nicole Schlegel

6 Focus 3 Thrombophilia in Asian countries: Myth or Reality? Thrombophilia in Western countries versus Asian countries By Nicole Schlegel, MD, PhD from Robert Debré Hospital, Paris, France Venous Thromboembolism (VTE) is a unique thrombotic process, starting by and abnormally expansive clot formation in a peripheral vein deep vein thrombosis (DVT) and leading in more severe cases to the migration of emboli towards the pulmonary artery, responsible for pulmonary embolism (PE). The risk of VTE varies in the different surgical and medical settings but the risk of death from PE is quite high. Thrombophilia is defined as a tendency to VTE, either acquired or genetic. Various risk factors for VTE have been identified. Their combined association and consequently the risk of thrombosis increase with advancing age. The sites of thrombosis may be suggestive of the origin acquired or genetic of VTE. An association of VTE with arterial thrombosis in one patient is possible. Previous studies have suggested that VTE was lower in Asians as compared to Whites / Caucasians. However recent prospective multicentric studies form large series show that VTE is not so rare in Asia, suggesting that VTE might have been underestimated in these countries. Interestingly, genetic risk factors for VTE differ in eastern and western populations. FV Leiden and G20210A mutation in FII gene are the most common genetic risk factors in western people but are quite absent in Asians. By contrast, deficiencies of the three major natural anticoagulants, antithrombin (AT), protein C (PC) and protein S (PS) seem very rare among whites as compared to Asians. However, till recently, the prevalence of such deficiencies in Asia has been estimated in small series only. New data from large series of several Asian countries will be presented during this symposium. Thrombophilia associated with AT deficiency was the first to be prescribed (Egeberg O, 1965), followed by PC and PS deficiency. The molecular basis for these deficiencies has been characterized and a number of genetic variants are known. The risk for VTE varies according to the genotype. The origin of a difference in the VTE rate and the genetic-related diversity between western and eastern populations might be explained by a genetic drift or natural selection. The phylogenic, genetic and environmental factors of these differences are discovered progressively owing to studies of populations from different geographic areas and to new sophisticated genetic tools. Acquired risk factors Old age History of VTE Immobiliz, plaster c Surgery, trauma Cancer Myeloprolif, Disorders Polycythemia vera Antiphospholipid Syndrome Hormonal treatment Central venous KT Obesity Main genetic risk factors Function loss Antithrombin (AT) deficiency Protein C (PC) deficiency Protein S (PS) deficiency Function gain Factor V mutations: Leiden Factor II mutations: G20210A Others Dysfibrinogenemia FXIII 34val Other risk factors* Hyperhomocysteinemia High levels of FVIII High levels of FIX High levels of FXI High levels of fibrinogen APC resistance in the absence of FV. Leiden High / low levels of TAFI? High levels of PC inhibitor * Possible genetic regulation

7 Focus 4 Hereditary Thrombophilia in Korea: What we learned from population and patients By Hee-Jin Kim, MD, PhD from Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Venous Thromboembolism (VTE) has long been considered to be rare in Asian countries. However, data from a couple of recent studies challenged this belief, warranting a revisit to the epidemiology of VTE and its risk factors including genetic defects leading to hereditary thrombophilia (HT), in particular, VTE and HT have, no doubt, under-recognized in Korea. From personal experience, the introduction of molecular genetic tests as a routine 2nd-line laboratory workup has greatly facilitated the accurate diagnosis of HT. on the other end, population screening revealed at least 0.72% of Korean population have HT (protein C/S [PC/PS] or antithrombin [AT] deficiency). Of note, AT deficiency was more common than PC or PS deficiency. It was also more common than PS deficiency among VTE patients; however, the mutation spectrums were strikingly different, Great efforts are needed to increase the awareness of VTE and HT in Asian countries, and this could be achieved by rigorous collection of evidences and active communication among healthcare providers and also with the general population. Genetic risk factors for deep vein thrombosis among Japanese By Toshiyuki Miyata, PhD from National Cardiovascular Center, Suita, Japan There is mounting evidence that mutations associated with a given disease arise with different frequencies among ethnic groups, thus ethnicity-specific studies are needed to identify causative mutations and properly assess risk. We evaluated the genetic contribution to venous thromboembolism (VTE) in Japanese and found that protein S mutation K1986E is a genetic risk factor. We estimated allele frequency to be 0.009, suggesting that 1 out of 12,000 Japanese may be homozygous for the E allele, thus possibly as many as 10,000 individuals. We intensively sequenced PROC, PROS1, SERPINC1, in 173 Japanese patients with VTE and found that about 30% carried nonsynonymous mutations. Mutation carriers showed early onset of VTE compared to noncarriers. Carriers should avoid environmental risk factors known to be associated with VTE.

8 Focus 5 Normal ranges and estimated deficiency prevalence of antithrombin, protein C and protein S in the general Chinese population By Y. Zhao, MD, PhD from Peking Union Medical College Hospital, Beijing, China This largest multicentric prospective survey in the healthy adult Chinese was aimed to determine the normal ranges of antithrombin (AT), protein C (PC) and protein S (PS), the prevalence of their plasma deficiency and the genetic variants healthy adult Chinese (1734 men / 1759 women) were included. Men showed higher levels of PC (p=0.03) and PS (p<0.0001) than women when adjusted to age. In women, mean PC and PS activity increased with increasing age. However, in men, mean PC activity levels increased with age up to 49 years (p<0.0001) but decreased after 50 years (p<0.0001) and mean PS activity levels significantly decreased after 50 years of age. AT activity plasma levels over time were no significant changes in women, but decreased in men and more importantly after 50 years of age. A genetic variant was found in 15 individuals: 3 in SERPINC gene (0.08%), 9 in PROC gene (0.25%), and 2 in PROS1 gene (0.057%). Among the 15 mutations, 6 were novel. The clinical relevance of statistically significant variations of the three proteins with age and gender should be further discussed in such a large series of subjects. It should be considered when evaluating the thrombotic risks or events in the Chinese population.

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10 Local Paper 7 Our deepest gratitude to Dr Wan Zaidah, HUSM, for submitting our first local paper APC-R test in the Investigation of Thrombophilic State By Dr Wan Zaidah from Hospital Universiti Sains Malaysia Activated protein C resistance (APC-R) state can be due to acquired or inherited disorders. This condition is closely associated with thrombophilic state leading to commonly venous thrombosis. Anti-phospholipid syndrome, deficiency of protein C, S and anti-thrombin are the most common causes investigated in thrombotic disorders. Haemostatic investigations for thrombophilia include protein C, protein S, antithrombin activity/antigen assays, lupus anticoagulant study and APC-R test. Thrombosis is the outcome of multiple contributing factors and hence the above mentioned factors might be compounded with other conditions such as hyperhomocysteinaemia, high factor VIII levels and etc. however, about 30-40% of cases were reported as no detectable abnormality from the routine thrombophilia investigation. APC-R test is used as a screening tool for the presence of hereditary cause of APC-R state which is commonly due to factor V Leiden (FVL) mutation. This condition has been reported to be high among Caucasian with the incidence of around 5-15% of the population. Although this condition is said to be rare in Malaysian population, FVL mutation has been reported and diagnosed among patients with venous thrombosis. A small study among 71 healthy Indians was conducted in Universiti Sains Malaysia to detect this mutation. Four individuals were found to have heterozygous state of FVL mutation in this study group. APC-R test is a reliable screening test for this mutation especially in centers where mutation analysis is not available. APC-R test is a simple and sensitive test to detect FVL mutation. It is a useful test to be included in thrombophilia study where facilities for molecular study are not available. This test can also be used as a screening method before DNA analysis. FVL mutation was reported in Malays with low prevalence. Malaysia is a multiracial country in which inter-racial marriages are common thus this gene can be transmitted to a new generation. APC-R test can be done by most coagulation analyzers. Although this test has a role to diagnose APC-R state, the interpretation of the result needs to be done carefully taking into consideration the pre-analytical factors, reagents and analyzers. This test can be done on patients taking warfarin (by using Factor V deficient plasma reagent in the test procedure) but the clotting time will be interfered in patients taking heparin or having coagulation inhibitors. Confirmatory test with DNA study is recommended for cases with positive or borderline APC-R results or when coagulation based test is not suitable to be done due to the above mentioned reasons. The significance of detecting APC-R state other than FVL mutation has not been shown clearly from the previous studies. Detection of APC-R state in a person without having clinical significance is doubtful and therefore the test is indicated only when the finding is useful for patient s management and in high risk family members. In conclusion, APC-R test is useful test in the investigation of thrombophilia and applicable to our setting as this generic risk for venous thrombosis exists in our population.

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12 Application 9 Installation & Validation Guidelines for Coagulation Analyzers The purpose of this issue is to establish guidelines for the installation and the validation of STA Coagulation analyzers. The Selection Process Issues that need to be addressed when selecting a coagulation analyzer include: Principle / Method Interference due to icteric & lipemic samples On-board quality control programs Autodilution methodology Bi-directional interface capability Reagent and sample inventory monitoring Patient and reagent barcode capabilities Stat testing capability Number of assays the analyzer is able to perform simultaneously Availability of chromogenic, clot detection and immunologic (latex immunoassay) methodologies Ease of use Ease of maintenance Rate of sample throughput Availability of cap piercing Automation availability (robotics) Reagents Selection: Note the reagent abilities to detect factor deficiencies & coagulation inhibitors. The selection of Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) reagents should be decided according to anticoagulant therapy monitoring. Finally but not least, the quality of technical support teams from the vendors should be considered. Having easy access to company personnel who are capable to perform necessary method validation procedures required by regulatory agencies is very helpful to laboratory technologists and pathologists. Method Validation The validation is determined in compliance with Clinical Laboratory Improvement Amendments of 1988 requirements for verification of precision, sensitivity, reportable range, correlation, accuracy and reference ranges. The method validation testing is standardized and applies onto PT, APTT, Fibrinogen, D-Dimer, Thrombin Time, Reptilase, Factor assays, Protein C, Protein S, Antithrombin III, Antiplasmin, Plasminogen, Heparin assay and Lupus Anticoagulant. Precision To assess the reproducibility of each assay on the instruments, 20 normal and 20 abnormal controls were assayed consecutively without interruption

13 Application 10 Analyte Intra-run Precision Inter-run Precision (QC) CV SD CV SD NL AB NL AB NL AB NL AB Prothrombin time NA NA NA NA APTT NA NA NA NA Fibrinogen NA NA NA NA D-Dimer NA NA NA NA Antithrombin III NA NA NA NA Protein C NA NA NA NA Protein S NA NA NA NA Plasminogen NA NA NA NA NA NA Antiplasmin NA NA NA NA Reptilase time NA NA NA NA Thrombin time NA NA NA NA Heparin assay NA NA NA NA vwf NA NA NA NA Extrinsic Factor NA NA NA NA Intrinsic Factor NA NA NA NA APTT: Activated Partial Thromboplastin Time; vwf: von Willebrand factor; NA: Not Available; NL: Normal; AB: abnormal Table 1: Coagulation system method validation acceptance criteria Citation from Selection and implementation for coagulation instruments/reagents in a multiple hospital/clinic network, Blood Coagulation and Fibrinolysis 2000, 11: Revised by Stago on 1/02. 4/02, 2/06, 8/06, 9/06. (intra-run precision). These controls were once again assayed over a 5-day period and randomly for four data points per day to evaluate day-today variation (inter-run precision). Intra- and inter-run precision assess the random analytical error of the system. Refer to Table 2 & Table 3, the data were analyzed by determining the mean (x), standard deviation (SD) and coefficient of variation (CV). The CV would be utilized to assess precision in all tests except the D-dimer. In this case, the SD would be utilized because it is the best indicator of precision performance. When the D-dimer is reported as less than a whole number (i.e. 0.2) the CV is no longer a useful tool because it becomes mathematically inflated CV = SD / x (100). Refer to Table 1 for the analyte acceptance criteria. Linearity, Sensitivity and Reportable Range In coagulation testing, linearity, sensitivity, and reportable range are closely related. It is required by CAP that each laboratory assesses and validates the linearity of all assays that it intends to perform. Based upon linearity and sensitivity studies, the reportable range of an analyte is determined. Westgard defines linearity, sensitivity, and reportable range as follows: Linearity: The measure of the degree to which a curve approximates a straight line. The linearity of a system is measured by testing levels of an analyte that are known relative to each other. Sensitivity: Minimal limit of quantification. The functional sensitivity is used to refer to an estimate of the detection limit that is calculated from replicate measurements of lowconcentration patient samples.

14 Application 11 Table 2: Intra-run precision using normal pool plasma Reagent STA-Neo Cl Plus STA-PTT A STA-Fib 2 Table 3: Inter-run precision using normal pool plasma Reagent STA-Neo Cl Plus STA-PTT A STA-Fib 2 No PT (sec) APTT (sec) Fib (g/l) No PT (sec) APTT (sec) Fib (g/l) N: N: Mean: Mean: SD: SD: CV (%): CV (%): Table 2 and Table 3: Example data for both Intra-run and Inter-run precision using normal pool plasma

15 Application 12 Reportable range: The range of concentration of the substance in the specimen for which method performance is reliable and test results can be reported (the lowest and highest test results that are reliable and can be reported). Linearity in this validation process was assessed within the context of the assay s standard curve. The evaluation was based upon the correlation coefficient (r) and the standard curve point values versus the recovered values as translated from the actual curve. The r-value must have been greater than and the recovered values must have been within 10% of the standard values. Once the linearity of an assay was validated within the standard curve, the reportable range was determined by setting up automatic re-dilution conditions at the highest standard curve point and at the lowest standard curve point. The redilute conditions would have higher dilutions for values that exceed the highest point on the curve; likewise, lower dilutions would be for values that are lower than the lowest point of the curve. This lowest point the curve was also used to define the sensitivity of the assay. Accuracy The accuracy of an assay may be defined as the closeness of the agreement between the result of a measurement and a true value of the measurement. Accuracy was evaluated by method comparison between the existing instrument/reagent system and the new instrument/reagent system. The selection of samples was important to the method comparison. The percentage of recovery is calculated by using mean of new system compare to existing system (the target value). System correlation The purpose of this procedure is to ensure the most homogeneous possible distribution of values between the two analyzers i.e. existing unit and the newly installed unit. At least 30 specimens are collected for the measurement. The collected specimens should span the entire physiological range, which consisted of normal specimens, low, mid and high range specimens as well. By using same lot number of reagents and prepared freshly, the specimens should be run on both analyzers within 2 hours. The existing instrument is plotted on the x-axis whereas the new instrument is plotted on the y-axis. The R value, slope & intercept % were analysed for comparison. The results were analyzed by linear regression. Comparison between identical instrument and reagent systems is shown in Table 4. Reference Range Study The purpose of this procedure is to establish laboratory s own expected reference range. Reference range varies from one laboratory to another laboratory, depending on reagents, instrument and method in use. At minimum of 20 healthy donors are collected. A greater number of donors increase the reliability of reference interval. The donors could not be on medication, such as Coumadin, heparin, antibiotics, birth control or estrogen-containing drugs, and could not have any known immunological conditions. A group of donors should represent a wide span of ages, ethnic groups and gender. Samples to be tested are collected fresh and tested for each parameter tested. The study can be carried out over a period of several days to minimize day-to-day variations. The results were analyzed for their distribution with the Gaussian Law. Mean (x) and standard deviation (SD) were calculated to determine the reference range. Reference range is the range of mean +/- 2SD.

16 Application 13 Analyte System Correlations R value Slope Mean Bias (%) from Average* Prothrombin time ± 5 INR ± 10 APTT ± 8 Fibrinogen ± 10 D-Dimer ± 20 Antithrombin ± 15 Antiplasmin ± 15 Extrinsic Factors ± 15 Instrinsic Factors ± 15 Heparin assay ± 15 Plasminogen ± 15 Protein C ± 15 Protein S ± 15 Reptilase time ± 8 Thrombin time ± 8 vwf ± 15 * The Mean Bias (Mean Difference) % is calculated using the following formula: (Mean of Raw Differences/Mean of Averages) x 100 Table 4: Comparison between Identical Instrument and Reagent Systems Citation from Selection and implementation for coagulation instruments/reagents in a multiple hospital/clinic network, Blood Coagulation and Fibrinolysis 2000, 11: Revised by Stago on 1/02. 4/02, 5/02, 6/02, 4/03, 1/05, 2/06, 8/06.

17 Application 14 Table 5: Example data for Correlation of APTT between Existing Instrument and New Instrument No ID Existing Instrument New Instrument 1 A A B A B B B B B A A B B B B A B A B B B A A A B A B B B A New Instrument Correlation of APTT between Existing Instrument and New Instrument y = x R² = R= Existing Instrument

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19 Information Updates 16 Haemostasis Symposium & Workshop 2009 Under the auspices of Hemophilia Society of Malaysia, All Eights (M) Sdn Bhd in conjunction with Diagnostica Stago will be organizing a Haemostasis Symposium & Workshop 2009 on 24 th 25 th of June which falls on Wednesday and Thursday. This event will be held at the Shangri-La Hotel, Kuala Lumpur. We cordially invite our Stago users / customers to join our user group meeting and enjoy the event. The theme for this event will focused on Paediatric Haemostasis and Accreditation & Quality Assurance. Overseas speakers as well as local haematologists will be presenting and lecturing at this symposium. The workshop on accreditation and quality assurance will be on the second day. This is a great opportunity for you to expand your knowledge and further your experience in this field. Please grace us with your presence and do not forget to bring your laptop along for the data interpretation during the workshop. We look forward to seeing you there. Regards, Organizing committee DATE: JUNE 2009 VENUE: SHANGRI-LA HOTEL, KUALA LUMPUR International buffet Free WiFi Free shuttle service to famous landmarks in KL

20 Information Updates Registration 24 JUNE 2009, WEDNESDAY Sarawak Room Welcome & opening address Topic and speaker to be advised Thrombosis and Thrombophilia in Children Dr Nicole Schlegel, Robert Debré Hospital, France Tea break Haemostasis in Neonates Dr Jameela Sathar, Ampang Hospital, Malaysia Establishing Paediatric Reference Range Dr Vera Ignjatovic, Royal Children s Hospital, Australia Lunch Acquired and Inherited Platelet Disorders in Children Dr Nicole Schlegel, Robert Debré Hospital, France Heparin Therapy In Children Dr Vera Ignjatovic, Royal Children s Hospital, Australia Tea Break Outpatient management of anticoagulant therapy. Heparin and Warfarin monitoring. Dr Patricia Roger, Diagnostica Stago, France Customer feedback forum with All Eights and Stago 25 JUNE 2009, THURSDAY Sabah Room ISO Dr Jamilah Bt Baharom, Penang Hospital, Malaysia Lupus Anticoagulant Diagnosis. Pool Norm: A new helpful tool Dr Patricia Roger, Diagnostica Stago, France Role of IQC and EQA in laboratory performance Dr Patricia Roger, Diagnostica Stago, France Topic and speaker to be advised Tea break Workshop: ISI Verification Discussion & Result Interpretation Prof Madya Dr Leong Chooi Fun, Hospital University Kebangsaan Malaysia Dr Wan Zaidah Bt Abdullah, Hospital University Sains Malaysia Workshop: APTT Sensitivity to Heparin Prof Madya Dr Leong Chooi Fun, Hospital University Kebangsaan Malaysia Dr Wan Zaidah Bt Abdullah, Hospital University Sains Malaysia Lunch Workshop: APTT Sensitivity to Heparin -Discussion & Results Interpretation Prof Madya Dr Leong Chooi Fun, Hospital University Kebangsaan Malaysia Dr Wan Zaidah Bt Abdullah, Hospital University Sains Malaysia APTT Sensitivity to Factors - Discussion & Results Interpretation Prof Madya Dr Leong Chooi Fun, Hospital University Kebangsaan Malaysia Dr Wan Zaidah Bt Abdullah, Hospital University Sains Malaysia Tea Break Discussion & Conclusion of Workshop

21 Information Updates 18 Pool Norm For safe clinical direction (Cat No ) Normal human plasma pool perfectly suited for the screening of Lupus Anticoagulants (LA) For the mixing study (1:1 mixture of patient and reference plasma) Reliable differentiation between a coagulation factor deficiency and the presence of a LA For the normalized ratio calculation Reference plasma for STA -Staclot DRVV Screen and STA -Staclot DRVV Confirm EASY TO USE SAFE o Suitable to all laboratories, regardless of their level of activity o Biological security: Pool Norm made from human plasma which tested negative for HIV, HCV and Hepatitis B o Analytical security: Specifications adapted to its use in LA screening, clinical validations with all Stago reagents for LA evaluation and factor deficiencies Pool containing a minimum of 20 normal human plasmas, rigorously selected, based on a complete haemostasis workup REPRODUCIBILITY o Strict plasma selection that guaranties reproducibility batch to batch VALIDATED o To be used with various cephalins: PTT-LA / STA -PTT Automate, STA -Cephascreen / STA -C.K. Prest o To be used for DRVV testing with STA -Staclot DRVV Screen / STA -Staclot DRVV Confirm Ordering Information: Cat No. Description Packing Pool Norm 12 vials Contact Mr Eric Teo ( )

22 Information Updates 19 INTERNATIONAL HAEMOSTASIS PROFICIENCY PROGRAMME EXTERNAL QUALITY ASSESSMENT (EQA) Assesses the performance of laboratory testing systems Complements the internal Quality Control Ensures harmonization of results and comparability between laboratories Identifies possible deficiencies in laboratory practice Increase results confidence and patient safety Helps to answer to regulatory requirements Collects information for laboratory accreditation purposes For all STA-Compact / STA-Compact CT User STA -QCE is an International Program for Stago Systems. STA - QCE has provided you with international haemostasis external quality assessment programs since It has more than 1,500 participants worldwide in over 50 countries. Stago supplies twice a year with 2 levels of STA -QCE. It includes routine and speciality tests: PT, APTT, Fibrinogen, Factors, AT, Protein C, Protein S, D-Dimer, vwf, Heparins. Ref. Designation Content Packaging STA -QCE 1&2 (May) STA -QCE 3&4 (November) 3 vials of STA -QCE 1 6 x 1 ml 3 vials of STA -QCE 2 6 x 1 ml 3 vials of STA -QCE 3 6 x 1 ml 3 vials of STA -QCE 4 6 x 1 ml For this season, STA -QCE & 2 is available from now. To those who wish to join this cycle, please do not hesitate to contact Ms. Yunnie Tan at this number QCE website for submission and view reports or Clear Reports A report with the complete results: We analyze the results test by test and we give the statistical distribution of the results A customized form with the name of the laboratory, the instrument used, and three tables A Youden Plot graph for each test performed by the laboratory Laboratory results Recap which summarizes the results of the last 5 participations of the laboratory

23 Contribution 20 Are you interested to contribute in this newsletter publication? If you have any technical or clinical experience in this field that you wish to share with everybody, please do not hesitate to contact us directly. As a token for your contribution, we would like to award the contributor with RM100 gift voucher on publication. Any comment or input, please send to: Marketing Department ALL EIGHTS (M) SDN BHD 45, Jalan TS 6/10A, Subang Industrial Park, Subang Jaya, Selangor Darul Ehsan, Malaysia. Tel: Fax: marketing@alleights.com.my Website:

24 Poster available from All Eights ALL EIGHTS (M) SDN BHD 45, Jalan TS 6/10A, Subang Industrial Park, Subang Jaya, Selangor Darul Ehsan, Malaysia. Tel: (603) Fax: (603) Website: ALL EIGHTS (S) PTE LTD 6, Harper Road, #03-02 &#06-07 Leong Huat Building, Singapore Tel: (65) Fax: (65) Website: