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The article discusses the challenges posed by lipemic samples in diagnostic laboratories due to lipid interference in spectrophotometric methods. The study examines the use of high-speed centrifugation to mitigate this interference in anti-Xa activity measurement for patients on anticoagulants. Results show that high-speed centrifugation did not significantly impact anti-Xa activity measurement and was effective in overcoming lipemia for unfractioned heparin and low molecular weight heparin. The study suggests that high-speed centrifugation is a simple and effective method to address lipemia interference in laboratory measurements. [Extracted from the article]

Introduction: This observational study conducted across seven emergency care units compares the efficacy of four D‐dimer detection methods, namely HemosIL D‐dimer HS (HS), HemosIL D‐dimer HS‐500 (HS‐500), VIDAS D‐dimer (VIDAS), and HemosIL AcuStar D‐dimer (ACUSTAR). The primary focus is on patients with a clinical suspicion of deep venous thrombosis (DVT) or pulmonary embolism (PE). Methods: A total of 149 samples were collected from patients with suspected DVT or PE. The confirmation of DVT/PE was based on calf ultrasound or computed tomography‐Angiography. Direct comparisons were made between the different detection methods, considering both their analytical performance and clinical utility. Additionally, the impact of an age‐adjusted cut‐off on the diagnostic accuracy of each method was assessed. Results: The results revealed comparable negative predictive value, sensitivity, and specificity across the methods, with a notable exception of increased specificity for HS compared with HS‐500 (50.8% vs. 41.5%, p = 0.03). Further analysis incorporating an age‐adjusted cut‐off demonstrated a significant improvement in specificity for HS. When using the age‐adjusted cut‐off, HS exhibited a substantial increase in specificity compared with HS‐500 (63.1% vs. 49.2%, p = 0.004) and demonstrated significantly higher specificity compared with VIDAS (63.1% vs. 53.8%, p = 0.04). Conclusion: The study emphasizes the nonuniversal effect of an age‐adjusted cut‐off and discusses the potential necessity for different cut‐off values, particularly in the case of HS‐500. These findings contribute to the understanding of D‐dimer detection methods in the context of DVT and PE, providing insights into their relative performances and the potential optimization through age‐adjusted cut‐offs. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to evaluate the effectiveness and reliability of the utilization for clinical reporting of the evaluation of digital images of bone marrow aspirates by morphologists and their comparability with the classic microscopic morphological evaluation. Methods: We scanned 180 consecutive bone marrow needle aspirates smears using the "Metafer4 VSlide" whole slide imaging (WSI) digital scanning system. We evaluated the statistical comparability and the risk of bias of the microscopic readings with those performed on the screen on the digitized medullary images. Results: The evaluation of cellularity on the screen was equivalent, with a higher frequency of "normal" than the analysis of digital preparations. The means and medians of the percentage values obtained on the different cell populations with the microscopic and digital reading were comparable as the main categories are concerned, with an average difference equal to 0 for the neutrophilic and eosinophilic granulocytic series, at −0.2% for the total myeloid cells, at 1.2% for the erythroid series, at −0.4% for the lymphocytes and at −0.4% for the blasts. Dysplastic features were consistently identified in 69/71 cell lineages. Conclusion: Our study demonstrated that screen evaluation of digitized bone marrow needle aspirates provides quantitative and qualitative results comparable to traditional microscopic analysis of the corresponding slide smears. Digital images offer significant benefits in reducing the workload of experienced operators, reproducibility and sharing of observations, and image preservation. Even in routine diagnostic activities, their use does not alter the quality of the results obtained in evaluating bone marrow needle aspirates. [ABSTRACT FROM AUTHOR]

Introduction: Recombinant porcine FVIII (rpFVIII) (Obizur, Susoctcog‐alfa, Takeda, Japan) is licensed for the treatment of bleeding in acquired Haemophilia A (AHA). The summary of product characteristics state that monitoring should be by one stage assay (OSA) rather than chromogenic assay (CSA). CSA have been shown to underestimate activity when rpFVIII is added to plasma in vitro. Methods: Samples from three AHA patients (n = 21) (pre‐ and post rpFVIII) were assessed using FVIII:C assays; OSA methods: Actin, Actin FS, Actin FSL and Pathromtin SL performed on CS5100i (Sysmex, Kobe, Japan); APTT‐SP, SynthASil and SynthAFax performed on ACL TOP (Werfen, Barcelona, Spain). CSA methods on CS5100i: Siemens Chromogenic Assay, Biophen FVIII:C, Technochrom FVIII:C; on ACL TOP: Rox Factor VIII, Coamatic Factor VIII and CRYOcheck Factor VIII. Results: OSA and CSA varied according to reagent used median OSA 61 IU/dL (range 41.5–81 IU/dL (ANOVA p < 0.0001)) median CSA 46.5 IU/dL (range of method specific medians 36.5–84 IU/dL (ANOVA p < 0.0001)). Amongst OSA, Actin FS was associated with the highest FVIII:C, APTT‐SP was associated with the lowest. Variation in CSA results by different methods was also seen with highest FVIII:C levels obtained using the Technochrom FVIII:C and the lowest levels obtained with Siemens Assay. Conclusion: The relationship between OSA and CSA was not consistent between method or patient. Previously there has been reports of underestimation by CSA in in vitro spiked samples. Investigation into concentration of phospholipids in the APTT reagents may explain some of these variations. [ABSTRACT FROM AUTHOR]

Introduction: This study investigates the potential contribution of structural and dispersion parameters, as well as alarms provided by Sysmex XN9000 haematology analyzer. The objective was to assess the need for a microscopic examination in the context of lymphocytosis. It also aims to contribute in differentiating rapidly lymphoproliferative disorders such as chronic lymphocytic leukaemia (CLL), non‐chronic lymphocytic leukaemia (NON‐CLL) and non‐infectious reactive lymphocytosis (REAC). Methods: We prospectively assessed lymphocyte parameters (Ly‐X, Ly‐Y, Ly‐Z, Ly‐WX, Ly‐WY, Ly‐WZ) provided by the Sysmex XN9000 analyzer; they were measured in the white blood cell differential (WDF) channel which also provides alarms via the precursor/pathological cellular channel (WPC). Blood samples from 71 subjects with CLL, NON‐CLL lymphoproliferative and REAC non‐infectious reactive lymphocytosis, as well as a control (NORM) group of 12 subjects without any abnormalities were analyzed. Results: The most discriminating parameters to distinguish the different groups were Ly‐X, Ly‐Z and Ly‐WZ. The lymphoid structural parameters Ly‐X and Ly‐Z significantly discriminated the CLL group from the other groups (p < 0.001), and the CLL group from the REAC group (p < 0.01), respectively. The Ly‐WZ parameter discriminated the CLL group from the NON‐CLL, REAC (p < 0.001) and NORM (p < 0.01) groups. Alarms were higher in all study groups compared to the NORM group. An algorithm integrating these structural and alarm parameters is proposed. Conclusion: This study demonstrated that Ly‐X, Ly‐Z, and Ly‐WZ lymphocyte parameters are useful for detecting morphological changes in lymphocytes; they provide useful information for the differential diagnosis of lymphocytosis, and this before the examination of the blood smear. An algorithm combining the WDF (parameters) and the WPC (alarms) makes it possible to decide whether or not to use a microscopic examination or flow cytometry immunophenotyping. [ABSTRACT FROM AUTHOR]

United States Food and Drug Administration (FDA)‐approved viscoelastic testing (VET) methodologies have significantly changed in the last 10 years, with the availability of cartridge‐based VET. Some of these cartridge‐based methodologies use harmonic resonance‐based clot detection. While VET has always allowed for the evaluation of real‐time clot formation, cartridge‐based VET provides increased ease of use as well as greater portability and robustness of results in out‐of‐laboratory environments. Here we review the use of VET in a variety of clinical contexts, including cardiac surgery, trauma, liver transplant, obstetrics, and hypercoagulable states such as COVID‐19. As of now, high quality randomized trial evidence for new generation VET (TEG 6s, HemoSonics Quantra, ROTEM sigma) is limited. Nevertheless, the use of VET‐guided transfusion algorithms appears to result in reduced blood usage without worsening of patient outcomes. Future work comparing the new generation VET instruments and continuing to validate clinically important cut‐offs will help move the field of point‐of‐care coagulation monitoring forward and increase the quality of transfusion management in bleeding patients. [ABSTRACT FROM AUTHOR]

Introduction: Non‐parallelism in factor assays can lead to incorrect factor activities. Parallelism can be assessed by calculating the coefficient of variation (CV) of results obtained on 3 dilutions of the same sample. Some authors have proposed that if there is <15% then the average activity is reportable. Some analysers use a slope ratio (SR) to calculate parallelism, with an acceptance range of approximately 0.9–1.1. Methods: We evaluated CV and SR in one stage FII–FXII assays on Sysmex CS5100i using Innovin or Actin FS. Frozen normal and pathological plasmas, plasmas containing Direct Oral Anticoagulants, Direct Thrombin Inhibitors or Lupus Anticoagulant were analysed to assess possible non‐parallelism. Results: In plasmas with factor levels >25 IU/dl (plus no interfering substances) all CVs were < 15%. One sample (low factor activities 10–15 IU/dl), had CVs > 15% in FII, FVII and FXII assays only. SR outside of 0.9–1.1 were seen in FII and FXII assays at different levels of clotting factor including some within the normal range. Non‐parallelism was detected more frequently with SR than CV for those with interfering substances. Conclusions: SR outside of 0.9–1.1 were seen in different levels of clotting factors, including samples which did not contain interfering substances. The target of 15% CV was a better discriminator than a SR for acceptance. When factor levels were reduced to around 10–15 IU/dl, a target 20 %CV was more appropriate than 15%. It might be appropriate for laboratories to assess locally whether their acceptance criteria need to be wider at low levels of clotting factors. [ABSTRACT FROM AUTHOR]

Introduction: The Yumizen H2500 (YH2500) cell analyser was compared to the Pentra DX Nexus (both from HORIBA Medical) to evaluate the efficiency of the new YH2500 technology for the WBC‐differential in samples from oncology patients with WBC‐diff abnormalities. Material and Methods: The 220 samples with slide review criteria on the Nexus were systematically analysed on the YH2500. The WBC‐diff was compared to flow cytometry (FCM). The 100 additional samples with Monocyte/Neutrophil separation flags were evaluated. The flagging performance and the accuracy of the WBC‐diff were analysed. Results: The YH2500 generated fewer flags than the Nexus (47.73% vs 66.64%; p <.0001), except for Monocyte/Neutrophil flag (15.5% vs. 2.7%; p < 0.0001). Overall performances were higher on the YH2500 (Sensitivity, 100 vs. 89.6%; Specificity 81.0% vs. 50.9%; PPV, 74.3% vs. 62.9%; NPV, 100% vs. 69.5%; Efficiency, 87.7% vs. 69.5%). YH2500 showed a statistically significant better correlation with FCM for the 6‐part differential than the Nexus. On 134 samples with Monocyte/Neutrophil separation flag, it was shown that, in samples with less than 10% monocytes on the YH2500, the results of monocyte and neutrophil counts were comparable to the manual count, and that these samples did not need a slide review if no other main criterion for review was present. Conclusion: The YH2500 demonstrated better performance characteristics than the previous cell counter, the Nexus. Its implementation in our laboratory routine work significantly improved the practice workflow, decreased the number of manual cell counts and increased the pertinence of slide review and reporting of the microscopic count. [ABSTRACT FROM AUTHOR]

Background: Statistical analyses are embedded as critical functions in the routine haematology laboratory. Aim: This educational article is aimed at providing an overview of these topics and practical application examples. Materials, Methods, and Results: Topics covered include mathematical conversion between units, maintaining a quality control (QC) system, statistical methods for reagent validation, and determining uncertainty of measurement (UoM). Discussion: Additional considerations may be required when a regional laboratory program is in place, such as the harmonization of INR results and determination of therapeutic reference intervals for unfractionated heparin therapy. Conclusion: The coauthors of this manuscript are fortunate to be part of regional network of hospital laboratories, the Eastern Ontario Regional Laboratory Association (EORLA). [ABSTRACT FROM AUTHOR]

Introduction: Thrombin generation assays assess overall coagulation system and are widely used in research; however, they still need standardization and clinical validation. The new ST Genesia is a benchtop, automated analyzer that normalizes each thrombin generation parameter using a reference plasma. The ThromboScreen reagent kit has two triggers, one of which contains thrombomodulin to assess the effect of the protein C pathway. This study aimed to make a pilot approach to the ThromboScreen reference range in children and evaluate the impact of sex, age, and pro‐ and anticoagulant plasma proteins on thrombin generation parameters. Methods: This study included 55 healthy children from the following age groups: 1‐6 years (n = 14), 7‐11 years (n = 15), and 12‐17 years (n = 26). Children younger than 1 year were excluded from the study. We measured thrombin generation using ThromboScreen, coagulation routine and test, pro‐ and anticoagulant proteins. Results: Age did not influence ThromboScreen results. Males showed significantly lower endogenous thrombin potential and peak height values than females. The strongest determinants of endogenous thrombin potential were von Willebrand factor parameters, whereas for endogenous thrombin potential inhibition, the strongest determinants were protein C and protein S. No statistically significant differences were found between groups on temporal parameters. Conclusions: For the ThromboScreen reagent kit, it may not be necessary to subdivide reference ranges according to age for children (>1 year). [ABSTRACT FROM AUTHOR]

Background: The antithrombotic effect of direct oral anticoagulants (DOAC) in specific clinical scenarios is difficult to assess. Objective: This study aimed to evaluate the effect of DOAC on thrombin generation (TG) in relation to their plasma level. Methods: Eighty patients newly started on anticoagulation were included, 20 patients for each DOAC—apixaban, edoxaban, rivaroxaban, and dabigatran. Plasma was sampled before DOAC (baseline), at plasma peak time, 6 and 12 hours after starting DOAC for quantification of drug levels and TG. Results: The baseline TG before DOAC intake showed inter‐individual variability. All DOACs significantly prolonged lag time (LT) and time to peak (TTP), but did not change endogenous thrombin potential (ETP). Anti‐Xa inhibitors but not dabigatran reduced thrombin peak, but the effect of apixaban at plasma peak was less pronounced (factor 1.6). LT and TTP prolongation of dabigatran was lower compared to anti‐Xa inhibitors. All DOACs showed a nonlinear dose‐response relationship, with the greatest antithrombotic effect at lower DOAC plasma levels. The inhibition of TG parameters between baseline and peak was parallel between individual patients but the coefficient of variation of TG was lower compared to drug levels. Conclusion: The antithrombotic effect at DOAC peak plasma level measured by TG depends on the patient‐specific baseline TG level and the drug‐specific inhibition by the particular DOAC. Although peak plasma levels have a high variability, the variation of TG is lower compared to drug levels. Therefore, TG assays may be superior to plasma levels in the assessment of the intensity of anticoagulation. [ABSTRACT FROM AUTHOR]

The article presents case of early detection of Candida parapsilosis sepsis in peripheral blood as a result of cytografic changes on the Sysmex XN-3000 hematology analyzer. It mentions diagnostic support tools such as microscopic blood smear reviews (MBSR) and cytographic changes caused by yeasts in the counting channels of the automated hematology analyzers; and also mentions spurious automated counts are observed along with abnormal leukocyte scatter plots.

There are many preanalytical variables (PAV) that are known to affect coagulation testing. The more commonly acknowledged PAV addressed by the clinical laboratory tend to start with their influence on blood collection, but realistically coagulation PAV starts with the patient, where the laboratory has less influence or control. Patient selection and appropriate timing for blood collection may be integral for assuring proper diagnosis and management. Laboratory control and assurance for ideal phlebotomy practice would mitigate most PAVs related to blood collection to minimize suboptimal sample collection. Laboratory oversight of sample transportation, processing and storage will assure sample integrity until testing can be facilitated. The purpose of this document is to review common PAV that should be taken into consideration when ordering, performing and interpreting a coagulation test result, with additional attention to the effect of direct oral anticoagulants (DOACs). [ABSTRACT FROM AUTHOR]

Heparin- induced thrombocytopenia (HIT) is a prothrombotic condition resulting from pathogenic antibodies to complexes of heparin and platelet factor 4 (PF4). The diagnosis of HIT can be challenging due to the widespread use of heparin and the frequency of thrombocytopenia in hospitalized patients. Laboratory testing for HIT typically includes an immunoassay to detect antibodies to PF4- heparin and a functional assay. Current HIT diagnostic algorithms recommend using the 4Ts score to determine the need for HIT laboratory testing. Automated calculation of HIT clinical prediction scores in the electronic health record may improve the identification of patients who should undergo HIT testing. Another challenge in the management of patients with suspected HIT is the turnaround time of the laboratory testing needed to confirm the diagnosis. Due to the high daily thrombotic risk of HIT, clinicians must treat patients with intermediate to high pretest likelihood of HIT empirically while awaiting the test results. Treatment for HIT often involves alternative anticoagulants that lack reversal agents, which may increase bleeding risk, prolong hospital stays, and increase costs for patients suspected of having HIT. Rapid immunoassays hold promise to improve the speed of HIT diagnosis. These assays must retain a very high sensitivity for this “can't miss” diagnosis, yet have sufficient specificity to be of diagnostic value. A Bayesian approach has been proposed using two rapid immunoassays in succession, which decreased analytic turnaround time to 60 minutes. Such an approach has the potential to be a much- needed clinical advance in improving accuracy and speed in the diagnosis of HIT. [ABSTRACT FROM AUTHOR]

Anemia is a global health problem in all age groups. According to World Health Organization (WHO), approximately 40% of pregnant women are anemic. Iron deficiency anemia (IDA) due to nutritional deficiency is the most common cause. The incidence of IDA varies worldwide depending on the socioeconomic status, but it remains the leading cause even in developed countries. Physiologic anemia of pregnancy due to relatively higher expansion of blood volume in comparison with elevated red blood cell mass also occurs frequently. Complete blood count (CBC) in the first trimester is recommended for all pregnant women to screen for anemia. The screening of pregnant women for IDA in absence of anemia is still debatable. If IDA is suspected, ferritin level of <30 ng/ml is diagnostic. Iron supplementation is recommended for all pregnant women to compensate the increased demand. [ABSTRACT FROM AUTHOR]

Introduction: Examination of a blood film is the second most common hematology test, after the complete blood count. Interpretation of a peripheral blood film by trained laboratory professionals provides valuable diagnostic information. The Institute for Quality Management in Healthcare (IQMH) Hematology Scientific Committee developed a questionnaire to gather information regarding current practices for manual blood film review and reporting from laboratories participating in IQMH Morphology proficiency testing (PT) surveys. Methods: An online survey was distributed to 174 laboratories, 97% submitted results. Results: Of the respondents, the majority (82%) indicated affiliation with small‐ or medium‐sized hospitals (<500 beds). 80% of respondents had core laboratory technologists performing manual blood film reviews, while only 2% utilized dedicated hematology technologists with morphology expertise. All respondents had a policy for manual blood film review by a technologist, 70% did not have blood films reviewed by a senior/charge technologist prior to review by a physician. The majority (88%) of participants included morphological findings in their critical result list; of these, 98% include malaria and 88% include the first‐time finding of blasts as critical results. 59% of participants indicated that they have a procedure in place to ensure that interpretation and confirmation of first‐time potentially significant morphological findings are available from a physician at all times. Conclusion: This survey identified significant variation in blood film review and reporting practices across participating laboratories. The IQMH Hematology Scientific Committee will develop best practice recommendations to guide and standardize practice. [ABSTRACT FROM AUTHOR]

Introduction: In daily practice in haematology laboratories, red blood cell (RBC) abnormalities are frequent and their management is a real challenge. The aim of this study is to establish a "decision tree" using RBC and reticulocyte parameters from the SYSMEX XN‐10 analyser to distinguish between patients with a hereditary RBC disease from iron deficiency anaemia and other patients. Methods: We analysed results of complete RBC counts in a cohort composed of 8217 adults divided into 5 different groups: iron deficiency anaemia (n = 120), heterozygous haemoglobinopathy (n = 92), sickle cell disease syndrome (n = 56), hereditary spherocytosis (n = 18) and other patients (n = 7931). A Classification And Regression Tree (CART) analysis was used to obtain a two‐step decision tree in order to predict these previous groups. Results: Five parameters and the calculated RBC score were selected by the CART method: mean corpuscular haemoglobin concentration, percentage of microcytes, distribution width of the RBC histogram, percentage of nucleated red blood cells, immature reticulocytes fraction and finally RBC Score. When applying the tree and recommended flowchart, 158/166 of the RBC hereditary disease patients and 114/120 iron deficiency anaemia patients are detected. Overall, the correct classification rate reached 99.4%. Sensitivity and specificity for RBC disease detection were 95.2% and 99.9%, respectively. These results were confirmed in an independent validation cohort. Conclusion: Based on the XN‐10 RBC and reticulocyte parameters, we propose a two‐step decision tree delivering a good prediction and classification of hereditary RBC diseases. These results can be used to optimize additional reticulocyte analysis and microscopy review. [ABSTRACT FROM AUTHOR]

Background: The CN‐6000 (Sysmex Corp.) is a new haemostasis analyser with blood coagulation, amidolytic, immuno‐turbidometric and light transmission aggregometry (LTA) capabilities. Transmitted light is monitored at multiple wavelengths (340, 405, 575, 660, 800 nm), from an LED light source. Aims: To evaluate the performance of the CN‐6000 against a predicate device. Methods: The CN‐6000 was evaluated against the CS‐5100 (Sysmex) for 14 different tests, using 880 samples from normal subjects, anticoagulated patients, critically ill patients, plasmas with high or low fibrinogen content or abnormal levels of interfering substances. Between‐day assay imprecision was assessed using commercial QC materials (n = 10 replicates on each of 5 days). Results: Acceptable levels of imprecision were obtained for all assays. Agreement between the two analysers was excellent for all assays. Throughput was 35% higher using the CN‐6000 (337 vs 250 tests per hour for PT, aPTT and fibrinogen). The CN‐6000 also demonstrated improved clot detection in plasmas with high levels of interfering substances as demonstrated by a 29% reduction in "vote‐outs" due to low light transmission (24 vs 34). Conclusions: The CN‐6000 demonstrated excellent comparability with the predicate instrument and acceptable levels of imprecision in all assays. Improvements in throughput and clot detection in the presence of interfering substances were also shown. [ABSTRACT FROM AUTHOR]

Introduction: Plasma samples with gross lipaemia present a challenge for coagulation laboratories using optical analysers. High‐speed centrifugation may be used to remove excess lipids but it has not established whether this affects haemostasis tests. The aims were to determine whether the removal of lipid by centrifugation affects PT, APTT, fibrinogen, D‐dimer and von Willebrand factor activity measurements. Methods: Twenty‐six lipaemic samples (median [range]): triglyceride 4.6 mmol/L [0.5‐17.0]; cholesterol: 4.06 mmol/L [2.20‐9.41] and 20 plasmas spiked with Intralipid 20 or lipid isolated from patient plasmas (median triglyceride of 11.95 mmol/L [5.0‐17.0] and cholesterol 4.33 [3.22‐7.06]), were tested before and after the removal of the lipid layer by centrifugation (10000 g for 10 minutes). Tests were performed using the CS‐5100 (Sysmex) coagulation analyser. Results: Thirteen, 9, 3 and 1 of the lipaemic or spiked samples failed to give PT, APTT, fibrinogen and D‐dimer results, respectively. Centrifugation significantly reduced triglyceride (median 2.7, [0‐6.1 mmol/L]) and cholesterol (median 0.52 [0‐3.5]), allowing clot detection in all tests. There were no statistically significant differences in fibrinogen, D‐dimer or VWF levels in samples before and after lipid removal. A small but clinically insignificant change in PT and APTT was observed after lipid removal. Conclusion: High‐speed centrifugation reduces lipaemia sufficiently to allow testing on an optical coagulation analyser without introducing clinically significant differences PT, APTT, fibrinogen, D‐dimer or VWF activity values. [ABSTRACT FROM AUTHOR]

The article explores A 76 year-old woman with diabetes mellitus and stage IV breast carcinoma (diagnosed in 2012) was admitted to the Emergency Department of the Hospital for asthenia, vomiting and fever (37.5ºC) in the last two weeks. White blood cell (WBC), red blood cell and platelet counts were normal.

Quality management (QM), including quality assurance and quality control, was developed in clinical laboratories in North America and Western Europe, but must be implemented worldwide to ensure accurate, reproducible, and clinically useful results. India, a middle income country with a population of over 1.34 billion, has limited budget allotted to health care. As yet accreditation for clinical laboratories is not mandatory, which contributes to challenges in implementing good laboratory practice. This review provides a summary of internationally laid down QM principles and their application in a middle income country like India. [ABSTRACT FROM AUTHOR]

The first direct oral anticoagulant (DOAC) to be approved for clinical use was dabigatran, a direct thrombin inhibitor, in 2010. Since that time, four additional DOACs, all direct anti‐Xa inhibitors, have been approved, including rivaroxaban, apixaban, edoxaban and betrixaban. Our knowledge about the effect of DOACs on laboratory testing, as well as the use of the laboratory for measuring DOACs has been an evolving process. These drugs are not routinely monitored in the same fashion as coumadin, but there is an increasing demand on the laboratory to have the capacity to adequately assess DOAC anticoagulant effect (pharmacodynamics) or levels (pharmacokinetics) in either emergent or the routine situations. This manuscript provides an update on laboratory guidance and progress of methods for measuring DOACs. [ABSTRACT FROM AUTHOR]

Introduction: Platelet function disorders (PFD) are an important group of bleeding disorders that require validated and practical laboratory strategies for diagnosis. Methods: This review summarizes the authors' experiences, current literature, and an international survey to evaluate the practices of diagnostic laboratories that offer tests for PFD. Results: Blood counts, blood film review, and aggregation tests are the most commonly performed investigations for PFD and help determine whether there is thrombocytopenia and/or defective platelet function due to a variety of causes. The performance characteristics of tests for PFD, and the level of evidence that these tests detect bleeding problems, are important issues to determine where tests are useful for diagnostic or correlative purposes, or research only uses. Platelet aggregation assays, and quantitative analysis of platelet dense granule numbers, are tests with good performance characteristics that detect abnormalities associated with increased bleeding in a significant proportion of individuals referred for PFD investigations. Lumiaggregometry estimates of platelet adenosine triphosphate release show greater variability which limits the diagnostic usefulness. Diagnostic laboratories report that fiscal and other constraints, including a lack of high‐quality evidence, limit their ability to offer an expanded test menu for PFD. Conclusion: PFD are clinically important bleeding disorders that remain challenging for diagnostic laboratories to investigate. While some PFD tests are well validated for diagnostic purposes, gaps in scientific evidence and resource limitations influence diagnostic laboratory decisions on which PFD tests to offer. [ABSTRACT FROM AUTHOR]

Introduction: Direct oral anticoagulants (DOACs) require no laboratory monitoring, but they interfere with almost all clotting tests to a varying degree, depending on the DOAC, assay principles and reagents used. DOAC Stop (Haematex Research, Sydney, Australia) has recently been shown to adsorb DOACs from spiked and patient plasmas. The aim of our work was to investigate the DOAC Stop effect on a range of haemostasis assays on plasmas collected from patients on rivaroxaban or apixaban, to see whether it removes the effect of these drugs to enable more accurate interpretation of coagulation assays. Methods: Samples from patients anticoagulated with either rivaroxaban, apixaban or no anticoagulant were tested for prothrombin time (PT), activated partial thromboplastin time (APTT), DOAC‐specific anti‐Xa assay, factor VIII (one‐stage and chromogenic assay) and DRVVT (low and high phospholipid) before and after sample treatment with DOAC‐Stop. Results: DOAC Stop significantly removed the effects of rivaroxaban and apixaban on PT, APTT, anti‐Xa activity, factor VIII (one‐stage and chromogenic assays), and DRVVT (low and high phospholipid reagents), and reduced the number of false positive of lupus anticoagulant interpretations in patients on rivaroxaban. There was no effect on the results from patients that were not anticoagulated. Conclusion: This small study suggests that it is likely that DOAC Stop can be used in laboratories to screen for coagulopathy or lupus anticoagulants in samples containing rivaroxaban or apixaban. Care should be taken in the interpretation of results since complete reversal of the anti‐Xa effect did not occur in every sample. [ABSTRACT FROM AUTHOR]

Introduction: No common or widely accepted criteria exist for physician review of blood films or for reported standards of physician rate of blood film review. Individual institutions generally have internal criteria for physician review of blood films. To better understand how and why blood film reviews are performed at different institutions across Canada, with a specific interest in physician blood film review, we undertook a survey to assess the current practise patterns of physician review of blood films across Canada. Methods: A 15 question survey was developed and sent to 24 academic, large community and corporate laboratories across Canada by e‐mail to laboratory directors of those institutions. Centres were chosen to include all provinces in Canada and most of the major academic centres. Twenty of the 24 centres responded. Results: The mean rate of physician review of blood films as a percentage of all CBCs processed per day was 4.1% (range 0.35%‐13%) and of all blood films made per day was 28.8% (range 1.9%‐66.5%). Data on factors which might affect physician review rates, physician preferences regarding what percentage of physician blood film review rates is reasonable and physician perspectives on the role of physician blood film review are discussed. Conclusion: This survey reveals that there is varying practise patterns and opinions with respect to blood film review by physicians in Canada. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Bone marrow biopsy (BMB) is crucial for the diagnosis, staging, and monitoring of a variety of hematologic diseases. Obtaining an adequate BMB can be challenging given the need to balance patient comfort with acquisition of high quality specimens. We had observed variable BMB quality at our institution with poor quality specimens sometimes affecting diagnosis. We thus undertook this quality improvement (QI) project to improve the quality of diagnostic BMB specimens. Methods: We used an A3 QI process to identify factors possibly influencing BMB quality. We collected baseline data on 211 BMB, with short and long‐term follow‐up data on a further 382 cases. We used clinical conferences to discuss data, perform peer comparisons and identify strategies to create a sustainable improvement in BMB quality. Results: Baseline data showed that BMB length was influenced most by the individual performer, with some influence of needle gauge. Other factors such as sedation, BMB indication were noncontributory. BMB lengths improved following performer education and individual performer data comparisons (15.2 mm post vs 12.8 mm baseline, P < .0001) and with use of an 8‐ rather than 11‐gauge needle (18.3 mm 8‐gauge vs 13.3 mm 11‐gauge P < .0001), and were sustained over the long term. Conclusions: Education on BMB standards, sharing of performer data, and changing needle gauge are relatively straightforward methods to improve BMB quality, leading to easier pathology diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Childhood acute lymphoblastic leukemia is one of the most frequent cancers of that age range. Tremendous progress has been achieved in the treatment of these diseases, and increasing numbers of patients are actually cured and live normal lives thereafter. The treatment however remains a complex and serious ordeal. Although statistics are more than encouraging, the specific care of any given patient must be considered with a personalized approach. Among modern tools of disease monitoring, minimal residual disease assessment has earned increasing appeal and now tends to be rather dubbed “measurable” residual disease as the major goal of therapy was the complete eradication of the pathological clone. In this review, the basic characteristics of ALL diagnosis will be briefly recalled, before summarizing available techniques and providing some considerations on the clinical relevance and strategies of childhood ALL MRD evaluation. [ABSTRACT FROM AUTHOR]

Abstract: The Japanese Society for Laboratory Hematology (JSLH) was launched in 2000 and has been developed by a mutual collaboration of hematologists, medical technologists, and the companies involved in hematological laboratory testing. The aim of JSLH is the progress and development of laboratory hematology by academic conferences, periodic publication of academic journal, training and education (in the meeting, the journal, or the website), promotion of the standardization of laboratory hematology, and certification of the laboratory hematology specialists. Among 3 specialized committees organized for the standardization of laboratory hematology, the standardization committee on blood cell morphology has been dealing with the various projects on peripheral/bone marrow blood cells and normal/abnormal morphology. Another independent organization, the Japanese National Research Group on idiopathic bone marrow failure syndromes (BMF), has raised the importance of the dysplasia of myelodysplastic syndromes (MDS) and has been conducting the prospective registration, central review, and follow‐up study of MDS. This group recently proposed the grading system for diagnostic accuracy of MDS, and the detailed procedure of morphological diagnosis of MDS is presented in the specialized color atlas with typical photographs of various dysplasia. JSLH has also approved the grading system for diagnostic accuracy of MDS and adopted this standardized diagnostic system to the educational item for certification of the laboratory hematology specialists, aiming at a nationwidely expanding morphological evaluation of myelodysplasia. Further and significant progress in the standardization of blood cell morphology will be expected in Japan through the activity of JSLH. [ABSTRACT FROM AUTHOR]

Introduction The purpose was to evaluate the analytical performances of Sysmex XN 3000 and UniCel DxH 800 comparing the obtained results with manual counting and between each other. Also flagging capabilities of abnormal cells were compared for both analyzers. Methods Two thousand one hundred and forty-two whole-blood samples were analyzed for evaluation. The samples flagged due to blast, atypical lymphocyte ( AL), immature granulocyte ( IG), or nucleated red blood cells ( NRBC) were microscopically reviewed (n=102). Results The within-run and between-day coefficient of variations ( CV%) of XN 3000 for hemoglobin, RBC, MCV, WBC, and platelets were lower than 5% and for WBC differentials lower than 10% except monocytes which was 15.6% at low level. The precision results of DxH 800 were also lower than 5.0% except platelets (9.5%) and monocytes (45%) at low level. The comparison of analyzers revealed good agreement ( R>.86), except monocytes and basophils. The flagging sensitivities of XN 3000 were higher for IGs, blasts, and ALs than those of DxH 800 and almost similar for NRBC. Conclusion The XN 3000 and DxH 800 are accurate, highly precise systems and can be used effectively in high-volume laboratories. The flagging sensitivity of XN 3000 was higher in detecting blasts, IGs, and ALs than that of DxH 800. The detection of abnormal cells with high sensitivity may improve laboratory workflow with a reduced slide review and accelerated turnaround time. [ABSTRACT FROM AUTHOR]

Clinical decision support ( CDS) is the use of information and communication technologies to improve clinical decision making and patient care. CDS applications have been used in many aspects of health care, including medication ordering and diagnostic prediction algorithms. As economic and regulatory pressures place a strain on laboratory resources, the potential of CDS to improve utilization of laboratory testing has also begun to be realized. Hematology and coagulation laboratories stand to gain tremendously from the implementation of CDS interventions, given their mixture of high-volume, low-cost tests (eg CBC, PT, aPTT) and tests that carry a high potential of being misused or misinterpreted (eg lupus anticoagulant, erythrocyte sedimentation rate, heparin-induced thrombocytopenia testing). This brief review will define the key terms in the field of clinical decision support, provide instructive examples of CDS interventions to improve utilization of hematology and coagulation testing, introduce methods to implement these interventions effectively, and discuss metrics by which the success of these interventions can be evaluated. [ABSTRACT FROM AUTHOR]

Introduction In daily practice in haematology laboratories, spurious increased MCHC induces an analytical alarm and needs prompt corrective action to ensure delivery of the right results to the clinicians. The aim of this study was to establish a 'decision tree' using the new parameters red blood cells (RBC-O) and haemoglobin (HGB-O) from the Sysmex XN-10 RET obtained by flow cytometry to deliver appropriate results. Methods From 128 unknown patients with MCHC > 365 g/L, all erythrocyte parameters including reticulocyte parameters were measured and analysed in parallel with blood smears, chemistry index and osmolarity. Differences between optical parameters (RBC-O, HGB-O) and usual parameters (RBC, HGB) obtained by impedance and photometry were reported also. Results Four groups were defined from observations: -RBC agglutination ( n = 22); -optical interference ( n = 17); -RBC disease ( n = 18); and -others ( n = 71). The use of RBC-O and HGB-O permitted efficient correction of the abnormalities when RBC agglutination and/or optical interference were present in 36 of 39 patients. Reticulocyte parameters permitted to elaborate an RBC score that allowed a highly sensitive detection of RBC disease patients (17/18). Conclusion Based on new parameters, we propose a 'decision tree' that delivers time savings and supports biological interpretation in case of elevated MCHC. [ABSTRACT FROM AUTHOR]

Introduction Peripheral blood smear review ( PBSR) is a labour-intensive test, and skilled morphologists are in short supply. It is therefore helpful for laboratories to establish rules for PBSR to improve laboratory efficiency. Previously published guidelines in this regard are useful, but make few recommendations specific to neonates. Neonatal blood is characterized by several peculiarities which would be considered pathological if present in adults. Consequently, smear review rules ( SRR) are often triggered in neonates without significant value being added on review. This study aimed to assess and fine-tune the SRR triggered in neonatal samples in order to improve laboratory efficiency. Methods Full blood counts collected from 188 neonatal inpatients of the Chris Hani Baragwanath Academic Hospital in South Africa were retrospectively reviewed, the triggered rules documented, and the value added on PBSR determined. Results Smear review rules were triggered in 148 (78.7%) samples, with significant morphological abnormalities identified in 84 (54.4%), and a false-positive rate of 34.0%. In patients with unhelpful review, the commonest rules triggered were the flags querying the presence of abnormal lymphocytes, blasts or nucleated red blood cells. When one or more of these flags were triggered in the absence of any other SRR, PBSR was always noncontributory. Disregarding these flags in the current cohort would reduce both the review and the false-positive rates by >20% without increasing the false-negative rate. Conclusion False-positive smear review is common in neonates, and minor modifications to SRR can substantially reduce the smear review rate without increasing the false-negative rate. [ABSTRACT FROM AUTHOR]

Introduction Given the importance of evidence-based guidelines in health care, we surveyed the laboratory hematology community to determine their opinions on guideline development and their experience and interest in developing clinical hematology laboratory practice guidelines. Methods The study was conducted using an online survey, distributed to members of the International Society for Laboratory Hematology ( ISLH) in 2015, with analysis of collected, anonymized responses. Results A total of 245 individuals participated. Most worked in clinical and/or research laboratories (83%) or industry (11%). 42% felt there were gaps in current guidelines. The majority (58%) recommended that ISLH engages its membership in guideline development. Participants differed in their familiarity with, and use of, different organizations' guidelines. Participants felt it was important to follow best practice recommendations on guideline development, including engagement of experts, statement about conflict of interests and how they were managed, systematic review and grading evidence for recommendations, identifying recommendations lacking evidence or consensus, and public input and peer review of the guideline. Moreover, it was considered important to provide guidelines free of charge. Industry involvement in guidelines was considered less important. Conclusions The clinical laboratory hematology community has high expectations of laboratory practice guidelines that are consistent with recent recommendations on evidence-based guideline development. [ABSTRACT FROM AUTHOR]

The article explores A 4-day-old newborn boy was hospitalized in the neonatal unit because of jaundice and poor feeding. The early neonatal period had been uneventful. There had been no abnormal findings on initial physical examination. On re-admission, clinical examination was normal, apart from intense jaundice. A full blood count showed a normal hemoglobin concentration (16.1 g/dL, normal range (NR) for ages 14–20 g/dL).

Introduction: Internal quality control (IQC) procedures are crucial for ensuring accurate patient test results. The IQMH Centre for Proficiency Testing conducted a web-based survey to gather information on the current IQC practices in coagulation testing. Methods: A questionnaire was distributed to 174 Ontario laboratories licensed to perform prothrombin time (PT) and activated partial thromboplastin time (APTT). Results: All laboratories reported using two levels of commercial QC (CQC); 12% incorporate pooled patient plasma into their IQC program; >68% run CQC at the beginning of each shift; 56% following maintenance, with reagent changes, during a shift, or with every repeat sample; 6% only run CQC at the beginning of the day and 25% when the instruments have been idle for a defined period of time. IQC run frequency was determined by manufacturer recommendations (71%) but also influenced by the stability of test (27%), clinical impact of an incorrect test result (25%), and sample's batch number (10%). IQC was monitored using preset limits based on standard deviation (66%), precision goals (46%), or allowable performance limits (36%). 95% use multirules. Failure actions include repeating the IQC (90%) and reporting patient results; if repeat passes, 42% perform repeat analysis of all patient samples from last acceptable IQC. Conclusion: Variability exists in coagulation IQC practices among Ontario clinical laboratories. The recommendations presented here would be useful in encouraging standardized IQC practices. [ABSTRACT FROM AUTHOR]

Introduction Among hemoglobin (Hb) H disease cases diagnosed by DNA testing in our hemoglobinopathy laboratory, we have noted instances of unreported Hb H from high-performance liquid chromatography ( HPLC) results of referring laboratories. Methods To characterize these issues, we identified all cases of genotypic Hb H disease diagnosed in our laboratory. HPLC chromatograms were reviewed to determine the presence and retention time of the Hb H peak. Results Hemoglobin H was not reported in 24.2% of patients (23 of 95) with genotypic Hb H disease. The characteristic prerun peak of Hb H was present on review of all eight Variant or Variant II β-thalassemia short-program chromatograms. Elevated Hb F (≥3%) was reported in 14 cases. The Hb H peak was found in the Hb F window in 11 dual program cases. The incorrect identification of Hb H as elevated Hb F resulted in two testing referrals for 'δβ-thalassemia'. Conclusions Hemoglobin H may go unreported due to failure to examine for or recognize its peak on Variant or Variant II β-thalassemia short-program chromatograms. Elution of Hb H in the Hb F window resulted in misidentification of Hb H for Hb F and may indicate a Variant II HbA2/HbA1C program software error. Our findings highlight the need for careful chromatogram inspection and clinical correlation in the diagnosis of Hb H disease. [ABSTRACT FROM AUTHOR]

Introduction Current recommendations for coagulation testing storage and thawing are based on historical studies that were performed using unbuffered 3.8% sodium citrate. We sought to measure the effects of freezing and thawing conditions 3.2% buffered sodium citrate plasma samples that have been stored in vials with either snap or sealed screw tops, frozen in −70 °C freezer or dry ice and thawed either capped or uncapped. Methods Shed blood samples were pooled and then aliquoted into four snap top and four screw tops vials. Half the vials were stored in a −70 °C freezer, and half on dry ice for at least 16 h. Afterwards, half the frozen samples were thawed in 37 °C waterbath capped, and other half were thawed capped. After thawing cycles, samples were tested for PT, activated partial thromboplastin time ( APTT), fibrinogen, D-dimer, factor assays, von Willebrand factor activity, plasminogen, antithrombin, protein C and lupus anticoagulant. Results Prothrombin time, APTT, factor X, and lupus anticoagulant testing were affected by all vials, freezing and thawing conditions, whereas fibrinogen, D-dimer, von Willebrand activity or protein C were not affected by any vial, freezing or storage condition. Conclusions Storage vials, freezing and thawing condition affect coagulation testing, although these differences may not be clinically significant. [ABSTRACT FROM AUTHOR]

Nonvitamin K antagonist oral anticoagulants ( NOACs) are being used with increasing frequency due to their safety profile, ease of use, and given that therapeutic monitoring is not required. As these agents have only recently been FDA approved, their effect on routine and specialty coagulation assays is not well appreciated. This article discusses NOAC effect on routine coagulation assays and whether these assays can be used to estimate drug concentration as well as which assays are suitable to quantitate drug concentration in plasma. Also reviewed is the use of manufactured drug calibrators to determine reagent responsiveness and the effect of these agents on various special coagulation assays. [ABSTRACT FROM AUTHOR]

Pediatric patients differ from adult patients in many clinical situations, and disorders of hemostasis and thrombosis are no exception. The current article presents clinical and laboratory features of two cases in which pediatric patients are evaluated for bleeding disorders. Discussion of the cases focuses on practical considerations for laboratorians. Review of these case studies highlights selected common and esoteric issues in pediatric hemostasis testing. [ABSTRACT FROM AUTHOR]

Introduction Practice guidelines provide helpful support for clinical laboratories. Our goal was to assemble an inventory of publically listed guidelines on hematology laboratory topics, to create a resource for laboratories and for assessing gaps in practice-focused guidelines. Methods PubMed and website searches were conducted to assemble an inventory of hematology laboratory-focused guidelines. Exclusions included annual, technical, or collaborative study reports, clinically focused guidelines, position papers, nomenclature, and calibration documents. Results Sixty-eight guidelines were identified on hematology laboratory practice topics from 12 organizations, some as joint guidelines. The median year of publication was 2010 and 15% were >10 years old. Coagulation topics had the largest numbers of guidelines, whereas some areas of practice had few guidelines. A minority of guidelines showed evidence of periodic updates, as some organizations did not remove or identify outdated guidelines. Conclusions This inventory of current practice guidelines will encourage awareness and uptake of guideline recommendations by the worldwide hematology laboratory community, with the International Society for Laboratory Hematology facilitating ongoing updates. There is a need to encourage best guideline development practices, to ensure that hematology laboratory community has current, high-quality, and evidence-based practice guidelines that cover the full scope of hematology laboratory practice. [ABSTRACT FROM AUTHOR]

The recent advances in the field of flow cytometry have resulted in instrumentation with increased capacity which is actually more user-friendly. Thus, the technology has become more valuable to research scientists, the pharmaceutical industry and clinical laboratories. The use of flow cytometry in regulated labs has been hampered by the challenges associated method validation and the lack of official guidance documents on the topic. Thus key stakeholders have published recommendation papers with the hope that these will be incorporated as official guidance documents. This review will focus on the achievements of the stakeholders and a high-level overview their recommendations. [ABSTRACT FROM AUTHOR]

Introduction Critical values are life-threatening results that require immediate notification to the patient's healthcare provider. Accreditation bodies require laboratories to establish critical values. A survey of Ontario laboratories was conducted to determine current practice for critical values in hematology. Methods The survey was sent to 182 participants questioning sources for establishing critical values, levels, review frequency, delta checks, and reporting. The survey was completed by laboratory managers, supervisors, technical specialists, senior technologists, and bench technologists working in hematology. Results The majority of participating laboratories have established critical values limits for hemoglobin, leukocyte counts, and platelet counts. Most laboratories also include the presence of malaria parasites and blast cells. Some laboratories reported the presence of plasma cells, sickle cells, schistocytes, and spherocytes as critical values. Multiple sources are used for establishing a critical value policy. There was variability for the frequency of critical values review. Rules may differ for a first-time patient sample vs. a repeat patient sample. Delta checks are seldom used to determine whether a result should be called a critical value. Most participants require the individual taking the critical result(s) to read back and confirm that they are directly involved with the patient's care. Conclusion There is a lack of consensus for critical values reporting in hematology. As critical value reporting is crucial for patient safety, standardization of this practice would be beneficial. [ABSTRACT FROM AUTHOR]

Hereditary red blood cell enzymopathies are genetic disorders affecting genes encoding red blood cell enzymes. They cause a specific type of anemia designated hereditary nonspherocytic hemolytic anemia ( HNSHA). Enzymopathies affect cellular metabolism, which, in the red cell, mainly consists of anaerobic glycolysis, the hexose monophosphate shunt, glutathione metabolism, and nucleotide metabolism. Enzymopathies are commonly associated with normocytic normochromic hemolytic anemia. In contrast to other hereditary red cell disorders such as membrane disorders or hemoglobinopathies, the morphology of the red blood cell shows no specific abnormalities. Diagnosis is based on detection of reduced specific enzyme activity and molecular characterization of the defect on the DNA level. The most common enzyme disorders are deficiencies of glucose-6-phosphate dehydrogenase (G6 PD) and pyruvate kinase ( PK). However, there are a number of other enzyme disorders, often much less known, causing HNSHA. These disorders are rare and often underdiagnosed, and the purpose of this review. In this brief review, we provide an overview of clinically relevant enzymes, their function in red cell metabolism, and key aspects of laboratory diagnosis. [ABSTRACT FROM AUTHOR]

Introduction The soluble fibrin monomer ( sFM) assay, like the D-dimer (DDi) assay, has the potential to be used both as an aid in the diagnosis of disseminated intravascular coagulation (DIC) and as a thrombotic marker. It differs from DDi in that it is a much earlier produced fragment produced only by thrombin action on fibrinogen, whereas DDi is a much later produced fragment formed by plasmin cleavage of cross-linked fibrin. Methods In our study, we compared two commercially available automated sFM assays in the routine hospital setting using samples obtained from the general hospital ward and the emergency room. The results obtained with the two automated assays (Stago LIA sFM assays and the LPIA-Iatro SF assay) were compared with each other and with the results obtained using the routine semiquantitative hemagglutination assay. Results The study showed that both automated assays were comparable with each other. No patient sample previously classified as positive would be missed, but with the higher sensitivity in the automated tests, more samples are positive. Conclusion In conclusion, we suggest that both automated tests are suitable for routine laboratory use. Both assays had the advantage over the hemagglutination assay in that previously frozen samples could be used, and the assays are easier and quicker to perform. The LIA sFM Stago has slightly better sensitivity but has a tendency to lower specificity than the Iatro SF test. [ABSTRACT FROM AUTHOR]

2013 is the centenary of Wallace Coulter's birth. He was an engineer, inventor, entrepreneur and visionary. He transformed the practice of laboratory hematology with his invention of the Coulter Principle and its application to blood cell analysis, together with the company he founded to bring it and his subsequent inventions and innovations to the world. He was born in modest circumstances and he remained modest in his outlook on life, despite his magnificent achievements, his successes, his numerous prestigious awards and his wealth later in life. This article traces his early life, his career, his achievements and the immense benefits he brought to the people of this planet. [ABSTRACT FROM AUTHOR]

Assays in the special coagulation laboratory are affected by numerous factors, including pre-analytical variables, anticoagulant drugs, and abnormalities of the coagulation system other than the analyte specifically being examined. By reviewing special coagulation tests as a group and in concert with clinical information, as well as understanding assay methodologies, interferences can be more easily recognized and incorrect interpretations avoided, preventing possibly unnecessary treatment of patients. Three case studies involving protein S activity, von Willebrand factor analysis, and factor V activity with Bethesda titer will highlight potential pitfalls in the interpretation of special coagulation tests. [ABSTRACT FROM AUTHOR]

Introduction The APTT is widely employed as part of a coagulation screening panel, used as a pre-operative assessment of bleeding risk, to detect hereditary and acquired haemostatic defects and to monitor anticoagulant therapy. External quality assessment ( EQA) exercises assess laboratory performance of individual tests, but rarely assess the approach to investigation of an abnormal result. Methods A multicentre exercise was carried out to investigate the ability of laboratories to identify the cause of a prolonged APTT. A sample was distributed with a request to carry out whichever tests were considered necessary to achieve a probable diagnosis. Results One hundred and ten centres in the UK NEQAS programme took part, and all 104 centres providing an interpretation correctly identified deficiency of FVIII in the sample. However, of these, 10 centres reported additional defects, including lupus anticoagulant, FIX deficiency, FXII deficiency and a FVIII inhibitor. Conclusions A markedly varied approach to investigation of a prolonged APTT was observed, although a lack of clinical information may have contributed to this finding. [ABSTRACT FROM AUTHOR]

Introduction With proper logistical support and sponsorship, a laboratory in an industrialized nation might be able to act as a reference laboratory for clinicians based in a developing country. Methods We built on previous experience in the clinical laboratory to see whether a specialized histopathology service (hematopathology) could be provided to a developing country without the expertise or experience to do it in country. Results Over an 13-year period, 582 cases from 579 individuals were analyzed. Principal pathologic findings included acute leukemia in 84 cases (14%), dyspoiesis in one or more of the hematopoietic lineages in 65 cases (11%, including three cases with high-grade myelodysplasia), 23 cases (4%) with findings suspicious for a chronic myeloproliferative disorder, 35 cases (6%) with findings suspicious for a lymphoproliferative disorder, and infectious organisms (presumably Leishmania in most instances) in 9 (1%) of cases. Specimens from 45 cases (8%) were unsatisfactory owing to extreme hemodilution and/or specimen degeneration. Conclusion With proper support, a medical laboratory in an industrialized nation may serve as a reference facility for a developing nation. The use of existing infrastructure may be remarkably effective to achieve optimal turnaround time. Although the lack of ancillary studies and follow-up biopsies limit the ability to achieve a definitive diagnosis in many cases, this must be viewed in the context of the limited ability to diagnose or manage hematopoietic neoplasia in developing nations. [ABSTRACT FROM AUTHOR]

The article presents clinical guidelines on the aspects of assays used in haemostasis and thrombosis to help laboratories perform valid and reliable assays of pro- and anticoagulant factors in blood. The guideline includes assay techniques and reagents like coagulation end-point assays, amidolytic substrate assays, and quantitative immunoassays.