International Council For Standardization In Haematology Research Articles

International Council for Standardization in Haematology (ICSH) recommendations for the performance and interpretation of activated partial thromboplastin time and prothrombin time mixing tests.

This guidance document has been prepared on behalf of the International Council for Standardization in Haematology (ICSH). The aim of the document is to provide guidance and recommendations for the performance and interpretation of activated partial thromboplastin time (APTT) and prothrombin time (PT) plasma mixing tests in clinical laboratories in all regions of the world. The following areas are included in this document: preanalytical, analytical, postanalytical, and quality assurance considerations as they relate to the proper performance and interpretation of plasma mixing tests. The recommendations are based on good laboratory practice, published data in peer-reviewed literature, and expert opinion.

Evaluation of blood cell morphology with the RBC Advanced Application: Which cut-offs are most needed for which specific abnormalities?

The detection of erythrocyte morphological abnormalities is a valuable and sometimes overlooked element in the diagnostic management of anemias. The aim of this article is to evaluate the clinical performance of the different detection thresholds tested by our laboratory using the Cellavision RBC Advanced module, after manual reclassification by an experienced operator, and comparing them to the guidelines by the ICSH (International Council for Standardization in Haematology). We arbitrarily set thresholds at 1% for "critical" abnormalities (tear drop cells, target cells, schizocytes and spherocytes) except for sickle cells (threshold set at 0.01%). Our data show excellent sensitivity of 100% for the cut-offs defined by the investigation for tear drop cells and sickle cells, but low specificity for detection of associated clinical pathology compared with ICSH cut-offs, varying from 4% for teardrop cells (detection of myelofibrosis), 26% for target cells (detection of martial deficiency) to 55% for schizyocytes (presence of hemolytic anemia). Our results show a better specificity of the thresholds established by ICSH than our studied thresholds for the detection of the pathologies of concern, suggesting a better clinical relevance.

Determination of Blood Sedimentation Rate (ESR) Referal Value in Us Women 20-50 Years Old

ESR (Erythrocyte Sedimentation Rate) is one of the parameters used for health checks. The ESR value is used to determine the presence of inflammation and infection and monitor disease. The reference value is an examination used to see a normal rather than a laboratory examination of a patient. The problem is that the current ESR reference values ​​refer to lab parameter insert kits and WHO, where reference values ​​may vary between geographic regions, age groups, gender and race. Based on the International Council for Standardization in Hematology (ICSH) and ISO 15189 Clause 5.2.2, the range of reference values ​​must be stated based on the local area minimum of 120 samples. The population used in this research was Periuk sub-district, Tangerang City, is 191 and the sample was 126 people with a random sample. Determining the reference value range in this study used primary data using statistical calculations based on CLSI EP28-A3C guidelines, namely the 2.5 and 97.5 percentiles. The research results obtained a degree of ESR reference values ​​of 0-39 mm/hour. Suggestions for further research are to determine reference values ​​based on gender and racial distance.

Traversing Their Path to the Peripheral Smear: The Journey of Traumatized Red Blood Cells.

Background Thrombotic microangiopathy encompasses a wide range of conditions, of which thrombotic thrombocytopenic purpura being a medical emergency requires prompt intervention, with schistocytes being a reliable morphological indicator of microvascular injury. However, there are conditions other than thrombotic microangiopathic anemia where schistocytes can be seen in large numbers. These nonthrombotic microangiopathic conditions are broadly grouped under cytoskeletal abnormalities, mechanical damage, and thermal injuries. Automated methods in schistocyte evaluation have shown varied reproducibility requiring manual identification. International Council for Standardization in Hematology (ICSH) recommends standardized morphological criteria and quantitative assessment as a percentage after counting at least 1,000 red blood cells in optimal areas of smear to reduce interobserver variability. Objectives The aim of this study was to evaluate and quantitate schistocytes in thrombotic microangiopathic and nonthrombotic microangiopathic groups using ICSH guidelines and to evaluate interobserver reproducibility of manual schistocyte count. Materials and Methods Overall, 157 peripheral blood smears showing schistocytes were studied by two independent observers using ICSH recommendations on light microscopy. The hematological findings were correlated with clinical diagnosis and other relevant investigations. Results Schistocytes were observed in five cases of thrombotic microangiopathic anemia and 152 cases of nonthrombotic microangiopathic anemia. Schistocyte count in thrombotic microangiopathic anemia and nonthrombotic microangiopathic anemia groups with mean (±standard deviation) value was 2.28 ± 2.65% and 0.76 ± 0.67%, respectively ( p < 0.001). The correlation coefficient between the two observers was 0.59 (confidence interval = 0.966-1.346) showing an excellent agreement on the reproducibility of schistocytes by application of ICSH guidelines. Conclusion Percentage of schistocytes more than 1% is a robust morphological indicator for diagnosis of thrombotic microangiopathic anemia in adults. Strict application of ICSH guidelines reduces interobserver bias.

Stability of Rivaroxaban and Apixaban Anti-Xa Activities in Whole Blood Samples: A French Bicentric Study.

Over the last 10 years, the use of direct oral anticoagulants (DOACs) in the management of venous thromboembolism and atrial fibrillation grew significantly, and in particular direct factor Xa inhibitors rivaroxaban and apixaban. Clinical trials of these molecules did not underline the necessity of systematic laboratory monitoring, and the measurement of anti-Xa activity was only indicated in urgent situations such as trauma or prior to acute surgery.[1] [2] [3] [4] However, in 2021, the International Council for Standardization in Haematology (ICSH) updated these recommendations and added several nonurgent indications for anti-Xa activity measurement: advanced age, severe renal failure, ahead of a surgical procedure at high bleeding risk, body mass index >40 kg/m2, and drug interactions.[5] [6] The 2018 ICSH recommendations stated that citrated whole blood samples for anti-Xa activity measurement should be processed within 4 hours of collection, but without providing evidence. Moreover, the French Working Group on Hemostasis and Thrombosis recommendations indicated a shorter stability, of 2 hours, in accordance with the only study then published in the literature.[7] [8] [9] In practice, some laboratories may find it difficult to comply with these short delays.

Bone Marrow Biopsy, Does CT Guidance Add Value?

Background: Bone marrow aspirate and biopsies (BMAB) remain a corner stone in the diagnosis and management of various hematologic disorders. Specialized testing, such as cytogenetics, immunophenotypic and molecular analysis performed on these specimens, plays a crucial role in diagnosis and staging of Leukemias/Lymphomas, as well as in finding out molecular targets for potential therapeutic benefits. Thus, inadequate, and poor-quality specimens can limit making a precise diagnosis and providing optimal treatment. At our institution, we recognized that a substantial number of non-CT guided BMAB were being reported as suboptimal, although diagnosis was being made. Also, recently more CT guided (CTG) BMAB are being implemented. A drawback with CTG BMAB is scheduling delays, that can potentially result in treatment delays, and fatal outcomes especially in conditions like Acute Leukemias. Additionally, there is concern of higher cost associated with CT guided BMAB. Therefore, we performed a retrospective analysis on BMAB procedures performed at our institution between January 2019 and April 2022. Purpose:Evaluate and compare the quality of BMAB procedures performed with and without CT guidance (blind procedure) at our institution, and their respective waiting times.Identify potential areas for improvement.Provide data to help guide in choosing the most appropriate procedure. Methods: We retrospectively reviewed all adult BMAB procedures performed at our institution between January 2019 and April 2022, including patient demographics. Pathology reports were reviewed for adequacy of aspirate smears and core biopsies. Samples were deemed inadequate even if one of bone marrow aspirate or core or clot specimens were described by the pathologist as "suboptimal", "inadequate", "fragmented", "crushed", "hemodiluted", "no spicules", or "scant". Waiting period for the procedure was defined as the duration of time (in days) from the date of placing an order for biopsy (CTG or blind) to the date of procedure. CTG BMAB are typically performed by intervention radiologists (IR) while bind BMAB are usually performed by Oncologists (Fellows or attendings) at our institutions. Results: A total of 469 posterior iliac crest bone marrow aspirate and biopsy procedures were performed. More patients underwent BMAB procedure under CT guidance (61% vs 39% for non-CTG). More CTG BMAB samples were categorized as adequate (69%), compared to the non CTG (55%), (p=0.02). No statistical difference was noted in patient's age (p=0.639) or gender (p=.22) or Body mass index (BMI) (p=2.05) of CTG and non CTG groups (see table). The mean waiting period was longer for CTG procedure (27 days +/- 20 (0-135), compared to non CTG (15 days +/- 17 (0-105) (p=0.031). Although our pathologist described a sample as "suboptimal", a definitive diagnosis was still able to be made in all cases using the available bone marrow clot, aspirate and core specimens. Conclusion/Interventions: CTG BMAB procedures were more likely to result in adequate samples when compared to non-CTG procedures, however with longer waiting period and higher costs. So, we propose that obtaining non-CTG BMAB will improve cost effectiveness and reduce the wait times. To improve the adequacy of non CTG BMAB, we propose some interventions: 1. Provide an organized training during fellowship that includes theory followed by simulation, and practice-based training under supervision. 2. Discuss ICSH (International Council for Standardization in Hematology) guidelines for bone marrow adequacy criteria with the providers. For example, the length of a core biopsy from an adult should be at least 2cm. As our study suggests significant scheduling delays with CTG BMAB, such orders when requested, may be considered as urgent procedures to avoid potential treatment delays and poor outcomes. Alternately, when an aggressive hematologic disorder like acute leukemia is suspected, blind approach may be undertaken for prompt diagnosis. Interestingly, BMI was not significantly different in the two groups. However, if locating physical landmarks is impaired by body habitus, then CT guided BMAB should be strongly considered. We would like to highlight the importance of having adequate personnel including nurse navigators, technicians who play a vital role in obtaining timely insurance clearance, and procedure scheduling. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Performance evaluation of the BC-720 auto hematology analyzer and establishment of the reference intervals of erythrocyte sedimentation rate in healthy adults.

BackgroundErythrocyte sedimentation rate (ESR) is a new reporting parameter of the BC-720 auto hematology analyzer; however, no biological reference interval for healthy adults has been established for this parameter.MethodsOutpatients or hospitalized patients with ESR test orders were selected. The ESR was measured by the standard method of ESR (Westergren) recommended by the International Council for Standardization in Hematology (ICSH), the BC-720 hematology analyzer, and the LBY-XC40B auto ESR analyzer. The data were statistically analyzed and compared among different methods. The repeatability and carryover rate (CR) of the BC-720 were assessed in randomly selected samples for each range segment. Blood Samples from three hospitals in China were collected, and the reference interval of the BC-720 ESR was determined.ResultsThe ESR results measured by the BC-720 correlated well with the Westergren method (r=0.957, y = 0.359 + 1.016x), and there was no significant difference between these two methods (P>0.05). The correlation between LBY-XC40B auto ESR analyzer and Westergren was y = 1 + 1.25x and r=0.856. The BC-720 ESR has good repeatability [standard deviation (SD) ≤1 mm/h, coefficient of variation (CV) ≤5%], and the CR was less than 1%. The 95th percentile of the biological reference interval for BC-720 ESR is 15 mm/h for men and 24 mm/h for women.ConclusionsThe Mindray BC-720 ESR showed high accuracy and good repeatability, which provided a faster, safer, and more reliable method to measure ESR. The reference intervals for BC-720 ESR could guide better clinical decisions for the laboratories utilizing this new method.

Feasibility of a mean platelet volume standard: an international council for standardization in hematology (ICSH) inter-laboratory study

We have evaluated a commercial-fixed porcine platelet preparation (with and without added fixed human red blood cells (RBC)) for the potential standardization of mean platelet volume (MPV) measurements. The standards (Biotechne) were distributed internationally to 19 laboratories including all major hematology instrument manufacturers and academic/pathology laboratories. Overall, the standards demonstrated excellent stability up to 1 month within both MPV values and platelet counts when stored at 4°C. The presence of RBC significantly increased the platelet count and MPV values compared to platelets alone. However, as expected, there were differences in MPV values between different instruments and manufacturers. MPV values were also significantly higher in the whole blood standard compared to the platelet standard in the majority of instruments except with some instruments, where MPV values were significantly higher in the platelet only preparation. To further investigate this phenomenon, two different Platelet MPV preparations (with low and high MPV) in combination with 3 different RBC MCV preparations (with low, normal or high MCVs) were tested to try and further elucidate how RBC populations may impact upon platelet analysis (count, MPV, and PDW) using a single impedance analyzer. Both MPV and MCV values showed good stability over the course of the study for up to 50 days. As expected, the RBC preparation with the lowest MCV had the greatest impact on the MPV. However, this was not observed with an increase in MCV of the RBC or by a larger MPV of the platelet population. To further understand how different gating strategies may also influence results, we investigated the effect of either fixed or floating gate strategies upon MPV raw data from patient samples in a single impedance analyzer. Overall, it was clear that floating and fixed gate strategies also significantly impact upon MPV values. In conclusion, we have demonstrated the potential of an MPV standard with good stability characteristics for calibrating and comparing full blood counters that use different analysis principles, gating and MPV calculations. This may facilitate future instrument calibration and harmonization of results between different technologies.

International Council for Standardization in Haematology (ICSH) recommendations for processing of blood samples for coagulation testing.

This guidance document has been prepared on behalf of the International Council for Standardization in Haematology (ICSH). The aim of the document is to provide guidance and recommendations for the processing of citrated blood samples for coagulation tests in clinical laboratories in all regions of the world. The following areas are included in this document: Sample transport including use of pneumatic tubes systems; clots in citrated samples; centrifugation; primary tube storage and stability; interfering substances including haemolysis, icterus and lipaemia; secondary aliquots-transport, storage and processing; preanalytical variables for platelet function testing. The following areas are excluded from this document, but are included in an associated ICSH document addressing collection of samples for coagulation tests in clinical laboratories; ordering tests; sample collection tube and anticoagulant; preparation of the patient; sample collection device; venous stasis before sample collection; order of draw when different sample types are collected; sample labelling; blood-to-anticoagulant ratio (tube filling); influence of haematocrit. The recommendations are based on published data in peer-reviewed literature and expert opinion.

2021 update of the 2012 ICSH Recommendations for identification, diagnostic value, and quantitation of schistocytes: Impact and revisions

In 2012, the International Council for Standardization in Hematology (ICSH) published recommendations for the identification, quantitation, and diagnostic value of schistocytes. In the present review, the impact of these recommendations is evaluated. This work is based on citations in peer-reviewed papers published since 2012. The first 2012 ICSH Recommendations have also been revised to incorporate newly published data in the literature and current best laboratory practice. Recommended reference ranges have been proposed for healthy adults and full-term neonates of 1% or less schistocytes. More than 1% of morphologically identified schistocytes on the blood film are considered suspicious for thrombotic microangiopathy. For preterm infants, a normal level of 5% or less is recommended. The fragment red cell count (FRC) generated by some automated hematological analyzers provides a valuable screening tool for the presence of schistocytes. Specifically, the absence of FRCs can be used as a valuable parameter to exclude the presence of schistocytes on the blood film. The validity and usefulness of microscope schistocytes and automated FRCs, respectively, are discussed in the context of the laboratory diagnostic tests used for thrombotic microangiopathies.

A Comparative Study of Erythrocyte Sedimentation Rate using Saline Diluted and Undiluted EDTA with TSC

Erythrocyte sedimentation rate (ESR) is the rate at which RBC sediment in a period of 1 hr. It is a common Haematology test that is a non-specific measure of inflammation and it became a common screening test worldwide for acute phase proteins and chronic diseases. The International Council for Standardization in Haematology (ICSH) recommended the Westergren method as the method of choice for ESR determination. TSC is almost exclusively used as the diluent of choice for setting up ESR, but some contemporary laboratories have resolved to use Normal saline (NS) as the diluent of choice while other set ESR using EDTA anticoagulated Blood (BLD) without any diluent. The objective of this study is to assess the comparison between saline diluted and undiluted EDTA with TSC as an anticoagulant in ESR detection and to find out any gender wise variations by using these anticoagulants. A total of 50 students were participated in this study. From each of the participants 5 ml of BLD was collected and it is then divided into 3 parts. 1.6 ml BLD to 0.4ml 3.8% TSC tube, 1.6 ml EDTA blood to 0.4 ml NS tube. 3rd tube with 2 ml EDTA BLD and set for ESR and obtained result within 1 hour. The Result is the mean +SD value of ESR were 19.48+5.7 mm/hr. in undiluted EDTA, 15.22+4.6 mm/hr. in saline diluted EDTA &amp; 15.36+4.5 mm/hr. in TSC. The mean difference of ESR value between saline diluted EDTA with TSC BLD was 0 and it with undiluted EDTA was 4 mm /hr. The study indicates that there was a significant difference between ESR value with undiluted EDTA and TSC while diluted EDTA and TSC were there is no significant difference. The mean +SD of ESR value using undiluted, diluted EDTA and TSC in males were 16.20+3.3, 11.05+2.8, 11.29+2.6 and while it for females were 21.69+5.2, 17.36+3.8, 17.45+3.8 respectively. In conclusion, TSC is the best diluent to be used in contemporary lab to set ESR as compared to EDTA BLD. But we can use saline diluted EDTA as an alternative to citrate diluted BLD to set ESR and it also showed there is a gender wise variation in ESR using these anticoagulants.

Plasmodium in the bone marrow: case series from a hospital in Pakistan, 2007\u20132015

BackgroundMalaria is a life-threatening, multisystem disease caused by the plasmodial parasite with a global incidence of approximately 229 million annually. The parasites are known to have unique and crucial interactions with various body tissues during its life cycle, notably the liver, spleen, and recent work has shown the bone marrow to be a reservoir of infection.MethodsThis study is a case series of patients in whom examination of bone marrow revealed malarial parasites. A retrospective record review of 35 parasite-positive bone marrow specimens examined at Aga Khan University Hospital (AKUH), Karachi, Pakistan, over the years 2007 to 2015 was conducted. Bone marrow aspirates were collected as per International Council for Standardization in Haematology (ICSH) guidelines.ResultsThe median age of patients was 22 years (range 1–75), and 60 % (n = 21) were male. 22 patients had evidence of Plasmodium falciparum, 12 had evidence of Plasmodium vivax and 1 patient had a mixed infection. Gametocytes and trophozoites were the most common stages identified on both peripheral blood and bone marrow examinations. Indications for bone marrow examination included fever of unknown origin and the workup of cytopenias and malignancies.ConclusionsThe incidental finding of Plasmodium in samples of bone marrow suggests the reticuloendothelial system may be regularly harbour these parasites, be the infection acute or chronic in character.

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants.

In 2018, the International Council for Standardization in Haematology (ICSH) published a consensus document providing guidance for laboratories on measuring direct oral anticoagulants (DOACs). Since that publication, several significant changes related to DOACs have occurred, including the approval of a new DOAC by the Food and Drug Administration, betrixaban, and a specific DOAC reversal agent intended for use when the reversal of anticoagulation with apixaban or rivaroxaban is needed due to life-threatening or uncontrolled bleeding, andexanet alfa. In addition, this ICSH Working Party recognized areas where additional information was warranted, including patient population considerations and updates in point-of-care testing. The information in this manuscript supplements our previous ICSH DOAC laboratory guidance document. The recommendations provided are based on (1) information from peer-reviewed publications about laboratory measurement of DOACs, (2) contributing author's personal experience/expert opinion and (3) good laboratory practice.

International Council for Standardization in Haematology (ICSH) laboratory guidance for the verification of haemostasis analyser-reagent test systems. Part 2: Specialist tests and calibrated assays.

Before a new method is used for clinical testing, it is essential that it is evaluated for suitability for its intended purpose. This document gives guidance for the performance, verification and implementation processes required by regulatory and accreditation bodies. It covers the planning and verification of specialist haemostatic tests, including factor assays, D-dimers, direct anticoagulants and thrombophilia testing.

An evaluation of existing manual blood film schistocyte quantitation guidelines and a new proposed method

Schistocytosis is the morphological hallmark of the microangiopathic haemolytic anaemia of thrombotic microangiopathy (TMA). Consensus guidelines for manual schistocyte quantitation are available, but limited research has evaluated them. The 2012 International Council for Standardization in Haematology (ICSH) recommends a schistocyte quantitation of 1% as a robust cut-off for significance, with the quantitation including helmet, crescent, triangle and keratocyte poikilocytes; and microspherocytes only in the presence of helmets, crescents/triangles, and keratocytes. We aimed to evaluate the relative contribution of these different poikilocytes to schistocyte counting; compare the ICSH method with our proposed method which counts only cells most specific for red cell fragmentation (helmet, crescent and triangular schistocytes); and evaluate inter- and intra-observer agreement. Blood films were sourced from the Australian Snakebite Project, including non-envenomed and envenomed cases, with and without TMA. In blood films across the range of schistocytosis, the predominant poikilocytes present were helmets and crescents. Triangles, keratocytes and microspherocytes were typically only present when ICSH schistocyte count was >1%. With results dichotomised as <1.0% or ≥1.0%, our proposed new method versus the ICSH method showed almost perfect agreement [observed agreement 95%, Cohen's kappa (κ)=0.84, SE 0.04, 95% CI 0.76-0.92, p<0.005]. Inter-observer strength of agreement for our method was moderate (Fleiss' κ for comparisons between three non-unique microscopists κ=0.50, SE 0.05, 95% CI 0.41-0.59, p<0.005). Intra-observer reproducibility assessed in two microscopists ranged from substantial (Cohen's κ=0.71, SE 0.08, 95% CI 0.55-0.86, p<0.005) to borderline almost perfect agreement (Cohen's κ=0.81, SE 0.07, 95% CI 0.68-0.93, p<0.005). Schistocyte quantitation using our new method is simpler than the 2012 ICSH method and had almost perfect agreement. Our finding of moderate inter-observer agreement in quantitating helmet, triangle and crescent schistocytes is applicable to both the ICSH and our newly proposed method. This finding underscores the importance of clinicopathological correlation and repeated examinations in the context of a clinically suspected TMA.

International Council for Standardization in Haematology (ICSH) laboratory guidance for the evaluation of haemostasis analyser-reagent test systems. Part 1: Instrument-specific issues and commonly used coagulation screening tests.

Before a new method is used for clinical testing, it is essential that it is evaluated for suitability for its intended purpose. This document gives guidance for the performance of verification, validation and implementation processes required by regulatory and accreditation bodies. It covers the planning and execution of an evaluation of the commonly performed screening tests (prothrombin time, activated partial thromboplastin time, thrombin time and fibrinogen assay), and instrument-specific issues. Advice on selecting an appropriate haemostasis analyser, planning the evaluation, and assessing the reference, interval, precision, accuracy, and comparability of a haemostasis test system are also given. A second companion document will cover specialist haemostasis testing.

Evaluation of the performance of sysmex XN-3100 automated hematology analyzer regarding the sysmex XE-2100 and microscopic examination

Abstract Objectives We performed a verification study of the Sysmex XN-3100 hematology analyzer in comparison with the XE-2100 according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI) and the International Council for Standardization in Hematology (ICSH). Materials and methods Blood samples and quality control materials were used for precision. For comparison, we used the current XE-2100 as the comparative method and analyzed 540 blood samples. The Passing-Bablok and Bland-Altman tests were performed according to the CLSI EP09-A3 and a carryover study was performed according to the CLSI H26-A2 guidelines. The flagging performance of the two analyzers was compared, using two experienced laboratory technicians as the reference method. Results The Sysmex XN-3100 demonstrated high levels of precision for most parameters. For the comparison analysis, all parameters, except for MCHC, monocytes and basophils were within the systematic error limits of desirable biological variability criterion (SeDBV). The carryover was less than 0.4% for all parameters. The flagging performance of the XN-3100 was satisfactory and the overall efficiency was high. Conclusions The XN-3100 not only showed a strong correlation and agreement with the XE-2100 but also displayed a comparable analytical sensitivity, and increased specificity, which may result in an improved turnaround time and throughpu.

International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of ADAMTS13.

This guidance document was prepared on behalf of the International Council for Standardization in Haematology (ICSH), by the ADAMTS13 Assay Working Group, which comprises an international group of both clinical and laboratory experts. The document provides recommendations on best practice for the performance of ADAMTS13 assays in clinical laboratories. ADAMTS13 assays support the differential diagnosis of thrombotic microangiopathies and have utility in the management of thrombotic thrombocytopenic purpura (TTP). There are three types of assay: activity, antigen and autoantibody/inhibitor assays. Methods for activity assays differ in terms of sensitivity, specificity, precision and turnaround time. The most widely used assays involve VWF peptide substrates and either chromogenic ELISA or FRET techniques, although chemiluminescence assays and rapid screening tests have recently become available. Tests for autoantibodies and inhibitors allow confirmation of acquired, immune-mediated TTP, while antigen assays may be useful in congenital TTP and as prognostic markers. In this document, we have attempted to describe ADAMTS13 assays and the conditions that affect them, as well as: blood collection, sample processing, quality control, standardization and clinical utility; recognizing that laboratories in different parts of the world have varying levels of sophistication. The recommendations are based on expert opinion, published literature and good clinical laboratory practice.

Guidelines for reporting blood cell morphology – Are laboratories following?

In 2015, the International Council for Standardization in Haematology (ICSH) released a report outlining recommendations for the standardisation of nomenclature and grading of peripheral blood cell morphological features. Based on these, lymphoid cells with a suspected malignant or clonal aetiology should be classified as abnormal lymphocytes with an accompanying description of the cells.1 We sought to evaluate if laboratories were following the ISCH reporting recommendations. Method: Laboratories enrolled in the 2019 RCPAQAP Manual Differential program were provided with clinical notes, a stained blood film (which featured a T-cell prolymphocytic leukaemia case) and asked to categorise the different white blood cells. Assessment was based on robust statistical analysis and the clinical scenario. Results: 79% (378/480) of labs reported the presence of abnormal lymphocytes, however, only 10% (41) provided a description of the abnormal cells. 23 participants included the abnormal cells as part of the lymphocyte count, while 15 participants counted the abnormal cells as ‘others’ without a description. Discussion and conclusion: The main morphological features that were expected to be reported were the presence of abnormal lymphocytes and an associated description (T-cell prolymphocytes). Based on the results for this survey, either laboratories have a low uptake on the ICSH guidelines or they are missing important morphological features indicating the need for standardisation in blood film morphology reporting. Reference1.Palmer L, Briggs C, McFadden S, et al. ICSH recommendations for the standardization of nomenclature and grading of peripheral blood cell morphological features. Int J Lab Haematol 2015; 37: 287–303.

Diagnosis in thrombotic microangiopathy

Thrombotic microangiopathies (TMA) are relatively rare multisystem diseases characterised by microvascular endothelial damage with platelet-rich thrombus formation, consumption thrombocytopenia, mechanical haemolytic anaemia with schistocytes and multiorgan failure of variable severity. Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) are the two major disorders; other clinical entities that can be associated with TMA, are the HELLP syndrome, (haemolysis, elevated liver enzymes, low platelet count), the catastrophic antiphospholipid syndrome (CAPS) and bone marrow transplant (BMT). On the peripheral blood smears, the detection of schistocytes, that are fragments of red blood cells produced by extrinsic mechanical damage within the circulation, still remains an important morphological clue for the diagnosis of TMA. The International Council for Standardization in Hematology (ICSH) has prepared specific recommendations to standardise schistocyte identification, enumeration, and reporting. Measurement of activity of ADAMTS13 (a zinc-containing metalloprotease enzyme which cleaves and degrades large multimers of von Willebrand factor) remains the most reliable test to distinguish HUS from TTP, presenting with detectable and undetectable ADAMTS13 activity, respectively. Main clues in HELLP are weight gain, arterial hypertension, massive proteinuria, DIC, marked elevation of AST/ALT/LDH and detectable ADAMTS13 activity, while patients with CAPS present with weight loss, recent polyuria–polydipsia, vomiting, hypoglycaemia, jaundice (conjugated bilirubin), prolonged prothrombin time, reduced factor V and antithrombin levels, DIC and renal failure.