Thursday, May 30, 2024 |
8:30 - 10:00 AM | Auditorium |
Opening Plenary |
Chair(s): John Frater |
8:30 |
Crosstalk Coagulation And Inflammation University Medical Center Hamburg-Eppendorf Combinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. The plasma contact system is a plasma protease cascade initiated by factor XII (FXII) that activates the proinflammatory kallikrein-kinin system and the procoagulant intrinsic coagulation pathway. Anionic surfaces induce FXII zymogen activation to form proteolytically active FXIIa. Bacterial surfaces also have the ability to activate contact system proteins, indicating an important role on host defense using the cooperation of the inflammatory and coagulation pathways. Recent research has shown that the inorganic polymer polyphosphate exposed by procoagulant platelets activates FXII in vivo and can induce coagulation in pathological thrombus formation. Experimental and clinical studies have shown that interference with FXII and polyphosphate provides thromboprotection without a therapy-associated increase in bleeding renewing interest in the FXIIa-driven intrinsic pathway of coagulation as a therapeutic target. A key aspect of the presentation will be analysis of common principles, interactions and cross-talk between coagulation and inflammation, to identify novel therapeutic targets. Elucidating the polyphosphate initiated FXII-driven contact system offers the exciting opportunity to develop strategies for safe interference with both thrombotic and inflammatory diseases. |
10:00 - 10:30 AM | Grand Hall |
Coffee Break/Exhibits |
10:30 - 12:00 PM | Auditorium |
Concurrent 1: Diagnosis in the bleeding patient |
Chair(s): Katrien Devreese |
10:30 - 12:00 PM | Room 300 |
Concurrent 2: Cellular Analysis and Flow Cytometry: Technical innovations |
Chair(s): George Deeb |
10:30 |
Flow Cytometry & Machine Learning For Schistocyte Quantification CHU Amiens-Picardie Background: Schistocyte counts are a cornerstone of the diagnosis of thrombotic microangiopathy syndrome (TMA). Their manual quantification is complex and alternative automated methods suffer from pitfalls that limit their use. We report a method combining imaging flow cytometry (IFC) and artificial intelligence for the direct label-free and operator-independent quantification of schistocytes in whole blood. Methods: We used 135,045 IFC images from blood acquisition among 14 patients to extract 188 features with IDEAS® software and 128 features from a convolutional neural network (CNN) with Keras framework in order to train a support vector machine (SVM) blood elements’ classifier used for schistocytes quantification. Finding: Keras features showed better accuracy (94.03%, CI: 93.75-94.31%) than ideas features (91.54%, CI: 91.21-91.87%) in recognising whole-blood elements, and together they showed the best accuracy (95.64%, CI: 95.39-95.88%). We obtained an excellent correlation (0.93, CI: 0.90-0.96) between three haematologists and our method on a cohort of 102 patient samples. All patients with schistocytosis (>1% schistocytes) were detected with excellent specificity (91.3%, CI: 82.0-96.7%) and sensitivity (100%, CI: 89.4-100.0%). We confirmed these results with a similar specificity (91.1%, CI: 78.8-97.5%) and sensitivity (100%, CI: 88.1-100.0%) on a validation cohort (n=74) analysed in an independent healthcare centre. Simultaneous analysis of 16 samples in both study centres showed a very good correlation between the 2 imaging flow cytometers (Y=1.001x). Interpretation: We demonstrate that IFC can represent a reliable tool for operator-independent schistocyte quantification with no pre-analytical processing which is of most importance in emergency situations such as TMA. |
12:15 - 1:15 PM | Room 300 |
Corporate Lunch Symposium - Sysmex |
12:15 - 1:15 PM | Room 150 |
Corporate Lunch Symposium - Scopio Labs |
1:30 - 3:00 PM | Auditorium |
Presidential Symposium |
Chair(s): Tracy George |
1:30 |
Bh Lecture Universita' Cattolica, Fondazione Policlinico Gemelli Hematological cytomorphology: where we are Gina Zini, Hematology Professor The discovery of the cell would not have been possible without advancements in microscope science. |
2:15 |
Whc Lecture McMaster University TITLE = A career in solving clinical-pathological conundrums: Heyde syndrome, HIT/VITT, and microvascular limb ischemic necrosis. Hematology is a clinical specialty with strong roots in the laboratory; accordingly, the lab can help solve perplexing clinical problems. This review highlights clinical-pathological conundrums addressed during my 35-year hematology career at McMaster University (Hamilton, Canada). Heyde syndrome is the association between aortic stenosis and bleeding gastrointestinal (GI) angiodysplasia where the bleeding is usually cured by aortic valve replacement; the chance reading of a neonatal study showing reversible deficiency of high-molecular-weight (HMW) multimers of von Willebrand factor (VWF) following surgical correction of congenital heart disease provided the key insight that a subtle deficiency of HMW multimers of VWF explains Heyde syndrome. The unusual immunobiology of heparin-induced thrombocytopenia (HIT)—a highly prothrombotic, antibody-mediated, anti-platelet factor 4 (PF4) disorder featuring rapid appearance and then disappearance (seroreversion) of the pathological IgG class platelet-activating antibodies—permitted identification of key clinical features that informed development of a scoring system (4Ts) to aid in diagnosis. Atypical clinical presentations of HIT provided unique insights into heparin-independent anti-PF4 antibodies, now recognized as the explanation for vaccine-induced immune thrombotic thrombocytopenia (VITT), as well as VITT-like disorders triggered by adenovirus infection. Another unusual feature of HIT is its strong association with limb ischemia, including limb amputation secondary to deep-vein plus microvascular thrombosis (venous limb gangrene). The remarkable observation that supratherapeutic warfarin anticoagulation explains HIT-and cancer-associated venous limb gangrene provided insights into disturbed procoagulant/anticoagulant imbalance; these concepts help explain microvascular thrombosis in critical illness (symmetrical peripheral gangrene), including a pathophysiological role for proximate “shock liver” (impaired hepatic synthesis of natural anticoagulants). |
3:00 - 3:30 PM | Grand Hall |
Coffee Break/Exhibits |
3:30 - 5:00 PM | Auditorium |
Concurrent 3: Anemias and Red Cell Disorders |
Chair(s): Kees Harteveld |
3:30 |
Congenital Dyserythropoietic Anemias Department of Molecular Medicine and Medical Biotechnologies, Congenital dyserythropoietic anemias (CDAs) are a group of rare inherited blood disorders characterized by defective erythropoiesis, leading to various degrees of anemia. The diagnosis of CDA is typically considered in cases presenting anemia and hemolytic signs, accompanied by reticulocytosis that is disproportionately low considering the level of anemia. A frequent complication in CDA patients is iron overload. Recent research has enhanced our understanding of how iron metabolism is dysregulated in CDAs, both at the systemic level and within the hepatic cells. The standard diagnostic workflow for CDAs involves three levels of investigation: (i) evaluating complete blood count, hemolysis, iron overload markers, and personal and family history; (ii) conducting a morphological evaluation of bone marrow; (iii) performing genetic testing. Historically, key diagnostic features of CDAs were morphological abnormalities in the bone marrow, such as erythroid hyperplasia with binuclearity or multinuclearity in late erythroblasts. However, these features are not exclusive to CDAs and can also appear in other conditions that involve erythropoietic stress. This overlap can complicate the diagnosis of CDAs. Despite these challenges, the classification of the three major types of CDAs (I, II, III) is still based on the morphological features of erythroblasts in the bone marrow. A significant advancement in the understanding of CDAs has been the identification of novel genetic variants and genes. Advanced genomic sequencing techniques have enabled the precise identification of gene variants associated with specific CDA subtypes. Currently, over ten genes associated with erythrocyte physiology have been identified as causative factors in CDAs. This genetic and clinical heterogeneity highlights the complexities involved in the differential diagnosis of these conditions. Genetic testing has become a crucial tool in the differential diagnosis of CDAs, leading to adjustments in the initial clinical diagnosis in approximately 10-40% of patients analyzed, many of whom exhibit erythrocyte enzyme defects such as pyruvate kinase deficiency. The hallmark of CDAs is the maturation arrest of erythroid lineage cells, resulting in reduced erythrocyte production. However, the specific pathogenic mechanisms of various mutated genes across all CDA subtypes are not yet fully understood. Despite the challenges these conditions pose to researchers and healthcare professionals, recent advancements in medical research have illuminated the underlying mechanisms and potential treatment strategies for these complex disorders. |
4:00 |
Role Of Clinical Laboratories To Identify Patients With Thalassemias: The Dutch Experience Dept. of Clinical Genetics, Hemoglobinopathy Expert Center, Leiden University Medical Center, Leiden, The Netherlands Role of clinical laboratories to identify patients with thalassemias: the Dutch experience
Cornelis L. Harteveld, Department of Clinical Genetics/Laboratory for Genome Diagnostics, Leiden University Medical Center, Leiden, The Netherlands
Recently the Dutch Society of Hematology Laboratories (VHL) have updated their Recommendations concerning the identification of hemoglobinopathy carriers in a clinical laboratory setting. The hemoglobinopathies are inherited autosomal recessive disorders caused by DNA variants in the globin genes. Variants in the alpha- and beta-globin genes (HBA1, HBA2 and HBB) which affect the expression of these genes cause thalassemia, while mainly exonic missense variants may cause structural Hb variants characterized by altered function, stability or oxygen affinity. In this presentation the diagnostic strategy is discussed applicable in the clinical genetic or chemistry laboratory to detect carriers and patients having thalassemia, sickle cell disease or Hb variants. To identify carriers of hemoglobinopathies providing genetic information to physicians and patients is of importance to identify couples at risk to be referred for counseling. Partner analysis preferably before the first pregnancy can only be realized by disseminating genetic information. The role of General Practitioners and other health professionals is essential based on the laboratory results reporting a carrier. A timely referral of couples at risk to a genetic counselor to discuss preventive options for severe forms of hemoglobinopathy in their offspring is crucial for informed decision making and prenatal diagnostics.
|
4:30 |
Erythrocytosis Queens University, Belfast An erythrocytosis is present when the red cell mass is more than 125% of predicted for body mass and sex. However, the presence of an erythrocytosis can be inferred from a raised hemoglobin and/or hematocrit. This can arise as a primary event where an intrinsic change in the bone marrow leading to increased red cell production or a secondary event where red cell production is driven by erythropoietin. A number of rare germline mutations, have been shown to account for some familial cases of erythrocytosis, and therefore cases can be divided into congenital and acquired. There remain a group, in whom no cause has yet been identified, termed idiopathic erythrocytosis. Searching for a diagnosis depends initially on taking a careful history, examination, and the pursuit of possible causes as suggested from the clinical scenario. Measurement of erythropoietin level is an initial guide as to whether the erythrocytosis is primary or secondary erythrocytosis. The direction, nature and extent of investigations will be driven by the clinical scenario. One of the current pressing clinical decisions, to allow effective work load management, is which patients sent to haematology for investigation should be followed up long-term. There is no definite evidence base to guide management of the various erythrocytosis and an individual patient needs assessed to decide if there are any measures that should be undertaken to attempt to ameliorate harm while not compromising physiological adaptation to the situation. Low dose aspirin and perhaps venesection are the measures which are may be considered in an individual patient. |
3:30 - 5:00 PM | Room 300 |
Concurrent 4: Molecular Analysis in Thrombosis and Hemostasis |
Chair(s): Olga Weinberg |
4:00 |
Inherited Thrombopenia Caused By Variants In Crucial Genes For Glycosylation Murcia, Spain Protein glycosylation, including sialylation, involves complex and frequent post-translational modifications, which play a critical role in different biological processes. The conjugation of carbohydrate residues to specific molecules and receptors is critical for normal hematopoiesis, as it favors the proliferation and clearance of hematopoietic precursors. Through this mechanism, the circulating platelet count is controlled by the appropriate platelet production by megakaryocytes, and the kinetics of platelet clearance. Platelets have a half-life in blood ranging from 8 to 11 days, after which they lose the final sialic acid, and are recognized by receptors in the liver and eliminated from the bloodstream. This favors the transduction of thrombopoietin, which induces megakaryopoiesis to produce new platelets. More than two hundred of enzymes are responsible for proper glycosylation and sialylation. In recent years, novel disorders of glycosylation caused by molecular variants in multiple genes have been described. The phenotype of the patients with genetic alterations in GNE, SLC35A1, GALE and B4GALT is consistent with syndromic manifestations, severe inherited thrombocytopenia, and hemorrhagic complications |
5:00 - 6:30 PM | Grand Hall |
Poster Session 1 / Welcome Reception / Exhibits |
Friday, May 31, 2024 |
8:30 - 10:00 AM | Auditorium |
Concurrent 5: Flow cytometry - Paroxysmal nocturnal haemoglobinuria |
Chair(s): David Barnett |
8:30 |
Complement Inhibition In Phn: From Biology To Therapy University of Milan Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement mediated intravascular hemolysis (IVH), thrombosis, and associated bone marrow failures. It is due to a somatic mutation of PIG-A gene in hematopoietic stem cells, impairing the production of glycosyl-phosphatidyl-inositol (GPI)-anchor molecule, and resulting in the loss of the natural complement inhibitory molecules CD55 and CD59 at the cell surface. Complement inhibition with the anti-C5 monoclonal antibody eculizumab revolutionized PNH treatment, reducing the most feared thrombotic risk and improving (nearly normalizing) survival. Several drawbacks of eculizumab included the route and schedule of administration (i.e. intravenous every 14 days), the risk of hemolytic exacerbations before the next dose (pharmacokinetic breakthrough hemolysis, PK-BTH), and residual anemia in about 2/3 of patients with transfusion need in some of them. The first two unmet needs were partly resolved by ravulizumab, a long-half-life analogue of eculizumab, administered every 8 weeks and able to exert a stable control of hemolysis abolishing PK-BTH. Additionally, the anti-C5 crovalimab, administered subcutaneously every 4 weeks, improved patient convenience and is active on C5 polymorphism not responding to eculizumab. As regards residual anemia, a role of iatrogenic extravascular hemolysis (EVH), due to C3 accumulation on erythrocytes after C5-blockade, has been demonstrated. C3-coated PNH-erythrocytes are in fact phagocyted in the reticuloendothelial system with consequent chronic anemia, unconjugated bilirubin increase, and direct Coombs test positive for C3. The development of “proximal” complement inhibitors was aimed at resolving EVH in suboptimal responders to anti-C5 and, further, to control IVH and prevent EVH in naïve PNH patients. The first to be studied is the anti-C3 pegcetacoplan, which is administered subcutaneously twice a week. In the phase 3 trial the drug was able to improve Hb and abolish transfusion need in a large proportion of suboptimal responders to eculizumab. Pegcetacoplan is now approved for all PNH patients in USA and for suboptimal responders after 3-month anti-C5 therapy in Europe. Similarly, oral small molecules inhibiting factor-B (iptacopan) and factor-D (danicopan) of the alternative complement pathway showed impressive results in early trials, and phase 3 trials are ongoing. The short half-life of these drugs, with the need of frequent self-administration, poses several questions regarding patient compliance. Additionally, the risk of “pharmacodynamic” (PD)-BTH due to over-activation of complement during infections, traumas, surgery, etc., warnings close monitoring and need of common management and prevention strategies. Individualizing treatment on disease/patient features will be the next step for PNH “modern” management. |
8:30 - 10:00 AM | Room 300 |
Concurrent 6: Hemostasis & Platelets |
Chair(s): Simon Davidson |
9:00 |
Non-Criteria Antiphospholipid Antibodies In Aps Ghent University Hospital Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic manifestations and/or obstetric complications in patients with persistently positive antiphospholipid antibodies (aPL). aPL are a heterogeneous group of autoantibodies, but only lupus anticoagulant (LA), anticardiolipin (aCL), and antibeta2-glycoprotein I antibodies (aβ2GPI) IgG or IgM are included as laboratory classification criteria. Seronegative APS patients are usually defined as patients with the clinical symptoms of APS but who test negative for aPL. The negativity to classic aPL criteria does not exclude the presence of other aPL. Several non-criteria aPL have been identified. Some non-criteria aPL are well studied, such as IgA aCL and aβ2GPI, the antiphosphatidylserine-prothrombin (aPS/PT) antibodies, and the antibodies against the domain I of beta2-glycoprotein I (aDI), both latter groups receiving more attention for their role in thrombotic events and pregnancy complications. Other non-criteria aPL that have been studied are antibodies against annexin V, prothrombin, phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, vimentin-cardiolipin complex, anti-protein S/protein C. Measurement of some of these non-criteria aPL (aPS/PT, aDI) is useful in the laboratory workup of APS in specific situations. We have to differentiate between patients who are positive for non-criteria aPL only, and patients who have both criteria and non-criteria aPL to enable us to study their role in the diagnosis or risk stratification of APS. The research on non-criteria aPL is continually developing as the clinical relevance of these antibodies is not yet fully clarified. |
9:30 |
Haemophilia And Thrombin Generation Lyon University Hospitals Hemophilia treatments have been tremendously improved over the past 10 years, but laboratory testing has not kept pace. Extended half-life FVIII and FIX molecules have very different structures from wild-type FVIII and FIX, but hospital laboratories use the same assays for all of these molecules. The development of FVIII mimetics and non-factor therapies also raises questions about the monitoring of these molecules.
Thrombin generation assay (TGA) may be a good candidate to fill this laboartory lack to further improve the management of patients with haemophilia. Even though the results of several studies are motivating to take the research in this field forward, the validation of the utility of TGA in haemophilia can only be conducted with prospective studies determining clinically relevant endpoints. The setup of such prospective studies is currently limited by the lack of standardization of TGT, which should be a priority of the experts. |
10:00 - 10:30 AM | Grand Hall |
Coffee Break/Exhibits |
10:30 - 12:00 PM | Auditorium |
Concurrent 7: Quality and Standards |
10:30 |
Interpretation Of Statistical Analysis Of External Quality Assurance Programs Department of Mechanical Engineering of Politecnico di Milano, Milan, Italy and at the Department of Statistics of the Athens University of Economics and Business, Greece |
11:30 |
French Hematology Proficiency Testing. The Probioqual Experience PROBIOQUAL and HCL French hematology proficiency testing, the ProBioQual experience. B. Poggi (1), L. Jallades (1) (2), E. Bugni (1). (1) ProBioQual, 7 rue Antoine Lumière, 69008 - LYON, FRANCE (2) Hematology laboratory of Hospices Civils de Lyon, C.H.L.S, PIERRE BENITE, FRANCE ProBioQual is a French non-profit, non-governmental organization founded in 1972, ISO 17043 accredited and ISO 9001 certified. ProBioQual offers 52 EQAS in 2024 in the different domains of clinical biology and 1 POC testing program on fresh blood. In hematology, we have numerous programs concerning hemostasis (all areas of hemostasis are covered by our EQA programs) and hematocytology with programs based on stabilized whole blood, but also on fresh blood and we propose also virtual microscopy (4 times per year for each program). ProBioQual developed his own informatic software for statistical analysis and laboratory evaluation, using the robust A algorithm described in ISO 13528. In 2023 and in 2024, around 600 laboratories participate in these EQAS. We will present the performance of the participating French laboratories. In 2015, ProBioQual published an article on LTUM determination using only EQAS results (LTUM = Long-Term Uncertainties Measurement). We will present the results uncertainties raised by the French laboratories participating in ProBioQual EQAS in 2023. |
10:30 - 12:00 PM | Room 300 |
Concurrent 8: Optical Genome mapping and Karyotype |
Chair(s): Florence Nguyen-Khac |
10:30 |
Applications Of Optical Genome Mapping In Chronic Lymphocytic Leukemia: From Clinical Assessment To Translational Research. Hospital del Mar, Barcelona Historically, cytogenetic abnormalities (CA) detected by FISH (Dohner’s hierarchical model) have been one the biomarkers for predicting the outcome of patients diagnosed with chronic lymphocytic leukemia (CLL), with the highest impact on TP53 deletions. Besides, in the last years, complex karyotype (CK, ≥3CA) identified by chromosome banding analysis (CBA) has also been described as a poor prognostic and potentially predictive biomarker, being ≥5CA the cut-off associated with worse evolution. At present, these aberrations need to be screened before treatment initiation (iwCLL guidelines, 2018) and in some CLL treatment guidelines (eg. German CLL Group), both TP53 status and the presence of CK guide patients treatment. With the introduction of optical genome mapping (OGM) is routine cytogenetic laboratories, attempts have been made to discern its ability to detect the aforementioned cytogenomic aberrations, as well as new balanced or unbalanced abnormalities in CLL which could also impact on prognosis or theranosis. Besides, the definition of karyotype complexity and the presence of catastrophic events (chromoanagenesis phenomena), named chromothripsis, chromoplexy and chromoanasysntesis are under investigation regarding prognostic/predictive impact. |
11:30 |
Optical Genome Mapping In T-All University Hospitals Leuven Optimizing the diagnostic workflow for T-lymphoblastic leukemia/lymphoma by optical genome mapping T-lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) is a rare malignancy resulting from the accumulation of malignant progenitor T-cells in the bone marrow, peripheral blood and (non-)lymphoid tissues. Specific morphologic and immunophenotypic features determine the diagnosis. Cytogenetic analysis is also recommended as it may have therapeutic implications. At present, the WHO discriminates no subgroups though among T‐ALL/‐LBL patients. Chromosome banding analysis (CBA) and Fluorescent In-Situ Hybridization (FISH) together with PCR-based methods form the backbone of current routine genetic diagnostics. This approach is labor-intensive, time-consuming and costly. New molecular technologies now exist that can detect SVs and CNAs in one test. Here we apply one such technology, optical genome mapping (OGM), to the diagnostic work-up of 12 T-ALL/T-LBL cases. Compared to our standard testing pathway, OGM identified all recurrent CNAs and SVs as well as additional recurrent SVs and the resulting fusion genes. Using the standard approach 6/9 recurrent chromosomal abnormalities were detected, while OGM identified all nine of them. For seven T‐ALL/LBL cases OGM was the sole method to either detect additional SVs, including a TCF7::SPI1 fusion gene and BCL11B, TAL1 rearrangements or to identify TRA/TRB fusion partners. All variants were confirmed using FISH and/or RNA seq. The BCL11B rearrangement designated by OGM in one case was due to a t(6;14) only rarely described in T‐ALL. Overall, there was excellent concordance between the results. OGM increased the detection rate and cytogenetic resolution, and abrogated the need for cascade testing, resulting in reduced turnaround times. However, for comprehensive cytogenomic testing, OGM still needs to be complemented with BCR::ABL1 FISH to assign patients as soon as possible to targeted therapy. Although currently not needed for prognostic purposes, we presume that the detection of SVs and CNAs by OGM might define personalized treatment options for T-ALL/T-LBL in the future. |
12:15 - 1:15 PM | Room 300 |
Corporate Lunch Symposium - Mindray |
12:15 - 1:15 PM | Room 150 |
Corporate Lunch Symposium - Cellavision |
1:30 - 2:30 PM | Auditorium |
Plenary Abstract Session |
Chair(s): Swati Pai |
2:30 - 4:00 PM | Auditorium |
Special Plenary: ICSH Session |
Chair(s): Bob Gosselin |
2:30 |
Schistocytes: Recommendations For Identification And Diagnostic Application Universita' Cattolica, Fondazione Policlinico Gemelli Schistocytes: recommendations for identification and diagnostic application Gina Zini, Hematology Professor Università Cattolica S. Cuore, Policlinico Universitario A. Gemeli, IRCSS- Rome -IT Rome Schistocytes are fragmented red blood cells (FRC) formed in peripheral blood (PB) as consequence of a mechanical damage. The abnormal red blood cell assumes a triangular, helmet-shaped form, with two or three pointed extremities. The most frequent cause of erythrocyte fragmentation is the formation of thrombi in the microvasculature as in thrombotic microangiopathies (TMA), with consumption of fibrin and platelets. The fragmentation occurs after the passage of RBC through the fibrin of microthrombi. Schistocytes can also increase after surgery, bone marrow transplantation, in HIV infection and in diseases, such as vasculitis, with vessel abnormalities. Haemolytic anaemia with circulating schistocytes occurs in patients with heart valve prosthesis. The search for schistocytes is performed in the haematology laboratories under a specific clinical query. Schistocytes are usually evaluated on PB smears using optical microscope observation and are estimated as percentage of total RBCs. Main problems concern: - lack of standardization of those fragments that can be classified as schistocytes (dd with the irregularly contracted cells) - high inter-laboratory variability on criteria for identification, enumeration and reporting of schistocytes under the optical microscope - increasing number of clinical papers in the literature considering the count of schistocytes as one diagnostic criteria - availability in the laboratories of an automated fragment count. In 2011 the International Council for Standardisation in Haematology (ICSH) published the first Recommendation for schistocyte identification, quantification and diagnostic value. in 2013, in a critical evaluation of clinically relevant published guidelines, Aake et al, included the Schistocyte ICSH Recommendation among the top 12 guidelines among those concerning laboratory tests in clinical practice. In 2021 the ICSH published an update of the recommentations.
Suggested references - Zini G, d'Onofrio G, Biggs C, et al. ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes. Int J Lab Hematol. 2012; 34: 107- 116. - Aakre KM, Langlois MR, Watine J, et al. Critical review of laboratory investigations in clinical practice guidelines: proposals for the description of investigation. Clin Chem Lab Med. 2013; 51: 1217- 1226. - Agarwal P, Khan R, Brannock K. Standardization of schistocyte identification and quantitation for the diagnosis of thrombotic microangiopathic anemia at University of Cincinnati Medical Center. Blood. 2019; 134(Suppl. 1): 4796. - Zini G. International Council for Standardization in Haematology (ICSH). Stability of complete blood count parameters with storage: toward defined specifications for different diagnostic applications. Int J Lab Hematol. 2014; 36: 111- 113. - Murphree CR, Nguyen NN, Shatzel JJ, et al. Biopsy-proven thrombotic microangiopathy without schistocytosis on peripheral blood smear: A cautionary tale. Am J Hematol. 2019; 94: E234- E237. - Zini G, De Cristofaro R. Diagnostic Testing for Differential Diagnosis in Thrombotic Microangiopathies. Turk J Hematol. 2019; 36: 222- 229. - Kratz A, Lee SH, Zini G, Riedl JA, Hur M, Machin S. Digital morphology analyzers in hematology: ICSH review and recommendations. Int J Lab Hematol. 2019; 41: 437- 447. - Zini G, d'Onofrio G, Erber WN, Lee SH, Nagai Y, Basak GW, Lesesve JF; International Council for Standardization in Hematology (ICSH). 2021 update of the 2012 ICSH Recommendations for identification, diagnostic value, and quantitation of schistocytes: Impact and revisions. Int J Lab Hematol. 2021 Dec;43(6):1264-1271. |
3:00 |
Validation Of Haemostasis Laboratory Developed Tests St James University Hospital Leeds Laboratory developed tests (LDTs) are widely used in clinical hemostasis laboratories. An LDT may be defined as an in vitro diagnostic test that is “designed, manufactured and used within a single laboratory”. As with all other clinical laboratory tests, LDTs must be validated to ensure fitness for purpose. This may include the assessment of accuracy/comparability, precision, precision, analytical sensitivity and specificity, reportable range, reference intervals, linearity and carryover. Not all validation elements will be applicable to all situations, and this will be dictated by the type of assay and the laboratory setting, e.g. a minor modification of an assay with regulatory approval will require fewer validation procedures than a wholly new test using reagents developed within the laboratory. Many LDTs in the haemostasis laboratory cannot be assessed in the usual fashion (e.g. platelet function testing), so alternative approaches must be developed. |
4:00 - 4:30 PM | Grand Hall |
Coffee Break/Exhibits |
4:30 - 5:30 PM | Auditorium |
Oral Abstract Concurrent Session: Hemostasis/platelets |
4:30 - 5:30 PM | Room 300 |
Oral Abstract Concurrent Session: Cell Analysis/Flow Cytometry |
5:30 - 7:15 PM | Grand Hall |
Poster Session 2 / Exhibits |
8:00 - 12:00 AM | Offsite |
Networking Event |
Saturday, June 1, 2024 |
8:00 - 8:15 AM | Auditorium |
Business Meeting |
8:30 - 10:00 AM | Auditorium |
Concurrent 9: Cell analysis - Hairy Cell Leukemia & MDS |
Chair(s): John Frater |
9:00 |
New Insights In The Biology Of Hairy Cell Leukemia And Hairy Cell-Like Disorders USZ/UZH/LOOP Zurich Presentation Title: New insights in the biology of hairy cell leukemia and hairy cell-like disorders
I will discuss the biology and diagnostics of hairy cell leukemia and related diseases based on morphology, immune phenotype and genetics. A detailed knowledge oft he disease provides the basis for precision medicine approaches to the treatment of hairy cell leukemia. |
1:30 - 3:00 PM | Auditorium |
Concurrent 11: New Developments in Flow Cytometry & Cellular Analysis |
Chair(s): Dr. A. Orfao |
2:30 |
Early Stem Cell Vs. Leukemic Stem Cell Immunophenotypic Features Amsterdam University Medical Centers, Cancer Center Amsterdam, Netherlands Many tumors are organized in a hierarchical structure with at its apex a cell that can maintain, establish, and repopulate the tumor – the cancer stem cell. Especially in hematopoiesis the hematopoietic stem cell (HSC) is the founder (apex) cell for all functional blood cells. Similarly in leukemia the leukemia stem cells (LSC) are hypothesized to be the leukemia initiating cells, which have features of stemness such as self-renewal, quiescence, and resistance to cytotoxic drugs. Immunophenotypically, HSCs are defined as CD34+CD38- with the addition of lineage negativity and CD90+CD45RA-. At which stage of maturation, the further differentiation is blocked, determines the type of leukemia, and determines the immunophenotype of the LSC specific to the leukemia type. In lymphoid leukemia’s no clear LSC phenotype has been described and it is debated if a specific acute lymphocytic leukemia initiating cell is present, as all cells are capable of engraftment in a secondary mouse model. In chronic lymphocytic leukemia, a B-cell clone is responsible for uncontrolled proliferation and not a specific LSC. In myeloid malignancies, the LSC are described as CD34+CD38- with the expression of an LSC marker, such as CD45RA, CD123 or in the case of chronic myeloid leukemia CD26. In acute myeloid leukemia, the LSC load had prognostic relevance and might be a biomarker that can be used for monitoring and as addition on measurable residual disease. However, challenges such as the CD34-negative immunophenotype needs to be explored. |
1:30 - 3:00 PM | Room 300 |
Concurrent 12: Updates in Hemostasis and Thrombosis |
Chair(s): Cathy Hayward |
2:00 |
Microparticles In Hemostasis Aix-Marseille Universite Microparticles in Hamostasis Microvesicles/microparticles or large extracellular vesicle (EV) are membrane-enclosed vesicles derived from activated cells whose composition and biological role vary according to the cellular origin and the stimuli that led to their generation. They have long been associated with a procoagulant activity due to the expression of anionic phospholipids and the exposure of Tissue Factor. However, their contribution to hemostasis is not exclusively procoagulant but depends on a balance between their procoagulant and fibrinolytic activities. We showed that fibrinolytic EV of granulocyte origin are protective in patients with severe sepsis, whereas procoagulant EV carrying tissue factor are predictive of severity and the occurrence of thrombosis in COVID-19 patients. A better understanding of the coagulolytic balance of EV opens the way to new biomarkers and therapeutic strategies for a more personalized medicine in the management of infectious coagulopathies. Nevertheless, several challenges regarding the standardization and automation of EV measurement still need to be addressed to allow their use in clinical practice. |
2:30 |
How To Investigate Bleeding Of Unknown Cause/Mild Bleeding Disorder? Division of Angiology and Hemostasis, University Hospitals of Geneva, Switzerland A bleeding tendency is one of the most common complaints observed by hematologists. It is challenging to differentiate a clinically insignificant bleeding from a bleeding phenotype that requires hemostatic evaluation and medical intervention. A thorough review of personal and familial history, objective assessment of bleeding severity using a bleeding assessment tool, and a focused physical examination are critical to correctly identifying suspected patients with mild to moderate bleeding disorders (MBDs). A basic laboratory work-up should be performed in all patients referred for a bleeding tendency. If a hemostatic abnormality is found such as evidence of von Willebrand disease, a platelet function disorder, or a coagulation factor deficiency, more extensive testing should be performed to further characterize the bleeding disorder. Conversely, if all results are normal the patient is considered to have bleeding disorder of unknown cause (BDUC). For patients with BDUC, further evaluation may include non-routine testing to look for rare bleeding disorders not detected by routine hemostasis tests, such as thrombomodulin-associated coagulopathy, tissue factor pathway inhibitor-related bleeding disorder, hyperfibrinolytic bleeding disorders or impaired tissue factor production. |
3:00 - 3:30 PM | Auditorium |
Best of ISLH 2024 - Looking Forward to 2025 - Awards |
Chair(s): John Frater |