International Council for Standardization in Haematology recommendations for laboratory measurement of factor VIII and FIX type I inhibitors.

This guidance document has been prepared on behalf of the International Council for Standardisation in Hematology. The aim of the document is to provide guidance and recommendations on the measurement of factor VIII (FVIII) and factor IX (FIX) inhibitors. After an introduction on the clinical background and relevance of factor VIII and factor IX inhibitor testing, the following aspects of laboratory testing are included: screening for inhibitors, assay principle, sample requirements, testing requirements and interpretation, quality assurance, interferences and recent developments. This guidance document focusses on recommendations for a standardised procedure for the laboratory measurement of FVIII and FIX type I inhibitors. The recommendations are based on published data in peer-reviewed literature and expert opinion.

Australian and New Zealand consensus guideline for paediatric newly diagnosed immune thrombocytopaenia endorsed by Australian New Zealand Children's Haematology and Oncology Group.

In children, the majority of cases are self-limiting and thus many paediatric patients can be managed conservatively with minimal complications. This varies considerably compared to adult newly diagnosed immune thrombocytopaenia (NDITP) where, in most cases, thrombocytopaenia persists with higher risk of moderate to severe bleeding complications. In the past decade, local and international guidelines have emerged to support approaches to the investigation and management of NDITP, with a focus primarily on adult immune thrombocytopaenia (ITP). International consensus guidelines on paediatric NDITP have been developed, however gaps remain, and approaches vary between North American, Asia, Europe and the UK. There are no current Australian or New Zealand paediatric ITP guidelines readily available, rather differing guidelines for each state, territory or island. These inconsistencies cause uncertainty for patients, families and physicians managing cases. Subsequently, physicians, including paediatric haematologists and general paediatricians, have come together to provide a consensus approach guideline specific to paediatric NDITP for Australian or New Zealand. Persistent or chronic paediatric ITP remains a complex and separate entity and are not discussed here.

Quality control validation for a veterinary laboratory network of six Sysmex XT-2000iV hematology analyzers.

BACKGROUND: Quality control (QC) validation is an important step in the laboratory harmonization process. This includes the application of statistical QC requirements, procedures, and control rules to identify and maintain ongoing stable analytical performance. This provides confidence in the production of patient results that are suitable for clinical interpretation across a network of veterinary laboratories. OBJECTIVES: To determine that a higher probability of error detection (Ped ) and lower probability of false rejection (Pfr ) using a simple control rule and one level of quality control material (QCM) could be achieved using observed analytical performance than by using the manufacturer's acceptable ranges for QCM on the Sysmex XT-2000iV hematology analyzers for veterinary use. We also determined whether Westgard Sigma Rules could be sufficient to monitor and maintain a sufficiently high level of analytical performance to support harmonization. METHODS: EZRules3 was used to investigate candidate QC rules and determine the Ped and Pfr of manufacturer's acceptable limits and also analyzer-specific observed analytical performance for each of the six Sysmex analyzers within our laboratory system using the American Society of Veterinary Clinical Pathology (ASVCP)-recommended or internal expert opinion quality goals (expressed as total allowable error, TEa ) as the quality requirement. The internal expert quality goals were generated by consensus of the Quality, Education, Planning, and Implementation (QEPI) group comprised of five clinical pathologists and seven laboratory technicians and managers. Sigma metrics, which are a useful monitoring tool and can be used in conjunction with Westgard Sigma Rules, were also calculated. RESULTS: The QC validation using the manufacturer's acceptable limits for analyzer 1 showed only 3/10 measurands reached acceptable Ped for veterinary laboratories (>0.85). For QC validation based on observed analyzer performance, the Ped was >0.94 using a 1-2.5s QC rule for the majority of observations (57/60) across the group of analyzers at the recommended TEa . We found little variation in Pfr between manufacturer acceptable limits and individual analyzer observed performance as this is a characteristic of the rule used, not the analyzer performance. CONCLUSIONS: An improved probability of error detection and probability of false rejection using a 1-2.5s QC rule for individual analyzer QC was achieved compared with the use of the manufacturers' acceptable limits for hematology in veterinary laboratories. A validated QC rule (1-2.5s) in conjunction with sigma metrics (>5.5), desirable bias, and desirable CV based on biologic variation was successful to evaluate stable analytical performance supporting continued harmonization across the network of analyzers.

Electronic case report forms generation from pathology reports by ARGO, automatic record generator for onco-hematology.

The unstructured nature of Real-World (RW) data from onco-hematological patients and the scarce accessibility to integrated systems restrain the use of RW information for research purposes. Natural Language Processing (NLP) might help in transposing unstructured reports into standardized electronic health records. We exploited NLP to develop an automated tool, named ARGO (Automatic Record Generator for Onco-hematology) to recognize information from pathology reports and populate electronic case report forms (eCRFs) pre-implemented by REDCap. ARGO was applied to hemo-lymphopathology reports of diffuse large B-cell, follicular, and mantle cell lymphomas, and assessed for accuracy (A), precision (P), recall (R) and F1-score (F) on internal (n = 239) and external (n = 93) report series. 326 (98.2%) reports were converted into corresponding eCRFs. Overall, ARGO showed high performance in capturing (1) identification report number (all metrics > 90%), (2) biopsy date (all metrics > 90% in both series), (3) specimen type (86.6% and 91.4% of A, 98.5% and 100.0% of P, 92.5% and 95.5% of F, and 87.2% and 91.4% of R for internal and external series, respectively), (4) diagnosis (100% of P with A, R and F of 90% in both series). We developed and validated a generalizable tool that generates structured eCRFs from real-life pathology reports.

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.

Specification and Evaluation of Plasticizer Migration Simulants for Human Blood Products: A Delphi Study.

Potentially toxic plasticizers are commonly added to polyvinyl chloride medical devices for transfusion in order to improve their flexibility and workability. As the plasticizers are not chemically bonded to the PVC, they can be released into labile blood products (LBPs) during storage. Ideally, LBPs would be used in laboratory studies of plasticizer migration from the medical device. However, short supply (i.e., limited stocks of human blood in collection centres) has prompted the development of specific simulants for each type of LBP in the evaluation of new transfusion devices. We performed a Delphi study with a multidisciplinary panel of 24 experts. In the first (qualitative) phase, the panel developed consensus definitions of the specification criteria to be met by each migration simulant. Next, we reviewed the literature on techniques for simulating the migration of plasticizers into LBPs. A questionnaire was elaborated and sent out to the experts, and the replies were synthesized in order to obtain a consensus. The qualitative study established specifications for each biological matrix (whole blood, red blood cell concentrate, plasma, and platelet concentrate) and defined the criteria required for a suitable LBP simulant. Ten criteria were suggested: physical and chemical characteristics, opacity, form, stability, composition, ability to mimic a particular clinical situation, ease and safety of use, a simulant-plastic interaction correlated with blood, and compatibility with analytical methods. The questionnaire data revealed a consensus on the use of natural products (such as pig's blood) to mimic the four LBPs. Opinions diverged with regard to synthetic products. However, an isotonic solution and a rheological property modifier were considered to be of value in the design of synthetic simulants. Consensus reached by the Delphi group could be used as a database for the development of simulants used to assess the migration of plasticizers from PVC bags into LBPs.

Maintaining an Adult Hematology/Oncology Service at a Tertiary Care Center during the SARS-CoV-2 Pandemic: An Eight-Week-Experience with a Newly Implemented Procedural Plan.

Treatment of cancer patients has become challenging when large parts of hospital services need to be shut down as a consequence of a local COVID-19 outbreak that requires rapid containment measures, in conjunction with the shifting of priorities to vital services. Reports providing conceptual frameworks and first experiences on how to maintain a clinical hematology/oncology service during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are scarce. Here, we report our first 8 weeks of experience after implementing a procedural plan at a hematology/oncology unit with its associated cancer center at a large academic teaching hospital in Germany. By strictly separating team workflows and implementing vigorous testing for SARS-CoV-2 infections for all patients and staff members irrespective of clinical symptoms, we were successful in maintaining a comprehensive hematology/oncology service to allow for the continuation of treatment for our patients. Notably, this was achieved without introducing or further transmitting SARS-CoV-2 infections within the unit and the entire center. Although challenging, our approach appears safe and feasible and may help others to set up or optimize their procedures for cancer treatment or for other exceedingly vulnerable patient cohorts.

Clinical laboratory reference values in adults in Kisumu County, Western Kenya; hematology, chemistry and CD4.

BACKGROUND: Clinical laboratory reference intervals (RIs) are essential for diagnosing and managing patients in routine clinical care as well as establishing eligibility criteria and defining adverse events in clinical trials, but may vary by age, gender, genetics, nutrition and geographic location. It is, therefore, critical to establish region-specific reference values in order to inform clinical decision-making. METHODS: We analyzed data from a prospective observational HIV incidence cohort study in Kombewa, Kenya. Study participants were healthy males and females, aged 18-35 years, without HIV. Median and 95% reference values (2.5th percentile to 97.5th percentile) were calculated for laboratory parameters including hematology, chemistry studies, and CD4 T cell count. Standard Deviation Ratios (SDR) and Bias Ratios (BR) are presented as measures of effect magnitude. Findings were compared with those from the United States and other Kenyan studies. RESULTS: A total of 299 participants were analyzed with a median age of 24 years (interquartile range: 21-28). Ratio of males to females was 0.9:1. Hemoglobin range (2.5th-97.5th percentiles) was 12.0-17.9 g/dL and 9.5-15.3 g/dL in men and women respectively. In the cohort, MCV range was 59-95fL, WBC 3.7-9.2×103/µL, and platelet 154-401×103/µL. Chemistry values were higher in males; the creatinine RI was 59-103 µmol/L in males vs. 46-76 µmol/L in females (BRUL>.3); and the alanine transferase range was 8.8-45.3 U/L in males vs. 7.5-36.8 U/L in females (SDR>.3). The overall CD4 T cell count RI was 491-1381 cells/µL. Some parameters including hemoglobin, neutrophil, creatinine and ALT varied with that from prior studies in Kenya and the US. CONCLUSION: This study not only provides clinical reference intervals for a population in Kisumu County but also highlights the variations in comparable settings, accentuating the requirement for region-specific reference values to improve patient care, scientific validity, and quality of clinical trials in Africa.

2021 update of the AGIHO guideline on evidence-based management of COVID-19 in patients with cancer regarding diagnostics, viral shedding, vaccination and therapy.

The worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated infectious coronavirus disease (COVID-19) has posed a unique challenge to medical staff, patients and their families. Patients with cancer, particularly those with haematologic malignancies, have been identified to be at high risk to develop severe COVID-19. Since publication of our previous guideline on evidence-based management of COVID-19 in patients with cancer, research efforts have continued and new relevant data has come to light, maybe most importantly in the field of vaccination studies. Therefore, an update of our guideline on several clinically important topics is warranted. Here, we provide a concise update of evidence-based recommendations for rapid diagnostics, viral shedding, vaccination and therapy of COVID-19 in patients with cancer. This guideline update was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology by critically reviewing the currently available data on these topics applying evidence-based medicine criteria.

Inhibitor development in mild haemophilia after a major surgery for periampullary cancer (Whipple's procedure) in an elderly man.

Around the world, with the availability of factor concentrates, patients with haemophilia have undergone major and minor surgeries. Inhibitor development in early postoperative period leading to inadequate factor recovery and ongoing bleeding is a nightmare for both operating surgeon as well as haematologists. We describe a case of an elderly man with mild haemophilia A, who was diagnosed with pancreatic carcinoma and underwent Whipple's procedure. After an uneventful procedure, he developed high-titre inhibitors and bleeding a week after surgery posing major challenges in his management. The case highlights the importance of experienced surgeons, trained haematologists, regular monitoring of factor assay/inhibitors, adequate factor and bypassing-agent support while performing such procedures.

Defining Normal Healthy Term Newborn Automated Hematologic Reference Intervals at 24 Hours of Life.

CONTEXT.­: Automated analyzers have advanced the field of clinical hematology, mandating updated complete blood count (CBC) reference intervals (RIs) to be clinically useful. Contemporary newborn CBC RI publications are mostly retrospective, which some authors have cited as one of their cardinal limitations and recommended future prospective studies. OBJECTIVE.­: To prospectively establish accurate hematologic RIs for normal healthy term newborns at 24 hours of life given the limitations of the current medical literature. DESIGN.­: This prospective study was conducted at an academic tertiary care center, and hematology samples were collected from 120 participants deemed to be normal healthy term newborns. Distributions were assessed for normality and tested for outliers. Reference intervals were values between the 2.5th percentile and 97.5th percentile. RESULTS.­: The novel RIs obtained for this study population are as follows: absolute immature granulocyte count, 80/µL to 1700/µL; immature granulocyte percentage, 0.6% to 6.1%; reticulocyte hemoglobin equivalent, 31.7 to 38.4 pg; immature reticulocyte fraction, 35.9% to 52.8%; immature platelet count, 4.73 × 103/µL to 19.72 × 103/µL; and immature platelet fraction, 1.7% to 9.8%. CONCLUSIONS.­: This prospective study has defined hematologic RIs for this newborn population, including new advanced clinical parameters from the Sysmex XN-1000 Automated Hematology Analyzer. These RIs are proposed as the new standard and can serve as a strong foundation for continued research to further explore their value in diagnosing and managing morbidities such as sepsis, anemia, and thrombocytopenia.

Central venous catheter-related infections in hematology and oncology: 2020 updated guidelines on diagnosis, management, and prevention by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

Cancer patients frequently require central venous catheters for therapy and parenteral nutrition and are at high risk of central venous catheter-related infections (CRIs). Moreover, CRIs prolong hospitalization, cause an excess in resource utilization and treatment cost, often delay anti-cancer treatment, and are associated with a significant increase in mortality in cancer patients. We therefore summoned a panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) and updated our previous guideline on CRIs in cancer patients. After conducting systematic literature searches on PubMed, Medline, and Cochrane databases, video- and meeting-based consensus discussions were held. In the presented guideline, we summarize recommendations on definition, diagnosis, management, and prevention of CRIs in cancer patients including the grading of strength of recommendations and the respective levels of evidence. This guideline supports clinicians and researchers alike in the evidence-based decision-making in the management of CRIs in cancer patients.

Laboratory practices for manual blood film review: Results of an IQMH patterns of practice survey.

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.

An assessment of the continuing medical education needs of US physicians in the management of patients with beta thalassemia.

Patients with beta thalassemia are benefitting from longer life expectancies, highlighting the importance of appropriate transition from pediatric to adult care. Data are limited regarding continuity of care and adult hematologists' management of patients with beta thalassemia. We conducted a survey of practicing US hematologists to identify practice gaps, attitudes, and barriers to optimal patient management among US-practicing hematologists. A total of 42 responses were collected, with 19 (45%) practicing at a beta thalassemia center of excellence (CoE). Nearly 90% of CoE physicians said they had a transition protocol or plan in place versus 30% of non-CoE physicians. Most physicians said parents should remain actively involved in medical visits. Adherence was rated as the most important patient education topic during transition. The most significant barrier cited was patient reluctance to transition away from pediatric care. Physicians in CoEs as compared with non-CoE physicians reported greater knowledge of beta thalassemia and familiarity with butyrates, gene therapy, and luspatercept. Highly rated topics for beta thalassemia-focused CME activities included management of complications and clinical trial updates. These findings suggest practice gaps and barriers to optimal care in the transition from pediatric to adult care, the ongoing management of adult patients, knowledge of the disease state, and familiarity with emerging treatments. Differences CoE vs non-CoE physician responses suggest variations in knowledge, practice, and attitudes that may be helpful in tailoring CME activities to different learner audiences. The small sample size used in some sub-analyses may not be representative of all hematologists treating beta thalassemia patients.