Innovations 2022 in hematological biology

Véronique Deneys1, Antoine Buemi2*, Virginie Chapelle1, Tom Darius2*, Martine De Meyer2*, Arnaud Devresse2,3*, Yannick France2*, Valérie Dumont2, Thibaut Gervais1, Eric Goffin3*, Louise Guillaume, Nada Kanaan³*, Youssra Khaouch1, Catherine Lambert1*, Urs Published in the journal : February 2023 Category : Biologie Hématologique

The year 2022 saw a gradual return to normal after the COVID-19 pandemic. This was an opportunity to optimize processes that had sometimes been undermined and to update procedures. It was also an occasion to take on new challenges: to consider acquiring new equipment for the coming years, to implement new techniques that are more sensitive, faster, and better adapted to the needs of prescribers.

In the Special Hematology Laboratory, and in particular in the specialized hemostasis sector, the automation of the ADAMTS13 protein assay was critical for the diagnosis and biological follow-up of patients with immune thrombotic thrombocytopenic purpura (iTTP). This uncommon condition can rapidly deteriorate if not diagnosed early and managed appropriately based on ADAMTS13 testing. This assay also allows identifying patients at risk of relapse who should receive preventive treatment.

The determination of erythrocyte blood groups is most often straightforward using serological techniques. However, in certain situations, it is necessary to use molecular biology techniques. The Immunohematology - Molecular Biology Laboratory has implemented a real-time PCR technique that allows for extensive erythrocyte genotyping and the detection of antigenic variants missed by serological techniques. This is an essential tool for determining blood groups in polytransfused patients and for selecting bags for individuals with a variant or deletion blood group.

It has been known for over 50 years that the HLA system plays a central role in human immunity and is at the same time one of the main obstacles to organ transplantation. The involvement of anti-HLA antibodies in early and late rejection is indisputable. In 2021, the Leuko-Platelet Immunology Laboratory has implemented a new test for a more specific identification of clinically relevant anti-HLA antibodies, which facilitates graft allocation. In 2022, the records of patients awaiting renal transplant who had anti-HLA antibodies were reviewed, and controls were performed on old sera using the new technique. This allowed the removal of "forbidden" antibody specificities in more than half of the patients, thereby increasing their chance of receiving a compatible graft. Six patients received a kidney graft carrying an HLA antigen previously listed as forbidden with the old technology and removed after revision. Currently, all these patients have displayed a functional graft without immunological complications. These results will be presented at the European Foundation for Immunogenetics (EFI) Congress in April 2023. Although transfusion is a common and beneficial therapeutic procedure for the patient, transfusion reactions can occur. The diagnosis of these reactions is sometimes confusing and difficult. The Hemovigilance Transfusion Sector has developed new decision-making algorithms based on the main symptoms presented by the patient and the blood component involved in the reaction. These algorithms are intended to guide towards a diagnosis and, in order to achieve this, to determine the controls and laboratory tests that must be carried out in each situation. These algorithms have been published in the journal of the Société Francophone de Transfusion Sanguine.

While there were already warning signs of a shortage in 2021, the supply situation for O-negative red blood cells worsened considerably in 2022. The Blood Bank, in consultation with the Medical Direction and the Transfusion Committee, had to deal with this by implementing various actions to try to stop the "hemorrhage". This is the subject of a specific procedure: implementation of very strict and closely monitored indicators, prioritization of transfusion indications, exclusive unitary distribution (outside of hemorrhagic situations), and medical decision to transfuse Rh-positive erythrocyte concentrates to Rh-negative recipients. Various very precise assessments of this situation are still underway and will soon be submitted for publication. Concerted action has been taken within the network hospitals and initiatives are also being taken at the national level.

Finally, the year 2022 also witnessed the publication of a new European directive and new EDQM (European Directorate for the Quality of Medicines) standards defining blood as a SoHO (Substance of Human Origin), similar to cells and tissues. For this reason, it was decided that the Blood Bank and the Erythrocyte Immunology Laboratory would join the Banking Department as of January 1, 2023.

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Case report of a pseudoaneurysm of the pedal artery: a rare ankle sprain complication

Yaseen Golamhossein, Pierre Milet Published in the journal : January 2023 Category : Clinical Report

Ankle sprains represent a frequent reason for general or emergency medicine consultations. The most common complications are ligament lesions, bone avulsions, and hemarthroses. The pseudoaneurysm of the pedal artery is an often overlooked and rare complication. The case presented in this article is that of a 32-year-old man treated for a sprained ankle 3 weeks before. He received conservative treatment because no fractures were detected during the X-ray examination. Two weeks later, he presented with a pulsatile mass in front of the anterior talofibular ligament, associated with a small wound.

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Use of a molecular multiplex real-time PCR system (BD MAX™) for enteric pathogens detection in microbiology laboratory

Ekaterina Melnik, Denis Daspremont, Tatiana Roy, Valérie Verbelen, Gatien Roussel Published in the journal : January 2023 Category : Microbiology

The development of molecular biology led to a new diagnostic tactic for gastrointestinal infections: a syndromic approach, which led to the development of numerous multipathogen molecular polymerase chain reaction (PCR) panels. We evaluated the BD MAX™ (BD Diagnostics, USA) system and compared the results with conventional methods used in our microbiology laboratory to determine if this approach could be implemented as a routine analysis. We also highlighted the practical advantages of a multipathogen molecular panel: reduction of the number of needed technologists needed per day to perform microbiological stool analyzes, easier stock management, and complete traceability for each clinical sample of reagents, expiry date, and user. Moreover, the the BD MAX™ system is easy to use, requires minimal training, and the bidirectional connection with the Laboratory Information System enables a more reliable encoding of the results. In some laboratories, molecular panels already replace conventional methods. Some of these panels’ performances are very satisfactory and their cost are gradually becoming more affordable. Each microbiology laboratory can therefore consider the integration of a multipathogen molecular PCR panel in their routine work.

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Endocrine side effects of opioids treatments

Anne Dysseleer, Dominique Maiter Published in the journal : January 2023 Category : Endocrinology

The first traces of opium use date back to the time of the Sumerians, around four thousand years before our era. The Egyptians employed it to soothe crying children. After briefly reviewing the pharmacology of opium derivatives and opioids, we will discuss their still poorly understood endocrine side effects. The steadily increasing use of opioids in medical practice and their misuse have uncovered a whole series of side effects on several hypothamic-pituitary endocrine axes. These side effects can have a significant impact on the general health and quality of life of patients who use them chronically. It is therefore crucial for clinicians to recognize them. In the present article, we will review the main symptoms to look for, the additional examinations which should be carried out, and the appropriate management of these patients.

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Platelet factor 4 (PF4): roles and pathophysiological implications

Hélène Georgery, Cédric Hermans Published in the journal : January 2023 Category : Hematology/Oncology

Platelet factor 4 (PF4) is a positively charged molecule stored in the alpha granules of blood platelets and secreted during platelet activation, endothelial breach, or in the presence of microorganisms. PF4 binds to glycosaminoglycans on the endothelial surface and neutralizes their anticoagulant properties. Moreover, PF4 can combine with heparin, mainly unfractionated, in heparin-induced thrombocytopenia (HIT), with cartilage components or other negatively charged polyanions (so-called spontaneous HIT), and with some constituents of the SARS-CoV-2 adenovirus vaccine, resulting in post-vaccination thrombocytopenia. The common feature of these molecules is their negative charges which induce their binding to PF4 and a conformational change of the latter. This complex is recognized by anti-PF4 antibodies, which activate platelets and inflammatory cells via the Fc receptor, induce a pro-thrombotic state, and venous, arterial, or microcirculation thrombosis. The diagnosis of HIT is based on the detection of anti-PF4-heparin antibodies by immunoassay in cases of clinical suspicion and intermediate or high pre-test probability, estimated by different scores, the 4T score being the most common. Functional tests may also be performed. HIT management consists in stopping heparin and starting non-heparin anticoagulant therapy.

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Spontaneous pneumothorax in a pregnant woman : difficulty of diagnosis and treatment

Natacha De Decker (1), Pol Vincent (1), Thierry Castelain (2), Paula Blaj (2), Pascale Grandjean (3), Sophie Gilles (3), Tudor Azoicai (1) Published in the journal : December 2022 Category : Clinical Report

Spontaneous pneumothorax is a frequent cause of admission to emergency departments. Its etiology and lethal potential if not diagnosed are well known. However, there are less common etiologies of this condition. The diagnosis can then be tricky, especially since the symptoms may be equivocal. This is the case of spontaneous pneumothorax in pregnant women with no risk factors, in whom the symptoms may mimic those observed during the last trimester of pregnancy.

In this context, we wish to report a case of spontaneous pneumothorax in a 32-week pregnant wo-man, without any known risk factor. We also propose a literature review on this subject.

Our analysis highlights that spontaneous pneumothorax in pregnant women is a rare condition whose diagnosis may be overlooked, given the clinical manifestations that may be confused with physiological phenomena of the last trimester of pregnancy.

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Recognizing, understanding, and treating angioedema in the emergency room

Cédric Hermans (1), Emilie Delloye (2), Françoise Pirson (3,4,5) Published in the journal : December 2022 Category : Urgence/Allergologie - Immunologie/Hématologie

Angioedema, whether related to histamine release or excessive bradykinin, is a common reason for admission to the emergency department. This condition is a potentially serious and even fatal condition. Its diagnostic and therapeutic management can be difficult. This article details the practical management of angioedema in the emergency room, particularly its bradykinic form, as well as the modalities and objectives of the specialized allergology assessment, which is frequently indicated. Finally, this article gives a special look at hereditary angioedema, a rare disease justifying a specialized therapeutic management, which has recently been revolutionized by the advent of new and very promising molecules.

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Primary care medicine in the management of the SARS-CoV-2 pandemic: international perspectives

Published in the journal : December 2022 Category : Médecine Générale

Why such a symposium?

In the winter of 2021, when the beginnings of a possible way out of the Covid-19 crisis were appearing, many of us made the same observation: primary care medicine, that is medicine that goes from individual or group medical practices to large urban policlinics and nursing homes, has certainly played an important role in the management of the pandemic, but its potential has been insufficiently exploited, particularly by the authorities in charge of public decisions. This observation has been confirmed by international bodies such as the WHO and the OECD. We therefore felt that it would be interesting to take our heads off the wheel, to distance ourselves from all of our activities deployed during the pandemic (care, screening, vaccination, etc.) and to organize an exchange of experiences in order to build a body of knowledge and propose recommendations in four countries: Belgium, Canada, France and Switzerland. The commonalities shared by these four countries, whether at the historical (thank you Napoleon!), linguistic, cultural, societal, academic and of course health system levels (universal coverage, private and/or public insurers, among others), facilitate such an exchange dynamic.

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COVID-19, cardiovascular manifestations, and competitive sport in the pediatric population

Jelena Hubrechts¹, Stéphane Moniotte¹ Published in the journal : December 2022 Category : Pediatrics

Since 2019, the SARS-CoV-2 has been associated with the occurrence of myocarditis. Moreover, specifically in the pediatric population, this virus can cause an exaggerated inflammatory response several weeks after the acute infection. This new entity is called “multisystem inflammatory syndrome in children” (MIS-C). Cardiovascular involvement is very common in this syndrome, particularly in the form of ventricular dysfunction with increased cardiac enzymes. As myocardial damage is one of the causes of sudden cardiac death in young athletes, resumption of sporting activities must be undertaken with caution. Depending on initial symptoms, a focused history taking and meticulous physical examination may be sufficient to permit resumption of sports after the legal duration of quarantine in case of simple COVID-19 infection. In other cases, the patient should be referred to a pediatric cardiologist for a more comprehensive workup. For patients with MIS-C, sport remains contraindicated for a period of 3 to 6 months. Sport should in any case be resumed gradually, with the patient, his parents, and trainers being made aware of the possible appearance of cardiorespiratory symptoms.

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Fulminant hepatitis complicated by a reactive hemophagocytic syndrome in an immunocompetent patient: two rare manifestations of Herpes simplex virus 1 infection.

Sarah Brilot (1), Esther Calvo Lasso De La Vega (2), Christian Michaux (2), Leïla Belkhir (1), Lucie Pothen (1) Published in the journal : December 2022 Category : Clinical Report

Fulminant hepatitis is a rare and fatal complication of Herpes simplex virus 1 (HSV1) infection, which can affect both immunocompetent and immunodeficient adults. The diagnosis is often delayed due to the rapid evolution of the infection, hence the importance of initiating rapid treatment with aciclovir. We report the case of a 36-year-old patient with no medical history who consulted for sudden asthenia after two days of fever and myalgia. The initial laboratory workup revealed hepatic cytolysis and bicytopenia (thrombocytopenia and leukopenia). The evolution was rapidly unfavorable, with the development of acute hepatic failure and a reactive hemophagocytic syndrome. The etiological workup then revealed an HSV1 infection. Treatment with aciclovir resulted in clinical and biological improvement, and the patient fully recovered.

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