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Non-BCR-ABL myeloproliferative neoplasms includes Vaquez polycythemia, essential thrombocythemia and primary myelofibrosis. Arterial and venous thrombosis are the main causes of morbidity and mortality in these diseases. Although the pathophysiology of thrombosis is becoming better understood, there are still many unknowns in the therapeutic management of these patients, both in terms of primary prevention and the management of an inaugural thrombosis or secondary prevention. In addition, there are few or no recommendations to help clinicians. In this review, we propose a course of action for the management of these complex situations, based on data from the literature and our own experience. We also devote a section to the role of direct oral anticoagulants and the management of splanchnic thrombosis, which is over-represented in myeloproliferative neoplasms. [ABSTRACT FROM AUTHOR]

During a blood test, the discovery of thrombocytosis is a frequent phenomenon with multiple origins. False thrombocytosis linked to analytical interferences is rare but must be eliminated before confirming the anomaly. The reaction origin, often very easily demonstrated by the context and/or the presence of a biological inflammatory syndrome, is the most frequent. More rarely, the diagnosis is oriented towards a clonal hematological pathology not limited to essential thrombocythemia. Currently, many biological tools, which have largely contributed to the recommendations of the latest WHO classification of chronic myeloid neoplasms, are available to classify these pathologies as precisely as possible, allowing optimal management. [ABSTRACT FROM AUTHOR]

Introduction. Essential thrombocythemia (ET) is a clonal disorder of the hematopoietic stem cells characterized by persistent thrombocytosis in the peripheral blood, excessive proliferation of megakaryocytes and minor reticulin fibrosis in the bone marrow. It seems that oxidative stress is involved in the development and progression of ET. Objective. To evaluate oxidative stress levels in ET patients treated with risk-adapted therapy. Material and methods. 62 ET patients and 20 controls (informed consent obtained) were enrolled. ET diagnosis was based on WHO criteria (2016 revised). Reactive oxygen species (ROS) levels and the total antioxidant capacity (TAC) were evaluated at time of diagnosis and after 6 months of risk-adapted therapy. ET patients were divided into 3 groups and treated with risk–adapted therapy: a low risk group, treated with low doses of aspirin 75 mg/day or watch-and-wait; an intermediate risk group treated with low doses of aspirin 100 mg/day or low-dose aspirin + cytoreductive treatment; a high-risk group, treated with low doses of aspirin and cytoreductive treatment (hydroxyurea) or platelet-lowering agents (anagrelide). Results. ET patients had at diagnosis higher ROS levels and a lower TAC vs. controls. After 6 months of risk-adapted therapy, ROS levels decreased and TAC increased. No significant differences were seen between the effect of hydroxyurea and the effect of anagrelide on oxidative stress levels. Conclusions. ROS levels are increased and TAC is decreased in ET patients vs. controls. These values depend on the risk group assigned to the patient. Risk-adapted therapy was useful to reduce ROS levels and increase TAC.

In patients with myeloproliferative neoplasms (MPNs), including essential thrombocythemia, current studies have demonstrated a JAK2V617F-dependent reactive oxygen species (ROS) elevation partially mediated by a decrease in catalase expression associated with DNA damage. Oxidative stress plays a major role in carcinogenesis as well as in genomic instability, disease progression, myelofibrotic and leukemic transformation, and possibly in the development of vascular events in patients with essential thrombocythemia. Further comprehensive studies are needed to establish the role of oxidative stress in the pathogenesis of essential thrombocythemia, disease progression, vascular complications and whether targeting ROS as a therapeutic option could prevent disease progression and the development of vascular events MPNs patients.

Résumé: Les syndromes myéloprolifératifs (SMP) sont des pathologies clonales myéloïdes ayant pour trait commun un excès de cellules matures myéloïdes, qui peut être à l'origine de complications hématologiques et/ou thrombotiques. Cette revue abordera les SMP classiques, « Philadelphie négatifs », que sont la polyglobulie de Vaquez, la thrombocytémie essentielle et la myélofibrose primitive. Nous n'aborderons pas dans cette revue la leucémie myéloïde chronique, les syndromes éosinophiliques chroniques ni la leucémie chronique à polynucléaires neutrophiles. Myeloproliferative neoplasm (MPN) is characterized by clonal myeloproliferation that is often but not always accompanied by JAK2, CALR, or MPL mutation associated with excel myeloid mature cell in blood. Thrombosis and hematologic evolution (fibrosis and acute myeloid leukemia) are the major complications. This review is about MPN Philadelphia negative, including polycythemia vera, essential thrombocythemia, and primitive myelofibrosis. Chronic myeloid leukemia and eosinophilic myeloproliferative disease will be not discussed. [ABSTRACT FROM AUTHOR]

Résumé Dans les classifications de l’OMS des néoplasies myéloprolifératives, l’analyse d’une biopsie ostéo-médullaire est un examen de premier plan nécessaire au diagnostic et à l’évaluation du pronostic. L’entité « pré-fibrose », décrite depuis plusieurs années comme distincte de la myélofibrose primitive avec myélofibrose franche, fait son entrée dans la version la plus récente de ces classifications, publiée en 2016. La place de la biopsie dans le diagnostic de maladie de Vaquez est également renforcée. Des comités de relecture regroupant des hémato-pathologistes se mettent en place afin d’améliorer la reproductibilité des critères histologiques. Summary In WHO classifications of myeloproliferative neoplasms, a bone marrow biopsy at diagnosis is mandatory in almost all cases to classify the disease as well as to evaluate the prognosis. The “pre-fibrotic” form, which has been described for several years as distinct from primary myelofibrosis with overt myelofibrosis, is included in the most recent version of these classifications published in 2016. The importance of the biopsy in the diagnosis of polycythemia vera is also growing. Re-evaluation committees bringing together hematopathologists are set up to improve the reproducibility of these histological criteria. [ABSTRACT FROM AUTHOR]

Résumé Le traitement de la polyglobulie de Vaquez et de la thrombocytémie essentielle consiste à limiter le risque de complications thrombo-hémorragiques et à la préservation de la qualité de vie en essayant de prévenir le risque de transformation hématologique à long terme. Dans la myélofibrose primitive, l’état général et la sévérité de la maladie doivent être appréciés pour juger de la meilleure stratégie thérapeutique incluant les thérapies ciblées et la place de l’allogreffe. Dans tous les cas, la présentation des dossiers en RCP d’hématologie est fortement recommandée et la biologie moléculaire prend une place croissante. Summary The treatment of polycythemia vera and essential thrombocythemia aims to limit the risk of thrombo-hemorrhagic complications, to preserve the quality of life and to prevent the risk of long-term hematologic transformation. In primary myelofibrosis, the patient's general condition and the severity of the disease should be assessed to adopt the best therapeutic strategy including new therapies and bone marrow transplantation. In all cases, the presentation in a hematological mutidisciplinary board is strongly recommended and place of molecular biology is growing. [ABSTRACT FROM AUTHOR]

Résumé Les syndromes myéloprolifératifs « non LMC » comprennent la polyglobulie de Vaquez (PV), la thrombocytémie essentielle (TE) et la myélofibrose primitive (MFP). La PV et la TE sont des maladies d’évolution lente alors que la MFP est une maladie plus sévère. À terme, la gravité des SMP est liée au risque d’évolution vers une transformation hématologique et, initialement, la morbidité est liée aux complications vasculaires. La découverte de la mutation V617F de JAK2 a amélioré les connaissances sur la physio-pathologie des SMP et en a modifié le diagnostic. La mise en évidence des mutations de CALR et de MPL permet, à l’heure actuelle, de disposer d’un marqueur moléculaire dans 90% des cas. Avec le développement du séquençage de nouvelle génération, d’autres mutations sont détectées dont le rôle est encore mal connu, mais qui sont parfois associées à un pronostic péjoratif. Dix ans après JAK2 V617F, et avec l’arrivée des thérapies ciblées, l’identification des patients avec un mauvais pronostic est un des enjeux dans les SMP. Summary Philadelphia negative myeloproliferative neoplasms (MPN) include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). PV and ET are very chronic diseases while MFP is a more severe one. Long-term prognosis of MPN is related to the risk of hematologic transformation, but initial morbidity is mainly related to vascular complications. The discovery of the JAK2 V617F mutation has improved our knowledge on the pathophysiology of MPN and has changed diagnosis algorithms. With the recent discovery of CALR and MPL mutations, a molecular marker is currently found in 90% of cases. With the development of next-generation sequencing, other mutations are detected whose role is still poorly known, but which may be associated with a poor prognosis. Ten years after JAK2 V617F, and in the targeted therapies era, the identification of poor prognosis patients is one of the challenges in MPN. [ABSTRACT FROM AUTHOR]

Résumé Le syndrome coronarien aigu (SCA) est une pathologie maintenant bien connue, et dont la prise en charge est parfaitement codifiée. Le mode de présentation principal reste la douleur thoracique, mais de plus en plus de cas sont révélés par un arrêt cardiorespiratoire grâce à la prise en charge pré-hospitalière. Et en fonction de l’évolution dans de telles situations, des techniques d’assistance circulatoire par membrane d’oxygénation extracorporelle veino-artérielle (ECMO) peuvent être mises en œuvre. Si l’étiologie la plus fréquente du SCA est l’athérosclérose, conséquence de l’association d’un ou plusieurs facteurs de risque cardiovasculaires, il existe des étiologies plus rares dont font partie les syndromes myélo-prolifératifs, et notamment la thrombocytémie essentielle. Nous décrivons le cas d’un patient de 34 ans qui a présenté un syndrome coronarien aigu avec sus-décalage du segment ST antérieur compliqué d’un arrêt cardio-circulatoire initial dont l’étiologie est une thrombocytémie essentielle méconnue, ainsi que sa prise en charge thérapeutique ayant nécessité une assistance circulatoire de type ECMO et IMPELLA ® . Acute coronary syndrome is now a well-known disease, with codified treatments. The main presentation is chest pain, but more and more cases are revealed by cardiorespiratory arrest thanks to pre-hospital care. And, depending on the evolution in such situations, cardiocirculatory support techniques like extracorporeal membrane oxygenation (ECMO) can be implemented. If the more common cause of SCA is atherosclerosis, consequence of the combination of one or more cardiovascular risk factors, there are rare aetiologies, which include myeloproliferative syndromes, in particular essential thrombocythemia. We describe the case of a 34-year-old man presenting with anterior ST-elevation myocardial infarction complicated by an initial cardiac arrest, whose aetiology is unknown essential thrombocythemia, and its therapeutic management requiring circulatory support by ECMO and IMPELLA ® techniques. [ABSTRACT FROM AUTHOR]

Résumé Introduction Les mutations du gène de la calréticuline (CALR) ont été récemment décrites dans les thrombocytémies essentielles (TE) et les myélofibroses primitives non mutées pour JAK2 ou MPL. L’objectif de cette étude était de comparer les caractéristiques clinico-biologiques d’une série monocentrique de patients atteints de TE en fonction de leur statut mutationnel. Méthodes Quarante patients atteints de TE et suivis en consultation d’hématologie ont été inclus. La recherche de la mutation JAK2 V617F a été effectuée par PCR quantitative. La technique utilisée pour la détection des mutations CALR était le séquençage direct après amplification de l’exon 9. Résultats Parmi les 40 patients analysés, 23 (57,5 %) avaient la mutation V617F de JAK2, 12 des 17 patients sans mutation JAK2 avaient des mutations CALR, aucun patient n’était muté sur le gène MPL et 5 étaient triple négatifs. Cinq types de mutations CALR ont été identifiés avec prédominance de la délétion de 52 pb et l’insertion de 5 pb (7/12 et 2/12 respectivement). L’incidence des accidents thrombotiques au moment du diagnostic était significativement plus élevée au cours des TE mutées JAK2 ( p < 0,05). Sur le plan biologique, les patients mutés CALR avaient un chiffre de plaquettes significativement plus élevé ( p < 0,01) et un taux d’hémoglobine significativement plus bas ( p < 0,05) que ceux présentant la mutation JAK2 V617F. Conclusion La recherche des mutations JAK2 et CALR au cours des TE a un intérêt diagnostique certain. Chaque mutation confère un profil phénotypique distinct dont l’impact pronostique reste à confirmer. Background Somatic mutations in the calreticulin gene (CALR) were recently described in essential thrombocythemia (ET) and primary myelofibrosis with non-mutated JAK2 or MPL. The aim of this single-center study was to compare the clinical and biological features of ET patients according to their mutational status. Methods We included 40 patients with ET followed in hematology consultation. The JAK2 V617F mutation was assessed by quantitative PCR. For the detection of CALR mutations, we performed a PCR amplification of CALR exon 9 followed by direct sequencing. Results Among 40 study patients, 23 (57.5%) harbored V617F JAK2, 12 of the 17 patients without JAK2 mutation harbored CALR, no patient expressed MPL mutation and 5 were negative for all three mutations. Five types of mutations were identified with predominance of 52 bp deletion and 5 bp insertion (7/12 and 2/12 respectively). The incidence of thrombotic events at diagnosis was significantly higher in JAK2 mutated patients ( P < 0.05). Biologically, patients with CALR mutation had significantly higher platelet count ( P < 0.01) and significantly lower hemoglobin level ( P < 0.05) than those with V617F JAK2 mutation. Conclusion JAK2 and CALR mutation screening in ET has a diagnostic value. Each mutation displays a distinct phenotype with uncertain impact on long-term outcome. [ABSTRACT FROM AUTHOR]

Résumé La découverte des mutations de CALR en 2013 a été un évènement important et surprenant dans l’histoire de la biologie des syndromes myéloprolifératifs. La protéine calréticuline mutée change de séquence et de fonction : la sublocalisation cellulaire de la protéine s’en trouve modifiée, elle devient capable d’activer le récepteur de la thrombopoïétine à la membrane et se comporte de fait comme une protéine du signal, activant les mêmes voies de signalisation que JAK2. Summary The discovery of CALR mutations in 2013 was another break outstanding event in the field of myeloproliferative neoplasms. The mutated form of the protein calreticulin has a new peptidic sequence leading to new functions and to cellular sublocalization changes. The mutant CALR activates MPL at the membrane, so acting as a signaling molecule on JAK-STAT pathways. [ABSTRACT FROM AUTHOR]

Résumé: La découverte d’une thrombocytose est un événement fréquemment rencontré lors de la réalisation d’un hémogramme. Cette anomalie est souvent d’origine secondaire et ne donne alors pas lieu à des complications thrombotiques. Si une cause réactionnelle est éliminée, la thrombocytose est primitive, rarement d’origine héréditaire mais est le plus souvent associée à une hémopathie maligne. Il faut alors savoir reconnaître une éventuelle thrombocytémie essentielle, en éliminant les diagnostics différentiels que sont certains syndromes myélodysplasiques et les autres syndromes myéloprolifératifs. Son traitement repose sur la prévention des risques thrombotiques et l’introduction éventuelle d’un traitement cytoréducteur. L’espérance de vie est sensiblement identique à celle de la population générale et dépend principalement de la survenue d’une myélofibrose ou de la transformation en leucémie aiguë myéloïde. [ABSTRACT FROM AUTHOR]

Abstract: Purpose. – Essential thrombocythemia (ET) is a myeloproliferative syndrome that rises many therapeutic problems. This affection is rarely life threatening, but hemorrhagic and thrombotic complications must be prevented when possible. The rarity of these complications makes difficult the assessment of treatment efficiency. Few randomised clinical trials were done, and treatment often rests on retrospective studies. The potential toxicity of treatments, their leukemogenicity in particular, rises a decisional problem for young patients. We propose to review available data in order to propose the most rational treatment for each patient. Current knowledge and key points. – After numerous years when we only disposed of retrospective studies, non-randomised prospective studies or isolated case-reports, two randomised trials allows us to more precisely define ET treatment. The first trial proved the efficiency of the hydroxyurea-aspirin association in the prevention of thrombotic events in high-risk patients. The second trial signalled to our attention the increased risk of bleeding of the association anagrelide-aspirin, with also the possibility of increased appearance of myelofibrosis. Future prospects and projects. – New perspectives in the treatment of ET will require to get more insights in the role of hydroxyurea and anagrelide in particular by longer follow-up. But not less important is a better definition of the thrombosis risks (who has to be treated?) and also of the diagnostic groups since ET can, in some particular cases, be misdiagnosed with polycythemia vera or idiopathic myelofibrosis. [Copyright &y& Elsevier]

During a blood test, the discovery of thrombocytosis is a frequent phenomenon with multiple origins. False thrombocytosis linked to analytical interferences is rare but must be eliminated before confirming the anomaly. The reaction origin, often very easily demonstrated by the context and/or the presence of a biological inflammatory syndrome, is the most frequent. More rarely, the diagnosis is oriented towards a clonal hematological pathology not limited to essential thrombocythemia. Currently, many biological tools, which have largely contributed to the recommendations of the latest WHO classification of chronic myeloid neoplasms, are available to classify these pathologies as precisely as possible, allowing optimal management.

Introduction: Spontaneous adrenal hemorrhages (AH) are a rare condition with no consensus about their management., Methods: Patients were identified using the Medicalization of the Information System Program database, imaging software and a call for observations to internists, intensivists and obsetricians working at our institution. Adult patients whose medical records were complete and whose diagnosis was confirmed by medical imaging were included., Results: From 2000 to 2007, 20 patients were identified, including 15 were women. The clinical onset of AH was non-specific. In five cases, AH occurred during pregnancy; four of them were unilateral and right sided. The etiology of the other fifteen (bilateral adrenal hemorrhage in 11) were as follows: antiphospholipid syndrome (n=8), heparin-induced thrombocytopenia (n=4), essential thrombocythemia (n=3), spontaneous AH due to oral anticoagulants (n=1), complication of a surgical act (n=3), and sepsis (n=3). In seven cases, two causes were concomitant. The diagnosis of AH was often confirmed by abdominal CT. An anticoagulant treatment was initiated in 16 cases. Ten of the eleven patients presenting with bilateral adrenal hematomas were treated using a long-term substitute opotherapy. One patient died because of a catastrophic antiphospholipid syndrome., Conclusion: The clinical onset of HS is heterogeneous and non-specific. The confirmatory diagnosis is often based on abdominal CT. The search for an underlying acquired thrombophilia is essential and we found in this study etiological data comparable to the main series in the literature. Adrenal insufficiency is most of the time definitive in cases of bilateral involvement., (Copyright © 2021 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Abstract: Essential thrombocythemia is a myeloproliferative disorder responsible for both hemorrhagic and thrombotic complications mostly venous but also arterial, especially of the microcirculation. We report a 64-year-old female who presented with an aortic thrombus and splenic infarcts indicating essential thrombocythemia. Outcome was favourable with medical treatment combining low-molecular-weight heparin secondarily switched to warfarin, associated with aspirin and hydroxyurea. [Copyright &y& Elsevier]

JAK 2 mutation is the molecular event responsible for 95% of polycythemia cases and 50% of thrombocythemia vera and myelofibrosis cases. It can be used as a tool for the diagnosis of myeloproliferative disorders. We report a case illustrating the fact that a negative result does not definitively eliminate the diagnosis. A 40-year old woman, with a medical history of familial deep vein thrombosis, developed thrombosis of the inferior vena cava with extension to the suprahepatic veins and pulmonary embolism. No constitutional or acquired thrombophilia was diagnosed; search for JAK 2 mutation was negative. The patient was treated with fluindione. Five years later, she relapsed with popliteo-femoral and vena cava deep vein thrombosis. The etiological work-up included a PET scan which revealed diffuse uptake in bones and suspected neoplasic bone marrow invasion. Progenitor cell cultures were positive and JAK 2 mutation was confirmed. The bone marrow aspirate had the cytologic appearance of a myeloproliferative disorder. This case illustrates the fact that JAK 2 mutation can be identified several years after onset of a latent myeloproliferative disorder. Cases with a high clinical likelihood should lead to renewed search for this mutation. Secondary discovery of this mutation can be explained by a higher proportion of mutation expressing clones., (Copyright © 2014. Published by Elsevier Masson SAS.)

The Kato-Katz technique has become the gold standard for all studies on intestinal schistosomiasis. Though repeatability and reproducibility can be disappointing and the sensitivity is low, it remains easy, inexpensive, and fast and as such, is perfectly suited for epidemiological surveys or to monitor the effectiveness of mass treatment. For optimal interpretation of the Kato-Katz results in a recent study of three endemic villages in the Senegal River basin, a study of the measurement uncertainties of this analysis was conducted according to Cofrac and ISO 15189 guidelines. Repeat examinations of stool smears from the same individual, taken a few days apart, can significantly increase the sensitivity of the Kato-Katz test, which allows its use as a technique in clinical biology.