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EJHaem Aug 2023Primary myelofibrosis (PMF) and polycythaemia vera (PV) are rare -negative myeloproliferative neoplasms, associated with an increased risk of thrombosis, haemorrhagic... (Review)
Review
Primary myelofibrosis (PMF) and polycythaemia vera (PV) are rare -negative myeloproliferative neoplasms, associated with an increased risk of thrombosis, haemorrhagic complications and progression to fibrosis or leukaemia or fibrosis for PV. Both diseases are characterised by biological and clinical heterogeneity, leading to great variability in their management in routine clinical practice. In this review, we present an updated overview of the diagnosis, prognosis and treatment of PMF and PV, and we discuss how our multidisciplinary expert group based across France translates this evidence-based knowledge into routine clinical practice.
PubMed: 37601853
DOI: 10.1002/jha2.734 -
EJHaem Aug 2023Myelofibrosis (MF) is a clonal malignancy frequently characterized by anemia and in 10%-20% of cases it can evolve into blast phase (BP). Anemia in MF is associated with...
Myelofibrosis (MF) is a clonal malignancy frequently characterized by anemia and in 10%-20% of cases it can evolve into blast phase (BP). Anemia in MF is associated with reduced survival and -in primary MF- also with an increased probability of BP. Conventional treatments for anemia have limited effectiveness in MF. Within a dataset of 1752 MF subjects largely unexposed to ruxolitinib (RUX), BP incidence was 2.5% patients per year (p-y). This rate reached respectively 4.3% and 4.5% p-y in case of patients with common terminology criteria for adverse events (CTCAE) grade 3/4 and grade 2 anemia, respectively, that represented together 32% of the cohort. Among 273 MF cases treated with RUX, BP incidence was 2.89% p-y and it reached 4.86% p-y in subjects who started RUX with CTCAE grade 2 anemia (one third of total). Within patients with red blood cell transfusion-dependency at 6 months of RUX (21% of the exposed), BP rate was 4.2% p-y. Our study highlights a relevant incidence of BP in anemic MF patients, with a similar rate whether treated with or without RUX. These findings will help treating physicians to make decisions on the safety profile of innovative anemia treatments.
PubMed: 37601878
DOI: 10.1002/jha2.745 -
Blood Advances Nov 2023Red blood cells (RBCs) and platelets contribute to the coagulation capacity in bleeding and thrombotic disorders. The thrombin generation (TG) process is considered to...
Red blood cells (RBCs) and platelets contribute to the coagulation capacity in bleeding and thrombotic disorders. The thrombin generation (TG) process is considered to reflect the interactions between plasma coagulation and the various blood cells. Using a new high-throughput method capturing the complete TG curve, we were able to compare TG in whole blood and autologous platelet-rich and platelet-poor plasma to redefine the blood cell contributions to the clotting process. We report a faster and initially higher generation of thrombin and shorter coagulation time in whole blood than in platelet-rich plasma upon low concentrations of coagulant triggers, including tissue factor, Russell viper venom factor X, factor Xa, factor XIa, and thrombin. The TG was accelerated with increased hematocrit and delayed after prior treatment of RBC with phosphatidylserine-blocking annexin A5. RBC treatment with ionomycin increased phosphatidylserine exposure, confirmed by flow cytometry, and increased the TG process. In reconstituted blood samples, the prior selective blockage of phosphatidylserine on RBC with annexin A5 enhanced glycoprotein VI-induced platelet procoagulant activity. For patients with anemia or erythrocytosis, cluster analysis revealed high or low whole-blood TG profiles in specific cases of anemia. The TG profiles lowered upon annexin A5 addition in the presence of RBCs and thus were determined by the extent of phosphatidylserine exposure of blood cells. Profiles for patients with polycythemia vera undergoing treatment were similar to that of control subjects. We concluded that RBC and platelets, in a phosphatidylserine-dependent way, contribute to the TG process. Determination of the whole-blood hypo- or hyper-coagulant activity may help to characterize a bleeding or thrombosis risk.
Topics: Humans; Thrombin; Phosphatidylserines; Annexin A5; Erythrocytes; Thrombosis; Coagulants; Anemia
PubMed: 37648671
DOI: 10.1182/bloodadvances.2023010027 -
Angiology Jul 2023Red palms syndrome consists of an intense redness on the palms of the hands and, occasionally, the soles of the feet. This infrequent condition may be primary or... (Review)
Review
Red palms syndrome consists of an intense redness on the palms of the hands and, occasionally, the soles of the feet. This infrequent condition may be primary or secondary. The primary forms are either familial or sporadic. They are always benign and do not require treatment. The secondary forms may have a poor prognosis related to the underlying disease, for which early identification and treatment are imperative. Red fingers syndrome is also rare. It manifests as a persistent redness on the fingers or toes pulp. It is typically secondary either to infectious diseases like human immunodeficiency virus, hepatitis C virus and chronic hepatitis B or to Myeloproliferative Disorders, such as Thrombocythemia and Polycythemia vera. Manifestations spontaneously regress over months or years without trophic alterations. Treatment is limited to that of the underlying condition. Aspirin has been shown effective in Myeloproliferative Disorders.
PubMed: 37410889
DOI: 10.1177/00033197231185459 -
Clinical and Experimental Medicine Dec 2023Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized clinically by the proliferation of one or more... (Review)
Review
Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized clinically by the proliferation of one or more hematopoietic lineage(s). The classical Philadelphia-chromosome (Ph)-negative MPNs include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The Asian Myeloid Working Group (AMWG) comprises representatives from fifteen Asian centers experienced in the management of MPN. This consensus from the AMWG aims to review the current evidence in the risk stratification and treatment of Ph-negative MPN, to identify management gaps for future improvement, and to offer pragmatic approaches for treatment commensurate with different levels of resources, drug availabilities and reimbursement policies in its constituent regions. The management of MPN should be patient-specific and based on accurate diagnostic and prognostic tools. In patients with PV, ET and early/prefibrotic PMF, symptoms and risk stratification will guide the need for early cytoreduction. In younger patients requiring cytoreduction and in those experiencing resistance or intolerance to hydroxyurea, recombinant interferon-α preparations (pegylated interferon-α 2A or ropeginterferon-α 2b) should be considered. In myelofibrosis, continuous risk assessment and symptom burden assessment are essential in guiding treatment selection. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in MF should always be based on accurate risk stratification for disease-risk and post-HSCT outcome. Management of classical Ph-negative MPN entails accurate diagnosis, cytogenetic and molecular evaluation, risk stratification, and treatment strategies that are outcome-oriented (curative, disease modification, improvement of quality-of-life).
Topics: Humans; Philadelphia Chromosome; Consensus; Myeloproliferative Disorders; Polycythemia Vera; Thrombocythemia, Essential; Interferon-alpha
PubMed: 37747591
DOI: 10.1007/s10238-023-01189-9 -
Frontiers in Genetics 2023The classical -negative myeloproliferative neoplasms such as polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are clonal diseases with the... (Review)
Review
The classical -negative myeloproliferative neoplasms such as polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are clonal diseases with the presence of characteristic "driver mutations" in one of the genes: JAK2, CALR, or MPL. The search for mutations in these three genes is required for the diagnosis of MPNs. Nevertheless, the progress that has been made in the field of molecular genetics has opened a new era in medicine. The search for additional mutations in MPNs is helpful in assessing the risk stratification, disease progression, transformation to acute myeloid leukemia (AML), or choosing the right treatment. In some cases, advanced technologies are needed to find a clonal marker of the disease and establish a diagnosis. This review focuses on how the use of new technologies like next-generation sequencing (NGS) helps in the diagnosis of -negative myeloproliferative neoplasms.
PubMed: 37745842
DOI: 10.3389/fgene.2023.1241912 -
Hematology (Amsterdam, Netherlands) Dec 2023Several observations have shown that patients with polycythemia have iron deficiency. Our objectives were to report the prevalence of iron deficiency and to evaluate the...
INTRODUCTION
Several observations have shown that patients with polycythemia have iron deficiency. Our objectives were to report the prevalence of iron deficiency and to evaluate the diagnostic performance of serum ferritin in polycythemia vera.
PATIENTS AND METHOD
This is a retrospective descriptive and analytical study carried out in the internal medicine department of the Henri Mondor Hospital, Aurillac, France. The study involved 114 patients with polycythemia, followed in the department from January 1, 2010 to December 31, 2021. To evaluate the diagnostic performance, the JAK2 mutation was considered as the gold standard of diagnosis.
RESULTS
Thirty-three patients had polycythemia vera and 76 patients had secondary polycythemia. The mean age of the patients was 61.79 years (±15.44) with a sex ratio of 4.43. The overall prevalence of iron deficiency was 21.05%. The prevalence was 53% in polycythemia vera group and 1.32% in secondary polycythemia group. The risk of iron deficiency was high in polycythemia vera (OR = 115; 95% CI [14.4-918.2], < 0.0001) and the sensitivity and specificity of serum ferritin were 52.63% and 100% respectively.
CONCLUSION
Assessment of iron deficiency should be part of the initial evaluation of polycythemia. Iron deficiency had a high specificity during polycythemia vera.
Topics: Humans; Middle Aged; Polycythemia; Polycythemia Vera; Retrospective Studies; Prevalence; Iron Deficiencies; Ferritins
PubMed: 37115586
DOI: 10.1080/16078454.2023.2204621 -
Blood Cancer Journal Nov 2023SRSF2 mutations are found in association with JAK2V617F in myeloproliferative neoplasms (MPN), most frequently in myelofibrosis (MF). However, the contribution of SRSF2...
SRSF2 mutations are found in association with JAK2V617F in myeloproliferative neoplasms (MPN), most frequently in myelofibrosis (MF). However, the contribution of SRSF2 mutation in JAK2V617F-driven MPN remains elusive. To investigate the consequences of SRSF2 and JAK2 mutations in MPN, we generated Cre-inducible Srsf2Jak2 knock-in mice. We show that co-expression of Srsf2 mutant reduced red blood cell, neutrophil, and platelet counts, attenuated splenomegaly but did not induce bone marrow fibrosis in Jak2 mice. Furthermore, co-expression of Srsf2 diminished the competitiveness of Jak2 mutant hematopoietic stem/progenitor cells. We found that Srsf2 mutant reduced the TGF-β levels but increased the expression of S100A8 and S100A9 in Jak2 mice. Furthermore, enforced expression of S100A9 in Jak2 mice bone marrow significantly reduced the red blood cell, hemoglobin, and hematocrit levels. Overall, these data suggest that concurrent expression of Srsf2 and Jak2 mutants reduces erythropoiesis but does not promote the development of bone marrow fibrosis in mice.
Topics: Animals; Mice; Janus Kinase 2; Mutation; Myeloproliferative Disorders; Neoplasms; Polycythemia; Primary Myelofibrosis; Serine-Arginine Splicing Factors
PubMed: 38012156
DOI: 10.1038/s41408-023-00947-y -
Clinical Obstetrics and Gynecology Dec 2023With an increasing incidence of twin gestations, understanding the inherent risks associated with these pregnancies is essential in modern obstetrics. The unique...
With an increasing incidence of twin gestations, understanding the inherent risks associated with these pregnancies is essential in modern obstetrics. The unique differences in placentation in monochorionic twins leads to unique complications, including twin-to-twin transfusion syndrome, the twin anemia-polycythemia sequence, and selective fetal growth restriction. Not only does the understanding of the monochorionic placenta lead to an understanding of the pathophysiology of the complications of monochorionic twins, but it also has led to the development of highly effective directed fetal therapy via fetoscopic laser coagulation used in twin-to-twin transfusion syndrome.
Topics: Pregnancy; Female; Humans; Fetofetal Transfusion; Fetal Growth Retardation; Polycythemia; Placenta; Placentation; Pregnancy, Twin; Twins, Monozygotic
PubMed: 37910135
DOI: 10.1097/GRF.0000000000000821 -
Hematology. American Society of... Dec 2023Myeloproliferative neoplasms (MPNs) are characterized by clonal myeloproliferation in 1 or more of the hematopoietic stem cell lineages. Primary myelofibrosis (MF),...
Myeloproliferative neoplasms (MPNs) are characterized by clonal myeloproliferation in 1 or more of the hematopoietic stem cell lineages. Primary myelofibrosis (MF), post-polycythemia vera MF, and post-essential thrombocythemia MF have the worst prognosis and are characterized by the presence of cytokine-mediated symptom complex, splenomegaly, progressive marrow failure, and clonal instability, leading to leukemic transformation. The key therapeutic aims encompass the management of symptoms, splenomegaly, and anemia and the improvement of survivals. These therapeutic aims have evolved with the availability of Jak inhibitors and novel agents, making disease modification potentially achievable. Novel agents may potentially target MPN stem cells, epigenetic alterations, signaling pathways, and apoptotic pathways. In this case-based review, we outline our approach to the management of MF and discuss the therapeutic landscape of MF, highlighting the utility of Jak inhibitors and novel Jak inhibitor-based combinations.
Topics: Humans; Primary Myelofibrosis; Splenomegaly; Janus Kinase Inhibitors; Thrombocythemia, Essential; Myeloproliferative Disorders
PubMed: 38066870
DOI: 10.1182/hematology.2023000452