WHO 2016 Prefibrotic Myelofibrosis in the Patients with WHO 2008 Essential Thrombocythemia

2021 ◽  
Vol 31 (3) ◽  
pp. 139-145
Author(s):  
SUDE HATUN AKTIMUR
Keyword(s):  
Essential Thrombocythemia ◽  
Who 2008

Sensitivity and Specificity of Laboratory Parameters to Detect Early/Prefibrotic Myelofibrosis in 857 Patients with Essential Thrombocythemia. A Diagnostic Algorithm

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5148-5148
Author(s):  
Alessandra Carobbio ◽  
Guido Finazzi ◽  
Juergen Thiele ◽  
Hans-Michael Kvasnicka ◽  
Francesco Passamonti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blood Cell ◽  
Sensitivity And Specificity ◽  
Essential Thrombocythemia ◽  
Diagnostic Algorithm ◽  
Roc Curves ◽  
Laboratory Parameters ◽  
Bone Marrow Histology ◽  
Validation Set ◽  
Who 2008

Abstract Abstract 5148 INTRODUCTION. Patients presenting with a clinical picture of essential thrombocythemia (ET) can actually have an early/prefibrotic myelofibrosis (PMF), according to current WHO criteria, in about 18% of cases. Laboratory tests which are significantly different in early/prefibrotic PMF as compared with histologically confirmed ET (WHO-ET) include decreased gender-matched hemoglobin (Hb), increased white blood cell (WBC), platelet (PLT) counts and lactate dehydrogenase (LDH) values. AIM. To evaluate sensitivity (SE) and specificity (SP) of blood cell counts and LDH, at presentation, for the diagnosis of early/prefibrotic PMF vs. WHO-ET. METHODS. Five hundred thirty-six cases (50%) who had complete laboratory data measured at diagnosis constituted the exploratory set of our study and were derived from an international ET database. The discriminatory ability of Hb, WBC, PLT and LDH in correctly classifying patients in the early/prefibrotic PMF or WHO-ET groups was initially tested by plotting their Receiving Operating Characteristic (ROC) curves and comparing the relative Areas Under the Curve (AUC) with the value of 0.50 (which stands for the completely useless of the test). Three parameters with statistically significant discriminatory power were chosen (Hb, WBC and LDH) and thresholds searched in order to guarantee at least 90% of SE or SP. Finally, a diagnostic algorithm was designed. The validation set of this analysis was constituted by 321 patients with WHO-ET (n=62) or early/prefibrotic PMF (n=259) diagnosed by the same pathologist who confirmed the training set cohort and collected in the Institute for Pathology, University of Cologne, Germany. SE and SP for the same parameters and thresholds as well as the final diagnostic algorithm were applied to this set of patients to demonstrate the results' reproducibility. RESULTS. Sensitivity and specificity to recognize early/prefibrotic PFM have been evaluated by ROC curves. The best performance was found for LDH (AUC = 0.7059). WBC and Hb had super imposable curves, with AUC of 0.6279 and 0.6257, respectively. The worst performance was registered for PLT count: its AUC was only 0.5628, not significantly different from the reference value of 0.50 (p=0.154). Thresholds of Hb, WBC and LDH were searched to achieve at least 90% of SE or SP. HB < 12 g/dL for women or <13 g/dL for men, and WBC >= 13 x109/L had higher SP (92% and 91%, respectively). High SP is highly related to the presence of early/prefibrotic PMF (true positives). On the contrary, LDH < 200 mU/mL and WBC < 7 x109/L had good sensitivity (91% and 94%, respectively). High SE is highly related to the absence of early/prefibrotic PMF (true negatives). By applying these SE and SP values in a step-by-step algorithm, nearly half of patients (48%) could be classified as WHO-ET or early/prefibrotic PMF, assuming at each step a margin of error of less than 10%. For the remaining 50% of patients, laboratory results didn't allow to suspect or exclude the presence of early/prefibrotic PMF. In the validation set of 321 patients classified by WHO 2008 as true ET or early/prefibrotic PMF (Cologne cohort) SP of anemia was 84%, WBC < 7 x109/L or >= 13 x109/L had 91% and 81% of SE and SP, respectively. LDH values < 200 mU/mL had 85% of SE. By applying the same flow-chart, 46% of patients were classified as WHO-ET or early/prefibrotic PMF. CONCLUSIONS. The present study provides clinicians with laboratory parameters that should increase suspicion of early/prefibrotic PMF in a patient with a working clinical diagnosis of ET. In fact, while patients presenting clinically with ET can now be discriminated as true ET or early/prefibrotic PMF by adopting the WHO 2008 criteria that require bone marrow histology, an algorithm including baseline anemia, WBC count and LDH, allows this differentiation in about 50% of patients with a good approximation. However, for a definitive proof, bone marrow histology is still an integral part for final diagnosis. Disclosures: Vannucchi: Novartis: Honoraria.

Decanucleotide Insertion Polymorphism of F7 Influences Significantly the Risk of Thrombosis in Patients with Essential Thrombocythemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1730-1730
Author(s):  
Veronika Buxhofer-Ausch ◽  
Damla Olcaydu ◽  
Bettina Gisslinger ◽  
Martin Schalling ◽  
Sophie Frantal ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Risk Factor ◽  
Single Nucleotide Polymorphisms ◽  
Essential Thrombocythemia ◽  
Entire Population ◽  
Insertion Polymorphism ◽  
Separate Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Who 2008

Abstract Abstract 1730 Thrombosis is one of the main complications observed in patients with myeloproliferative neoplasm (MPN). The underlying mechanisms of thrombosis are not entirely clarified. The incidence of, and risk factors for, thrombosis appear to differ in distinct and accurately diagnosed sub-entities of MPN. Similar incidences have been reported for essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (PMF) diagnosed according to the WHO 2008 criteria. However, the two sub-entities differ in terms of their risk factor profiles (Carobbio et al, Blood 2011; Buxhofer-Ausch et al, Am J Haematol 2012). A gain of function in procoagulant pathways is believed to be the reason for an inherited hypercoagulable state (Anderson et al, Crit Care Clin 2011). There is strong evidence indicating that certain thrombophilic single nucleotide polymorphisms account for increased risk of thrombotic complications (Di Castelnuovo et al, Thromb Res 2000; Shimasaki et al, J Am Coll Cardiol 1998; Elbaz et al, Stroke 2000; Mollaki et al, J Thromb Haemost 2004). Data concerning the impact of an inherited risk in patients with underlying MPN are scarce (Shetty, Thromb Res 2011). We aimed to investigate the influence of three pre-selected thrombophilic single nucleotide polymorphisms (SNPs) on the risk of thrombosis in patients diagnosed with ET or prefibrotic PMF according to the WHO 2008 criteria. In 167 patients with a valid consensus diagnosis of ET (n= 105) or prefibrotic PMF (n= 62), the thrombophilic SNPs of NOS3 (Glu 298 Asp), F7 (10 nucleotide insertion-deletion) and FCGR2A (His 131 Arg) were determined by AS-PCR or sequencing. These variables and certain disease-specific and laboratory parameters were correlated with the incidence of major arterial and venous thrombosis by using Cox-regression analysis. The latter was performed in the entire population as well as separately for ET and prefibrotic PMF. The frequency of SNPs of F7, NOS3 and FCGR2A did not differ significantly in ET and prefibrotic PMF. Notably, the homo- or heterozygous insertion variant of F7 was found to be a significant (multivariate analysis) risk factor for total thrombosis and arterial thrombosis in the entire population (HR 3.06, p= 0.0082 and HR 3.94, p= 0.0007, respectively) as well as on separate analysis of those patients with ET (HR 5.94, p= 0.001 and HR 9,47, p= 0.00024, respectively). The homozygous 298 Asp NOS variant was significantly (univariate analysis) associated with total thrombosis in the entire population (HR 3.29, p= 0.0257) as well as on separate analysis of the ET cohort (HR 4.739, p= 0.0161). These significances were lost on multivariate analysis. No significant associations were established with any of the tested thrombophilic SNPs and the risk of thrombosis in the prefibrotic PMF cohort. Our data show that the risk of thrombosis in ET diagnosed according to WHO 2008 is increased many-fold by the inherited insertion polymorphism of F7. This is very interesting because, in patients without an underlying pathological condition, this polymorphism appears to protect the organism against thrombosis by reducing FVII activity (Humphries et al, Thromb Haemost 1996). Moreover, the different impact of thrombophilic SNPs in ET compared to prefibrotic PMF might provide further evidence of the presumed difference in risk profiles between these two sub-entities of MPN. These data emphasize the importance of considering the inherited as well as acquired hypercoagulable state in patients with MPN. Larger studies are needed to confirm these findings. If proven true, we would be able to more accurately define the risk of thrombosis in an individual patient and subsequently tailor treatment and anticoagulation strategies. Disclosures: No relevant conflicts of interest to declare.

Role of JAK2 V617F mutation and aberrant expression of microRNA-143 in myeloproliferative neoplasms

2015 ◽  
Vol 53 (7) ◽  
Author(s):  
Marco Benati ◽  
Martina Montagnana ◽  
Elisa Danese ◽  
Giovanna De Matteis ◽  
Dino Veneri ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Blood Cells ◽  
Healthy Subjects ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Idiopathic Myelofibrosis ◽  
Aberrant Expression ◽  
Who 2008

AbstractMyeloproliferative neoplasms (MPNs) are clonal myeloid disorders characterized by the overproduction of mature blood cells. The pathogenetic hallmark of MPNs is the dysregulation of JAK-STAT signaling, usually associated with theIn total 78 patients with a clinical diagnosis of polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IM), made according to the WHO 2008 criteria, were included in the study. Twenty healthy subjects were checked as controls. Quantification ofThe miR-143 expression in MPNs patients was 2.97-fold higher than in controls.Our findings of aberrant miR-143 expression support the concept that factors other than

scholarly journals Clinical and Prognostic Features of Essential Thrombocythemia: Comparison of Who 2001 Versus Who 2008/2016 Criteria in a Large Single Center Cohort

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5464-5464
Author(s):  
Sofia Chiatamone Ricci ◽  
Maria Antonietta Arleo ◽  
Stefania Trasarti ◽  
Cristina Santoro ◽  
Massimo Breccia ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Features ◽  
Essential Thrombocythemia ◽  
Advisory Board ◽  
World Health ◽  
Thrombotic Risk ◽  
Entire Cohort ◽  
Prognostic Features ◽  
Who 2008

Abstract According to the World Health Organization (WHO) 2008/2016 criteria for classification of myeloid neoplasms, a platelet (PLT) count ≥ 450X109/l, thus reduced from the previous WHO 2001 level ≥ 600 x 109/l, was considered the new PLT threshold for the diagnosis of Essential Thrombocythemia (ET). Aim of the study was to validate in a setting of current clinical practice this important diagnostic change and compare clinical and hematological features at diagnosis and during follow-up of patients with PLT ≥600 x 109/l versus patients with PLT < 600 x 109/l. We retrospectively analyzed data from 264 patients with ET according to WHO 2008/2016 criteria, enrolled in our center from 1/2008 to 12/2017. Patients were divided into Group A (G-A) (PLT ≥600 x 109/l at diagnosis) (199 patients - 75.4%) and Group B (G-B) (PLT ≥ 450 x 109/l < 600 x 109/l at diagnosis) (65 patients - 24.6%) and compared for clinical features at the onset, clinical course and follow-up. Main features and commonly recognized pro-thrombotic risk factors at diagnosis of the entire cohort as well as of G-A and G-B are reported in the Table 1. Among clinical features, only the median value of leukocytes was significantly higher in G- A [9.1 x 109/l, interquartile range (IQR) 7.8-10.3 vs 7.4 x 109/l, IQR 6.0-9.6; p = 0.001]. Among pro-thrombotic risk factors, only the median cholesterol value was significantly lower in the G-A [187 mg/dl (IQR 164-220) vs 204 mg/dl (RIQ 177-238); p = 0.048]. Cytostatic treatment was administered in 175 patients (71.1%) of entire cohort at different intervals from diagnosis, with a significantly higher rate in patients of G-A (76.9% versus 49.2%, p <0.001). After a median follow-up of 37.5 months (IQR 19.8 - 60.7), 13 thrombotic events (4.9%) were recorded in the entire cohort (7 episodes in the G-A and 6 episodes in the G-B), with a 5-year Cumulative Incidence of Thrombosis (CIT) significantly higher in the G-B [79.6% (95%CI 59.6 - 99.6) versus 95.4% (95%CI 91.8 - 99.0); p=0.047] (Figure 1). No patient evolved in myelofibrotic phase, 2 patients evolved in blastic phase (BP) after 42 and 58 months, respectively [1 patient (0.5%) in the G-A and 1 patient (1.3%) in the G-B; p=0.40). At the last follow-up, 4 patients (1.5%) died (1 from BP, 1 from cerebral hemorrhage, 2 from unavailable cause), 15 (5.7%) were lost to follow-up and 245 (92.8%) are still alive and currently followed at our Institute. The 5-year Overall Survival (OS) of the entire cohort was 96.2% (IC95% 92.2 - 100), without differences between the two groups [96.3% (95% CI 92.0 - 100) in the G-A versus 96.7% (IC95% 91.7 - 100) in the G-B; p=0.898]. Our data indicate a substantial homogeneity among ET patients regardless of the PLT number at diagnosis, thus confirming the usefulness of 2008/2016 WHO diagnostic criteria. Furthermore, the counterintuitive lower CIT observed in G-A, due to a larger use of cytostatic treatments and/or to an acquired Von Willebrand phenomenon when PLT levels > 1.000 x 109/l, highlights how thrombotic risk is unrelated to PLT value and leads to consider the administration of adequate cytostatic therapy even in patients with relatively lower PLT count at diagnosis. Disclosures Breccia: Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria. Foà:INCYTE: Other: ADVISORY BOARD; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; CELTRION: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; ROCHE: Other: ADVISORY BOARD, Speakers Bureau; NOVARTIS: Speakers Bureau.

scholarly journals Leukocyte Count Defines Patients on Risk for Thrombotic Complications with Well Controlled Essential Thrombocythemia- Data from a Patient- Registry

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1863-1863
Author(s):  
Veronika Buxhofer-Ausch ◽  
Michael Steurer ◽  
Siegfried Sormann ◽  
Ernst Schloegl ◽  
Robert Kralovics ◽  
...  
Keyword(s):  
Essential Thrombocythemia ◽  
Thrombotic Event ◽  
Real Life ◽  
Patient Registry ◽  
Event Free Survival ◽  
Thrombotic Risk ◽  
Free Survival ◽  
Platelet Counts ◽  
Wbc Count ◽  
Who 2008

Abstract There is compelling evidence that white blood cell (WBC) counts impact the risk of thrombosis in patients with myeloproliferative neoplasms (MPN) (Barbui Blood 2013). Moreover, recent publications disclosed significant differences regarding certain disease characteristics and the course of disease in WHO 2008 (Tefferi Blood 2007) classified essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (PMF) (Kvasnicka Am J Hematol 2008; Barbui JCO 2011; Buxhofer-Ausch Am J Hematol 2012). Hence, patients cohorts classified prior to WHO 2008 may likely consist of a mix of patients with ET and prefibrotic PMF. We aimed to reproduce the influence of WBC counts on the thrombotic risk in patients under real-life conditions. Therefore we assessed data of 825 Austrian patients from a patient registry for anagrelide in ET that was initiated 2001 in Austria due to an official authorities demand and is now being maintained in several Central European countries. Efficacy of treatment was assessed by investigating the course of platelet counts and event free survival relating to the first minor or major thrombotic event. WBC counts from the first available time points were correlated with the first thrombotic event. The cut off for the WBC subgroup analysis was set at 8,5 G/l. Statistical analysis was performed using the open-source R statistical software package, version 3.0.2. Non-parametric two-sided 95% confidence intervals for medians were calculated. Survival probabilities were assessed by applying the Kaplan-Meier method. For the comparison of time to event between the leukocyte- specific subgroups the log-rank test was used. Median Follow up of the study cohort is 3,07 years. Platelet count at start of anagrelide was median 777 G/l (95% CI 757-803). After 12, 24 and 36 months patients presented with median platelet counts of 473, 457 and 438 G/l, respectively. Median WBC count at start of therapy was 9 G/l (95% CI 8,7-9,3) and after 12, 24 and 36 months 8,5 G/l, 9,2 G/l and 8,7G/l, respectively. Incidence of thrombotic events per 100 patient- years was 5,14 for all events and 1,65 for major events only. 102 patients experienced at least one minor or major thrombotic event (major events n=36). Median time to the first minor or major thrombotic event was 1,27 years. Probability of event free survival at 1 year is 94,4% and at 3 years 87,6%. Patients with a baseline WBC count of higher than 8,5 G/l exhibit a significantly shorter probability of event free survival than patients below the cut off (p= 0,007 for all thrombotic events; p= 0,026 for major events only). This data proof the efficacy of anagrelide in lowering platelet counts and reducing significantly the risk of thrombotic events in patients with ET. The significantly shorter event free survival of patients with a WBC count above 8,5 G/l confirms earlier studies for the first time in a real-life setting. This result emphasizes the separation of true ET from prefibrotic PMF by using the WHO 2008 classification. Moreover, further investigations are needed to assess, whether a correlation of certain platelet and leukocyte counts modifies the risk of thrombotic events in MPN. Disclosures Schloegl: AOP Orphan Pharmaceuticals AG: Research Funding.

Increased Thromboxane Biosynthesis in Essential Thrombocythemia

1995 ◽  
Vol 74 (05) ◽  
pp. 1225-1230 ◽  
Author(s):  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Raffaele Tartaglione ◽  
Sergio Cortelazzo ◽  
Tiziano Barbui ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Essential Thrombocythemia ◽  
Therapeutic Strategy ◽  
Low Dose ◽  
Thrombotic Risk ◽  
Dose Aspirin ◽  
Gender And Age ◽  
Low Dose Aspirin

SummaryIn order to investigate the in vivo thromboxane (TX) biosynthesis in essential thromboeythemia (ET), we measured the urinary exeretion of the major enzymatic metabolites of TXB2, 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 40 ET patients as well as in 26 gender- and age-matched controls. Urinary 11-dehydro-TXB2 was significantly higher (p <0.001) in thrombocythemic patients (4,063 ± 3,408 pg/mg creatinine; mean ± SD) than in controls (504 ± 267 pg/mg creatinine), with 34 patients (85%) having 11-dehydro-TXB2 >2 SD above the control mean. Patients with platelet number <1,000 × 109/1 (n = 25) had significantly higher (p <0.05) 11 -dehydro-TXB2 excretion than patients with higher platelet count (4,765 ± 3,870 pg/mg creatinine, n = 25, versus 2,279 ± 1,874 pg/mg creatinine, n = 15). Average excretion values of patients aging >55 was significantly higher than in the younger group (4,784 ± 3,948 pg/mg creatinine, n = 24, versus 2,405 ± 1,885 pg/mg creatinine, n = 16, p <0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB2 excretion in 7 thrombocythemic patients, thus suggesting that platelets were the main source of enhanced TXA2 biosynthesis. The platelet count-corrected 11-dehydro-TXB2 excretion was positively correlated with age (r = 0.325, n = 40, p <0.05) and inversely correlated with platelet count (r = -0.381, n = 40, p <0.05). In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB2 excretion, belonged to the subgroup with age >55 and platelet count <1,000 × 1099/1. We conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB2 excretion largely reflects platelet activation in vivo;2) age as well as platelet count appear to influence the determinants of platelet activation in this setting, and can help in assessing the thrombotic risk and therapeutic strategy in individual patients.

Implementação do programa "Cirurgias seguras salvam vidas"

2014 ◽  
Author(s):  
Rosa Prozil ◽  
Carminda Morais ◽  
Cristina Sales
Keyword(s):  
Joint Commission ◽  
Healthcare Organizations ◽  
Who 2008

PERTINÊNCIA DO ESTUDO: A assistência cirúrgica constitui uma componente essencial dos sistemas de saúde. Contudo, apesar de terem ocorrido progressos importantes nas últimas décadas, infelizmente a qualidade e a segurança da assistência cirúrgica tem variado em todas as partes do mundo. Embora as taxas de mortalidade e as complicações após cirurgia sejam difíceis de comparar, devido à diversificação/variabilidade dos casos, nos países desenvolvidos as complicações cirúrgicas major ocorrem em 3-16% dos procedimentos cirúrgicos, provocando invalidez permanente ou morte em 0,4-0,8%. Segundo a mesma fonte, cerca de metade dos eventos adversos nesses estudos foi determinado como evitável (WHO, 2008). Neste contexto, em 2003, a Joint Commission on Accreditation of Healthcare Organizations propunha a criação de protocolo universal para o doente cirúrgico. No seguimento, 4 anos depois, a OMS, iniciou um programa denominado “Cirurgias seguras salvam vidas”. Em 2010, a DGS emitiu uma Circular Normativa determinando a implementação do referido programa em todos os blocos operatórios do Sistema Nacional de Saúde, sendo desconhecidos os resultados concretos da sua aplicação. OBJETIVOS: O presente trabalho, procurando contribuir para a consolidação de uma cultura de segurança e promover adesão a esta prática, propôs-se estudar a sua aplicação em todas as intervenções cirúrgicas do bloco operatório central, realizadas na Instituição de Saúde em Estudo, entre 19 de julho e 19 de setembro de 2011. Seguindo, a metodologia que lhe está subjacente aos programas de melhoria contínua da qualidade, o ciclo de Deming (PDCA), procedeu-se ao diagnóstico, implementaram-se ações para resolver problemas detetados. Preconiza-se, ainda, a avaliação dos efeitos dessa intervenção e da possibilidade da implementação de medidas corretivas. RESULTADOS: Os principais problemas encontrados dizem respeito à adesão à LVSC, cuja taxa de realização se situa nos 24% (242) e sua utilização nos diferentes momentos preconizados de forma incorreta em 43,4% (86). A marcação do local cirúrgico, quando aplicável, apenas está presente em 22,7% (55) sendo o percentual da não marcação superior em cerca de 8%. A administração de profilaxia antibiótica e tromboembólica e a visibilidade de exames durante o ato operatório são também questões de relevo na análise dos resultados. Destaca-se ainda um aspeto relativo à comunicação escrita, enquanto necessidade de obter resposta a todos os itens bem como transmitir informação pertinente acerca do utente/procedimento cirúrgico. Procurando manter o envolvimento da equipa, negociaram-se as medidas corretivas, que se encontram em implementação.

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