scholarly journals Clinical Features of Idiopathic Erythrocytosis in a Racially Diverse Population

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-1
Author(s):  
Caitlin O'Neill ◽  
Ah-Reum Jeong ◽  
Ibrahim Syed ◽  
Casey L. O'Connell
Keyword(s):  
Polycythemia Vera ◽  
Hepatic Steatosis ◽  
Clinical Features ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Abdominal Ultrasound ◽  
Janus Kinase ◽  
Symptom Intensity ◽  
History Of ◽  
Idiopathic Erythrocytosis

Background: Idiopathic erythrocytosis (IE) is an entity characterized by a persistently elevated hemoglobin, variable erythropoietin (EPO) level, absence of janus kinase 2 (JAK2) mutations suggestive of polycythemia vera (PV) and no identifiable secondary cause. Previous studies have compared IE to PV, showing a lower incidence of venous thrombosis and leukemic transformation in IE but similar incidence of arterial events. PV is known to be associated with constitutional symptoms and splenomegaly, while hereditary erythrocytosis can be associated with recurrent headaches and fatigue. A comprehensive assessment of clinical features including symptoms in IE has not been performed. Methods: Patients signed informed consent to participate in an observational study approved by the Institutional Review Board. Enrollment criteria included: age 18 years or older; hemoglobin level greater than 16 g/dL on two occasions at least 3 months apart or greater than 15 g/dL if undergoing phlebotomy; negative testing for JAK2 mutations; and negative work up for secondary causes of erythrocytosis. Baseline assessment included history and physical exam, vital signs, pulse oximetry, and body mass index. Baseline laboratory exams included a complete blood cell count, complete metabolic panel, C-reactive protein, iron panel, ferritin, hemoglobin A1C, erythropoietin level. Abdominal ultrasound was performed to evaluate for splenomegaly. The Myeloproliferative Symptom Assessment Form (MPN-SAF) was used to assess for the presence and severity of a broad range of symptoms that may be expected to occur in patients with IE. The MPN-SAF was administered at baseline and every 6 months thereafter. Results: 35 patients had data available for analysis. Patient characteristics are shown in Table 1. The most prevalent co-morbid conditions were those known to be associated with cardiovascular disease risk and metabolic syndrome, including hepatic steatosis identified on abdominal ultrasound in 63% of patients. Three (8.6%) patients had a history of venous or arterial thrombosis. Two (5.8%) patients had a history of lymphoma (NK/T-cell and Hodgkin). Three patients (8.6%) had a first-degree relative with a myeloproliferative neoplasm (chronic myelomonocytic leukemia, essential thrombocytosis and polycythemia vera) and one patient had a son with IE and history of stroke. 16 (46%) patients were taking aspirin and 11 (31%) had undergone phlebotomy within 3 months of study enrollment. Patients reported the following symptoms on the MPN-SAF at baseline: fatigue (77%), early satiety (57%), difficulty sleeping (57%), numbness/tingling (51%), headaches (49%), concentration problems (40%), itching (40%), bone pain (37%), night sweats (37%), depression (37%), abdominal pain (37%), abdominal discomfort (37%), inactivity (37%), problems with sexual desire/function (34%), dizziness/lightheadedness (31%), cough (26%), fever (17%), and unintentional weight loss (17%). Fatigue carried the highest average symptom intensity (3.77, SD 3.17). Discussion: In this study, we describe the clinical features associated with IE in a multiracial cohort. Patients with IE are frequently symptomatic and have a high incidence of hepatic steatosis by ultrasound. Disclosures No relevant conflicts of interest to declare.

Clinical Features of Idiopathic Erythrocytosis Compared to Polycythemia Vera JAK-2 V617F Positive and Negative Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5172-5172
Author(s):  
Roberto Latagliata ◽  
Agostino Tafuri ◽  
Antonio Spadea ◽  
Antonietta Ferretti ◽  
Daniela Diverio ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Clinical Features ◽  
Conflicts Of Interest ◽  
Real Life ◽  
Diagnostic Process ◽  
Number Of Patients ◽  
V617f Mutation ◽  
Spleen Enlargement ◽  
Idiopathic Erythrocytosis

Abstract Abstract 5172 The introduction of JAK-2 V617F mutation in the diagnostic process of patients with erythrocytosis has led to a better definition of Polycythemia Vera (PV) patients, who had the mutation in > 90% of cases: however, in the real-life many patients with otherwise unexplained Hb and Ht elevation and lack of JAK-2 V617F mutation are located in the gray zone of the so-called Idiopathic Erythrocytosis (IE). In order to highlight clinical features of patients with IE, we revised 247 patients with primary erythrocytosis (i.e. excluding cases with respiratory and/or severe cardiovascular diseases) diagnosed in 2 Hematological Institutions in Rome from 6/1985 to 12/2010 with a evaluable JAK-2 mutational status at diagnosis or during the follow-up. Were considered as “PV JAK-2 positive” all patients with presence of mutation V617F at diagnosis or during follow-up. Among the patients who resulted JAK-2 V617F negative, were considered as “PV JAK-2 negative” all patients classifiable as PV according to PVSG criteria (if diagnosed before 1/2002) or WHO 2002 criteria (if diagnosed after 1/2002): the remaining patients were classified as “IE”. With these criteria, 181 patients (73.2%) were PV JAK-2 positive, 26 (10.5%) PV JAK-2 negative and 40 (16.3%) IE: the main clinical features of these 3 groups at diagnosis and during the course of disease are summarized in the table.PV JAK-2 positivePV JAK-2 negativeIENo of patients1812640Male87 (48%)22 (84%)38 (95%)Median age yrs (IR)59.3 (49.7–68.5)47.9 (42.6–64.5)57.8 (44.2–65.9)Median WBC x 109/l (IR)10.0 (8.4–13.0)10.6 (6.3–12.5)7.3 (6.4–8.3)Median PLTS x 109/l (IR)481 (349–651)214 (189–344)205 (165–236)No with palpable spleen63 (35.0%)7 (27.0%)2 (5.0%)Previous thrombosis29 (16.0%)2 (7.6%)1 (2.5%)Thrombosis during disease32 (17.7%)1 (3.8%)4 (10.0%)Fibrotic/Blastic evolution12 (6.6%)00 Comparing the 3 groups for the above features, there was a very significative (p<0.001) male predominance in both IE and PV JAK-2 negative vs PV JAK-2 positive patients: in addition, patients with PV JAK-2 negative were younger (p=0.017). Compared to patients with IE, myeloproliferative features were significantly more prominent in patients with PV JAK-2 positive [higher WBC (p<0.001) and PLTS (p<0.001) median values and higher number of patients with spleen enlargement (p<0.001)]; furthermore, also patients with PV JAK-2 negative had higher WBC median value (p=0.008) and more cases with spleen enlargement (p=0.007) compared to patients with IE, but not higher PLTS median value (p=0.166). Previous thrombotic events were more frequent in PV JAK-2 positive patients vs patients with IE (p=0.032), while no difference was revealed among the 3 groups as to thrombotic events during follow-up and fibrotic/blastic evolution. In conclusion, the 3 groups were based on simple clinical data and seem to differ in some important baseline characteristics: the groups of PV JAK-2 negative and IE, however, seem still quite heterogeneous and deserve further and more accurate biological (exon 12 mutations) as well as clinical (venous blood p50 measurement) insights. The role of male gender and its predominance in unexplained erythrocitosis JAK-2 negative remain to be clarified. Disclosures: No relevant conflicts of interest to declare.

How Epidemiology of Polycythemia Vera Has Changed in the Last 10 Years: Results From the Whole Prospective Cohort of Patients in Cyto-PV Trial As Compared with Eclap Prospective Cohort

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1748-1748
Author(s):  
Arianna Masciulli ◽  
Tiziano Barbui ◽  
Rosa Maria Marfisi ◽  
Riccardo Cavazzina ◽  
Guido Finazzi ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Prospective Cohort ◽  
Cardiovascular Events ◽  
Conflicts Of Interest ◽  
Clinical Epidemiology ◽  
Myeloproliferative Neoplasms ◽  
Dominant Role ◽  
Janus Kinase ◽  
Coronary Syndrome ◽  
History Of

Abstract Abstract 1748 Introduction: Polycythemia vera (PV) is a chronic myeloproliferative neoplasms characterized by erythrocytosis, vasomotor disturbances, pruritus, risk of disease progression into acute myeloid leukemia or myelofibrosis and cardiovascular events, the last representing the main cause of morbidity and mortality. Since 2005 the V617F point mutation in Janus Kinase 2 (JAK2) gene gained a dominant role in determining the molecular basis and the diagnosis of PV. We compared the clinical epidemiology of the 1638 patients included in the ECLAP trial in the years 1997 to 2001, with that of a “modern” cohort of 365 PV, JAK2-positive patients included in the Italian CYTO-PV randomized clinical trial and followed from the year 2008 to 2012. Methods: Patients were eligible in CYTO-PV trial and in ECLAP study if they met WHO-2008 diagnostic criteria and the criteria established by the PVSG or Pearson/Messinezy respectively. Clinical characteristics have been compared. The incidence of major cardiovascular events (CV death plus major thrombosis [stroke, acute coronary syndrome, transient ischemic cerebral attack, peripheral arterial thrombosis, pulmonary embolism, abdominal thrombosis, deep vein thrombosis) and total CV events incidence has been evaluated. The median follow up was 31.0 months (range 0– 48.13 months) and 33.1 months (range 0–63.6) for patients included CYTO-PV and in ECLAP respectively. Results: In CYTO-PV 49.3% patients with recent PV diagnosis were included (within 2 years prior inclusion) while in ECLAP the proportion was 35.5%. Mean age at recruitment was similar for patients in CYTO-PV (64.5 yrs) and ECLAP (65.4 yrs). History of thrombosis was reported in 28.9 % vs 38.6% patients in the CYTO-PV and in ECLAP, respectively (p<0.05). Consistently higher proportions of arterial and venous thrombotic events were found in ECLAP as compared to CYTO-PV. History of major bleeding was reported in 1.7% vs 4.8% of the patients in CYTO and ECLAP, respectively. Medical treatment at recruitment was more intensive in CYTO-PV vs. ECLAP: phlebotomy 72.3% vs 63.5% (ns), hydroxyurea (HU) 54.2 vs 48.4, antiplatelet drugs 84.9% vs 58.3% (p<0.05), aspirin 77.0% vs 50.2% (p<0.05), anti-hypertensive and hypocholesterolemic medications were administered respectively in 48.5% and 13% of CYTO–PV patients vs. 39% and 3.5% of ECLAP population (p<0.05) As compared with ECLAP, the incidence of risk of major thombosis in CYTO-PV was 2.7 vs 4.4 and of total CV events was 3.4 vs 5.5 per 100 person/years, respectively. The incidence of total CV events in CYTO-PV for the subgroups of patients with age <65 and no previous thrombosis (PT), age > 65 and no PT, age <65 and PT, age > 65 and PT at randomization was 2.2, 4.8, 3.5 and 3.4 per 100 person/years, respectively. Conclusions: The comparison of these two cohorts of PV patients followed 10 years apart suggests that JAK-2 PV patients are currently better managed for the control of classical CV risk factors, are more frequently administered aspirin, and HU with better control of their disease, and eventually have a risk of thrombosis approximately half than in the past. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Ruxolitinib for the Treatment of Polycythemia Vera: Response on Alternative Dose Versus Standard Dose

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 28-28
Author(s):  
Emma Cacciola ◽  
Veronica Vecchio ◽  
Elio Gentilini Cacciola ◽  
Rossella Rosaria Cacciola
Keyword(s):  
Polycythemia Vera ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
Myeloproliferative Neoplasm ◽  
Symptom Burden ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Allele Burden ◽  
Night Sweats ◽  
Jak2v617f Allele Burden

The polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by increased hematocrit (HCT), elevated white-cell and platelet counts and splenomegaly. The most commonly used first line cytoreductive agent is hydroxyurea (HU). However, some patients have an inadequate response or have inacceptable side effects from HU. Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with PV. A phase 3 study (RESPONSE) have shown that PV patients on Ruxolitinib at dose of 10 mg twice daily at week 32 had a complete hematologic remission. In this study were enrolled 40 patients with PV (30 men, 10 women; mean age 54 years, range 51-57) according to WHO criteria, assigned to Ruxolitinib at dose of 5 mg twice daily for clinical evidence of liver dysfunction. All patients were evaluated for JAK2V617F allele burden, HCT, white cells and platelets, splenomegaly and symptom burden, including pruritus, fatigue and night sweats. The mean duration of disease was 9 years. All patients received low-dose aspirin and underwent phlebotomy. Before Ruxolitinib, all patients had JAK2V617F allele burden &gt; 50%, HCT control on phlebotomy, high white cells (12x109/L) and elevated platelets (600x109/L) and spleen volume of 450 cm3 or more as measured by magnetic resonance imaging (MRI) or computed tomography (CT). After Ruxolitinib we observed a shortened response time at week 6 marked by JAK2V617F allele burden &lt; 50%, HCT &lt; 45% in the absence of phlebotomy, normal white cells and platelets (6x109/L and 320x109/L, respectively) and reduced spleen size as assessed by palpation and absence of symptoms. These data suggest that the Ruxolitinib treatment at the alternative dose of 5 mg twice daily can be effective in achieving a rapid and complete hematologic remission that is still present in these patients receiving this dose of Ruxolitinib at the time of this analysis. Disclosures No relevant conflicts of interest to declare.

scholarly journals Janus kinase 2 negative polycythemia vera

2017 ◽  
Vol 9 (5) ◽  
pp. 697-700
Author(s):  
Pravinwan Thungthong ◽  
Supat Chamnanchanunt ◽  
Tawatchai Suwanban ◽  
Chajchawan Nakhakes ◽  
Kunapa Iam-arunthai
Keyword(s):  
Polycythemia Vera ◽  
Previous History ◽  
Rare Condition ◽  
Janus Kinase ◽  
Janus Kinase 2 ◽  
Jak2 Mutation ◽  
History Of ◽  
British Committee ◽  
Common Manifestation ◽  
Cell Disorder

Abstract Background A Janus kinase 2 (JAK2) mutation polycythemia vera (PV) is a common manifestation of stem cell disorder. However, available data on the clinical and treatment response of JAK2-negative PV patients are limited. Objectives We report the case and clinical course of a patient with PV and left hemiparesis who was JAK2V617-negative. Methods We conducted a literature review and compared our patient with previously published reports of JAK2-negative patients with P V. Results Our patient presented with hemiparesis without a previous history of hematological disease. He was diagnosed with PV based on the British Committee for Standards in Haematology guidelines 2007. He underwent only phlebotomy with subsequent improvement of his neurological condition. He was discharged with therapeutic phlebotomy for one and a half months. Conclusions Although this rare condition required complex diagnostic criteria, the patient achieved good clinical outcome with therapeutic phlebotomy alone.

The Natural History Of Polycythemia Vera In Two Diagnostic Eras

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4078-4078
Author(s):  
Brady L Stein ◽  
Zheng Zhou ◽  
Jerry L. Spivak ◽  
Alison R. Moliterno
Keyword(s):  
Natural History ◽  
Polycythemia Vera ◽  
Disease Duration ◽  
Conflicts Of Interest ◽  
Cell Mass ◽  
Jak2 V617f ◽  
Time Dependent ◽  
Jak2 Mutation ◽  
History Of ◽  
Modern Era

Abstract Introduction The 2005 identification of the JAK2 V617F mutation ushered in a new era of discovery for Polycythemia Vera (PV), allowing for its molecular classification, improved diagnostic capabilities, and a potential for targeted therapy. In this era, aspirin has been shown to lower the risk of thrombosis, the hematocrit (hct) target has been validated, and there has been renewed interest in interferon (IFN). These changes in diagnosis (dx) and therapy may impact the natural history of PV in its modern era. To this end, we analyzed 399 PV patients (pts) diagnosed in two eras (pre-2005 and post-2005) from two tertiary centers. (JHH, N=294; NU, N=105). Methods Pts were seen between 2005 and 2013. Testing to verify PV included an absolute erythrocytosis, JAK2 status, erythropoietin assay, red blood cell mass testing, and bone marrow biopsy. Pts were diagnosed by treating physicians using criteria relevant to the era of dx, between 1968 and 2013. Pts in each era were compared with regard to differences in demographic and clinical factors. The prevalence of myelofibrotic (MF) and leukemic (AML) transformation, as well as deaths was also determined. Results Of 105 NU and 294 JHH pts, 45 (43%) and 113 (38%) were diagnosed post-2005 (p=0.43). Pre-2005 and post-2005 pts were similar in age at dx at NU (52 vs. 57 yrs) and JHH (53 vs. 59 yrs). As expected, median disease duration was longer in pre-2005 NU (12 vs. 3 yrs) and JHH pts (9 vs. 2 yrs). 52% and 60% of pre-2005 pts, and 62% and 60% of post-2005 pts were women at NU (p=0.28) and JHH (p=1), respectively. JAK2 V617F testing was positive 33/37 (89%) and 41/44 (93%) of pre-2005 and post-2005 NU patients. At JHH, JAK2 V617F was positive in 286/294 (97%); JAK2 exon 12 was positive in 6/294 (0.02%). RBC mass testing was infrequently done at NU (9/105); only 2 were performed post-2005. At NU, pre-2005 and post-2005 pts had similar median leukocyte counts (8.9 and 8.7 x 109/L) and hct below 45% (40.5 vs. 42.9%). The prevalence of current anti-platelet and hydroxyurea use was similar at NU (pre-2005: 79%, 49% vs. post-2005: 82%, 48%, respectively). 5% and 11% of pre-2005 and post-2005 pts were on IFN. At NU and JHH, 29% and 27% of pre-2005 and 18% and 21% of post-2005 pts had thrombosis (pre vs. post: p=0.2 for NU; p=0.26 for JHH). Thrombosis in pre-2005 NU pts occurred at a median of 8 yrs from dx compared to post-2005 pts that frequently had events at presentation (median 0 yr; p=0.017). Similarly, fewer pre-2005 JHH pts had events at presentation compared to post-2005 pts (19/49 (39%) vs. 16/24 (67%); p=0.025). At NU, 19/105 (18%) developed MF, at a median of 12 yrs. Only 2/19 (11%) occurred in post-2005 pts, due to shorter disease duration. At JHH, 49/294 (15%) developed MF at a median of 11 yrs, but only in 4/49 (8%) post-2005 pts. At NU and JHH, 5/105 (5%) and 11/294 (4%), developed AML at a median of 15 and 8 yrs from dx. 1 and 4 post-2005 NU and JHH pts developed AML. At NU and JHH, 20/105 (19%) and 42/294 (14%) died. At NU, 16 were pre-2005 pts and 4 were post-2005 pts. At JHH, 35 were pre-2005 pts and 7 were post-2005 pts. AML-deaths were overrepresented in the post-2005 pts (25% NU, 57% JHH). Conclusion Remarkably, the epidemiology and natural history of PV was quite similar between two eras of diagnosis and between two large tertiary centers. Age at dx in pre and post-2005 patients was similar, arguing against a notion that pts are diagnosed earlier in adulthood. At NU, hct was typically below 45%, implying adherence to a recently validated target and aspirin use was prevalent regardless of the era of dx. Regardless, thrombosis at presentation was more common in modern era PV patients, whereas pre-2005 patients had more thrombotic events after an official PV diagnosis. As expected, time-dependent complications such as MF and death were more common in pre-2005 pts, and occurred within the 2nd decade of disease. MF was rare in post-2005 pts, who remain in their 1st decade of disease. Overall, AML was rare, but each cohort still had 1st decade transformations (post-2005 pts), over-representing deaths in this group. While the JAK2 mutation discovery has modernized PV dx, the natural history of PV has not changed. It is in this modern era of PV that we will learn whether or not new (JAK-inhibitors) and renewed (IFN) therapies can prevent or delay onset of feared time-dependent complications. Disclosures: No relevant conflicts of interest to declare.

Jak2 Exon 12 Mutational Status in a Cohort of Idiopathic Erithrocytosis V617F Negative Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4648-4648
Author(s):  
Martina Bernardi ◽  
Marco Ruggeri ◽  
Elena Albiero ◽  
Domenico Madeo ◽  
Silvia Finotto ◽  
...  
Keyword(s):  
Clinical Features ◽  
Peripheral Blood ◽  
High Performance ◽  
White Blood Cells ◽  
Myeloproliferative Disorders ◽  
Janus Kinase ◽  
Who Criteria ◽  
Erythroid Hyperplasia ◽  
Mutational Status ◽  
Idiopathic Erythrocytosis

Abstract Background: V617F gain-of-function mutation in exon 14 of Janus Kinase 2 gene (JAK2) has been recognized as a major pathogenetic event of many cases of chronic myeloproliferative disorders, in particular in Polycythemia Vera (PV). The molecular basis of myeloproliferative disorders in patients without the V617F is still unclear but, recently, four new heterozygous allelic variants affecting JAK2 exon 12 have been described in V617F negative patients receiving a diagnosis of PV or Idiopathic Erythrocytosis (IE) (Scott et al, NEJM 2007). Revised WHO criteria for PV have been proposed considering these mutations as indicative for PV diagnosis (Tefferi et al, 2007). Aim: To determine the JAK2 exon 12 mutational status in patients with IE in a cohort of 40 consecutive IE V617F negative patients; 2 PV patients, V617F negative, were also included. 36 males and 6 females with a median age of 63 years (range: 25–85), median follow-up 109 months (range: 7–205) were studied. IE was diagnosed in presence of increased haemoglobin (>186 gr/L) and hematocrit levels (>51%) and normal white blood cells and platelet counts. In addition, no splenomegaly, and a normal or low serum erythropoietin (Epo) levels were present along with a bone marrow biopsy showing erythroid hyperplasia with normal megakaryopoiesis and granulopoiesis. They were treated only with phlebotomy therapy. PV was diagnosed according to the WHO criteria. Methods: Granulocytes were isolated from the lower interface of a density gradient separation of peripheral blood samples; the granulocytes were then submitted to erythrocytes lysis (mean purity of the granulocytes 97%) and DNA was extracted. Exon 12 was amplified using the couple of JAK2exon12F (5′-ctcctctttggagcaattca-3′) and JAK2exon12R (5′-caatgtcacatgaatgtaaatcaa-3′) primers. The amplicons were submitted to denaturing high performance liquid chromatography (dHPLC) analysis and runs were performed at 53° C. The amplicons showing a heteroduplex profile were sequenced directly in both strands. Results: 4 of the 40 (10%) IE patients were heterozygous positive for N542-E543del JAK2 exon 12 mutation; both PV patients were negative for JAK2 exon 12 mutations (figure 1). Conclusion: N542-E543del JAK2 was found only in 10% of patients with a diagnosis of IE, a frequency lower than that previously reported (Scott et al, NEJM 2007). This result could be due to the low levels of mutation prevalence in peripheral blood granulocytes. The sensitivity could be increase using erythroid colonies grown on colture media. In addition, different patients selection criteria could explain our results. Accordingly with the proposed revised WHO criteria for Polycythemia, a diagnosis of PV instead of IE should be made in these four patients. figure 1: Clinical features of patients with JAK2 exon 12 mutations and Idiopathic Erythrocytosis. figure 1:. Clinical features of patients with JAK2 exon 12 mutations and Idiopathic Erythrocytosis.

Molecular and Clinical Features of the Myeloproliferative Neoplasm Associated with JAK2 Exon 12 Mutations: a European Multicenter Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3904-3904 ◽  
Author(s):  
Francesco Passamonti ◽  
Susanne Schnittger ◽  
François Girodon ◽  
Jean-Jacques Kiladjian ◽  
Mary Frances McMullin ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Clinical Features ◽  
Conflicts Of Interest ◽  
Collaborative Study ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Female Ratio ◽  
Significant Difference ◽  
Wbc Count

Abstract Abstract 3904 Poster Board III-840 While about 95% of patients with polycythemia vera carry the unique V617F mutation in JAK2 exon 14, several mutations in exon 12 have been described in the minority of JAK2 (V617F)-negative subjects. The initial study [N Engl J Med 2007 Feb 1;356(5):459-68] led to the conclusion that JAK2 exon 12 mutations define a distinctive myeloproliferative syndrome that affects patients who currently receive a diagnosis of polycythemia vera or idiopathic erythrocytosis. Very recent studies suggest that the 'GGCC' haplotype of JAK2 confers susceptibility to the somatic acquisition of both JAK2 (V617F) and exon 12 mutations [Nat Genet 2009 Apr;41(4):450-4, Leukemia 2009 May 14, Epub ahead of print]. Indeed, we reported pedigrees with familial polycythemia vera in which there were both JAK2 (V617F)-positive and JAK2 exon 12 mutation-positive siblings [Blood 2008 Feb 1;111(3):1686-9]. The myeloproliferative neoplasm associated with JAK2 exon 12 mutations is a rare disorder, and only small groups of patients have been reported so far by various investigators. We therefore started a collaborative study in Europe with the aim of collecting about 100 patients with this condition in order to define the molecular and clinical features of this myeloproliferative neoplasm. An ad hoc database was developed for data collection and management. As of August 1, 2009, 77 patients with the required clinical and hematologic data at diagnosis have been recruited (median follow-up 3.2 years, range 0-27 years), while complete follow-up information was available for 57 of these patients. Various approaches were employed for the detection of JAK2 exon 12 mutations, including genomic DNA sequencing, allele-specific PCR assays, and high resolution melting. Overall, 16 different exon 12 mutations were identified. The most frequent mutation were N542-E543del (26 patients), K539L (12 patients), R541-E543delinsK (6 patients), and F537-K539delinsL (6 patients); the remaining mutations occurred less frequently. With respect to the clinical phenotype at presentation, the Kruskal-Wallis test did not reveal any significant difference between the above most frequent mutations. Median age at diagnosis was 53 years (range 15-92), and the male/female ratio was 43/34. Mean hemoglobin level was 19.3 ± 2.2 g/dL, mean WBC count 8.5 ± 3.2 × 109/L, and mean PLT count 334 ± 197 × 109/L. Overall, 48 out of 77 (62%) patients presented with isolated erythrocytosis, 12 (16%) with erythrocytosis and leukocytosis (WBC count > 10 × 109/L), 8 (10%) with erythrocytosis and thrombocytosis (PLT count > 400 × 109/L), and 8 (10%) displayed a full myeloproliferative pattern (erythrocytosis, leukocytosis and thrombocytosis). Serum erythropoietin level was below the lower normal limit in 46 out of 58 (79%) patients. Twenty-one of 25 (84%) patients had endogenous erythroid colonies. During follow-up, two patients had deep venous thrombosis, two progressed to post-polycythemia vera myelofibrosis (diagnosed according to the IWG-MRT criteria) and two developed a myelodysplastic syndrome. In conclusion, the available data indicate that the myeloproliferative neoplasm associated with JAK2 exon 12 mutations is mainly associated with isolated erythrocytosis at clinical onset, but also suggest that the subsequent clinical course may be similar to that of JAK2 (V617F)-positive polycythemia vera, at least in a portion of patients. Disclosures: No relevant conflicts of interest to declare.

Evaluation Of The JAK2-V617F Gene Mutation In Egyptian Patients With Essential Thrombocythemia and Polycythemia Vera

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5254-5254
Author(s):  
Maha Ibrahim El Zaafarany ◽  
A. Hasan Abdel-Ghaffar ◽  
Tawfik R. Elkhodary ◽  
Dalia A. Salem ◽  
Eman A. Soliman ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Conflicts Of Interest ◽  
Hematological Parameters ◽  
Mutation Screening ◽  
Jak2 V617f ◽  
Janus Kinase ◽  
Jak2 V617f Mutation ◽  
Egyptian Patients ◽  
V617f Mutation

Abstract An activating mutation of Janus kinase 2 (JAK2-V617F) was previously described in chronic myeloproliferative disorders (MPD). In previously published studies, the frequency of the JAK2-V617F mutation was determined to be 80–90 % for patients with polycythemia vera (PV) and 40–70 % for essential thrombocythemia (ET). In this study, we analyzed the relationship between the JAK2-V617F mutation and clinical-hematological parameters in Egyptian patients with MPD and compared these findings with published studies from other geographic regions and previous studies in EGYPT. A total of 56 patients were studied; of which, 32 were diagnosed with PV and 24 with ET. The mutation status of JAK2 was determined using allele-specific oligonucleotide (ASO) PCR assay. We found that 53% of the PV group and 79% of the ET group were positive for the JAK2-V617F mutation. When all patients were analyzed; patient age, levels of WBCs, levels of hemoglobin, levels of platelets and splenomegaly were significantly different in patients with the JAK2-V617F mutation (p < 0.05). The JAK2-V617F mutation is frequently detected in the Egyptian patients with MPD, and especially in patients with ET. Hence, it would be useful to include JAK2 mutation screening in the initial evaluation of patients suspected to have MPD especially ET. Disclosures: No relevant conflicts of interest to declare.

Polycythemia Vera Vs. Secondary Erythrocytosis Mortality Outcome in a Multiracial Inner City Cohort

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5183-5183
Author(s):  
Jose Nahun Galeas ◽  
Yiting Yu ◽  
Rahul Polineni ◽  
Vineeth Sukrithan ◽  
Cosmin Tegla ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Conflicts Of Interest ◽  
Population History ◽  
Mortality Data ◽  
P Value ◽  
Inpatient Setting ◽  
Kaplan Meier ◽  
Significant Difference ◽  
History Of ◽  
Secondary Polycythemia

Abstract Background Life expectancy of patients with Polycythemia Vera is reduced compared with the general population. History of thrombosis has been found to be the main predictor of death in this disease. Factors like older age, leukocytosis and thrombosis have been shown to increase the risk of mortality. Secondary polycythemia on the other hand is largely an unknown entity. This study aims to compare the various prognostic and predictive factors for mortality between primary polycythemia vera and secondary polycythemia group. Patients and Methods Patients &gt;=18 years of age seen at a Montefiore outpatient clinic and/or inpatient setting from 1998 to 2014 with a diagnosis of polycythemia, either primary or secondary, who have died, were included. This was done with the help of Clinical Looking Glass software after obtaining Institutional Review Board approval. Patients were stratified by race and ethnic groups. Primary polycythemia was confirmed by evaluating each medical record in detail, lab values including erythropoietin level, JAK2 mutation status and bone marrow biopsy reports. Other laboratory results evaluated were WBC, Hg, platelets, hemoglobin, MCV, RDW and albumin. Morbidity including history of arterial/venous thrombosis and mortality data were obtained to compare survival and identify potential predictors of morbidity and mortality. All analyses were conducted using STATA statistical software. Baseline characteristics were compared using two sample tests of proportions and Student t-tests for means. Kaplan-Meier curves were constructed to compare survival by various subgroups. Hazard ratios were calculated using multivariate Cox regression models to adjust for co-variates to compare mortality risk and identify potential independent predictors of mortality. Results Total of 112 patients with polycythemia, who have died within the period of 1998-2014, were identified. 64 (57%) patients had primary polycythemia and 48 (43%) patients were diagnosed with secondary erythrocytosis. The median age for diagnosis was 63 years for secondary and 72 years for primary. The commonest causes of secondary polycythemia in these patients were severe COPD, congenital heart disease and severe pulmonary hypertension. In patients with polycythemia who died within the specified period of 16 years, median time to mortality from diagnosis was significantly shorter (p value: 0.004) in secondary polycythemia (21.1 months or 634 days) compared to primary polycythemia group (42.6 months or 1277 days). Figure 1 illustrates the duration in survival from time to diagnosis between the two groups. There was no significant difference amongst the white, black and Hispanic populations in the 2 groups. 23 (38%) patients in the primary polycythemia group had venous/arterial thrombosis compared to 6 (5%) in the secondary group. This difference was also significant with a p value of 0.005. As expected, erythropoietin was lower in primary compared to secondary group. Also, WBC and platelet counts were significantly higher in primary polycythemia versus secondary polycythemia group. An interesting finding was that the mean albumin was significantly lower in the secondary polycythemia (3.3) patients who died compared to the primary polycythemia patients (3.8) with a p value of 0.004. Conclusions Our findings demonstrate that patients who die with secondary erythrocytosis have shorter time to death from diagnosis compared to primary polycythemia vera. This is most likely due to the worse prognosis associated with the underlying disease causing erythrocytosis. Even though, secondary polycythemia is not generally treated in the same way as primary polycythemia, development of increased hemoglobin should be taken as a cautionary sign for these patients as this is likely a strong predictor of mortality. Moreover, patients who died with secondary polycythemia have lower albumin levels compared to primary polycythemia vera patients. This signifies the importance of albumin levels as a prognostic factor in patients with secondary erythrocytosis. This is a novel study which compares primary and secondary polycythemia and helps to delineate various prognostic factors in these disease groups. Figure 1. Kaplan Meier curve: Primary Polycythemia Vera vs Secondary Erythrocytosis Figure 1. Kaplan Meier curve: Primary Polycythemia Vera vs Secondary Erythrocytosis Disclosures No relevant conflicts of interest to declare.

scholarly journals Awareness and knowledge about glaucoma among patients visiting the screening clinic in Jeddah Eye Hospital, Saudi Arabia

2021 ◽  
Vol 14 (6) ◽  
pp. 887-895
Author(s):  
Saleh M. Alqahtani ◽  
◽  
Ahmed Almanjoumi ◽  
Sami H. Alzahrani ◽  
◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Features ◽  
Disease Risk ◽  
Knowledge Score ◽  
Cross Sectional Study ◽  
Care Hospital ◽  
Cross Sectional ◽  
History Of ◽  
Screening Clinic ◽  
University Degree

AIM: To explore levels and determinants of awareness and knowledge about glaucoma among patients. METHODS: This was a cross-sectional study that included adult patients from October to the end of December 2018. A semi-structured questionnaire was designed by the researchers to measure the levels of awareness and knowledge about 18 basic information about glaucoma. The sheet was divided into 4 domains: types of glaucoma, risk factors, clinical features, and management. A knowledge score (KS, range=0-18) was calculated, with higher scores indicating higher levels. RESULTS: A total of 383 patients responded to the questionnaire, 61.9% males, mean±SD age was 38.5±12.94 years old, and 61.6% had a university degree or higher. Of them, 6.3% and 23.2% reported personal and family history of glaucoma, respectively. The most frequently reported source of information about glaucoma was another person with glaucoma (28.2%), followed by physicians (24.8%) and TV (19.6%). Knowledge by item ranged from 3.1% to 82.5% correctness rate, while KS showed mean=5.91 and median=5; and reliability testing of the knowledge scale showed Cronbach’s alpha=0.782. Higher KS were found among respondents with higher educational level (P=0.036), diabetes history (P=0.025), and personal (P<0.001) and family (P<0.001) history of glaucoma. CONCLUSION: This study reveals low awareness and knowledge levels about glaucoma among the attendees of a local eye care hospital, where several misconceptions about disease risk factors, clinical features, and management are identified.

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