Updated threshold, renewed problems: should the diagnostic criteria of polycythemia vera be reconsidered? A retrospective cross-sectional cohort study.

OBJECTIVE: This aim of this study was to evaluate hemoglobin and hematocrit values of polycythemia vera and secondary polycythemia patients with updated World Health Organization thresholds. In addition, by determining our own threshold values, we aimed to demonstrate the necessity of bone marrow biopsy and genetic analysis to be used for further diagnosis in patients with high-normal hematocrit and hemoglobin values. METHODS: A cross-sectional and retrospective study was performed with the medical records of patients from Eskisehir City Hospital hematology clinics and outpatient clinics between July 1, 2019 and July 1, 2020. The study included patients with polycythemia, divided into two groups according to polycythemia vera and secondary polycythemia. A bone marrow biopsy was performed on patients with either Janus kinase mutation positivity and/or subnormal erythropoietin levels. Receiver operating characteristics analysis was used to find threshold values, and the diagnostic efficiency of these values in differentiating World Health Organization thresholds in 2008 and 2016 was evaluated. RESULTS: A total of 73 patients were included. The median age was 43.5 years (min: 18; max: 84). The hematocrit value of 54.1 was predicted to diagnose polycythemia vera with a sensitivity of 45% and a specificity of 80%. Subsequent analysis revealed that an hemoglobin value of 17.7 was indicative of diagnosing polycythemia vera with a sensitivity of 60% and a specificity of 63%. The mean follow-up length was 6.4 months (2-12). CONCLUSION: Our study demonstrated that modified World Health Organization criteria might lead to unnecessary additional tests for polycythemia vera patients with high-normal hemoglobin and hematocrit values.

Myomatous erythrocytosis syndrome: a uterine fibroid associated with polycythaemia.

Myomatous erythrocytosis syndrome (MES) is a rare form of secondary erythrocytosis seen with myomas. Here, we present a case of a postmenopausal, nulliparous woman in her 50s incidentally found to have asymptomatic erythrocytosis on routine laboratory work. She was found to have an 18.5 cm myoma and after surgical resection, the patient's haematological values returned to normal ranges after a few weeks. This established the diagnosis as MES. The aetiology of MES continues to remain unknown but is most likely caused by an autonomous production of erythropoietin from the myomatous tissue. This case highlights obtaining a detailed history and physical examination to differentiate between the different causes of erythrocytosis, considering MES as a rare cause of secondary erythrocytosis and to prevent unnecessary procedures such as phlebotomy as surgery is the mainstay of treatment.

Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera.

BACKGROUND: Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide, an injectable peptide mimetic of the master iron regulatory hormone hepcidin, restricts the availability of iron for erythropoiesis. The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown. METHODS: In part 1 of the international, phase 2 REVIVE trial, we enrolled patients in a 28-week dose-finding assessment of rusfertide. Part 2 was a double-blind, randomized withdrawal period in which we assigned patients, in a 1:1 ratio, to receive rusfertide or placebo for 12 weeks. The primary efficacy end point was a response, defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Patient-reported outcomes were assessed by means of the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary (scores range from 0 to 10, with higher scores indicating greater severity of symptoms). RESULTS: Seventy patients were enrolled in part 1 of the trial, and 59 were assigned to receive rusfertide (30 patients) or placebo (29 patients) in part 2. The estimated mean (±SD) number of phlebotomies per year was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). The mean maximum hematocrit was 44.5±2.2% during part 1 as compared with 50.0±5.8% during the 28 weeks before the first dose of rusfertide. During part 2, a response was observed in 60% of the patients who received rusfertide as compared with 17% of those who received placebo (P = 0.002). Between baseline and the end of part 1, rusfertide treatment was associated with a decrease in individual symptom scores on the MPN-SAF in patients with moderate or severe symptoms at baseline. During parts 1 and 2, grade 3 adverse events occurred in 13% of the patients, and none of the patients had a grade 4 or 5 event. Injection-site reactions of grade 1 or 2 in severity were common. CONCLUSIONS: In patients with polycythemia vera, rusfertide treatment was associated with a mean hematocrit of less than 45% during the 28-week dose-finding period, and the percentage of patients with a response during the 12-week randomized withdrawal period was greater with rusfertide than with placebo. (Funded by Protagonist Therapeutics; REVIVE ClinicalTrials.gov number, NCT04057040.).

[How I manage polycythemia]. / Comment j'explore une polyglobulie.

Polycythemia is suspected when hemoglobin and/or hematocrit levels exceed established norms based on gender and age. This biological anomaly can arise from a myeloproliferative neoplasm known as polycythemia vera, or be secondary to excess erythropoietin (EPO) or decreased in plasma volume. Faced with polycythemia, the search for JAK2 mutations and measurement of serum EPO levels can guide toward the etiology. In polycythemia vera, thromboembolic events are the most lethal complications and unfortunately often the initial manifestation of the disease. The condition can also progress to myelofibrosis or acute leukemia. Management aims at reducing the hematocrit below 45 %, in order to limit, but not completely prevent, thrombo-embolic complications. This article elaborates on the clinical considerations around this biological anomaly, relevant complementary examinations, and briefly the therapeutic management.

La polyglobulie est suspectée lorsque le taux d'hémoglobine et/ou d'hématocrite est au-dessus des normes définies selon le sexe et l'âge. Cette anomalie biologique peut survenir à la suite d'une néoplasie myéloproliférative appelée polycythemia vera (PV), être secondaire à un excès d'érythropoïétine (EPO) ou à une diminution du volume plasmatique. Face à une polyglobulie, la recherche de mutations du gène JAK2 et un dosage d'EPO sérique permettront d'orienter vers l'étiologie. En cas de PV, les phénomènes thrombo-emboliques sont les complications les plus léthales et sont malheureusement souvent la première manifestation de la maladie. La maladie peut également évoluer en myélofibrose ou en leucémie aiguë. La prise en charge vise à réduire le taux d'hématocrite en-dessous de 45 %, afin de limiter, sans les empêcher complètement, les complications thrombo-emboliques. Dans cet article, nous développons la réflexion clinique autour de cette anomalie biologique, les examens complémentaires pertinents dans ce domaine et, brièvement, la prise en charge thérapeutique.

Neonatal polycythemia: prevalence, risk factors and predictors of severity.

BACKGROUND: Polycythemia is a disorder with several causes and risk factors. The clinical presentation is variable, ranging from asymptomatic newborns to cases with severe physiological changes. The aim of this study was to assess the prevalence, risk factors and predictors of severity of polycythemia in a Portuguese level III Neonatal Intensive Care Unit (NICU). METHODS: Case-control study of all term newborns with the diagnosis of polycythemia admitted to the NICU of the São João Universitary Hospital Center, Porto, Portugal, from January 1, 1999 to December 31, 2019; and who met one of the following inclusion criteria were eligible for the study: 1) Hct>65% or Hb>22 g/dL; and 2) Hb≥21 g/dL with clinical manifestations of polycythemia. RESULTS: A total of 53 newborns fulfilled the inclusion criteria and were included in the study, corresponding to a prevalence of 0.57%. Birth outside the hospital was the only risk factor with statistical significance. Of 53 cases, 51 (96.23%) had symptomatic polycythemia. The most frequent symptoms were: hyperbilirubinemia (69.81%), hypoglycemia (52.83%), thrombocytopenia (50.94%), cardiorespiratory (33.96%), and neurological symptoms (33.96%). Of the 53 newborns evaluated, 41 (77.36%) needed treatment. The only risk factors that influenced the hematocrit value were maternal diabetes and fetal growth restriction. CONCLUSIONS: The best way to improve the prognosis of polycythemia is to identify the risk factors present throughout pregnancy and make an early diagnosis and treatment. Out-of-hospital births should be avoided. The diagnosis should not be excluded, even if hemoglobin and hematocrit are within normal limits.

Falsely prolonged prothrombin time test in a patient with erythrocytosis: a case report.

The prothrombin time (PT) test is commonly used to monitor deficiencies in coagulation factors. A prolonged PT may indicate a deficiency of factors II, V, VII, X, and fibrinogen, or the presence of an inhibitor. However, further tests are required to differentiate between a true factor deficiency and the presence of an inhibitor. It is important to note that falsely prolonged PT can lead to misdiagnosis and inappropriate clinical intervention that can have life-threatening consequences. A 19-year-old woman with elevated hematocrit levels and prolonged PT was diagnosed with secondary erythrocytosis due to cyanotic congenital heart disease with ventricular septal defect (VSD). However, further investigation revealed that the prolonged PT result was false. Excess citrate in the blood sample, caused by polycythemia, led to this misleading outcome, resulting in unnecessary and potentially harmful treatment. This incident emphasizes the importance of laboratory personnel and clinicians being aware of the test's limitations. Not only should specialists in thrombosis and hemostasis possess this knowledge, but it is also pertinent for general laboratory staff, as well as laboratory directors and specialists. The significance of accurate laboratory testing for the proper diagnosis and treatment of patients is highlighted in this case.

Idiopathic erythrocytosis: a germline disease?

Polycythemia Vera (PV) is typically caused by V617F or exon 12 JAK2 mutations. Little is known about Polycythemia cases where no JAK2 variants can be detected, and no other causes identified. This condition is defined as idiopathic erythrocytosis (IE). We evaluated clinical-laboratory parameters of a cohort of 56 IE patients and we determined their molecular profile at diagnosis with paired blood/buccal-DNA exome-sequencing coupled with a high-depth targeted OncoPanel to identify a possible underling germline or somatic cause. We demonstrated that most of our cohort (40/56: 71.4%) showed no evidence of clonal hematopoiesis, suggesting that IE is, in large part, a germline disorder. We identified 20 low mutation burden somatic variants (Variant allelic fraction, VAF, < 10%) in only 14 (25%) patients, principally involving DNMT3A and TET2. Only 2 patients presented high mutation burden somatic variants, involving DNMT3A, TET2, ASXL1 and WT1. We identified recurrent germline variants in 42 (75%) patients occurring mainly in JAK/STAT, Hypoxia and Iron metabolism pathways, among them: JAK3-V722I and HIF1A-P582S; a high fraction of patients (48.2%) resulted also mutated in homeostatic iron regulatory gene HFE-H63D or C282Y. By generating cellular models, we showed that JAK3-V722I causes activation of the JAK-STAT5 axis and upregulation of EPAS1/HIF2A, while HIF1A-P582S causes suppression of hepcidin mRNA synthesis, suggesting a major role for these variants in the onset of IE.

Monochorionic Twins: TTTS, TAPS, and Selective Fetal Growth Restriction.

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.

ST-Segment Elevation Myocardial Infarction and Bleeding Complications in JAK2-Negative Polycythemia.

Thrombotic and bleeding complications are major causes of morbidity and mortality in patients with polycythemia vera, who predominantly present with an alteration in the JAK2 gene. Because of their hypercoagulable state and risk of hemorrhage, patients with polycythemia vera who present with an acute myocardial infarction pose a challenge to physicians. This case report describes the presentation and treatment of a Hispanic patient with JAK2 V617F-negative primary polycythemia who developed cardiac arrest and ST-segment elevation myocardial infarction owing to complete occlusion of the left anterior descending artery as well as bleeding complications and postmyocardial pericarditis.

The utility of testing erythropoietin level in polycythemia diagnosis.

OBJECTIVES: Polycythemia vera (PV) is classically thought to be associated with low erythropoietin (EPO) levels. Here, we present a review of the utility of using EPO levels in diagnosing polycythemia. METHODS: We conducted a systematic literature review of the Medline data through Pubmed and Google Scholar. We included the articles which described confirmed PV associated with elevated EPO level. Our search strategy included the following terms in Pubmed (((polycythemia vera[MeSH Terms]) OR (jak2 protein tyrosine kinase[MeSH Terms])) OR (Myeloproliferative Disorders[MeSH Terms])) AND (Erythropoietin[MeSH Terms]), and 'polycythemia vera with erythropoietin' in Google Scholar. RESULTS: Our research yielded four cases of PV with elevated EPO levels. The most common symptom was a headache. Thrombotic phenomena happened in a single case in the form of Budd-Chiari syndrome. The mean Hb level was 20.2 gm/dl, and the EPO level was 213 mlU/mL. DISCUSSION: Although PV is usually associated with low EPO levels, high levels do not exclude this diagnosis. Workup should include testing for JAK2 mutation and bone marrow biopsy in the presence of suggestive signs and symptoms. Novel biomarkers are also being proposed to aid in the diagnosis. CONCLUSION: Although elevated EPO levels suggest secondary causes of polycythemia, cases where elevated EPO levels were associated with an underlying PV are reported in the literature, and we have summarized a review of them. Workup for polycythemia should include JAK2 mutation testing if signs and symptoms suggest PV even if EPO is elevated.

Selective intrauterine growth restriction without concomitant twin-to-twin transfusion syndrome, natural history, and risk factors for fetal death: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the natural history of selective intrauterine growth restriction in monochorionic twin pregnancies based on the Gratacós classification, including progression of, improvement in, or stability of umbilical artery Dopplers and progression to twin-to-twin transfusion syndrome or twin anemia polycythemia syndrome. We also aimed to investigate risk factors for smaller twin demise. DATA SOURCES: A systematic search was performed to identify relevant studies published in English up to June 2022 using the databases PubMed, Scopus, and Web of Science STUDY ELIGIBILITY: We used retrospective and prospective studies published in English that reported on selective intrauterine growth restriction without concomitant twin-to-twin transfusion syndrome. STUDY APPRAISAL AND SYNTHESIS METHODS: Articles that investigated selective intrauterine growth restriction progression and outcomes by umbilical artery Doppler end-diastolic flow (Gratacós classification) were included. Type I included selective intrauterine growth restriction cases with positive end-diastolic flow, type II included those cases with persistently absent end-diastolic flow, and type III included cases with intermittent absent or reversed end-diastolic flow. Pregnancies in which a diagnosis of twin-to-twin transfusion syndrome or twin anemia polycythemia sequence was made before the diagnosis of selective intrauterine growth restriction were not included in the analysis. A random effects model was used to pool the odds ratios and the corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. RESULTS: A total of 17 studies encompassing 2748 monochorionic pregnancies complicated by selective intrauterine growth restriction were included in the analysis. The incidence of stable, deteriorating, or improving umbilical artery Dopplers in type I cases was 68% (95% confidence interval, 26-89), 23% (95% confidence interval, 7-40), and 9% (95% confidence interval, 0.0-100), respectively. In type II cases, the incidence was 40% (95% confidence interval, 18-81), 50% (95% confidence interval, 23-82), and 10% (95% confidence interval, 4-37), respectively, and in type III cases, the incidence was 55% (95% confidence interval, 2-99), 23% (95% confidence interval, 9-43), and 22% (95% confidence interval, 6-54), respectively. The risk for progression to twin-to-twin transfusion syndrome was comparable between type I (7%) and type III (9%) cases and occurred in 4% (95% confidence interval, 0-67) of type II cases with no significant subgroup differences. Progression to twin anemia polycythemia syndrome was highest in type I cases (12%) and comparable between type II (2%) and III (1%) cases with no significant subgroup differences. Risk factors for smaller twin demise were earlier gestational age at diagnosis (mean difference, -2.69 weeks; 95% confidence interval, -4.94 to -0.45; I2, 45%), larger intertwin weight discordance (mean difference, 34%; 95% confidence interval, 1.35-5.38; I2, 28%), deterioration of umbilical artery Dopplers for each of type II and III cases (odds ratio, 3.05; 95% confidence interval, 1.36-6.84; I2, 24%; and odds ratio, 4.5; 95% confidence interval, 2.31-8.77; I2, 0.0%, respectively), and absent or reversed ductus venosus a-wave for each of type II and III cases (odds ratio, 3.35; 95% confidence interval, 2.28-4.93; I2, 0.0%; and odds ratio, 2.36; 95% confidence interval, 1.08-5.13; I2, 0.0%, respectively). Progression to twin-to-twin transfusion syndrome was not significantly associated with smaller twin demise for each of type II and III selective intrauterine growth restriction cases. CONCLUSION: These findings improve our understanding of the natural history of the types of selective intrauterine growth restriction and of the predictors of smaller twin demise in type II and III selective intrauterine growth restriction cases. The current data provide vital counseling points and support the need for modifications of the current selective intrauterine growth restriction classification system to include the variations in umbilical artery and ductus venosus Dopplers to better identify a cohort that might benefit from fetal intervention for which future multicenter prospective randomized trials are needed.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as new possible minor criteria for diagnosis of polycythemia vera.

INTRODUCTION: The role of inflammation in the pathophysiology of polycythemia vera (PV) is important. The presence of JAK2 mutations is important in the diagnosis of PV, and serum levels of erythropoietin (EPO) also play a supporting role. However, serum EPO levels show some limitations. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are a readily available marker of inflammation. Thus, we examined whether NLR & PLR might diagnose PV in erythrocytosis patients. We compared NLR & PLR and EPO diagnostic values. METHODS: We retrospectively reviewed clinical and laboratory data from two referral hospitals. Two hundred and eighty-five patients with erythrocytosis who underwent a test for the JAK2 mutation were included. It wac classified as the PV group and the secondary polycythemia (SP) group. RESULTS: The median NLR & PLR in the PV group (n = 70) was significantly higher than that in the SP group (n = 170) (NLR: 6.04 vs. 1.77, PLR: 283.18 vs. 101.56, respectively, p < 0.001). In the receiver operating characteristic analysis, the area under the curve of NLR & PLR was significantly higher than that of serum EPO (NLR vs EPO: 0.921 vs. 0.827, p = 0.003; PLR vs EPO: 0.917 vs 0.827, p = 0.003). CONCLUSION: In conclusion, NLR & PLR were higher in PV than in SP and showed better diagnostic value than serum EPO level, highlighting their potential as minor diagnostic criteria in patients with PV.

Characterization of genetic variants in the EGLN1/PHD2 gene identified in a European collection of patients with erythrocytosis.

Hereditary erythrocytosis is a rare hematologic disorder characterized by an excess of red blood cell production. Here we describe a European collaborative study involving a collection of 2,160 patients with erythrocytosis sequenced in ten different laboratories. We focused our study on the EGLN1 gene and identified 39 germline missense variants including one gene deletion in 47 probands. EGLN1 encodes the PHD2 prolyl 4-hydroxylase, a major inhibitor of hypoxia-inducible factor. We performed a comprehensive study to evaluate the causal role of the identified PHD2 variants: (i) in silico studies of localization, conservation, and deleterious effects; (ii) analysis of hematologic parameters of carriers identified in the UK Biobank; (iii) functional studies of the protein activity and stability; and (iv) a comprehensive study of PHD2 splicing. Altogether, these studies allowed the classification of 16 pathogenic or likely pathogenic mutants in a total of 48 patients and relatives. The in silico studies extended to the variants described in the literature showed that a minority of PHD2 variants can be classified as pathogenic (36/96), without any differences from the variants of unknown significance regarding the severity of the developed disease (hematologic parameters and complications). Here, we demonstrated the great value of federating laboratories working on such rare disorders in order to implement the criteria required for genetic classification, a strategy that should be extended to all hereditary hematologic diseases.

Is Erythrocytosis More Common After Simultaneous Pancreas Kidney Transplantation? A Single-Center Experience.

Post-transplant erythrocytosis (PTE) is reported in 8% to 22% of kidney transplant recipients. Few studies have evaluated the prevalence of PTE in simultaneous kidney-pancreas transplantation (SPKT). This study aimed to evaluate the prevalence of PTE in a cohort of SPKT and same-donor single kidney transplant patients and find predictive factors for erythrocytosis development. A single-center retrospective cohort study was performed with 65 SPKT recipients and 65 same-donor single kidney transplant patients. Post-transplant erythrocytosis was defined as a hematocrit persistently >51% without a known cause of erythrocytosis. The PTE prevalence was 23.1% and was more frequent in SPKT patients than in single donor patients (38.5% vs 7.7%; P < .001). The mean time for PTE development was 11.2 ± 13.3 months. In the multivariate model, SPKT was the only predictor for PTE development. De novo hypertension was more frequent in the PTE group (P = .002), but there was no difference in stroke and pancreatic or kidney thrombosis occurrence. Post-transplant erythrocytosis is more common after SPKT than after single kidney transplantation. De novo hypertension was more frequent in the erythrocytosis group, but allograft thrombosis rates.

A Young Patient with Undiagnosed Polycythemia-Paraganglioma Syndrome: A Case Report.

BACKGROUND Erythrocytosis results from primary or secondary causes and is characterized by an increased red blood cell count. Secondary erythrocytosis is a result of an underlying cause outside the bone marrow and is often mediated by erythropoietin. Paragangliomas are rare tumors characterized by increased release of catecholamines with symptoms such as hypertension, hematuria, headache, sweating, and post-micturition syncope. Polycythemia-paraganglioma syndrome (PPS) is exceedingly rare, and reports in the literature are limited. CASE REPORT A 14-year-old female patient presented to our clinic with sweating, palpitations, and palmar erythema. The patient's history was significant for uninvestigated hypertension diagnosed at the age of 9. There was no history of smoking or illicit drug use. Blood investigations revealed an elevated hemoglobin level of 18.5 g/dL and a hematocrit of 57.5%. Whole-genome sequencing found no mutations, excluding polycythemia vera from the differential diagnosis. Computed tomography (CT) revealed 2 lesions compatible with urinary bladder paragangliomas and retroperitoneal lesions, likely representing metastatic lymphadenopathy. Whole-body gallium-68 DOTATATE PET/CT scan demonstrated significant tracer uptake within the necrotic retroperitoneal lymph nodes. However, evaluation of the bladder lesion was limited due to physiological urinary excretion of the tracer. A 24-hour urine collection demonstrated high normetanephrine levels of 24 µmol/L. These findings confirmed the diagnosis of PPS. CONCLUSIONS PPS is largely associated with HIF2A mutations. This article describes the case of a young PPS patient and highlights the importance of considering neoplasms in the differential diagnosis of hypertension in young patients. Further, it is crucial to conduct clinical investigations on young hypertensive patients to exclude underlying causes such as renal diseases, coarctation of the aorta, and neuroendocrine disorders.

Hematometabolic Index as a New Discriminator of Cardiometabolic Risk in Middle-Aged Men with Polycythemia and High Leukocyte Count in Peripheral Blood.

Background: Both polycythemia and high leukocyte count are associated with the risk of cardiovascular disease. However, it remains to be determined whether polycythemia and high leukocyte count show synergistic increasing effects on cardiometabolic risk. Methods: Cardiometabolic risk was evaluated by cardiometabolic index (CMI) and metabolic syndrome in a cohort of middle-aged men (n = 11,140) who underwent annual health check-up examinations. The subjects were divided into three tertile groups by hemoglobin concentration or leukocyte count in peripheral blood, and their relations with CMI and metabolic syndrome were investigated. A new index, named hematometabolic index (HMI), was defined as the product of hemoglobin concentration (g/dL)-minus-13.0 and leukocyte count (/µL)-minus-3000. Results: When the subjects were further classified by tertiles for hemoglobin concentration and leukocyte count into nine groups, the odds ratios for high CMI and metabolic syndrome of the group categorized in the highest (third) tertiles for both hemoglobin concentration and leukocyte count versus the group of the lowest (first) tertiles for both of them were highest among the nine groups. In receiver-operating characteristic (ROC) analysis for relationships of HMI with high CMI and metabolic syndrome, areas under the ROC curves (AUCs) were significantly larger than the reference level and tended to be smaller with an increase in age. In subjects from 30 to 39 years of age, the AUC for the relationship between HMI and metabolic syndrome was 0.707 (0.663-0.751) and the cutoff of HMI was 9850. Conclusions: HMI, reflecting hemoglobin concentration and leukocyte count, is thought to be a possible marker for discriminating cardiometabolic risk.

Association between polycythemia and risk of ischemic stroke in males based on the national health insurance service-health screening cohort.

BACKGROUND: Polycythemia, a state in which the hematocrit or hemoglobin (Hb) concentration in the peripheral blood increases, is associated with several thrombosis-related diseases, of which cerebral infarction is relatively common. This study aimed to investigate the association between ischemic stroke and polycythemia, as a potential risk factor. RESEARCH DESIGN AND METHODS: This study included men who had undergone national health checkups between 2002 and 2003; the data were extracted from the Korean National Health Insurance Service-Health Screening database. The primary outcome was the risk ischemic stroke; adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for ischemic stroke were calculated using Cox proportional hazards regression models. RESULTS: In total, 207,737 male participants aged 40-79 years were included in this study. At the baseline, 13972 (6.7%) participants met the polycythemia criteria (Hb >16.5 g/dL). During the study period, 897 and 12,440 cases of ischemic stroke occurred in the polycythemia and normocythemia (13.0 g/dL ≤ Hb ≤16.5 g/dL) groups, respectively. Compared with the normocythemia group, the polycythemia group showed an adjusted HR (95% CI) for ischemic stroke of 1.12 (1.04-1.20). CONCLUSIONS: The risk of ischemic stroke was higher in participants with polycythemia than in those with normocythemia.

Germline JAK2 E846D Substitution as the Cause of Erythrocytosis?

The discovery in 2005 of the JAK2 V617F gain-of-function mutation in myeloproliferative neoplasms and more particularly in polycythemia vera has deeply changed the diagnostic and therapeutic approaches to polycythemia. More recently, the use of NGS in routine practice has revealed a large number of variants, although it is not always possible to classify them as pathogenic. This is notably the case for the JAK2 E846D variant for which for which questions remain unanswered. In a large French national cohort of 650 patients with well-characterized erythrocytosis, an isolated germline heterozygous JAK2 E846D substitution was observed in only two cases. For one of the patients, a family study could be performed, without segregation of the variant with the erythrocytosis phenotype. On the other hand, based on the large UK Biobank resource cohort including more than half a million UK participants, the JAK2 E846D variant was found in 760 individuals, associated with a moderate increase in hemoglobin and hematocrit values, but with no significant difference to the mean values of the rest of the studied population. Altogether, our data as well as UK Biobank cohort analyses suggest that the occurrence of an absolute polycythemia cannot be attributed to the sole demonstration of an isolated JAK2 E846D variant. However, it must be accompanied by other stimuli or favoring factors in order to generate absolute erythrocytosis.