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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. [ABSTRACT FROM AUTHOR]

Polycythemia vera (PV) is a BCR-ABL1-negative myeloproliferative neoplasm (MPN) characterized by excessive proliferation of erythroid, myeloid, and megakaryocytic components in the bone marrow, mainly due to a Janus kinase 2 gene mutation (JAK2V617F). Givinostat, a histone-deacetylase inhibitor that selectively targets JAK2V617F cell growth, has demonstrated good efficacy and safety in three phase 1/2 studies in patients with PV. This manuscript focuses on the 4-year mean (2.8 year median) follow-up of an open-label, long-term study that enrolled 51 patients with PV (out of a total of 54 with MPN) who received clinical benefit from givinostat in these previous studies or on compassionate use, and who continued to receive givinostat at the last effective and tolerated dose. The primary objectives are to determine givinostat's long-term safety and tolerability, and efficacy evaluated by the investigators according to internationally recognized response criteria. During follow-up, only 10% of PV patients reported Grade 3 treatment-related adverse events (AEs), while none had Grade 4 or 5 treatment-related AEs. The overall response rate for the duration of follow-up was always greater than 80% in patients with PV. In conclusion, givinostat demonstrated a good safety and efficacy profile in patients with PV, data supporting long-term use in this population. [ABSTRACT FROM AUTHOR]

Background: Tetralogy of Fallot is the most common cyanotic congenital heart disease. Patients with the condition have a high risk of developing chronic kidney disease. Treatment of kidney disease in patients with complex hemodynamics presents unique challenges. However, there are very few reports on the treatment of end-stage renal failure in patients with tetralogy of Fallot.Case Presentation: We present a rare case of peritoneal dialysis in a 47-year-old man with tetralogy of Fallot who had not undergone intracardiac repair. Peritoneal dialysis successfully removed fluids and solutes without adversely affecting the patient's hemodynamics. Our patient was managed with peritoneal dialysis for 5 years before he succumbed to sepsis secondary to digestive tract perforation.Conclusions: In this paper, we discuss the importance of monitoring acid-base balance, changes in cyanosis, and hyperviscosity syndrome during peritoneal dialysis in patients with tetralogy of Fallot. Lower leg edema and B-type natriuretic peptide level were useful monitoring parameters in this case. This case illustrates that with attention to the patient's unique requirements, peritoneal dialysis can provide successful renal replacement therapy without compromising hemodynamics in patients with tetralogy of Fallot. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical features, treatment and prognosis of high altitude polycythemia mainly manifested as bilateral papilledema. Methods Clinical data of 7 patients with high altitude polycythemia mainly manifested as bilateral papilledema in our hospital from March 2007 to September 2017 were retrospectively analyzed, including clinical manifestations, laboratory results, ophthalmologic examinations, head imaging features, mitochondrial gene detection, treatment and prognosis. Results There were 6 male patients and one female patient, with mean age (44.43 ± 9.05) years old, high altitude residence 7 (4, 13) months, and duration (28.43 ± 10.05) d. All patients were detected with high concentrations of hemoglobin (> 210 g/L), and different degrees of bilateral papilledema after onset. One eye had severe vision impairment [best corrected visual acuity (CVA) was finger counting], and the CVA of other 13 eyes were > 0.10. Visual field defects included enlargement of psychological blind spot (2 eyes), lower altitudinal visual field defect (4 eyes), central scotoma (2 eyes) and diffuse visual field defect (6 eyes). Brain MRI of 7 cases showed dot - like and patchy long T1 and long T2 signals in frontal lobe, parietal lobe and paraventricular region. Optic nerve MRI showed hyperintense signal and slight enhancement in 7 eyes and no abnormality in other 7 eyes. All patients were treated by antiplatelet therapy and microcirculation improvement. Best CVA of all patients were remarkably improved within follow up of 6 months. Conclusions High altitude polycythemia mainly manifested as bilateral papilledema was easily misdiagnosed as other diseases. Moving away from plateau, decreasing hemoglobin, anti - platelet therapy and microcirculation improvement may play an important role in the favorable prognosis. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 6-year-old boy presented to the Emergency Department after a fall from a bicycle with loss of consciousness. It mentions that Molecular testing for von Hippel-Lindau (VHL) gene mutations revealed the presence of two previously reported mutations confirmed the diagnosis of Chuvash polycythaemia in this child. It further offers information about Chuvash polycythaemia, a rare autosomal recessive congenital polycythaemia.

Hydroxycarbamide (HC) is the first-line treatment for certain myeloproliferative neoplasms, such as polycythemia vera and essential thrombocytosis (ET). In a subset of these patients long-term treatment with HC can result in the development of confluent actinic keratoses (AK) followed by invasive keratinocytic carcinomas (“squamous dysplasia”), preferentially on sun-exposed skin. Discontinuation or dose reduction of HC may result in partial improvement. A 59-year-old farmer after 14 years on HC (2 gr/d) and acetylsalicylic acid (100 mg/d) for ET, was referred for numerous, hyperkeratotic AK on face, scalp, and hands that could not be controlled with repeated (N=15) cryosurgery sessions in the previous 3 years. Acitretin (0.32 mg/kg daily) and topical treatments (cryosurgery with ingenol mebutate) were initiated with only marginal improvement after 3 months. Acitretin dose was doubled and HC was switched to anagrelide (0.5 mg twice daily). Within a month the AK load regressed significantly and, at 3 months follow-up, complete clinical remission was achieved and acitretin was discontinued. Twenty months later the patient is clear from AK. In conclusion, the impressive and sustainable AK remission under anagrelide draws attention to a possible role of the phosphodiesterase 3 pathway, the major pharmacological target of anagrelide, as a potential therapeutic target for keratinocytic cancers. [ABSTRACT FROM AUTHOR]

The Tibetan high plateau is a low-oxygen environment, which may cause the pathogenesis of high-altitude polycythemia (HAPC). Gastric mucosal lesions (GML) are a common complication of HAPC. The molecular mechanisms involved in HAPC-induced GML have remained to be fully elucidated and were therefore investigated in the present study. Gastric tissues of patients with heavy, HAPC-induced GML and healthy controls were assessed by ultrastructural and histopathological analysis. In addition, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis were used to detect cell apoptosis in the gastric mucosa tissues. Moreover, the expression of genes associated with the phosphoinositide-3 kinase (PI3K) pathway was assessed by RT-qPCR to investigate the mechanism of cell apoptosis in HAPC-induced GML. The results revealed a significant increase in the number of red blood cells, gastric vessels and the diameter of gastric mucosal vessels in HAPC-induced GML patients compared with those in healthy controls. In addition, more red blood cells were distributed in gastric tissue not only at the vascular level but also in the tissue space. The number of vacuoles was increased in the gastric mucosal cells. Furthermore, a significant increase in apoptosis of the gastric mucosal cells was identified. The expression of phosphatase and tensin homolog was significantly higher in gastric mucosa from patients with HAPC-induced GML compared with that in the healthy controls. All of the pathologic changes suggested that significant cell apoptosis occurred in the HAPC-induced GML tissues, which may be associated with the PI3K pathway. These findings may provide novel insight for the treatment of gastric lesions caused by HAPC in the future. [ABSTRACT FROM AUTHOR]

Key Clinical Message Primary polycythemia (PCV) may coexist in otherwise asymptomatic patients particularly in the presence of unsuspecting conditions such as Thrombotic thrombocytopenic purpura (TTP). In presumed 'idiopathic TTP,' autoimmune conditions such as rheumatoid arthritis (RA) should be investigated as a possible etiology for TTP. Standardization of targeted therapy with immunomodulatory agents may be recommended for this subset of patients. [ABSTRACT FROM AUTHOR]

Gene expression profiling in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have unraveled significant deregulation of several immune and inflammation genes of potential importance for clonal evolution. Other mechanisms might be downregulation of major histocompatibility class I and II genes used by tumor cells to escape antitumor T-cell-mediated immune responses. Several genes encoding human leukocyte antigen (HLA) class I and II molecules have been shown to be significantly downregulated. Upregulation of HLA genes is considered one of the mechanisms of action of interferon (IFN)-alpha2, but regulation of these genes during IFN-alpha2 treatment in MPNs has never been studied. Our findings show a significant upregulation of several HLA genes of importance for tumor immune surveillance by IFN-alpha2 treatment in MPNs. This mechanism might enhance the cytotoxic potential of immune cells against MPNs and explain the induction of minimal residual disease by IFN-alpha2 treatment in these patients. [ABSTRACT FROM PUBLISHER]

Background: Postoperative major bleeding is a relatively common complication of patients undergoing corrective surgery of tetralogy of Fallot (TOF). Life-threatening blood losses can lead to aggressive transfusions or reoperation. Little is known about the risk factors associated with a bleeding tendency in TOF patients. This study aimed to establish predictive models for postoperative blood loss and mortality in TOF patients.Methods: We conducted a retrospective observational study involving patients with TOF who were posted for corrective cardiac surgery in a single hospital between 2010 and 2015. Hospital records including sociodemographic, pre- and intra-operative characteristics were extracted. Postoperative blood loss (within 24 and 48 h) and 30-day mortality were the primary and secondary outcomes, respectively. Multivariate linear and logistic regression models were used to identify determinants of outcomes.Results: A total of 60 patients were included in this study. The median age was 1 year (interquartile range = 0.62-5) and the male to female ratio of 1.7:1. Mean postoperative blood loss within 24 h was 283 ± 212 mL. In multivariate linear regression, preoperative hematocrit (β = 6.63, P = 0.042) and duration of intraoperative oxygenator with CPB (β = 5.16, P = 0.025) were significantly correlated with postoperative blood loss within 24 h. After adjusting for sociodemographic, intra- and post-operative characteristics, preoperative hematocrit (odds ratio [OR] = 1.10, 95% confidence interval [CI] = 1.01-1.21), and postoperative red blood cell transfusions (OR = 3.88, 95% CI = 1.16-12.9) showed statistically significant association with 30-day mortality. The area under the receiver operating characteristic curve of the multivariable model was 0.863.Conclusions: Preoperative levels of erythrocytosis appear to predict postoperative blood loss and short-term mortality in TOF patients undergoing corrective surgery. [ABSTRACT FROM AUTHOR]

Purpose We evaluated the relative prevalence of secondary polycythemia in hypogonadal men treated with clomiphene citrate or testosterone replacement therapy. Materials and Methods In this retrospective, multi-institutional study, we included 188 men who received clomiphene citrate and 175 who received testosterone replacement therapy with symptomatic hypogonadism. The overall prevalence and ORs of secondary polycythemia for clomiphene citrate treatment vs testosterone replacement were primarily measured, as were baseline characteristics. Subset analysis included polycythemia rates for different types of testosterone replacement therapy. Results Overall, men on testosterone replacement therapy were older than clomiphene citrate treated men (age 51.5 vs 38 years). Men on testosterone replacement had longer treatment duration than clomiphene citrate treated men (19.6 vs 9.2 months). For testosterone replacement therapy and clomiphene citrate the mean change in hematocrit was 3.0% and 0.6%, and the mean change in serum testosterone was 333.1 and 367.6 ng/dl, respectively. The prevalence of polycythemia in men on testosterone replacement was 11.2% vs 1.7% in men on clomiphene citrate (p = 0.0003). This significance remained on logistic regression after correcting for age, site, smoking history and pretreatment hematocrit. Conclusions The prevalence of polycythemia in men treated with clomiphene citrate was markedly lower than that in men on testosterone replacement therapy. The improvement in absolute serum testosterone levels was similar to that in men on testosterone replacement. There is no significant risk of polycythemia in men treated with clomiphene citrate for hypogonadism. [ABSTRACT FROM AUTHOR]

Background: The driver mutations JAK2V617F, MPLW515L/K and CALR influence disease phenotype of myeloproliferative neoplasms (MPNs) and might sustain a condition of chronic inflammation. Pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) are inflammatory biomarkers potentially useful for refining prognostic classification of MPNs. Methods: We evaluated 305 with essential thrombocythemia (ET) and 172 polycythemia vera (PV) patients diagnosed according to the 2016 WHO criteria and with full molecular characterization for driver mutations. Results: PTX3 levels were significantly increased in carriers of homozygous JAK2V617F mutation compared to all the other genotypes and triple negative ET patients, while hs-CRP levels were independent of the mutational profile. The risk of haematological evolution and death from any cause was about 2- and 1.5-fold increased in individuals with high PTX-3 levels, while the thrombosis rate tended to be lower. High hs-CRP levels were associated with risk of haematological evolution, death and also major thrombosis. After sequential adjustment for potential confounders (age, gender, diagnosis and treatments) and the presence of JAK2V617F homozygous status, high hs-CRP levels remained significant for all outcomes, while JAK2V617F homozygous status as well as treatments were the factors independently accounting for adverse outcomes among patients with high PTX3 levels. Conclusions: These results provide evidence that JAK2V617F mutation influences MPN-associated inflammation with a strong correlation between allele burden and PTX3 levels. Plasma levels of hs-CRP and PTX3 might be of prognostic value for patients with ET and PV, but their validation in future prospective studies is needed. [ABSTRACT FROM AUTHOR]

Summary Background In the pivotal RESPONSE study, ruxolitinib, a Janus kinase (JAK)1 and JAK2 inhibitor, was superior to best available therapy at controlling haematocrit and improving splenomegaly and symptoms in patients with polycythaemia vera with splenomegaly who were inadequately controlled with hydroxyurea. In this study, we assessed the efficacy and safety of ruxolitinib in controlling disease in patients with polycythaemia vera without splenomegaly who need second-line therapy. Methods RESPONSE-2 is a randomised, open-label, phase 3b study assessing ruxolitinib versus best available therapy in patients with polycythaemia vera done in 48 hospitals or clinics across 12 countries in Asia, Australia, Europe, and North America. Eligible patients (aged ≥18 years) with polycythaemia vera, no palpable splenomegaly, and hydroxyurea resistance or intolerance were stratified by their hydroxyurea therapy status (resistance vs intolerance) and randomly assigned (1:1) by an interactive response technology provider using a validated system to receive either oral ruxolitinib 10 mg twice daily or investigator-selected best available therapy (hydroxyurea [at the maximum tolerated dose], interferon or pegylated interferon, pipobroman, anagrelide, approved immunomodulators, or no cytoreductive treatment). Investigators and patients were not masked to treatment assignment; however, the study sponsor was masked to treatment assignment until database lock. The primary endpoint was the proportion of patients achieving haematocrit control at week 28. Analyses were done according to an intention-to-treat principle, including data from all patients randomly assigned to treatment. This study is registered with ClinicalTrials.gov ( NCT02038036 ) and is ongoing but not recruiting patients. Findings Between March 25, 2014, and Feb 11, 2015, of 173 patients assessed for eligibility, 74 patients were randomly assigned to receive ruxolitinib and 75 to receive best available therapy. At randomisation, best available therapy included hydroxyurea (37 [49%] of 75 in the best available therapy group), interferon or pegylated interferon (ten [13%] of 75), pipobroman (five [7%] of 75), lenalidomide (one [1%] of 75), no treatment (21 [28%] of 75), and other (one [1%] of 75). Haematocrit control was achieved in 46 (62%) of 74 ruxolitinib-treated patients versus 14 (19%) of 75 patients who received best available therapy (odds ratio 7·28 [95% CI 3·43–15·45]; p<0·0001). The most frequent haematological adverse events of any grade were anaemia (ten [14%] of 74 in the ruxolitinib group vs two [3%] of 75 in the best available therapy group) and thrombocytopenia (two [3%] vs six [8%]). No cases of grade 3–4 anaemia or thrombocytopenia occurred with ruxolitinib; one patient (1%) reported grade 3–4 anaemia and three patients (4%) reported grade 3–4 thrombocytopenia in the group receiving best available therapy. Frequent grade 3–4 non-haematological adverse events were hypertension (five [7%] of 74 vs three [4%] of 75) and pruritus (0 of 74 vs two [3%] of 75). Serious adverse events occurring in more than 2% of patients in either group, irrespective of cause, included thrombocytopenia (none in the ruxolitinib group vs two [3%] of 75 in the best available therapy group) and angina pectoris (two [3%] of 74 in the ruxolitinib group vs none in the best available therapy group). Two deaths occurred, both in the best available therapy group. Interpretation RESPONSE-2 met its primary endpoint. The findings of this study indicate that ruxolitinib could be considered a standard of care for second-line therapy in this post-hydroxyurea patient population. Funding Novartis. [ABSTRACT FROM AUTHOR]

Objective: The antenatal diagnosis of twin anemia-polycythemia sequence (TAPS) in monochorionic-diamniotic (MCDA) twin pregnancies is based on elevated peak systolic velocity in the middle cerebral artery (MCA-PSV) in the donor twin and decreased MCA-PSV in the recipient twin. However, the association between these parameters and polycythemia has not yet been established. The aim of this study was to determine whether MCA-PSV can predict polycythemia in MCDA pregnancies.Methods: This was a prospective cohort study of MCDA pregnancies recruited at 14-18 weeks' gestation from a single tertiary care center between January 2011 and June 2014. Fetal MCA Doppler waveforms were recorded every 2 weeks from 18 weeks' gestation until delivery. Only those with an MCA-PSV measurement within 1 week of delivery were included in the analysis. Neonatal hematocrit level was determined in all twins from venous blood obtained within 4 h of delivery. Polycythemia was defined as a hematocrit of > 65%, and anemia as a hematocrit of < 45%. TAPS was diagnosed when an intertwin hemoglobin difference of > 8 g/dL and reticulocyte count ratio of > 1.7 were observed.Results: Of 162 MCDA pregnancies followed during the study period, 69 had an MCA-PSV measurement within 1 week of delivery and were included in the study. Twenty-five neonates were diagnosed with polycythemia and nine twin pairs met the criteria for TAPS. In a pooled analysis, MCA-PSV was negatively correlated with neonatal hematocrit (P = 0.017, r = -0.215) and was significantly higher in anemic fetuses than in normal controls (1.15 multiples of the median (MoM) vs 1.02 MoM, respectively; P = 0.001). However, MCA-PSV was similar among polycythemic and normal fetuses (0.95 MoM vs 1.02 MoM, respectively; P = 0.47). Intertwin difference in MCA-PSV (delta MCA-PSV) was positively correlated with intertwin hematocrit difference (P = 0.002, r = 0.394). Moreover, twin pregnancies with an intertwin hematocrit difference of > 24% had a significantly greater delta MCA-PSV than did those with an intertwin hematocrit difference of ≤ 24% (delta MCA-PSV, 19 vs 5 cm/s; P < 0.001).Conclusions: MCA-PSV is not significantly decreased in polycythemic MCDA twins. However, delta MCA-PSV is associated with a large intertwin difference in hematocrit, and its use may be better than conventional methods for the risk assessment of TAPS. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Erythropoietin (EPO) has beneficial tissue-protective effects in several diseases but erythrocytosis may cause deleterious effects in EPO-treated patients. Thus carbamylated-EPO (C-EPO) and other derivatives retaining tissue-protective but lacking bone marrow-stimulating actions have been developed. Although EPO modulates ventilatory responses, the effects of C-EPO on ventilation have not been investigated. Here, basal breathing and respiratory chemoreflexes were measured by plethysmography after acute and chronic treatments with recombinant human C-EPO (rhC-EPO; 15,000 IU/kg during 5 days) or saline (control group). Hematocrit, plasma and brainstem rhC-EPO levels were also quantified. Chronic rhC-EPO significantly elevated tissue rhC-EPO levels but not hematocrit. None of the drug regimen altered basal ventilation (normoxia). Chronic but not acute rhC-EPO enhanced hyperoxic ventilatory depression, and sustained the hypoxic ventilatory response mainly via a reduction of the roll-off phase. By contrast, rhC-EPO did not blunt the ventilatory response to hypercapnia. Thus, chronic C-EPO may be a promising therapy to improve breathing during hypoxia while minimizing adverse effects on cardiovascular function. [ABSTRACT FROM AUTHOR]

Mutations in JAK2 exon 12 are frequently found in patients with polycythemia vera (PV) that do not carry a JAK2-V617F mutation. The majority of these patients display isolated erythrocytosis. We generated a mouse model that expresses JAK2-N542-E543del, the most frequent JAK2 exon 12 mutation found in PV patients. Mice expressing the human JAK2-N542-E543del (Ex12) showed a strong increase in red blood cell parameters but normal neutrophil and platelet counts, and reduced overall survival. Erythropoiesis was increased in the bone marrow and spleen, with normal megakaryopoiesis and absence of myelofibrosis in histopathology. Erythroid progenitors and precursors were increased in hematopoietic tissues, but the numbers of megakaryocytic precursors were unchanged. Phosphorylation Stat3 and Erk1/2 proteins were increased, and a trend toward increased phospho-Stat5 and phospho-Stat1 was noted. However, Stat1 knock out in Ex12 mice induced no changes in platelet or red cell parameters, indicating that Stat1 does not play a central role in mediating the effects of Ex12 signaling on megakaryopoiesis or erythropoiesis. Ex12 mice showed decreased expression of hepcidin and increased expression of transferrin receptor-1 and erythroferrone, suggesting that the strong erythroid phenotype in Ex12 mutant mice is favored by changes in iron metabolism that optimize iron availability to allow maximal production of red cells. [ABSTRACT FROM AUTHOR]

Myelofibrosis (MF) and polycythemia vera (PV) are BCR-ABL1-negative myeloproliferative neoplasms associated with somatic hematopoietic stem cell mutations leading to over activation of JAK-STAT signaling. MF and PV are pathogenically related and share specific clinical features such as splenomegaly and constitutional symptoms. The MF phenotype is dominated by the effects of progressive bone marrow fibrosis resulting in shortened survival. In contrast, elevated thrombosis risk due to erythrocytosis is the primary clinical concern in PV. Ruxolitinib, an oral JAK1/JAK2 inhibitor, is approved in the USA for the treatment of patients with intermediate- or high-risk MF and patients with PV who have had an inadequate response to or are intolerant of hydroxyurea. For MF, results of two phase III studies demonstrated that ruxolitinib therapy reduced spleen volume and MF-related symptom burden, improved quality-of-life measures, and was associated with prolonged overall survival. Treatment benefits were generally sustained with continued therapy. Dose-dependent cytopenias were common but generally manageable with transfusions (for anemia), dose reduction, or treatment interruption. Optimal dosing management is critical to maintain long-term treatment benefit, because cessation of therapy resulted in rapid return of symptoms to baseline levels. Results of the phase III PV trial showed that ruxolitinib was significantly more effective than standard therapy in controlling hematocrit levels and improving splenomegaly and PV-related symptoms. Only 1 of 110 patients in the ruxolitinib arm compared with 6 of 112 patients in the control arm experienced a thromboembolic event through week 32. Grade ≥3 cytopenias were uncommon. [ABSTRACT FROM AUTHOR]

Twin anemia-polycythemia sequence (TAPS) is a rare condition in monochorionic twin pregnancies. Small intertwin placental vascular communications allow transfusion, which results in a hemoglobin difference in the twins in the absence of oligohydramnios or polyhydramnios. We report here a case of TAPS diagnosed at 17 weeks’ gestation in an obese patient (BMI 42) with a whole anterior placenta. The only possible treatment at this stage of pregnancy was intra-uterine transfusion (IUT), which was repeated weekly until photocoagulation of placental anastomoses was feasible. Fetoscopic laser surgery is the only curative treatment, but is challenging in TAPS because of the absence of polyhydramnios and the presence of minuscule anastomoses. An anterior placenta and high BMI can make the procedure even more challenging. This case report demonstrates that very early and rapidly progressing TAPS with technically complicated conditions (elevated BMI and anterior placenta) can be successfully managed with IUT until laser procedure is achievable. [ABSTRACT FROM PUBLISHER]

Background: The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) negatively affect patient quality of life (QoL) and are associated with increased risk of mortality.Methods: The MPN Landmark survey was conducted from May to July 2014 in patients with MF, PV, or ET under active management in the United States. The survey assessed respondent perceptions of disease burden and treatment management and included questions on overall disease burden, QoL, activities of daily living, and work productivity. Outcomes were further analyzed by calculated (ie, not respondent-reported) prognostic risk score and symptom severity quartile.Results: The survey was completed by 813 respondents (MF, n = 207; PV, n = 380; ET, n = 226). The median respondent age in each of the 3 MPN subtypes ranged from 62 to 66 years; median disease duration was 4 to 7 years. Many respondents reported that they had experienced MPN-related symptoms ≥1 year before diagnosis (MF, 49 %; PV, 61 %; ET, 58 %). Respondents also reported that MPN-related symptoms reduced their QoL, including respondents with low prognostic risk scores (MF, 67 %; PV, 62 %; ET, 57 %) and low symptom severity (MF, 51 %; PV, 33 %; ET, 15 %). Many respondents, including those with a low prognostic risk score, reported that their MPN had caused them to cancel planned activities or call in sick to work at least once in the preceding 30 days (cancel planned activities: MF, 56 %; PV, 35 %; ET, 35 %; call in sick: MF, 40 %; PV, 21 %; ET, 23 %).Conclusions: These findings of the MPN Landmark survey support previous research about the symptom burden experienced by patients with MPNs and are the first to detail the challenges that patients with MPNs experience related to reductions in activities of daily living and work productivity. [ABSTRACT FROM AUTHOR]

Polycythaemia vera ( PV) is a chronic blood cancer; its clinical features are dominated by myeloproliferation (erythrocytosis, often leucocytosis and/or thrombocytosis) and a tendency for thrombosis and transformation to myelofibrosis or acute myeloid leukaemia. In the past 10 years the pathophysiology of this condition has been defined as JAK/STAT pathway activation, almost always due to mutations in JAK2 exons 12 or 14 ( JAK2 V617F). In the same time period our understanding of the optimal management of PV has expanded, most recently culminating in the approval of JAK inhibitors for the treatment of PV patients who are resistant or intolerant to therapy with hydroxycarbamide. It has also been demonstrated that life expectancy for many patients with PV is not normal, nor is their quality of life. We critically explore these findings and discuss their impact. In addition, we highlight persisting gaps in our current management strategy; for example, what is the optimal first line cytoreductive therapy and, indeed, which patients need cytoreductive drugs. [ABSTRACT FROM AUTHOR]

Idiopathic erythrocytosis (IE) is an absolute erythrocytosis with no known cause, diagnosed by exclusion of primary and secondary erythrocytosis. Familial erythrocytosis (FE) is a rare disease and as the rare patients with JAK2-wild-type polycythemia vera (PV) may be misdiagnosed as IE. We compared 78 patients with IE, 21 with FE and 136 with PV in the effort to identify simple features capable of discriminating between them. FE patients were younger at diagnosis either than IE and PV (p < 0.001); IE and FE had lower WBC, platelet counts and higher serum EPO levels, and had splenomegaly and thrombotic events less frequently than PV patients. Phlebotomies to obtain a haematocrit lower than 45 % induce platelet count increase in 70 % of PV but not in IE. Mainly in men, normal spleen, normal platelet counts and no history of thrombosis at diagnosis argue against PV; diagnosis of IE could be supported by means of a cycle of venesection to see how it affects their platelet count. No simple data capable of distinguishing between IE and FE were identified; therefore, a case of sporadic erythrocytosis in a young patient should be investigated as a possible genetic cause. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to evaluate the interest in the in utero treatment of twin anemia-polycythemia sequence (TAPS).Methods: The obstetrical and neonatal data on all cases of TAPS followed up in our institution between 2006 and 2013 were reviewed. Statistical analyses were conducted using Bayesian methods.Results: Twenty cases of TAPS were included. Laser therapy or intrauterine transfusion (IUT) was performed on the donor twin in 9 cases. Eleven cases were included in the 'nontreated' group (managed expectantly or diagnosed at birth). The gestational age at diagnosis was lower in the group with treated TAPS [difference (diff) = -22.20 days (-57.13, 14.28), probability (Pr) (diff >0) = 10.6%]. The rate of preterm premature rupture of membranes was higher in the group with treated TAPS [diff = 22.5% (-14, 57), Pr (diff >0) = 89%], but overall mortality was similar. The interval between diagnosis and delivery was longer [diff = 44.37 days (9.41, 77.90), Pr (diff >0) = 99.2%], the TAPS resolution rate was higher [diff = 49.9% (12, 81), Pr (diff >0) = 99.4%], and the neonatal transfusion rate was lower [diff = -30.5% (-60, 0), Pr (diff >0) = 2.6%] in the treated group.Conclusion: In utero treatment for TAPS is associated with a higher resolution rate of TAPS and a longer time between diagnosis and birth, but overall mortality is the same as with expectant management. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the diagnostic accuracy of middle cerebral artery peak systolic velocity (MCA-PSV) Doppler measurements in prediction of hemoglobin levels in twin anemia-polycythemia sequence (TAPS).Methods: This study involved a consecutive cohort comprising monochorionic twin pregnancies complicated by TAPS managed at three European fetal medicine centers between 2005 and 2013. The accuracy of MCA-PSV, measured immediately prior to fetal hemoglobin (Hb) measurement by fetal or cord blood sampling, for prediction of anemia and polycythemia was assessed using 2 × 2 tables.Results: A total of 116 measurements (74 recorded in donors and 42 in recipients) from 43 twin pregnancies complicated by TAPS were available for analysis. MCA-PSV multiples of the median (MoM) values correlated well with Hb levels (r = - 0.86; P < 0.001). The sensitivity of MCA-PSV ≥ 1.5 MoM to predict severe anemia (Hb deficit > 5 SD below the mean) in TAPS donors was 94% (95% CI, 85-98%); specificity was 74% (95% CI, 62-83%); positive and negative predictive values were 76% (95% CI, 65-85%) and 94% (95% CI, 83-98%), respectively. The sensitivity of MCA-PSV ≤ 1.0 MoM to predict polycythemia (Hb level > 5 SD above the mean) in TAPS recipients was 97% (95% CI, 87-99%); specificity was 96% (95% CI, 89-99%); positive and negative predictive values were 93% (95% CI, 81-97%) and 99% (95% CI, 93-100%), respectively.Conclusion: MCA-PSV measurement has high diagnostic accuracy for predicting abnormal Hb levels in fetuses with TAPS. [ABSTRACT FROM AUTHOR]

Renal lymphangiectasia is a disorder of the lymphatic system of the kidneys, which can be congenital or acquired. Although the exact etiology remains unknown, an obstructive process resulting from several causes, including infection, inflammation or malignant infiltration, has been suggested to be responsible for the acquired form. This disorder may be associated with several pathologies. We report a case of a 24-year-old man with renal lymphangiectasia presenting with polycythemia, ascites and pleural effusion associated with hepatitis C virus (HCV) infection in an intravenous (IV) drug user. Our case is the first in the literature that shows an association between HCV infection and IV drug use. [ABSTRACT FROM AUTHOR]

Purpose Erythrocytosis is the most common dose limiting adverse effect of testosterone therapy but the mechanisms of testosterone mediated erythropoiesis remain unclear. In this study we examine risk factors for erythrocytosis associated with testosterone therapy. Materials and Methods A retrospective review was performed of 179 hypogonadal men on testosterone therapy at a single andrology clinic. Demographic data, testosterone therapy formulation and duration of treatment, and 5α-reductase inhibitor use were assessed. Serum dihydrotestosterone, total testosterone, free testosterone, follicle-stimulating hormone, luteinizing hormone, hematocrit and lipid levels were extracted, and changes during treatment were determined. Spearman’s rank correlation was used to identify relationships between change in hematocrit and study variables. Results Of 179 patients 49 (27%) experienced a 10% or greater change in hematocrit and erythrocytosis (hematocrit 50% or greater) developed in 36 (20.1%) at a median followup of 7 months. Topical gels were used by 41.3% of patients, injectable testosterone by 52.5% and subcutaneous pellets by 6.1%. More men who experienced a change in hematocrit of 10% or greater used injectable testosterone than men with a change in hematocrit of less than 10% (65% vs 48%, p=0.035), and were less likely to be on a 5α-reductase inhibitor (2% vs 15%, p=0.017). Men with a change in hematocrit of 10% or greater had higher posttreatment dihydrotestosterone levels (605.0 vs 436.0 ng/dl, p=0.017) and lower luteinizing hormone and follicle-stimulating hormone levels than men with a change in hematocrit of less than 10%. Spearman’s rank correlations yielded relationships between change in hematocrit and posttreatment dihydrotestosterone ρ=0.258, p=0.001) and total testosterone (ρ=0.171, p=0.023). Conclusions Dihydrotestosterone may have a role in testosterone therapy related erythrocytosis and monitoring dihydrotestosterone levels during testosterone therapy should be considered. In men in whom erythrocytosis develops, 5α-reductase inhibitors may be therapeutic. [ABSTRACT FROM AUTHOR]

A 44-year-old male patient presented with features suggestive of transient central retinal artery occlusion (CRAO) followed by permanent CRAO and lateral posterior ciliary artery occlusion. He had diagnostic features of polycythemia vera (PV). When presented for the first time, the patient had features of ocular ischemia such as ocular pain, conjunctival congestion, and retinal opacification but with normal arm-to-retina time and normal arteriovenous transit time. During the second presentation, he had ocular pain, congested conjunctiva, retinal opacification, cherry red spot with box-carrying of retinal vessels, and choroidal infarct (Amalric's sign). He had lost light perception in that eye. Patients with polycythemia are prone to multifocal vascular occlusions and this can be the presenting feature in PV. A timely diagnosis and prompt management can prevent these repeated thromboembolic occlusive episodes. [ABSTRACT FROM AUTHOR]

Objective:We compared intra-procedural neonatal pain, agitation and sedation scale (N-PASS) scores between a novel 'continuous arteriovenous exchange' (CAVE) and conventional pull-push (PP) techniques of partial exchange transfusion (PET) among neonates with polycythemia.Study Design:Neonates >32-0/7 weeks gestation, requiring PET for polycythemia, were randomized to PP or CAVE techniques. The procedure was video-recorded and edited to mask the technique. Intra-procedural N-PASS scores assigned by two trained and masked neonatal fellows were compared.Result:Twenty-two neonates were randomized to CAVE (n=12) or PP (n=10) method. The area under curve for cumulative N-PASS scores was significantly lesser in CAVE group (mean difference−11.9 (95% CI=−4.2, −19.6), P=0.005)). Decrease in hematocrit and complications of PET were comparable. Time for PET was longer with CAVE technique (16 (9, 29) min vs 10 (6, 12) min, P=0.016).Conclusion:CAVE technique of PET was associated with lesser procedure-related pain (N-PASS scores) as compared with PP technique among neonates >32 weeks gestation. [ABSTRACT FROM AUTHOR]

We report a case of twin anemia-polycythemia sequence (TAPS) treated by fetoscopic laser equatorial placental dichorionization, also known as the 'Solomon technique', at 24 weeks of gestation. TAPS was present despite the absence of fetoscopically visualized chorionic anastomoses from the donor to the recipient twin. The goal of this procedure was to prevent post-laser TAPS in cases of twin-twin transfusion syndrome. The surgery and subsequent intrauterine blood transfusion to the donor twin could result in the survival of both twins without hematologic or neurological complications. Following the surgery, a placental injection test revealed no residual anastomoses. At present, laser therapy is not always feasible for TAPS, primarily because of its difficulty. However, laser therapy using the Solomon technique could be a viable approach for early-onset TAPS, especially in difficult situations in which undetectable vascular anastomoses related to TAPS are present. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Patients with myeloproliferative neoplasms (MPN) have an increased risk for thrombosis and bleeding and show a defect in adenosine diphosphate (ADP)-induced platelet aggregation. This risk of thrombosis is further increased in MPN patients bearing the JAK2V617F mutation. Two ADP receptors, P2Y1 and P2Y12, are present on platelets. Although the pattern of defective ADP-induced platelet aggregation in MPN suggests an abnormality in the P2Y12 pathway, no previous studies have specifically evaluated P2Y12 function in MPN or the relationship between P2Y12 function and the JAK2V617F mutation. Methods: Forty-one MPN patients were enrolled, including 24 with essential thrombocythemia (ET), 16 with polycythemia vera (PV) and 1 with primary myelofibrosis. Platelet P2Y12 function in MPN was evaluated by flow-cytometric measurement of the phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Clinical data were collected by review of medical records. JAK2V617F mutation was detected by allele-specific polymerase chain reaction. JAK2V617F allele burden was measured by the pyrosequencing method. Results: In patients with MPN, platelet P2Y12 function determined by VASP platelet reactivity index (PRI) was inversely correlated with platelet and white blood cell (WBC) counts. In subgroup analysis, PRI was inversely correlated with platelet and WBC counts in PV. PRI was also inversely correlated with platelet counts in ET, but the correlation of PRI and WBC counts did not reach statistical significance. Eight of the 41 patients had a history of thrombosis and only 2 had a bleeding history. Neither thrombosis nor bleeding patients were found to have significantly different PRIs. JAK2V617F mutation data were available in 35 cases. PRI was not different between JAK2V617F mutation and wild-type patients but PRI had a trend towards an inverse correlation with JAK2V617F allele burden for patients with mutations. Conclusions: The present study provides the first explicit demonstration of a defect in the P2Y12 pathway in platelets of patients with MPN. Furthermore, platelet P2Y12 function, assayed by VASP, is inversely correlated with platelet and WBC counts in patients with MPN. Platelet P2Y12 function also appears to be inversely correlated with JAK2V617F allele burden. This compromised P2Y12 function may be a novel mechanism for the bleeding tendency associated with extreme thrombocytosis in MPN. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents a case study of a 15-year-old female presented to the pediatric oncology clinic after lab work for a routine sports physical exam that confirmed increased hemoglobin, hematocrit, and platelet count with the normal leukocyte count. Her past medical history included attention deficit disorder and asthma. The patient is kept on a therapeutic JAK2V617F inhibitor for treatment of polycythemia vera (PV) in pediatric patients. She was homozygous for the MTHFRC677T mutation.

According to Dameshek, true polycythemia (polycythemia vera: PV) is a chronic myeloproliferative disorder of the total bone marrow without any evidence of invasiveness, in which erythrocytosis, leukocytosis, and thrombocytosis are all simultaneously present. A possible hereditary or transmitted tendency may be present, but actual familial polycythemia is rare. As to the etiology, Dameshek proposed 2 highly speculative possibilities in 1950: the presence of excessive bone marrow stimulation by an unknown factor or factors, and a lack or a diminution in the normal inhibitory factor or factors. Dameshek's hypothesis was confirmed in 2005 by Vainchenker in France by the discovery of the acquired JAK2V617F mutation as the cause of 3 phenotypes of classical myeloproliferative neoplasms: essential thrombocythemia, PV, and myelofibrosis. The JAK2V617F mutation induces a loss of inhibitory activity of the JH2 pseudokinase part on the JH1 kinase part of Janus kinase 2 (JAK2). This leads to enhanced activity of the normal JH1 kinase activity of JAK2, which makes the mutated hematopoietic stem cells hypersensitive to the hematopoietic growth factors thrombopoietin, erythropoietin, insulin-like growth factor-1, stem cell factor, and granulocyte colony-stimulating factor, resulting in trilinear myeloproliferation. In retrospect, the situation observed by Dameshek where all "stops" to blood production in the bone marrow are pulled in PV is caused by the JAK2V617F mutation. Dameshek considered PV patients as fundamentally normal and therefore the treatment should be as physiologic as possible. For this reason, a systematic phlebotomy/iron deficiency method of treatment was recommended; the use of radioactive phosphorus is reserved for refractory cases and cases of major thrombosis. If the patient lives long enough and does not succumb to the effects of thrombosis or other complications, the marrow will gradually show signs of diminished activity. The blood smear shows nucleated red cells, increased polychromatophilia, and immature granulocytes of various types. With increasing reduction of erythropoietic tissue, myelofibrosis becomes more of an organized mass of fibrous tissue. There is prominent extramedullary hematopoiesis in the spleen, which becomes extraordinarily large and in some cases occupies almost the entire abdominal cavity. The enlarged spleen is made up largely of metaplastic marrow tissue in primary myeloid metaplasia of the spleen. [ABSTRACT FROM AUTHOR]

Givinostat, a histone-deacetylase inhibitor ( HDACi), inhibits proliferation of cells bearing the JAK2 V617F mutation and has shown significant activity with good tolerability in patients with chronic myeloproliferative neoplasms ( MPN). In this multicentre, open-label, phase II study, 44 patients with polycythaemia vera ( PV), unresponsive to the maximum tolerated doses ( MTD) of hydroxycarbamide ( HC), were treated with Givinostat (50 or 100 mg/d) in combination with MTD of HC. The European LeukaemiaNet response criteria were used to assess the primary endpoint after 12 weeks of treatment. Complete or partial response was observed in 55% and 50% of patients receiving 50 or 100 mg of Givinostat, respectively. Control of pruritus was observed in 64% and 67% of patients in the 50 and 100 mg groups, respectively. The combination of Givinostat and HC was well tolerated: eight patients (18%) discontinued, four in each treatment arm; grade 3 adverse events were reported in one patient (4·5%) in each treatment arm. The combined use of Givinostat and HC was safe and clinically effective in HC-unresponsive PV patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of erythrocytapheresis (ECP) in the treatment of polycythemia. Methods: Patients diagnosed with polycythemia were included in this retrospective analysis and treated with ECP (n =20) or conventional treatments (exsanguination; n =20). Blood laboratory values and adverse effects were recorded. Results: In ECP-treated patients mean red blood cell (RBC) collection time was 25.7±4.5min (range: 19–37min), with a mean collection volume of 773.5±129.3mL (range: 600–1002mL). From baseline, ECP reduced the mean number of RBCs (0.6×1012/L [7.6%]), mean hemoglobin (31.1g/L [14.8%]), and mean hematocrit (13.1% [20.2%]) (P <0.001 for each). After ECP, a marked reduction in symptoms associated with polycythemia was also observed. Conclusions: Treatment of patients with polycythemia using ECP reduces RBC count, hemoglobin, and hematocrit. The advantages associated with ECP over conventional therapy should be considered when choosing a treatment plan for patients with polycythemia. [ABSTRACT FROM AUTHOR]

In Chuvash polycythemia, a homozygous 598C>T mutation in the von Hippel-Lindau gene ( VHL) leads to an R200W substitution in VHL protein, impaired degradation of α-subunits of hypoxia-inducible factor (HIF)-1 and HIF-2, and augmented hypoxic responses during normoxia. Chronic hypoxia of high altitude is associated with decreased serum glucose and insulin concentrations. Other investigators reported that HIF-1 promotes cellular glucose uptake by increased expression of GLUT1 and increased glycolysis by increased expression of enzymes such as PDK. On the other hand, inactivation of Vhl in murine liver leads to hypoglycemia associated with a HIF-2-related decrease in the expression of the gluconeogenic enzyme genes Pepck, G6pc, and Glut2. We therefore hypothesized that glucose concentrations are decreased in individuals with Chuvash polycythemia. We found that 88 Chuvash VHL homozygotes had lower random glucose and glycosylated hemoglobin A1c levels than 52 Chuvash subjects with wild-type VHL alleles. Serum metabolomics revealed higher glycerol and citrate levels in the VHL homozygotes. We expanded these observations in VHL homozygote mice and found that they had lower fasting glucose values and lower glucose excursions than wild-type control mice but no change in fasting insulin concentrations. Hepatic expression of Glut2 and G6pc, but not Pdk2, was decreased, and skeletal muscle expression of Glut1, Pdk1, and Pdk4 was increased. These results suggest that both decreased hepatic gluconeogenesis and increased skeletal uptake and glycolysis contribute to the decreased glucose concentrations. Further study is needed to determine whether pharmacologically manipulating HIF expression might be beneficial for treatment of diabetic patients. [ABSTRACT FROM AUTHOR]

Seabuckthorn (Hippophae rhamnoides L.) has been used to treat high altitude diseases. The effects of five-week treatment with total flavonoids of seabuckthorn (35, 70, 140 mg/kg, ig) on cobalt chloride (5.5 mg/kg, ip)- and hypobaric chamber (simulating 5,000 m)-induced high-altitude polycythemia in rats were measured. Total flavonoids decreased red blood cell number, hemoglobin, hematocrit, mean corpuscular hemoglobin levels, span of red blood cell electrophoretic mobility, aggregation index of red blood cell, plasma viscosity, whole blood viscosity, and increased deformation index of red blood cell, erythropoietin level in serum. Total flavonoids increased pH, pO2, SpO2, pCO2 levels in arterial blood, and increased Na+, HCO3-, Cl-, but decreased K+ concentrations. Total flavonoids increased mean arterial pressure, left ventricular systolic pressure, end-diastolic pressure, maximal rate of rise and decrease, decreased heart rate and protected right ventricle morphology. Changes in hemodynamic, hematologic parameters, and erythropoietin content suggest that administration of total flavonoids from seabuckthorn may be useful in the prevention of high altitude polycythaemia in rats. [ABSTRACT FROM AUTHOR]

The discovery of the JAK2V617F mutation in most patients with Ph-negative myeloproliferative neoplasms has led to the development of JAK2 kinase inhibitors. However, JAK2 inhibitor therapy has shown limited efficacy and dose-limiting hematopoietic toxicities in clinical trials. In the present study, we describe the effects of vorinostat, a small-molecule inhibitor of histone deacetylase, against cells expressing JAK2V617F and in an animal model of polycythemia vera (PV). We found that vorinostat markedly inhibited proliferation and induced apoptosis in cells expressing JAK2V617F. In addition, vorinostat significantly inhibited JAK2V617F-expressing mouse and human PV hematopoietic progenitors. Biochemical analyses revealed significant inhibition of phosphorylation of JAK2, Stat5, Stat3, Akt, and Erk1/2 in vorinostattreated, JAK2V617F-expressing human erythroleukemia (HEL) cells. Expression of JAK2V617F and several other genes, including GATA1, KLF1, FOG1, SCL, C/EPBα, PU.1, and NF-E2, was significantly down-regulated, whereas the expression of SOCS1 and S0CS3 was upregulated by vorinostat treatment. More importantly, we observed that vorinostat treatment normalized the peripheral blood counts and markedly reduced splenomegaly in Jak2V617F knock-in mice compared with placebo treatment. Vorinostat treatment also decreased the mutant allele burden in mice. Our results suggest that vorinostat may have therapeutic potential for the treatment of PV and other JAK2V617F-associated myeloproliferative neoplasms. [ABSTRACT FROM AUTHOR]

Sixty-four patients < 20 years of age, investigated for a suspicion of Philadelphia-negative myeloproliferative disease (MPD), were retrospectively evaluated to characterize the different forms and to examine the treatments used and long-term outcome. JAK2 mutations, endogenous erythroid colony growth, and clonal-ity were investigated in 51 children. Mutations of thrombopoietin, the throm-bopoietin receptor (MPL), and the erythropoietin receptor and mutations of other genes involved in the pathogenesis of MPD were investigated in JAK2 wild-type patients. Based on our criteria for childhood MPD, we identified 34 patients with sporadic thrombocythemia (ST), 16 with hereditary thrombocytosis (HT), 11 with sporadic polycythemia (SP), and 3 with hereditary polycythemia (HP). JAK2V617F mutations were present in 47.5% of ST and in no HT. The MPLS505A mutation was detected in 15/16 HT patients and in no ST (P < .00001). The JAK2V617F mutation occurred in 27% of SP patients diagnosed according to the Polycythemia Vera Study Group or World Health Organization 2001 criteria. Children with ST received more cytoreductive drugs than those with HT (P = .0006). After a median follow-up of 124 months, no patient had developed leukemia or myelofibrosis and 5% had thrombosis; the miscarriage rate in thrombocythemic patients was 14%. The low complication rate in our population suggests that children with MPD may be managed by tailored approaches. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the short term effects of partial exchange transfusion on the morbidity of preterm and term polycythemic neonates. Material and Method: Late preterm and term infants with polycythemia hospitalized in Zeynep Kamil Maternity and Children's Training Hospital Neonatal Intensive Care Unit from January 2009 to May 2010 were evaluated retrospectively. Results: One hundred-sixty-three of 16.000 infants who were born during the study period were hospitalized with a diagnosis of polycythemia. The incidence of polycythemia was 1%. Late preterm polycythemic (n=68/163; 41.7%) patients were divided into two groups as symptomatic (n=23/163; 14.1%) and asymptomatic (n=45/163; 27.6%) infants. Term polycythemic (n=95/163; 58.3%) patients were divided into two groups as symptomatic (n=21/163; 12.9%) and asymptomatic (n=74/163; 45.4%) infants. Partial exchange transfusion was performed in 102 patients. Of these infants, 18/102 (17.7%) were symptomatic late preterm, 23/102 (22.6%) were asymptomatic late preterm, 14/102 (13.7%) were symptomatic term and 47/102 (46%) were asymptomatic term infants. The number of the patients who were treated medically (hydration) was 61. Of these patients 5/61 (8.2%) were symptomatic late preterm, 22/61 (36 %) were asymptomatic late preterm, 7/61 (11.5%) were symptomatic term and 27/61 (44.3%) were asymptomatic term patients. Duration of hospitalization in the term symptomatic group and time to reach full enteral feeding in the asymptomatic term group were longer in patients in whom partial exchange transfusion was performed (p<0.05). There were four patients (2 preterm, 2 term) who developed necrotizing enterocolits following partial exchange transfusion. Conclusions: Our results showed that partial exchange transfusion influences duration of hospitalization and time to reach full enteral feeding and increases the risk of necrotizing enterocolits in asymptomatic patients. We believe that more studies should be performed to determine the indications of partial exchange transfusion in asymptomatic infants. [ABSTRACT FROM AUTHOR]

Partial exchange transfusion (PET) is traditionally suggested as treatment for neonates diagnosed with polycythemia. Nevertheless, justification of this treatment is controversial. We evaluated the risk for short-term complications associated with a restrictive treatment protocol for neonatal polycythemia. A retrospective cross-sectional analytical study was conducted. Three treatment groups were defined and managed according to their degree of polycythemia, defined by capillary tube filled with venous blood and manually centrifuged hematocrit: group 1, hematocrit 65 to 69% and no special treatment was recommended; group 2, hematocrit 70 to 75% and intravenous fluids were given and feedings were withheld until hematocrit decreased to <70%; and group 3, hematocrit ≥76% or symptomatic neonates and PET was recommended. During the study period, 190 neonates were diagnosed with polycythemia. The overall rate of short-term complications was 15% (28 neonates). Seizures, proven necrotizing enterocolitis, or thrombosis did not occur in any participating neonates. PET was performed in 31 (16%) neonates. The groups did not differ in their rate of early neonatal morbidities or length of hospitalization. Restrictive treatment for neonatal asymptomatic polycythemia is not associated with an increased risk of short-term complications. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the use of partial exchange transfusion (PET) performed for polycythemia hyperviscosity syndrome (PHS) over time. A retrospective review of 141 infants who received a PET for PHS at Yale-New Haven Hospital between 1986 and 2007 was performed, querying maternal and neonatal medical records. Patient demographics, risk factors for PHS, indications for PET, and complications associated with PET and PHS were collected. Overall, there was no change in the number of PET performed over the study period (r2=0.082, p=0.192). Eighty-eight percent of patients had at least one risk factor for PHS, most commonly maternal diabetes. Over time, there was a statistically significant decrease in maternal diabetes as a risk factor for PHS. Forty percent of patients had a significant complication attributed to PHS prior to PET. Eighteen percent of patients had a complication attributed to PET. Life-threatening complications of PHS or PET were rare. In conclusion, PHS continues to be a problem observed in neonatal intensive care units, particularly in at-risk populations. PHS and PET are associated with significant complications. Well-designed studies with long-term follow up are needed to assess the risks and benefits of PET for PHS. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Testosterone formulations that have more steady-state pharmacokinetics, such as subcutaneously implanted testosterone pellets, may cause less erythrocytosis than i.m. injections of shorter acting androgen esters. We, therefore, sought to define the prevalence, predictors, and proximate basis (role of erythropoietin) for polycythemia (hematocrit >0.50) in hypogonadal men receiving testosterone implants long term. DESIGN: A cross-sectional study was conducted in an academic andrology center with a longitudinal subgroup analysis. PATIENTS: A total of 158 hypogonadal men aged 14–84 years (mean age 46.7 years) treated on average for 8 years (range 0–21 years). MEASUREMENTS: Trough blood testosterone and hematocrit. Serial serum erythropoietin concentrations were measured in 16 volunteers. RESULTS: Positive univariate associations between polycythemia (hematocrit >0.50) and log(testosterone) (odds ratio (OR) 24.7, 95% confidence interval (CI): 4.3, 141.2, P<0.01) and age (OR 1.1, 95% CI: 1.0, 1.1, P=0.03) and a borderline relationship with current smoking (OR 4.2, 95% CI: 0.9, 20.0, P=0.08) were unveiled. A sensitivity analysis using alternate definitions of polycythemia was performed to capture all potential covariants. Multivariate regression analysis incorporating all potential covariants disclosed the independent OR of developing polycythemia (after adjusting for smoking and age) for log(testosterone) to be 15.0 (95% CI: 2.5, 90.8). Duration of testosterone therapy did not alter the risk of polycythemia. A direct relationship between testosterone and erythropoietin was observed (P=0.05). CONCLUSIONS: Higher trough serum testosterone concentrations but not duration of treatment predict the development of polycythemia in men receiving long-acting depot testosterone treatment. [ABSTRACT FROM AUTHOR]

Rare mutations in the VHL gene may lead to polycythemia in children. Ruxolitinib resulted in clinical improvement in three people with this disorder. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hyperuricemia and posttransplantation erythrocytosis (PTE) are frequent complications after kidney transplantation and are important risk factors for cardiovascular events. Losartan decreases serum uric acid and hemoglobin (Hb) concentrations and may be a useful agent for treatment of hyperuricemia and PTE. Objective: To evaluate the influence of losartan on serum creatinine (SCr), serum uric acid, and hemoglobin (Hb) concentrations in patients after kidney transplantation and to evaluate the safety profile of losartan in these patients. Patients and Methods: Sixty-six Han Chinese patients (43 men and 23 women; mean [SD] age, 40.45 [11.50] years) were enrolled in the study. All patients had undergone a first cadaveric donor kidney transplantation at least 3 months previously and had stable graft function with SCr concentration less than 176.8 μmol/L and Hb concentration greater than 110 g/L. The patients were divided into 2 groups (losartan group, n = 34; and control group, n = 32) according to the odevity of patient identification number. Patients in the losartan group received losartan, 50 mg/d; patients in the control group did not receive losartan. Each patient was followed up for 6 months. Results: Nine patients in the losartan group and 5 patients in the control group dropped out because of acute renal insufficiency, anemia, acute rejection, or poor compliance. The serum uric acid concentration in the losartan group continuously decreased at months 1, 2, 3, and 6 (P = .12, P = .01, P = .04, and P = .005 compared with baseline, and P = .02, P = .003, P = .02, and P = .006 compared with control), especially in the patients with hyperuricemia (P = .02, P < .001, P = .003, and P < .001 compared with baseline, and P = .02, P = .002, P = .02, and P = .002 compared with control). The Hb level in the losartan group decreased significantly at months 1, 2, 3, and 6 (P = .003, P < .001, P = .004, and P = 0.02 compared with baseline, and P = .001, P < .001, P = .001, and P = .005 compared with control), especially in patients with PTE. In patients without PTE, there was no significant decline in Hb concentration in the losartan group compared with baseline. There was no significant decline in estimated glomerular filtration rate in the losartan group. Conclusions: Losartan may be an effective agent for treatment of hyperuricemia and PTE in Han Chinese patients after kidney transplantation. However, in some patients, losartan may not be safe. [Copyright &y& Elsevier]

It has been suggested that polycythemia vera (PV) could be preceded by an "early" phase of the disease (e-PV), in which the increase in the red cell parameters is lower than required for a PV diagnosis. In this study, we compared the clinicopathologic and molecular features of 17 patients with e-PV with those of 14 patients with essential thrombocythemia (ET) and 19 with PV.The results for e-PV were more similar to those for PV than for ET. In fact, patients with e-PV were characterized by an increase in the red cell parameters, splenomegaly (P .05), and hepatomegaly (P = .038), together with hypercellular bone marrow due to increased erythropoiesis and granulopoiesis, associated with megakaryocytic hyperplasia, with pleomorphic aggregates (P .001). The frequency of the JAK2V617F mutation was similar in e-PV (16 cases tested [100%]) and PV (18/19 [95%]) but was significantly lower (7/13 [54%]) in ET (P = .0007). We propose a diagnostic algorithm helpful to distinguish ET from the early prepolycythemic phase of PV. [ABSTRACT FROM AUTHOR]

Objective: Hypothermia is a known symptom of neonatal polycythemia (NP) and its pathophysiology is unclear. The effect of partial dilutional exchange transfusion (PET) upon resting energy expenditure (REE) is unknown. We aimed to test the hypothesis that PET leads to an increase in REE.Study Design: 11 patients with NP who underwent PET and 10 controls without polycythemia were studied. NP was defined as a venous HCT >/=0.65. Per protocol, symptomatic infants and/or those with venous HCT > or =0.70 underwent PET. REE was measured just prior and 23 hours after PET in patients with NP and at identical ages in the control group. Infants were studied in a skin servo controlled radiant warmer, while clinically and thermally stable, prone and asleep. Measurements were stopped during body movements (less than 5% of the time of measurement). Metabolic measurements were performed by indirect calorimetry, using the Deltatrac II Metabolic monitor (Datex-Ohmeda, Helsinki, Finland). This instrument uses the principle of the open circuit system that allows continuous measurements of oxygen consumption (Vo(2)) and carbon dioxide production (Vco(2)) using a constant flow generator. REE measurements were corrected for the infant weight (Kcal/kg/d). Comparison of REE values between groups was performed using paired Wilcoxon ranked test.Results: Patients with and without NP had nearly identical baseline REE. In patients with NP, REE increased from 44.0 +/- 6.6 Kcal/Kg/d to 48.3 +/- 5.1 Kcal/Kg/d after PET (P<0.05). Furthermore, the increase in REE following PET correlated inversely with the decrease in hematocrit. There was no significant change in REE over time in the control group. In the NP group, symptomatic infants (n=5) had a significantly greater increase in REE following PET than non-symptomatic ones (1.4 +/- 6.3 vs. 7.8 +/- 4.9 Kcal/Kg/d, p<0.05).Conclusions: Energy expenditure of polycythemic infants increases following PET, in a manner proportional to the decrease in hematocrit. Symptomatic polycythemic infants have a greater rise in REE following PET than non-symptomatic ones. We speculate that polycythemia leads to a decreased REE that might be remedied by PET. [ABSTRACT FROM AUTHOR]