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The article presents a case study of a 64-year-old man was admitted to a hospital due to neutropenia and thrombocytopenia. The patient had significant weight loss prior to his admission. He was diagnosed with aggressive systemic mastocytosis following clinical and laboratory investigations specifically bone marrow aspiration and biopsy. The patient received cladribine which improved thrombocytopenia but no significant change in neutropenia after a two-hour intravenous infusion of the drug.

JAK2 V617F mutation and BCR-ABL translocation have been considered to be mutually exclusive. However, many cases where both hits coexisted have been reported. We have personally managed a case too. We believe this hybrid entity is underdiagnosed. Thus, we decided to shed light on this "double hit" disease to improve its diagnosis and optimize its treatment. We reviewed the English literature in PubMed since JAK2 discovery. We found 33 cases reported so far. We summarized patient characteristics and analyzed possible interactions between JAK2 and BCR-ABL clones.

Fucosylated glycans are essential molecules that facilitate signal transductions in several signal pathways and play important roles in development, inflammation, infection, and tumor metastasis. The fucosylated glycans are difficult to be developed into clinical biomarkers due to their complicated structures, but the decreased or increased activities of serum α-l-fucosidase, the lysosomal enzyme required for fucosylated glycan degradation, are diagnostic biomarker for patients with fucosidosis and hepatocellular carcinoma, respectively. However, the relationship between serum α-l-fucosidase activities and other human diseases is largely unknown. By taking advantage of the serum α-l-fucosidase activity data collected in the clinical laboratory of our hospital during the past 5 years, the serum α-l-fucosidase activities from 188,077 patients with 64 clinically defined diseases were compared to that of healthy controls (9519) with at least 30 data sets for each type of disease. Based on the mean, median, and -Log 10 p values, we found that patients with preeclampsia, liver cancer, hepatitis, psoriasis, and multiple myeloma had serum α-l-fucosidase activities higher, while patients with Wilms' tumor, breast cancer, hepatic encephalopathy, or postbreast surgery had comparable activities to that of healthy controls. Unexpectedly, patients with the rest of 36 diseases had the statistically lower levels of serum α-l-fucosidase activities compared to that of healthy controls. Moreover, patients with uremia, azotemia, myeloproliferative disorder, and Alzheimer's disease had lowest median levels of serum α-l-fucosidase activities among the 64 diseases studied. Taken together, our data showed that serum α-l-fucosidase activities are not only useful for liver cancer diagnosis but also valuable indicators for different types of human diseases., (© 2019 Elsevier Inc. All rights reserved.)

A letter to the editor is presented in response to the article on deliberate hydroxycarbamide overdose in an adult with essential thrombocythaemia.

A letter to the editor is presented in response to the article concerning the prevalence of JAK2 V617F and exon 12 mutations in polycythaemia vera.

Chronic neutrophilic leukemia is a rare myeloproliferative disorder characterized by a sustained peripheral blood neutrophilia, absence of the BCR/ABL oncoprotein, bone marrow hypercellularity with less than 5% myeloblasts and normal neutrophil maturation, and no dysplasia. This leukemia has been associated with mutations in the colony-stimulating factor 3 receptor (CSF3R) that may activate this receptor, leading to the proliferation of neutrophils that are the hallmark of chronic neutrophilic leukemia. We present a case of chronic neutrophilic leukemia and discuss the criteria for diagnosis and the significance of mutations found in this leukemia.

Presents a letter to the editor about serum thrombopoietin concentration and peripheral platelet counts in essential thrombocythemia.

Individuals with Down syndrome (DS) frequently have hematopoietic abnormalities, including transient myeloproliferative disorder and acute megakaryoblastic leukemia which are often accompanied by acquired GATA1 mutations that produce a truncated protein, GATA1s. The mouse has been used for modeling DS based on the syntenic conservation between human chromosome 21 (Hsa21) and three regions in the mouse genome located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. To assess the impact of the dosage increase of Hsa21 gene orthologs on the hematopoietic system, we characterized the related phenotype in the Dp(10)1Yey/+;Dp(16)1Yey/+;Dp(17)1Yey/+ model which carries duplications spanning the entire Hsa21 orthologous regions on Mmu10, Mmu16 and Mmu17, and the Dp(10)1Yey /+; Dp(16)1Yey /+; Dp(17)1Yey/+ ; Gata1 Yeym2 model which carries a Gata1s mutation we engineered. Both models exhibited anemia, macrocytosis, and myeloproliferative disorder. Similar to human DS, the megakaryocyte-erythrocyte progenitors (MEPs) and granulocyte-monocyte progenitors (GMPs) were significantly increased and reduced, respectively, in both models. The subsequent identification of all the aforementioned phenotypes in the Dp(16)1Yey/ + model suggests that the causative dosage sensitive gene(s) are in the Hsa21 orthologous region on Mmu16. Therefore, we reveal here for the first time that the human trisomy 21-associated major segmental chromosomal alterations in mice can lead to expanded MEP and reduced GMP populations, mimicking the dynamics of these myeloid progenitors in DS. These models will provide the critical systems for unraveling the molecular and cellular mechanism of DS-associated myeloproliferative disorder, and particularly for determining how human trisomy 21 leads to expansion of MEPs as well as how such an alteration leads to myeloproliferative disorder., Competing Interests: CONFLICTS OF INTEREST None of the authors has any conflicts of interest.

Kidney disease in the setting of a hematologic malignancy is common, with the frequency and type of kidney disease varying depending on the specific malignancy. Various glomerular diseases and tumor infiltration of the kidneys have been reported in patients with lymphoproliferative disorders. Descriptions of kidney involvement in myeloproliferative disorders have been much rarer. We report a case of membranous nephropathy accompanied by kidney injury in a patient with primary myelofibrosis with additional features considered related to the patient's myeloproliferative disorder. A 63-year-old patient with primary myelofibrosis underwent kidney biopsy to investigate nephrotic-range proteinuria and reduced kidney function. Histologic analysis revealed mesangial sclerosis and hypercellularity, changes indicative of membranous nephropathy, and infiltration of hematopoietic cells into the renal interstitium, peritubular capillaries, and perirenal tissue consistent with extramedullary hematopoiesis. He was treated with renin-angiotensin blockade and a Janus kinase inhibitor, resulting in improvement in kidney function and proteinuria., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Presents a case report on systemic mastocytosis associated with myeloproliferative disorder in a neonate. Brief information on the disease; Clinical presentation of the patient; Course of the disease; Role of proto-oncogene c-kit in the pathogenesis of the disease.

Background: This analysis of the myeloproliferative neoplasm (MPN) Landmark survey evaluated gaps between patient perceptions of their disease management and physician self-reported practices., Methods: The survey included 813 patient respondents who had MPNs (myelofibrosis [MF], polycythemia vera [PV], or essential thrombocythemia [ET]) and 457 hematologist/oncologist respondents who treated patients with these conditions., Results: Greater proportions of physician respondents reported using prognostic risk classifications (MF, 83%; PV, 59%; ET, 77%) compared with patient recollections (MF, 54%; PV, 17%; ET, 31%). Most physician respondents reported that their typical symptom assessments included asking patients about the most important symptoms or a full list of symptoms, whereas many patient respondents reported less specific assessments (eg, they were asked how they were feeling). Many patient respondents did not recognize common symptoms as MPN-related. For example, approximately one-half or more did not believe difficulty sleeping resulted from their MPN (MF, 49%; PV, 64%; ET, 76%). Physician respondents underestimated the proportion of patients who had symptomatic PV or ET at diagnosis compared with patient respondents. There was discordance regarding treatment goals: among patient respondents with MF or PV, "slow/delay progression of condition" was the most important treatment goal, whereas physician respondents reported "symptom improvement" and "prevention of vascular/thrombotic events," respectively. Finally, more than one-third of patient respondents were not "very satisfied" with their physician's overall management/communication., Conclusions: The care and satisfaction of patients with MPN may be improved with increased patient education and improved patient-physician communication. Cancer 2017;123:449-458. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society., (© 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

A patient with no conventional cardiovascular risk factors presented with inferior ST-elevation myocardial infarction which was finally diagnosed as a case of essential thrombocytosis. This case demonstrated that thrombectomy alone was sufficient for the treatment of his coronary occlusion. Furthermore, this case report highlights the importance of evaluating rare causes of myocardial infarction other than atherosclerosis and that internists and cardiologists should be aware of essential thrombocytosis as a known cause of myocardial infarction, particularly in patients with no underlying cardiovascular risk factors.

Myeloproliferative disorders are a rare cause of focal segmental glomerulosclerosis (FSGS), although the mechanism is unclear. Hydroxyurea is commonly used in these disorders for its cytoreductive properties; however, the effect of this treatment on proteinuria or kidney function remains unclear in cases of myeloproliferative disorder-associated FSGS. We describe the clinical course of a patient with polycythemia vera and nephrotic-range proteinuria, demonstrated to have FSGS on biopsy. The patient had a distant history of granulomatosis with polyangiitis (Wegener's), for which he routinely had his kidney function and proteinuria measured, allowing for early detection of nephrotic syndrome soon after being diagnosed with polycythemia vera. Treatment with hydroxyurea resulted in rapid improvement in proteinuria that correlated with a decrease in hematocrit. This response was replicated 2 additional times when the patient was taken off and then restarted on hydroxyurea therapy. He now maintains a steady dose of hydroxyurea with favorable kidney measures (proteinuria with <1g/d of protein excretion and serum creatinine of 1.27mg/dL [corresponding to estimated glomerular filtration rate of 56mL/min/1.73 m(2)]). This case suggests that early screening and treatment for myeloproliferative disorder-associated FSGS may lead to improved long-standing kidney function., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Hypereosinophilia is an uncommon clinical problem encountered in hematology practice. While most of such cases are secondary or reactive, a significant fraction of cases are due to clonal myeloproliferative disorders. We report a young patient who presented with marked hypereosinophilia and was investigated extensively for its cause. Finally a common tropical infection was responsible for such marked eosinophilia fulfilling the principle of Occam's razor. The case emphasizes the need to search for treatable reactive causes even in presence of marked hypereosinophilia in a tropical country.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis and the presence of Janus kinase ( JAK ) 2 V617F or similar mutations. This review summarizes the pathophysiology of PV, the challenges associated with traditional treatment options, and the scientific rationale and supportive clinical evidence for targeted therapy with ruxolitinib. Accumulating evidence indicates that activating mutations in JAK2 drive the PV disease state. Traditional PV treatment strategies, including aspirin, phlebotomy, and cytoreduc-tive agents such as hydroxyurea, provide clinical benefits for some but not all patients and may not adequately treat PV-related symptoms. Furthermore, traditional treatment approaches are associated with potential side effects that may limit their usage and lead some patients to discon-tinue the treatment. Ruxolitinib is an orally available small-molecule tyrosine kinase inhibitor that is a potent and selective inhibitor of JAK1/JAK2. Ruxolitinib is approved in the US for patients with PV with an inadequate response or intolerance to hydroxyurea and in Europe for adults with PV who are resistant to or intolerant of hydroxyurea. In the Phase III RESPONSE registration trial, ruxolitinib was superior to the best available therapy in patients with PV who were resistant to or intolerant of hydroxyurea in controlling hematocrit levels, reducing spleen volume, and improving PV-related symptoms and quality-of-life measures. The most common nonhematologic adverse events in ruxolitinib-treated patients were headache, diarrhea, pruritus, and fatigue in the RESPONSE trial; hematologic adverse events were primarily grade 1 or 2. In the Phase IIIb nonregistration RELIEF trial, there were nonsignificant trends toward an improved symptom control in patients with PV on a stable hydroxyurea dose who were generally well controlled but reported disease-associated symptoms and switched to ruxolitinib vs those who continued hydroxyurea therapy. Updated treatment guidelines will be important for educating physicians about the role of ruxolitinib in the treatment of patients with PV., Competing Interests: Disclosure KV is an employee of Incyte Corporation. SV participated in advisory boards and received research funding from Incyte Corporation. JJK served as a consultant for Incyte Corporation and Novartis and received a travel grant and research funding paid by Novartis to Hôpital Saint-Louis. The authors report no other conflicts of interest in this work.

Mastocytosis is a disorder characterized by the clonal proliferation of mast cells and their accumulation in skin, bone marrow, liver, and spleen. Cutaneous mastocytosis presents in children in over 90% of the cases and any cutaneous manifestation in an adult is the earliest sign of the systemic disease. A 45-year-old patient presented with itchy dark lesions over the body since childhood and Darier's sign was positive. Skin biopsy showed features of mastocytosis and immunohistochemistry was positive for CD34. Since the patient was refractory to treatment with antihistamines and psoralen-ultraviolet A therapy, injections of interferon alpha were given - 3 million IU twice weekly subcutaneously as they have been proven to improve constitutional symptoms. Very few reports of successful treatment of cutaneous mastocytosis using interferon alpha have been published.

Essential thrombocythemia (ET) is a risk factor for ischemic stroke and, far more rarely, hemorrhage. We report the case of an untreated 32-year-old woman with a history of JAK2 V617F–positive ET with cerebellar and subarachnoid hemorrhages without evidence of sinus vein thrombosis. She was commenced on oral cytotoxic and antiplatelet therapy. This case report discusses the underlying mechanism of hemorrhagic thrombocythemia and the management dilemma presented by the recommended treatment implications. [Copyright &y& Elsevier]

The inv (4)(p13q13) cytogenetic abnormality is uncommon in hematologic malignancies. So far, it has not been previously reported in patients with essential thrombocythemia (ET). We report a first case of ET with inv (4)(p13q13) karyotype in a 69-year-old female patient who developed myelofibrosis at follow up. Conventional cytogenetic analysis from a bone marrow sample showed 46, XX, inv (4)(p13q13) [3]/46, XX [4] at diagnosis and subsequent analysis revealed the same abnormal karyotype during the myelofibrosis phase (46, XX, inv (4)(p13q13) [13]/46, XX [26]). The prognostic significance of this chromosomal abnormality is unknown., (Copyright © 2015 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

Most cases of Noonan syndrome (NS) result from mutations in one of the RAS-MAPK signaling genes, including PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, SHOC2, MEK1 (MAP2K1), and CBL. Cardiovascular diseases of varying severity, such as pulmonary stenosis and hypertrophic cardiomyopathy (HCM), are common in NS patients. RAF1 mutations are most frequent in NS with HCM, while PTPN11 mutations are also well known. Thr73Ile is a gain-of-function mutation of PTPN11, which has been highly associated with juvenile myelomonocytic leukemia and NS/myeloproliferative disease (MPD), but has not previously been reported in HCM. Here, we report a Japanese female infant with NS carrying the PTPN11 T73I mutation with NS/MPD, complete atrio-ventricular septal defect, and rapidly progressive HCM. No other HCM-related mutations were detected in PTPN11, RAF1, KRAS, BRAF, and SHOC2. This patient provides additional information regarding the genotype-phenotype correlation for PTPN11 T73I mutation in NS., (© 2015 Wiley Periodicals, Inc.)

MicroRNAs (miRNA) are small non-coding RNA molecules that play critical roles in cell differentiation, proliferation and apoptosis and thus regulate haematopoietic stem cells and committed progenitor cells. We analyzed expressions of miRNAs associated with hematopoietic transformation of myeloid, erythroid and megakaryocytic progenitor cells during haematopoiesis (mir155, mir181a, mir221, mir222, mir223, mir451), in patients with primary myelofibrosis (PMF) (n = 22), polycythemia vera (PV) (n = 33), essential thrombocythemia (ET) (n = 49) and in healthy controls (n = 40) by quantitate/real time polymerase chain reaction. RT-PCR testing was negative for BCR-ABL1 fusion gene in all the patients. Mir155 was expressed in higher levels in all 3 disorders (p < 0.05). Mir221 was higher especially in ET and PMF group (p < 0.05). Mir222 expression was lower in PV patients (p < 0.05) and higher in ET and PMF patients compared to control group. Mir223 expression was higher in ET and PMF group than control group (p > 0.05). Mir451 levels were lower in all three groups compared to control group (p < 0.05). There was no difference in expression levels of mir181a between groups. JAK2V617F positivity, co-morbidities, drugs, and gender did not affect miRNA expressions. This study holds promise for the future application of these molecules for differential diagnosis and as therapeutic targets in Philadelphia chromosome negative myeloproliferative neoplasms.

Rare patients suffering from myeloid neoplasms share clinical and cytological features indistinguishable from chronic myeloid leukemia (CML) but lack the BCR-ABL1 fusion gene. Several studies provide evidence that alterations in genes encoding tyrosine kinase receptors such as the platelet-derived growth factor receptor (PDGFR) may be involved in the pathogenesis of these disorders. Here we describe a patient with a rare CML-like disease in whom we identified a novel in-frame BCR-PDGFRA rearrangement joining BCR exon 17 to PDGFRA exon 13, resulting in overexpression of PDGFRA. The design of a specific quantitative PCR assay to monitor the molecular response during treatment with imatinib, a multitargeted tyrosine kinase inhibitor (TKI) with activity against ABL, c-Kit, and PDGFRA revealed an outstanding disease control with durably undetectable BCR-PDGFRA transcripts. Multiple TKIs are currently available yet with distinct target profiles; thus, accurate molecular diagnosis and monitoring tools are essential to establish tailored treatments and assess response to therapy in this type of rare hematological malignancy., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

CD4(+) T cells maintain cancer surveillance and immune tolerance. Chronic inflammation has been proposed as a driver of clonal evolution in myeloproliferative neoplasms (MPN), suggesting that T cells play an important role in their pathogenesis. Treatment with JAK inhibitors (JAKi) results in improvements in MPN-associated constitutional symptoms as well as reductions in splenomegaly. However, effects of JAKi on T cells in MPN are not well established and the baseline immune signature remains unclear. We investigated the frequency and function of CD4(+) T cell subsets in 50 MPN patients at baseline as well as during treatment with either ruxolitinib or fedratinib in a subset. We show that CD4(+)  CD127(low)  CD25(high)  FOXP3(+) T regulatory cells are reduced in MPN patients compared to healthy controls and that this decrease is even more pronounced following JAKi therapy. Moreover, we show that after 6 months of treatment the number of T helper (Th)-17 cells increased. We also describe a functional 'silencing' of T helper cells both in vivo and in vitro and a blockade of pro-inflammatory cytokines from these cells. This profound effect of JAKi on T cell function may underlay augmented rates of atypical infections that have been reported with use of these drugs., (© 2015 John Wiley & Sons Ltd.)

Hypereosinophilic syndrome (HES) encompasses numerous diverse conditions resulting in peripheral hypereosinophilia that cannot be explained by hypersensitivity, infection, or atopy and that is not associated with known systemic diseases with specific organ involvement. HES is often attributed to neoplastic or reactive causes, such as chronic eosinophilic leukemia, although a majority of cases remains unexplained and are considered idiopathic. Here, we review the current diagnosis and management of HES and present a unique case of profound hypereosinophilia associated with warm autoimmune hemolytic anemia requiring intensive management. This case clearly illustrates the limitations of current knowledge with respect to hypereosinophilia syndrome as well as the challenges associated with its classification and management.

Although more than 90% systemic mastocytosis (SM) patients express gain of function mutations in the KIT receptor, recent next generation sequencing has revealed the presence of several additional genetic and epigenetic mutations in a subset of these patients, which confer poor prognosis and inferior overall survival. A clear understanding of how genetic and epigenetic mutations cooperate in regulating the tremendous heterogeneity observed in these patients will be essential for designing effective treatment strategies for this complex disease. In this review, we describe the clinical heterogeneity observed in patients with mastocytosis, the nature of relatively novel mutations identified in these patients, therapeutic strategies to target molecules downstream from activating KIT receptor and finally we speculate on potential novel strategies to interfere with the function of not only the oncogenic KIT receptor but also epigenetic mutations seen in these patients.

Background: Immunophenotyping has replaced cytochemical staining as the preferred technique for classifying acute leukemia. However, some acute myeloid leukemias (AML) lack lineage-associated markers. In our experience, alkaline phosphatase (ALP) is expressed in immature canine monocytes. We hypothesized that ALP is a useful marker for monocytic AML., Objectives: The objective was to compare ALP expression in neoplastic cells from dogs with lymphoma, chronic lymphocytic leukemia (CLL), acute lymphoid leukemia (ALL), and AML., Methods: Alkaline phosphatase results were retrieved from medical records of dogs with acute leukemia. Smears from dogs with lymphoma or leukemia were also prospectively stained for ALP activity. CLL was based on persistent lymphocytosis (10 × 10(9) /L) and acute leukemia on ≥ 20% blasts in blood or bone marrow. ALL was classified based on positive phenotyping for T- or B-lymphocyte antigens, and AML on positive phenotyping for CD11b, CD11c or CD14, or cytochemical staining for chloroacetate esterase, Sudan Black B, or myeloperoxidase., Results: There was no ALP activity in all 49 lymphomas and 7 CLLs. Weak ALP activity was seen in 31% of 14 ALL (all T-ALL). ALP activity was seen in all 20 AML (P < .001 vs ALL) with strong activity in 64% (vs 25% ALL) in most neoplastic cells (median 75% vs 9% ALL, P = .020). Of AML, 80% were CD34+ (vs 39% ALL, P = .027) and 100% were MHCII- (vs 43% ALL, P = .002)., Conclusions: ALP activity may be useful for AML confirmation in dogs, particularly if neoplastic cells only express CD34+ on immunophenotyping., (© 2014 American Society for Veterinary Clinical Pathology.)

A response to a letter to the editor is presented about the article "Inconsistencies in the Association Between the JAK2V617F Mutation and PRV-1 Over-Expression Among the Chronic Myeloproliferative Diseases," published in the 2005 issue.

Therapeutic options for gastric variceal bleeding in the presence of extensive portal vein thrombosis associated with a myeloproliferative disorder are limited. We report a case of a young woman who presented with gastric variceal bleeding secondary to extensive splanchnic venous thrombosis due to a Janus kinase 2 mutation associated myeloproliferative disorder that was managed effectively with partial splenic embolization.

The chronic myeloproliferative disorders are a group of diseases in which there is an increased proliferation of one or more subtypes of myeloid cells; they include essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). In ET and PV the main neurologic manifestations are headaches, dizziness and macro- and microvascular, both venous and arterial, thrombosis and intracranial hemorrhages. Paresthesias and chorea also occur in PV. In PMF neurologic complications are very rare and consist predominantly of spinal cord compression by extramedullary hematopoiesis tissue., (© 2014 Elsevier B.V. All rights reserved.)

Background: Sweet syndrome is a neutrophilic dermatosis with cutaneous tender lesions that can be associated with malignancies, infections, systemic inflammatory disorders, and medications. Although numerous studies have described Sweet syndrome, few studies have systematically investigated Sweet syndrome., Objective: We sought to describe characteristics and treatments of patients with Sweet syndrome and evaluate clinical differences depending on the underlying cause., Methods: A retrospective study was conducted to identify patients with Sweet syndrome evaluated at Mayo Clinic from 1992 to 2010., Results: Of 77 patients with Sweet syndrome (mean age of onset 57 years), 43 (56%) were male. Eighteen patients (23%) reported a preceding infection. A total of 41 (53%) patients were classified as having classic Sweet syndrome, 27 (35%) patients had malignancy-associated Sweet syndrome, and in 9 (12%) patients drug-induced Sweet syndrome was considered. In all, 21 patients had a hematologic malignancy or myeloproliferative/myelodysplastic disorder, whereas 6 patients had solid tumors. The mean hemoglobin level, in both male and female patients (P < .0443 and P < .0035, respectively), was significantly lower in malignancy-associated versus classic and drug-induced Sweet syndrome. Systemic corticosteroids were the most frequently used treatment (70%)., Limitations: This is a retrospective study and represents patients from a single academic center., Conclusions: Sweet syndrome is a distinctive disorder with certain clinical and histologic characteristics, which usually has a complete response to systemic corticosteroids. It is important to evaluate Sweet syndrome patients who have laboratory evidence of anemia for an underlying malignancy., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Aim: To evaluate long-term complications and survival in patients with Budd-Chiari syndrome (BCS) referred to a Danish transjugular intrahepatic portosystemic shunt (TIPS) centre., Methods: Twenty-one consecutive patients from 1997-2008 were retrospectively included [15 women and 6 men, median age 40 years (range 17-66 years)]. Eighteen Danish patients came from the 1.8 million catchment population of Aarhus University Hospital and three patients were referred from Scandinavian hospitals. Management consisted of tests for underlying haematological, endocrinological, or hypercoagulative disorders parallel to initiation of specific treatment of BCS., Results: BCS was mainly caused by thrombophilic (33%) or myeloproliferative (19%) disorders. Forty-three percents had symptoms for less than one week with ascites as the most prevalent finding. Fourteen (67%) were treated with TIPS and 7 (33%) were manageable with treatment of the underlying condition and diuretics. The median follow-up time for the TIPS-treated patients was 50 mo (range 15-117 mo), and none required subsequent liver transplantation. Ascites control was achieved in all TIPS patients with a marked reduction in the dose of diuretics. A total of 14 TIPS revisions were needed, mostly of uncovered stents. Two died during follow-up: One non-TIPS patient worsened after 6 mo and died in relation to transplantation, and one TIPS patient died 4 years after the TIPS-procedure, unrelated to BCS., Conclusion: In our BCS cohort TIPS-treated patients have near-complete survival, reduced need for diuretics and compared to historical data a reduced need for liver transplantation.

Background: Hyperkalemia is a potentially life-threatening medical condition; on the other hand pseudohyperkalemia is a benign entity, which should be suspected when serum potassium is elevated without concomitant electrolyte imbalances or remarkable degree of renal dysfunction. Patients seldom have the classical manifestations of hyperkalemia. Failure to recognize this condition causes anxiety among physicians, unnecessary laboratory testing and unwarranted treatments., Case Report: We describe a sixty-year-old woman with persistent hyperkalemia and mean platelet count over a six-month period of 1015×10(3) cells/cumm. Based on this finding of thrombocytosis an immediate hematological evaluation has detected a myeloproliferative disorder, specifically essential thrombocythemia. Normalizing platelet count was paralleled by resolution of hyperkalemia., Conclusions: Pseudohyperkalemia might be the tip of the iceberg to a major underlying pathological process. Unless a high index of suspicion to diagnose this disorder is maintained it will continue to be remarkably under diagnosed, subjecting patients to numerous unnecessary tests and treatments.

The discovery of somatic mutations in the JAK-STAT signaling pathway was a major breakthrough in our understanding of the molecular pathogenesis of the myeloproliferative neoplasms (MPNs) polycythemia vera, essential thrombocytosis, and primary myelofibrosis. This finding led to the development of small molecule inhibitors targeting Janus kinase (JAK) 2 and other JAK family members. Currently, there are a number of research and clinical trials ongoing with JAK inhibitors. While the appeal of inhibiting JAK2 is clear, studies to date suggest that JAK2 inhibitor monotherapy might not be sufficient to cause reductions in disease allele burden in MPN patients. There is compelling evidence that JAK inhibitors are improving symptoms and therefore quality of life for patients. It will be important to investigate the efficacy of JAK inhibitors in preclinical and clinical studies to better understand their effects, while at the same time pursuing alternative therapies which might offer benefit to MPN patients alone and in combination with JAK inhibitors.

Background: It is not rare to observe in blood donors a level of haematocrit (Hct) above or close to the highest normal limit. In the case of blood donors the diagnosis and clinical evaluation of this alteration may be complicated by regular blood donations that can mask an underlying disease such as polycythaemia vera. Recently a single acquired mutation in the Janus kinase 2 gene (JAK2) on chromosome 9 was identified and it was found that the incidence of this mutation was high in patients with polycythaemia vera., Material and Methods: From the January 1, 2006 to December 31, 2006 all consecutive donors with a Hct above 50% if males (n=84) and 46% if females (n=19) underwent JAK2 mutation analysis. Seventy-nine donors (59 males and 20 females) whose Hct was normal at their last blood donation were randomly selected and used as controls., Results: Among the group of blood donors with a high Hct, we identified one donor who was positive for the JAK2 mutation. This man had a Hct of 50.6% at his last donation, while his average Hct in the preceding year was 51.7%. The prevalence of the JAK2 mutation could be estimated to be 1%, 0.6% or 0.02% in the three different populations considered: donors with a Hct level above the upper limit of normal, all tested donors or the entire donor cohort attending our transfusion service, respectively., Conclusions: The present study suggests that apparently healthy subjects with repeatedly high levels of Hct may have the acquired mutation in JAK2. Laboratory screening tests for JAK2 may be offered to blood donors at transfusion services with expertise in molecular genetics.