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Essential Thrombocythemia (essential + thrombocythemia)

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Selected Abstracts

Analysis of risk factors predicting thrombotic and/or haemorrhagic complications in 306 patients with Essential Thrombocythemia

HEMATOLOGICAL ONCOLOGY, Issue 3 2007
Franca Radaelli
Abstract Thrombotic and haemorrhagic complications are the main causes of morbidity in Essential Thrombocythemia (ET). We investigated the clinical and laboratory characteristics associated with the occurrence of these events with the aim of identifying subgroups of patients who might benefit from anti-aggregant and/or cytoreductive therapy. The study involved 306 consecutive ET patients (median age 58 years and median follow-up 96 months); the investigated variables were age, gender, platelet count, previous history of thrombotic or haemorrhagic events, disease duration and cardiovascular risk factors. Forty-six patients (15%) experienced thrombotic complications during the follow-up: 26/64 patients with a previous history of thrombosis (40.6%) and 20/242 patients without (8.3%; p,<,0.0001). Thirty-one patients (10%) experienced major haemorrhagic complications, mainly gastrointestinal tract bleeding: 3 with and 28 without a history of haemorrhagic events (p,=,0.052). When the patients with a negative history of thrombosis were stratified on the basis of the number of cardiovascular risk factors (none vs. one vs. more than one), there was a significant correlation with the occurrence of thrombotic events (p,<,0.05). ET patients with a positive history of thrombosis are at high risk of thrombotic complications, and should receive cytoreductive and anti-aggregant treatment. Asymptomatic patients with a negative thrombotic history and no cardiovascular risk factors are at low risk, and should not be treated. Patients with a negative thrombotic history and one or more cardiovascular risk factors are at intermediate risk, and should be treated with anti-aggregant and/or cytoreductive therapy. The need for treatment should be periodically re-evaluated. Age and platelet count, generally accepted as very important risk factors for thrombosis, did not seem in our series associated with an increased risk for thrombosis. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Long-term follow-up of 386 consecutive patients with essential thrombocythemia: Safety of cytoreductive therapy,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2009
Francesca Palandri
Cytotoxic agents like Hydroxyurea, Busulfan and Interferon-alpha are to date the most commonly used therapeutic approaches in Essential Thrombocythemia (ET). However, few data on the efficacy and safety of these agents in the long-term are currently available. We report a retrospective analysis of the long-term outcome of 386 consecutive ET patients, followed at single Institution for a median follow-up of 9.5 years (range, 3,28.5). Cytoreductive therapy was administered to 338 patients (88%), obtaining a response in 86% of cases. Forty-five patients (12%) experienced a thrombosis. Among baseline characteristics, only history of vascular events prior to ET diagnosis predicted a higher incidence of thrombosis. Evolution in acute leukemia/myelofibrosis occurred in 6 (1,5%) and 20 (5%) patients, and was significantly higher in patients receiving sequential cytotoxic agents. Overall survival was 38% at 19 years and was poorer for patients older than 60 years, with higher leukocytes count (>15 × 109/L), hypertension and mellitus diabetes at ET diagnosis and for patients experiencing a thrombotic event during follow-up. Cytoreductive therapy was effective in decreasing platelet number with negligible toxicity; however, thrombocytosis control did not reduce the incidence of thrombosis and, for patients who received sequential therapies, the probability of disease evolution was higher and survival was poorer. Am. J. Hematol. 2009. © 2008 Wiley-Liss, Inc. [source]

Factor V Leiden mutation carriership and venous thromboembolism in polycythemia vera and essential thrombocythemia

AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2002
Marco Ruggeri
Abstract Polycythemia Vera (PV) and Essential Thrombocythemia (ET) are chronic myeloproliferative disorders complicated by a high incidence of thrombotic complications. Extensive coagulation studies failed to demonstrate a consistent pattern of abnormalities associated with thrombosis. Recently, a poor anticoagulant response to activated protein C (APC), due to a mutation of factor V (FV Leiden), has been identified as the most frequent hereditary disorder associated with venous thrombophilia. We investigated in 304 patients with PV and ET whether the presence of FV Leiden could be a risk factor for thrombosis. FV Leiden was found in 14/304 patients (4.6%) and was associated with venous thromboembolism (VTE) occurred before and at diagnosis (5/27,16%, with a significant difference of prevalence in comparison of that observed in asymptomatic patients, 9/263, 3%, p = 0.003). Carriership of FV Leiden was associated with VTE relapse, with a prevalence of 3.6% in asymptomatic patients, 6.9% in patients with a single episode of VTE and 18.1% in patients with recurrent VTE. The prevalence of FV Leiden in patients with and without arterial thrombosis was similar (5/79, 6% and 9/211, 4%, respectively, p = 0.337). This study indicates that the prevalence of the FV Leiden mutation in patients with PV and ET is comparable with that observed in the general population. FV Leiden mutation is a risk factor for VTE before and at time of diagnosis and for VTE recurrences. Screening for FV Leiden may be considered to identify PV and ET patients at higher risk of recurrences. Am. J. Hematol. 71:1,6, 2002. © 2002 Wiley-Liss, Inc. [source]

Essential Thrombocythemia: A Case of Acute ST-Segment Elevation Myocardial Infarction in a Young Female

CLINICAL CARDIOLOGY, Issue 2 2009
Ulas Bildirici MD
Abstract Essential thrombocythemia (ET) is a clonal disorder of the myeloid stem cell that causes abnormal proliferation of the megakaryocytes. The main feature of the disease is arterial and venous thrombosis caused by platelet dysfunction. Coronary artery involvement leading to acute coronary syndromes is a rare complication of the ET. We report a coronary angioplasty and stenting in a 30-year-old female patient with acute ST-segment elevation myocardial infarction (MI) as the first clinical sign of essential thrombocythemia. Facilitated percutaneous coronary intervention with GPIIb/IIIa and/or thrombolytic therapy may be considered as the first treatment modality for this patient group. Copyright © 2009 Wiley Periodicals, Inc. [source]

Essential thrombocythemia and pregnancy: Observations from recent studies and management recommendations,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2009
Ayalew Tefferi
No abstract is available for this article. [source]

Essential versus reactive thrombocythemia in children: Retrospective analyses of 12 cases

PEDIATRIC BLOOD & CANCER, Issue 1 2007
Abeer Abd El-Moneim
Abstract Background Essential thrombocythemia (ET) rarely occurs in the pediatric population and little is known about the clinical course and the molecular characteristics. Procedure In this retrospective multi-institutional study we examine the clinical, hematological, and molecular features of 12 children aged 5,16 years with thrombocytosis and a suspected diagnosis of ET. Results Median follow-up was 59 months (range 10,72). Seven patients presented with clinical symptoms potentially related to thrombocytosis. The remaining five patients were diagnosed incidentally. Median platelet count at diagnosis was 1,325,×,109/L (range 600,3,050). In 11 out of 12 cases bone marrow morphology was consistent with ET, the remaining patient had chronic idiopathic myelofibrosis. Cytogenetic analyses were normal in all studied cases and only one out of nine analyzed cases harbored a JAKV617F allele. Within 6 months after initial presentation one patient who was initially asymptomatic developed thrombosis and another patient had mild bleeding. Eight patients were treated with acetylsalicylic acid, one patient received hydroxyurea, and two patients received anagrelide. At last follow-up, all patients were alive and none had developed leukemia. Five patients experienced hematological remission. Two children had not received any therapy. During the course of their disease, nine patients developed symptoms possibly attributable to an elevated platelet count. Conclusions In JAK2 mutation negative cases, long-term follow-up is helpful to distinguish between primary and secondary thrombocytosis. Secondary cases are not associated with organomegaly but may present with unspecific symptoms. Indications for treatment in children remain unclear. Pediatr Blood Cancer 2007;49:52,55. © 2006 Wiley-Liss, Inc. [source]

Essential thrombocythemia in patients with platelet counts below 600x109/L: Applicability of the 2008 World Health Organization diagnostic criteria revision proposal,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2009
Mi Kwon
No abstract is available for this article. [source]

Essential Thrombocythemia: A Case of Acute ST-Segment Elevation Myocardial Infarction in a Young Female

Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shunt

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010
Elena Mishchenko
Abstract Clinical care of patients with polycythemia vera, essential thrombocythemia and myelofibrosis (MF) requires not only a broad understanding of general treatment principles but also familiarity with the management of hydroxyurea-refractory disease complications. The latter include progressive splenomegaly, symptomatic portal hypertension (e.g. ascites, variceal bleeding), pulmonary hypertension, bone pain, intractable pruritus, constitutional symptoms (e.g. fatigue, night sweats) and cachexia (i.e. loss of lean body mass, general ill health, poor appetite). Some of these symptoms are directly or indirectly related to extramedullary hematopoiesis (EMH) and others to proinflammatory cytokine excess. Results from recent clinical trials of JAK inhibitors suggest remarkable activity in MF-associated constitutional symptoms, cachexia, pruritus and hydroxyurea-refractory splenomegaly. Involved-field radiotherapy is best utilized in the setting of EMH-associated symptoms, including ascites, bone (extremity) pain and pulmonary hypertension. Splenectomy is indicated in the presence of drug-refractory splenomegaly and frequent red cell transfusion requirement. Transjugular intrahepatic portosystemic shunt is used to alleviate symptoms of portal hypertension. [source]

Chromosome 1 abnormalities in myeloid malignancies: a literature survey and karyotype,phenotype associations

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010
Domenica Caramazza
Abstract Chromosome 1 is the largest human chromosome and contains over 1600 known genes and 1000 novel coding sequences or transcripts. It is, therefore, not surprising that recurrent chromosome 1 abnormalities are regularly encountered in both neoplastic and non-neoplastic medical conditions. The current review is focused on myeloid malignancies where we summarize the relevant published literature and discuss specific karyotype,phenotype associations. We show that chromosome 1 abnormalities are most frequent in BCR-ABL -negative classic myeloproliferative neoplasms (MPN): polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Specific abnormalities include duplications (e.g. 1q12,1q32 in PV, 1q21,32,1q32,44 in post-PV MF or PMF), deletions (e.g. 1p13,36,pter in PV or PMF, 1q21 in PMF) and unbalanced translocations involving chromosome 6, such as der(6)t(1;6)(q21,25;p21.3,23), and other partner chromosomes involving 1q10/1p11 and 1q21,25 breakpoints. Although occasionally seen in chronic phase MPN, unbalanced 1;7 translocations, e.g. der(1;7)(q10;p10), are usually seen in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and post-MPN AML/MDS. These observations suggest that certain chromosome 1 regions, especially 1q21,1q32 and 1p11,13, might harbor oncogenes or tumor suppressor genes that are pathogenetically relevant to both chronic and advanced phases of MPN. [source]

Cytogenetic abnormalities in essential thrombocythemia: prevalence and prognostic significance

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2009
Naseema Gangat
Abstract Objectives:, In the current study we describe cytogenetic findings as well as clinical correlates and long-term prognostic relevance of abnormal cytogenetics at the time of diagnosis of essential thrombocythemia (ET). Patients and methods:, The study cohort consisted of a consecutive group of patients with ET who fulfilled the World Health Organization diagnostic criteria, and in whom cytogenetic analysis was performed at diagnosis. Results:, A total of 402 patients were studied (median age, 56 yrs; median follow-up 70 months). The prevalence of abnormal cytogenetics at diagnosis was 7% (28 of 402). The most common cytogenetic anomalies were trisomy 9 (four patients), abnormal chromosome 1 (three patients) and trisomy 8 (two patients). Parameters at diagnosis that were significantly associated with abnormal cytogenetics included palpable splenomegaly (P = 0.03), current tobacco use (P = 0.04); venous thrombosis (P = 0.02), and anemia with a hemoglobin of <10 g/dL (P = 0.02); but did not include JAK2V617F mutation status, or advanced age. During follow up, patients with abnormal cytogenetics did not have shorter survival, or increased transformation to acute leukemia or myelofibrosis. Conclusion:, Cytogenetic anomalies at diagnosis are relatively uncommon in ET, and do not predict evolution into more aggressive myeloid disorders, or inferior survival. [source]

Conventional cytogenetics in myelofibrosis: literature review and discussion

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2009
Kebede Hussein
Abstract The clinical phenotype of myelofibrosis (MF) is recognized either de novo (primary) or in the setting of polycythemia vera (post-PV) or essential thrombocythemia (post-ET). Approximately one-third of patients with primary MF (PMF) present with cytogenetic abnormalities; the most frequent are del(20q), del(13q), trisomy 8 and 9, and abnormalities of chromosome 1 including duplication 1q. Other less frequent lesions include ,7/del(7q), del(5q), del(12p), +21 and der(6)t(1;6)(q21;p21.3). In general, cytogenetic abnormalities are qualitatively similar among PMF, post-ET MF and post-PV MF although their individual frequencies may differ. Based on prognostic effect, cytogenetic findings in MF are classified as either ,favorable' or ,unfavorable'. The former include normal karyotype or isolated del(20q) or del(13q) and the latter all other abnormalities. Unfavorable cytogenetic profile in both PMF and post-PV/ET MF confers an independent adverse effect on survival; it is also associated with higher JAK2V617F mutational frequency. In addition to their prognostic value, cytogenetic studies in MF ensure diagnostic exclusion of other myeloid neoplasms that are sometimes associated with bone marrow fibrosis (e.g. BCR-ABL1 -positive or PDGFRB -rearranged) and also assist in specific treatment selection (e.g. lenalidomide therapy is active in MF associated with del(5q). [source]

Pseudothrombocytopenia as a pitfall in the treatment of essential thrombocythemia

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2003
Dr Andre Braester
No abstract is available for this article. [source]

A single institutional experience with 43 pregnancies in essential thrombocythemia

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2001
Curtis A. Wright
Abstract: Objectives: We describe the periconception circumstances and outcome of 43 consecutive pregnancies in an unselected group of young women with essential thrombocythemia (ET). Patients and methods: We retrospectively studied 74 consecutive cases of young women with ET seen at our institution, among whom 43 pregnancies occurred in 20 patients. Results: Of the 43 pregnancies, 22 (51%) were successful (21 term and 1 preterm live births) and 21 (49%) ended in miscarriages (1 ectopic pregnancy, 2 elective abortions, 16 first-trimester spontaneous abortions, 1 stillbirth at 22 wk, and 1 abruptio placentae at 33 wk). Management of ET at the time of conception included either no specific therapy (16 cases) or the use of aspirin alone (24 cases), a cytoreductive agent (2 cases), or heparin (1 case). There were no significant differences with respect to platelet count or the effect of treatment with aspirin, either at the time of conception or during the first trimester, among cases of successful pregnancies (22), all miscarriages (21), or first-trimester spontaneous abortions (16). The findings were similar when the analysis was restricted to only first-time pregnancies. In patients with multiple pregnancies, the outcome of a subsequent pregnancy was not predicted by the outcome of the first. In general, in successful cases the last two trimesters were mostly uneventful, with healthy offspring being reported in all cases. Conclusions: Pregnant patients with ET have an increased risk of first-trimester abortion which is not predictable by preconception platelet count or aspirin therapy. In addition, our experience does not support the use of prophylactic platelet apheresis during delivery. [source]

Treatment of the myeloproliferative disorders with 32P

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2000
Nathaniel I. Berlin
After World War II when 32P became widely available, it was used extensively to treat the chronic leukemias and polycythemia vera. Its use in the treatment of essential thrombocythemia began later in 1950. Today it is not widely used in the treatment of the chronic leukemia, if at all, its use in polycythemia vera appears to have decreased substantially and replaced by hydroxyurea, and its use in the management of essential thrombocythemia is not widespread. In each instance it has been replaced by a drug developed for use in cancer chemotherapy, and in some instances by interferon. It probably has wider use in polycythemia vera in the rest of Western Europe than in the UK, and there are cogent reasons to suggest that it may be the best tool for the treatment of polycythemia vera. Thus have we discarded a treatment modality that in polycythemia vera may be the best? [source]

Familial chronic myeloproliferative disorders: the state of the art,

HEMATOLOGICAL ONCOLOGY, Issue 3 2008
Elisa Rumi
Abstract Familial chronic myeloproliferative disorders are defined when in the same pedigree at least two relatives have a chronic myeloproliferative disorder (CMD) as polycythemia vera (PV), essential thrombocythemia (ET) or primary myelofibrosis (PMF). This condition should be distinguished from inherited disorders with Mendelian transmission and single haematopoietic lineage proliferation, named hereditary erythrocytosis and thrombocytosis. The recently discovered mutations in patients with CMD (V617F and exon 12 of JAK2 gene, MPL gene), and those identified in hereditary erythrocytosis and in hereditary thrombocytosis have improved our ability to discriminate these conditions. In familial CMD, the JAK2 mutations are acquired and occur as secondary genetic events. As both mutations of the JAK2 gene have been reported in the same pedigree, a genetic predisposition to the acquisition of the JAK2 mutations is supposed to be inherited. The prevalence of familial cases within CMD is at least 7.6%. The inheritance pattern of familial CMD is consistent with an autosomal dominant trait with decreased penetrance. The clinical presentation at diagnosis of patients with familial CMD does not differ from that of patients with sporadic CMD. In addition, patients with familial CMD develop the same type of complications (thrombosis and haemorrhage) and disease evolution (post-PV myelofibrosis, post-ET myelofibrosis and leukaemia) observed in patients with sporadic CMD. The 10-year survival is 83% for patients with familial PV, 100% for those with familial ET, and 30% for those with familial PMF. The aim of this review is to focus the state of the art of familial CMD and to offer an overview of inherited conditions causing erythrocytosis and thrombocytosis. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Leg ulcers and hydroxyurea: report of three cases with essential thrombocythemia

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2002
Zeynep Demirçay MD
Case 1,A 65-year-old woman with essential thrombocythemia (ET) had been taking oral hydroxyurea (HU), 1000 mg daily, for 7 years. Six months ago, she developed an ulcer on the outer part of her left ankle, which healed spontaneously within 2 months. She presented with a new, tender, shallow ulcer, 2 cm × 2 cm in size, at the same site. Doppler examination revealed thrombosis of the left common femoral vein and a calcified atheroma plaque of the left common femoral artery. The dosage of HU was decreased to 500 mg daily when the platelet counts were found to be within normal levels. The ulcer completely healed within 2 months with occlusive wound dressings, and has not recurred within the follow-up period of 1 year. Case 2,A 56-year-old women presented with multiple, painful, leg ulcers of 1 year duration. She had been diagnosed as having ET and had been on HU therapy, 1500 mg/day, for the past 5 years. Interferon-,-2b was started 3 months ago, in addition to HU, which was tapered to 1000 mg daily. She had suffered from hypertension for 20 years treated with nifedipine and enalapril, and had recently been diagnosed with diabetes mellitus which was controlled by diet. Examination revealed three ulcers located on the lateral aspects of both ankles and right distal toe. Arterial and venous Doppler examinations were within normal limits. Histopathology of the ulcer revealed nonspecific changes with a mixed inflammatory cell infiltrate around dermal vessels. The ulcers completely healed within 10 weeks with topical hydrocolloid dressings. After healing, she was lost to follow-up. A year later, it was learned that she had developed a new ulcer at her right heel, 3 months after her last visit (by phone call). This ulcer persisted for 8 months until HU was withdrawn. Case 3,A 64-year-old woman with ET presented with a painful leg ulcer of 6 months' duration. She had been taking oral HU for 5 years. She had a 20-year history of hypertension treated with lisinopril. Examination revealed a punched-out ulcer of 2 cm × 2 cm over the right lateral malleolus (Fig. 1). Doppler examination of the veins revealed insufficiency of the right greater saphenous and femoral veins. Angiography showed multiple stenoses of the right popliteal and femoral arteries. As her platelet count remained high, HU was continued. During the follow-up period of 13 months, the ulcer showed only partial improvement with local wound care. Figure 1. Punched-out ulcer surrounded by an erythematous border over the right malleolus (Case 3) [source]

Splenectomy in a case of splenic vein thrombosis unmasks essential thrombocythemia

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2002
R. DAS
We report a patient with splenic vein thrombosis (SVT) in whom splenectomy resulted in the unmasking of essential thrombocythemia (ET). He had portal hypertension with haematemesis, resulting in anaemia requiring repeated blood transfusions. Investigations revealed SVT. Following splenectomy, he suffered a transient ischaemic attack episode, associated with persistent thrombocytosis (> 2000 × 109/l). Other myeloproliferative disorders were excluded and a diagnosis of ET was established. He responded to hydroxyurea but, due to financial constraints, he discontinued treatment and subsequently relapsed. The association of ET with SVT is rare and the diagnosis of ET was missed initially as the platelet count was normal prior to splenectomy. [source]

Multiple thrombophilic factors in a patient with Budd,Chiari syndrome

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2002
V. BRANCACCIO
Myeloproliferative disorders are the main cause of Budd,Chiari syndrome in western countries. Inherited or acquired thrombophilic factors have also been implicated. A novel mutation of the prothrombin gene (G,A20210) has only been described in a few cases of Budd,Chiari syndrome so far. Venous thrombosis is often the result of multiple concomitant thrombophilic factors. We report the case of a patient with essential thrombocythemia and Budd,Chiari syndrome in which heterozygosity for both factor V Leiden and the mutation G20210A of the prothrombin gene were identified. [source]

Long-term outcome after percutaneous coronary intervention in patients with essential thrombocythemia

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2009
G. CAMPO
[source]

Incidence of the JAK2 V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2007
V. DE STEFANO
Summary., Background:, Thrombosis of splanchnic or cerebral veins is a typical manifestation of polycythemia vera (PV) or essential thrombocythemia (ET). The recently identified Janus kinase 2 (JAK2) V617F somatic mutation is closely related to chronic myeloproliferative disorders (CMD). Objective:, To assess the incidence of the JAK2 V617F mutation among patients with splanchnic or cerebral venous thrombosis with or without overt CMD. Patients and methods:, We searched for the mutation in 139 adult patients (> 18 years old) with thrombosis of hepatic veins (HVT, n = 15), or extrahepatic portal vein (PVT) and/or mesenteric vein (MVT) (n = 79), or cerebral veins (CVT, n = 45). Only 19 patients fulfilled criteria for diagnosis of PV (n = 8) or ET (n = 11) at the time of thrombosis: four had HVT, 11 PVT and/or MVT, and four CVT. Results:, The JAK2 V617F mutation was found in 94.7% [95% CI 75.3,99.0] of the patients with overt CMD at the time of thrombosis, in 21.5% (95% CI 13.8,31.7) of the patients with abdominal venous thrombosis and without overt CMD, and in 4.8% (95% CI 1.3,16.1) of the patients with CVT and without overt CMD. Among the patients without overt CMD or thrombophilia and with unprovoked thrombosis, 29.4% (95% CI 16.8,46.1) with splanchnic venous thrombosis and 42.8% (95% CI 24.4,63.4) with PVT had the JAK2 V617F mutation. Conclusions:, A substantial proportion of patients with splanchnic venous thrombosis and a small, but significant, number of patients with CVT can be recognized as carriers of the JAK2 V617F mutation in the absence of overt signs of CMD. The clinical significance of such findings deserves further investigation. [source]

Leukocytosis is a risk factor for recurrent arterial thrombosis in young patients with polycythemia vera and essential thrombocythemia,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2010
Valerio De Stefano
There is evidence that leukocytosis is associated with an increased risk of first thrombosis in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Whether it is a risk factor for recurrent thrombosis too is currently unknown. In the frame of a multicenter retrospective cohort study, we recruited 253 patients with PV (n = 133) or ET (n = 120), who were selected on the basis of a first arterial (70%) or venous major thrombosis (27.6%) or both (2.4%), and who were not receiving cytoreduction at the time of thrombosis. The probability of recurrent thrombosis associated with the leukocyte count recorded at the time of the first thrombosis was estimated by a receiver operating characteristic analysis and a multivariable Cox proportional hazards regression model. Thrombosis recurred in 78 patients (30.7%); multivariable analysis showed an independent risk of arterial recurrence (hazard ratio [HR] 2.16, 95% CI 1.12,4.18) in patients with a leukocyte count that was >12.4 × 109/L at the time of the first thrombotic episode. The prognostic role for leukocytosis was age-related, as it was only significant in patients that were aged <60 years (HR for arterial recurrence 3.35, 95% CI 1.22,9.19). Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source]

Prodromal myeloproliferative neoplasms: The 2008 WHO classification,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010
Hans Michael Kvasnicka
The concept of prodromal chronic myeloproliferative neoplasms has been endorsed by the WHO classification implicating a stepwise evolution of disease. Histology of the bone marrow (BM) and borderline to mildly expressed clinical features play a pivotal role for diagnosing prefibrotic-early primary myelofibrosis. By lowering the platelet count for essential thrombocythemia and regarding BM morphology, early manifestations are tackled. Pre-polycythemic stages of polycythemia vera with a low hemoglobin level at onset are diagnosed by positive JAK2V617F mutation status, a low erythropoietin value, and characteristic BM features. The revised WHO classification incorporates hematological, morphological, and moleculargenetic parameters to generate a consensus-based working diagnosis. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source]

Outcome of 122 pregnancies in essential thrombocythemia patients: A report from the Italian registry

AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2009
Lorella Melillo
Pregnancy is a high-risk event in women with essential thrombocythemia (ET). This observational study evaluated pregnancy outcome in ET patients focusing on the potential impact of aspirin (ASA) or interferon alpha (IFN) treatment during pregnancy. We retrospectively analyzed 122 pregnancies in 92 women consecutively observed in the last 10 years in 17 centers of the Italian thrombocythemia registry (RIT). The live birth rate was 75.4% (92/122 pregnancies). The risk of spontaneous abortion was 2.5-fold higher than in the control population (P < 0.01). ASA did not affect the live birth rate (71/93, 76.3% vs. 21/29, 72.4%, P = 0.67). However, IFN treatment during pregnancy was associated with a better outcome than was management without IFN (live births 19/20, 95% vs. 73/102, 71.6%, P = 0.025), and this finding was supported by multivariate analysis (OR: 0.10; 95% CI: 0.013,0.846, P = 0.034). The JAK2 V617F mutation was associated with a poorer outcome (fetal losses JAK2 V617F positive 9/25, 36% vs. wild type 2/24, 8.3%, P = 0.037), and this association was still significant after multivariate analysis (OR: 6.19; 95% CI: 1.17,32.61; P = 0.038). No outcome concordance between first and second pregnancies was found (P = 0.30). Maternal complications occurred in 8% of cases. In this retrospective study, in consecutively observed pregnant ET patients, IFN treatment was associated with a higher live birth rate, while ASA treatment was not. In addition, the JAK2 V617F mutation was confirmed to be an adverse prognostic factor. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source]

Blast phase of essential thrombocythemia: A single center study,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2009
Francesco Passamonti
Blast phase (BP) may occur as a late event in essential thrombocythemia (ET). This study includes 19patients with post-ET BP diagnosed and followed in a single institution. At BP, 63% of patients had leukocytosis (white blood cell count >10 × 109/L), 74% had anemia (hemoglobin value <10 g/dL), 74% had thrombocytopenia (platelet count <100 × 109/L), and 84% were over 65 years of age. Cytogenetic analysis was available in 10 patients: six had karyotype aberrations. According to cytogenetic-based risk stratification of de novo acute leukemia (AL), all patients had an unfavorable profile. JAK2 (V617F) mutational status was evaluated in five patients. In two of them, the JAK2 mutation was undetectable in blast cells (one with JAK2 -positive ET), whereas in three both granulocytes and blast cells displayed the mutation. Treatment of BP was patient-based according to the performance status and co-morbidities and consisted of palliation in 14 patients, and of induction of remission in five. Median survival was 2.3 months (range 0.2,22.3), irrespective of the treatment received. In conclusion, this study indicates that AL evolved from ET has unfavorable clinical and biological features. JAK2 (V617F)-positive ET may evolve in few instances into JAK2 -negative leukemia. The outcome of patients is poor whatever the treatment used. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source]

Long-term follow-up of 386 consecutive patients with essential thrombocythemia: Safety of cytoreductive therapy,

Platelet turnover, coagulation factors, and soluble markers of platelet and endothelial activation in essential thrombocythemia: Relationship with thrombosis occurrence and JAK2 V617F allele burden,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2009
Eduardo Arellano-Rodrigo
Patients with essential thrombocythemia (ET) have an increased frequency of thrombosis, but the relationship of both thrombosis and JAK2 V617F allele burden with platelet turnover, acquired activated protein C resistance (aAPCR), and levels of coagulation factors and soluble markers of platelet, and endothelial activation is not well known. In 53 ET patients (26 with a history of thrombosis), reticulated platelets (RP) percentage, aAPCR, platelet tissue factor (TF) expression, and plasma levels of TF, coagulation factors, soluble P-selectin (sP-selectin), soluble CD40 ligand (sCD40L), von Willebrand factor antigen (VWF:Ag), soluble thrombomodulin (sTM), D -dimer and prothrombin fragment 1 + 2 were compared with those in matched healthy individuals and correlated with thrombosis occurrence and JAK2 mutational load. ET patients with thrombosis had significantly higher values for RP percentage, aAPCR, and levels of factors V and VIII, VWF:Ag, sP-selectin, and sCD40L than patients without thrombosis and controls. At multivariate study, RP percentage, factor V levels, and aAPCR were independently associated with an increased risk of thrombosis. Patients with JAK2 mutation had significantly lower levels of free protein S (PS) and higher levels of TF, sP-selectin, sCD40L, VWF:Ag, and sTM than those with wild-type allele. A mutant allele dosage effect (, 12%) was observed for TF, sP-selectin, sCD40L, VWF:Ag, and PS levels. These results support a role for platelet turnover, factor V, and aAPCR in the thrombosis of ET as well as the association between JAK2 V617F allele burden and either decreased free PS or increased TF and soluble markers of platelet and endothelial activation. Am. J. Hematol., 2009. © 2008 Wiley-Liss, Inc. [source]

Absence of FTL3 mutations in patients with JAK2V617F mutation negative essential thrombocythemia

AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2007
Bruno C. Medeiros
Abstract A common point mutation in the JAK2 tyrosine kinase leads to constitutive hematopoietic growth factor receptor signaling and was recently described in many patients with myeloproliferative disorders (MPDs). However, this JAK2 mutation is present in only a subset (35,50%) of patients with essential thrombocythemia (ET). Thus, the proliferative signals responsible for MPDs in the absence of JAK2 mutations remain largely unknown. Despite intriguing pre-clinical data, where transgenic mice overexpressing FLT3-ITD developed a MPD resembling ET, none of the patient samples from ET patients who were JAK2V617F -negative demonstrated the presence of activating mutations in the FLT3 receptor. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc. [source]

Acute biphenotypic leukemia arising in a patient with essential thrombocythemia

AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2006
Gee Chuan Wong
Abstract Acute leukemia is an uncommon complication of patients with essential thrombocythemia (ET). We describe a patient with ET, who transformed to acute biphenotypic leukemia 4 and 1/2 years after initial ET diagnosis. She had received hydroxyurea, anagrelide, and interferon, in different combinations and varying doses, before leukemic transformation. Acute biphenotypic leukemia was confirmed on bone marrow studies and immunophenotyping. Complete remission (CR) was achieved with induction chemotherapy for acute leukemia. This was followed with consolidation chemotherapy and the patient has remained in CR 9 months after initial induction chemotherapy. To our knowledge, this is a rare event of acute biphenotypic leukemic transformation of a patient with ET. Am. J. Hematol. 81:624,626, 2006. © 2006 Wiley-Liss, Inc. [source]

Acute promyelocytic leukemia developing in untreated essential thrombocythemia

AMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2002
Naoaki Sato
Abstract We describe a patient with untreated essential thrombocythemia (ET) who developed microgranular variant of acute promyelocytic leukemia, 9 years after the initial diagnosis of ET. He achieved complete remission (CR) but relapsed 11 months later. After achieving the second CR, he received peripheral stem cell transplantation from his HLA complete-matched sibling. Five months after the transplantation, he relapsed again with meningeal infiltration of leukemic cells. In this paper, we review cases of promyelocytic transformation of myeloproliferative diseases (MPD) other than chronic myeloid leukemia (CML). To our knowledge, this is the first case of promyelocytic transformation of Philadelphia chromosome negative untreated ET, in whom both t(15;17) and PML-RAR, fusion were proven. Am. J. Hematol. 71:114,116, 2002. © 2002 Wiley-Liss, Inc. [source]