Management Of Essential Thrombocythemia Research Articles

Diagnosis and Management of Essential Thrombocythemia: A Comprehensive Review

Diagnosis and Management of Essential Thrombocythemia: A Comprehensive Review

Diagnosis and Management of Essential Thrombocythemia in Sanjiwani Hospital Gianyar, Bali: A Case Report

Abstract.
 Essential thrombocythemia (ET) is a very rare disorder with 1- /100,000 population in the world. The incidence of this abnormality is still obscure in Indonesia. We report a case of ET, women of age 74 years old that came to Sanjiwani Hospital with gum bleeding. This case is confirmed based on WHO criteria of ET which are the increasing of thrombocyte of a number of increase >450 /µL3, proliferation of megakaryocyte cell on bone marrow biopsy, also not meeting any other WHO criteria for also not meeting any other WHO criteria for BCR-ABL1+CML, Polycythemia Vera, Chronic Myeloid Leukemia, Myelodysplastic Syndrome, or other myeloid neoplasm diseases. Management of this case is based on risk adapted treatment algorithm considering three major risk factors for thrombosis (history of thrombosis, JAK2/MPL mutations, and advanced age). This case is categorized as high risk patient for thrombosis, so that treated with antiplatelet aggregation (aspilets) and anagrelide after hydroxyurea clinically unresponsive.

Diagnosis and Management of Essential Thrombocythemia in Sanjiwani Hospital Gianyar, Bali: A Case Report

Abstract.
 Essential thrombocythemia (ET) is a very rare disorder with 1- /100,000 population in the world. The incidence of this abnormality is still obscure in Indonesia. We report a case of ET, women of age 74 years old that came to Sanjiwani Hospital with gum bleeding. This case is confirmed based on WHO criteria of ET which are the increasing of thrombocyte of a number of increase >450 /µL3, proliferation of megakaryocyte cell on bone marrow biopsy, also not meeting any other WHO criteria for also not meeting any other WHO criteria for BCR-ABL1+CML, Polycythemia Vera, Chronic Myeloid Leukemia, Myelodysplastic Syndrome, or other myeloid neoplasm diseases. Management of this case is based on risk adapted treatment algorithm considering three major risk factors for thrombosis (history of thrombosis, JAK2/MPL mutations, and advanced age). This case is categorized as high risk patient for thrombosis, so that treated with antiplatelet aggregation (aspilets) and anagrelide after hydroxyurea clinically unresponsive.

Management of essential thrombocythemia in a resource-limited country: A Nigerian case study

Essential thrombocythemia (ET) is one of the classical clonal myeloproliferative neoplasms (MPNs) that constitute a clinical entity distinct from the other MPNs such as polycythemia vera and primary myelofibrosis despite the similarities in their molecular basis. The genetic basis of ET has been associated with the detection of the mutation of three mutually exclusive driver mutations, namely, Janus kinase 2 (JAK2), calreticulin, and myeloproliferative leukemia genes, making them important biomarkers in the diagnosis of ET. This condition is clinically characterized by thrombohemorrhagic complications and progression to myelofibrosis and acute myeloid leukemia. The reduction of the thrombotic complication and/or the associated hemorrhage constitutes the primary goal of the therapeutic practice for the management of ET. We report here seven cases of ET referred to the University College Hospital within a 3-year period (2014–2016). This case series describes the management practices and the therapeutic outcomes in the patients (using the resolution of the clinical presentations and decrease in platelet count). The report also highlights some of the challenges encountered in the management of ET in a resource-limited country like Nigeria.

How we diagnose and treat essential thrombocythaemia.

The approach to the diagnosis and management of essential thrombocythaemia (ET) is steadily changing, influenced by advances in molecular biology, data from clinical trials and retrospective analyses of patient cohorts. In the past decade options for clinical management largely remain unchanged, but who we treat, and with what target in mind, is evolving. A further area of change is recognition of symptoms that may be associated with ET, as well as other myeloproliferative neoplasms, and that potential options for their management are becoming available. Judicious and careful diagnosis is increasingly a fundamental key to successful management followed by cytoreductive therapy in a subset of patients. In this review we demonstrate our management strategies for ET using a case-based format.

Advances and challenges in the management of essential thrombocythemia.

The new World Health Organization (WHO) diagnostic criteria for essential thrombocythemia (ET) issued in 2008 made an important distinction between true ET and early myelofibrosis (MF), which has helped to identify a more homogenous population for the diagnosis with longer survival and much less transformation to overt MF. The recent finding of a new mutation (CALR), which is mutually exclusive with JAK2 and MPL mutations, adds to the characterization of ET patients, since there are important phenotypic differences between the mutation types. CALR patients are younger, have lower white blood cell counts (WBC) and a lower thrombosis incidence. A growing field of interest is the state of hypercoagulation due to dysfunction of hemostatic systems, cell-cell interaction and hereditary prothrombotic traits. Activation of platelets, WBC and endothelial cells has been found, making the whole intravascular milieu prothrombotic. Several risk score models, based on retrospective studies, have been developed lately, distinguishing patient groups with graded risk for complications and death. Even if these may be helpful in evaluating patients, they have not been validated in prospective studies and there are not enough data to support their use as a basis for treatment algorithms. The traditional risk factors age, previous thrombosis and platelets >1500 × 10(9)/l are still recommended for the distinction between high risk and low risk ET and the decision to give cytoreductive therapy. However, cardiovascular (CV) risk factors add to thrombosis risk and should be considered both for specific treatment in any risk group and for upgrading low risk patients with high CV risk to an intermediary group where active therapy with aspirin and cytoreduction may be considered. First-line cytoreductive therapy differs with age; in younger patients interferon (IFN) or anagrelide are preferable, in older patients hydroxycarbamide (HC). Second-line therapy for younger patients is HC, for older patients IFN or anagrelide (ANA). JAK2 inhibitors may be suitable in rare cases with symptoms not responding to other therapy.

Management of MPN beyond JAK2.

Thrombocytosis has a large number of potential underlying causes, but the dominant group of hematological conditions for consideration in this setting are the myeloproliferative neoplasms (MPNs). In this chapter, we consider several key linked questions relating to the management of thrombocytosis in MPNs and discuss several issues. First, we discuss the differential diagnosis of thrombocytosis, which myeloid disorders to consider, and practical approaches to the discrimination of each individual MPN from other causes. Second, there have been several major advances in our understanding of the molecular biology of these conditions and we discuss how these findings are likely to be practically applied in the future. Third, we consider whether there is evidence that thrombocytosis contributes to the complications known to be associated with MPN: thrombosis, hemorrhage and transformation to leukemia and myelofibrosis. Last, we review current ideas for risk stratification and management of essential thrombocythemia and polycythemia vera as the 2 entities within the MPN family that are most frequently associated with thrombocytosis.

Management of refractory essential thrombocythemia with anagrelide in a patient undergoing hemodialysis

Background: Management of essential thrombocythemia (ET) in high-risk patients is difficult because high platelet numbers can lead to vascular occlusive events and bleeding. Therapeutic interventions in ET are limited to hydroxyurea and anagrelide; however, in Europe, anagrelide is contraindicated in patients with chronic renal disease. Objective: The aim of this case report was to describe the use of anagrelide in a patient with ET and renal impairment. Case summary: A 73-year-old white female patient with severe renal impairment who was diagnosed with ET was receiving treatment with hydroxyurea 1 g/d since 2001. At this time she was also receiving aspirin 80 mg/d; calcium carbonate 1 g/d; pravastatin 40 mg/d; folic acid 5 mg/d; furosemide 40 mg/d; cetirizine 10 mg/d; erythropoietin 10,000 U once monthly; a vitamin B complex, 1 tablet a day; and iron tablets 105 mg/d. In February 2007, because her white blood cell count fell to 2.1 × 10 9/L, myelodepression was suspected and hydroxyurea was stopped. This led to enhanced platelet levels and the introduction of anagrelide at an initial dose of 0.5 mg/d that was steadily increased to 2.5 mg/d. All other treatments were continued with some dosage adjustments. Sodium bicarbonate 1 g/d and vitamin D were added to her regimen. After 18 months of anagrelide treatment, a sudden but moderate fall of platelets to 142 × 10 3/μL with severe anemia (hemoglobin, 6.5 g/dL) was observed. The patient had anemia since 2004, but the condition worsened due to bleeding related to an ulcer at the cecal valve. The patient refused blood and platelet transfusions and surgical intervention for religious reasons. Because of hemodynamic instability, she was admitted to the intensive care unit in December 2008 and died 24 hours after admission. Conclusion: We report a case of ET and chronic renal failure treated with anagrelide and low-dose aspirin in a patient who did not receive transfusion and surgical intervention due to religious reasons, and had a fatal outcome.

Role of platelet counts in the management of essential thrombocythemia: experience with anagrelide

An elevated platelet count is the hallmark of essential thrombocythemia (ET). Therapeutic control of platelet counts in ET has proven effective for minimizing the risk of bleeding complications. By contrast, the relationship between platelet count and thrombotic complications is less well defined. The beneficial effects of lowering the platelet count are greatest when levels are reduced close to or within the normal range, thus supporting the trend within the medical community to reduce platelet treatment targets to below 400–450 × 109/l. Platelet counts have further utility in ET as a marker to indicate intolerance/resistance to hydroxyurea according to recently published guidelines. In the current era, where novel risk factors for ET complications are being discussed, this article takes a back-to-basics approach, considering what platelet counts reveal in practice as a risk factor for complications and a marker of treatment efficacy, with particular focus on data for the platelet-selective agent anagrelide.

Anagrelide for the treatment of essential thrombocythemia: a survey among European hematologists/oncologists

Two hundred and fifty hematologists and oncologists (50 each from France, Germany, Italy, Spain and the United Kingdom) participated in this survey to assess the current management of essential thrombocythemia (ET), with particular reference to the use of anagrelide. Data were collected between October 9 and November 2, 2006 on 2000 patients with ET. Thirty-eight per cent of patients had been tested for the Janus kinase 2 (JAK2) mutation (JAK2V617F), of whom 54% tested positive. JAK2V617F mutation status was not influenced by age, gender or cardiovascular risk. Overall, 297 patients (14·9%) were receiving anagrelide hydrochloride; 16·8% of these patients were aged 18–40 years, 43·1% aged 41–60 years and 40·1% aged over 60 years. Hydroxycarbamide, alone or in combination with aspirin, was the most commonly prescribed treatment in 136/191 (71·2%) patients prior to switching to anagrelide. In conclusion, this survey provides a useful insight into the epidemiology of ET and current prescribing patterns for anagrelide in Europe.

Pathogenesis and management of essential thrombocythemia

The last four years have seen an explosion in our understanding of the myeloproliferative neoplasms. Important and often unexpected insights into the molecular mechanisms responsible for these disorders have been accompanied by the development of new diagnostic tests and by an improved understanding of the relationship between the different disease entities. This review will focus on recent developments in the pathogenesis and management of essential thrombocythemia with a particular emphasis on its phenotypic overlap with polycythemia vera and primary myelofibrosis.

Options in the management of essential thrombocythaemia

Options in the management of essential thrombocythaemia

Evolving management of essential thrombocythaemia

Evolving management of essential thrombocythaemia

Update on Diagnosis and Management of Essential Thrombocythemia

Patients with essential thrombocythemia carry a high risk for thromboembolic and bleeding events but they have an almost normal life expectancy. A careful evaluation of the medical history and an exact diagnosis is mandatory to estimate each patient's risk for morbidity and to choose the most appropriate treatment measure. In patients with the need of cytoreductive therapy, the benefits of therapy have to outweigh the potential risks of drug toxicities. Hydroxyurea is the most useful cytoreductive drug for elderly patients; in younger persons, interferon alpha or anagrelide may be the drugs of choice. The combination of anagrelide with acetylsalicylic acid may be contraindicated in patients with a history of bleeding.

Management of Essential Thrombocythemia: Implications of the Medical Research Council Primary Thrombocythemia 1 Trial

There has been a dearth of prospective randomized studies in essential (or primary) thrombocythemia (ET). To date, only two reports have been published. Cortelazzo et al reported the first study in 1995. The second is the Medical Research Council Primary Thrombocythemia 1 trial (MRC PT-1), the results and implications of which are the subject of this article.

Treatment of the myeloproliferative disorders with 32P.

The use of radioactive phosphorus (32P) to treat the myeloproliferative disorders (chronic leukemia, polycythemia vera and essential thrombocythemia) began in 1939 when John H. Lawrence treated the first patient on the basis of work done in the laboratory animals that found localization of the radioisotope in the spleen, liver, bone and in leukemic cells sufficient to indicate a therapeutic potential. 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?

Management of essential thrombocythaemia during pregnancy.

Essential thrombocythaemia is a rare myeloproliferative disorder that often presents with haemorrhagic or thrombotic complications. It may be detected incidentally in an asymptomatic younger adult and there are only a few case reports of essential thrombocythaemia in pregnant women. The risks posed by essential thrombocythaemia during pregnancy and its optimal management are uncertain. To determine if there is increased incidence of obstetric complications seen in women who have essential thrombocythaemia, we collected a large case series from a number of tertiary obstetric units in Australia and New Zealand. There were 30 pregnancies in 12 women who had essential thrombocythaemia. There were 17 live births (57%), 7 stillbirths (23%), 5 miscarriages (17%) and 1 ectopic (3%). Five pregnancies were complicated by placental abruption. When the outcomes of those women who received treatment with aspirin or interferon were compared to those that did not receive any treatment, there was a trend towards a higher livebirth rate (79% v. 38%, p = 0.06). Seven women were treated with aspirin and 5 had successful outcomes with no fetal complications. Four women were treated with alpha-interferon which reduced their platelet counts and all had successful outcomes with no fetal complication. These findings suggest that there is a high incidence of miscarriage, stillbirth and abruption in women with essential thrombocythaemia. Their pregnancies should be carefully monitored. Treatment with low dose aspirin and/or the use of alpha-interferon may be associated with an improved pregnancy outcome.

Role of anagrelide in the treatment of thrombocytosis.

To review the role of anagrelide in the management of essential thrombocythemia. A MEDLINE search (January 1966-August 1998) was performed using the key terms anagrelide, thrombocytosis, and essential thrombocythemia. In addition, the package insert, product monograph, and patient information pamphlets were reviewed. Recently, there has been a trend toward the use of anagrelide in the management of thrombocythemia. Anagrelide lacks leukemogenic and mutagenic potential and possesses a more favorable adverse effect profile compared with other therapeutic agents. At recommended doses, anagrelide induces thrombocytopenia in thrombocythemic patients with a concomitant reduction in the incidence of disease-related symptoms. Although the treatment of choice for thrombocythemia is still an area of debate, anagrelide has distinct advantages over alternative therapies. Anagrelide represents an important therapeutic option in the treatment of patients with thrombocythemia.

Management of essential thrombocythemia

3. Risk stratification of patients with ET . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258 3.1. Bleeding and thrombosis in ET . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258 3.2. Risk factors for major bleeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259 3.3. Risk factors for thrombosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259

Issues in the Diagnosis and Management of Essential Thrombocythemia

To summarize the current trends in the diagnosis and management of essential thrombocythemia (ET) and to discuss the treatment of young and pregnant patients with ET. We review our experiences in the diagnosis and management of ET. A definitive diagnosis of ET at initial examination is seldom possible because of the low incidences of associated clonal cytogenetic abnormalities and palpable splenomegaly. The criteria of the Polycythemia Vera Study Group for the diagnosis of ET are provided, as are the clinical and laboratory features that help to distinguish ET from reactive thrombocytosis. Patients with ET have an almost normal life expectancy if thrombohemorrhagic complications are controlled. Although a previous history of thrombosis is an established risk factor for further episodes, the adverse effects of extreme thrombocytosis and age are less well defined. Determining which patients require therapy is controversial. The management of young or pregnant patients necessitates special considerations. Until additional data become available, no strong recommendations can be given in support of or against specific therapy for asymptomatic young patients. We favor treatment in asymptomatic patients with cardiovascular risk factors but not in asymptomatic women who are pregnant or are of childbearing age.