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Annals of Hematology Aug 2009Polycythemia vera (PV) in children and adolescents is very rare. Data on clinical and laboratory evaluations as well as on treatment modalities are sparse. Here, we... (Review)
Review
Polycythemia vera (PV) in children and adolescents is very rare. Data on clinical and laboratory evaluations as well as on treatment modalities are sparse. Here, we report the long-term clinical course of a PV patient first diagnosed more than 40 years ago at age 12. In addition, after a systematic review of the scientific medical literature, clinical and hematological data of 35 patients (19 female and 17 male) from 25 previous reports are summarized. Three patients developed PV following antecedent hematological malignancies. Budd-Chiari syndrome was diagnosed in seven patients indicating a particular risk of young patients of developing this disorder. One patient presented with ischemic stroke, one patient with gangrene, and three patients with severe hemorrhage. Three patients died from disease-related complications. Hematocrit levels and platelet counts were not correlated with disease severity. Leukocytosis >15 x 10(9)/L was present in 9/35 patients and associated with a thromboembolic or hemorrhagic complication in seven patients. The few available data on molecular genetics and endogenous erythroid colony growth indicate changes comparable to those detectable in adult patients. Treatment varied enormously. It included aspirin, phlebotomy, hydroxycarbamide, busulfan, melphalan, pyrimethamine, and interferon-alpha. Two patients successfully underwent stem cell transplantation. Currently, it is impossible to treat an individual pediatric PV patient with an evidence-based regimen.
Topics: Adolescent; Budd-Chiari Syndrome; Child; Erythropoiesis; Hematologic Neoplasms; Hematologic Tests; Humans; Middle Aged; Polycythemia; Polycythemia Vera
PubMed: 19468728
DOI: 10.1007/s00277-009-0758-y -
Lupus Aug 2021Antiphospholipid syndrome (APS) and myeloproliferative neoplasms (MPN) are associated with an increased risk of thrombosis. The optimal management of patients with...
Antiphospholipid syndrome (APS) and myeloproliferative neoplasms (MPN) are associated with an increased risk of thrombosis. The optimal management of patients with coexistent APS and MPN has not been defined. A single centre and systematic literature review of patients with coexistent APS and MPN was performed. Cases were divided into two groups based on whether they met international consensus criteria for APS. Of the 12 studies identified, eight were excluded (leaving five of a total 54 patients), as although antiphospholipid antibodies (aPL) were documented, the diagnosis of APS was not conclusively demonstrated. Another ten patients with definite APS were identified at our centre. Fifteen patients (ten females, five males) were therefore included in this analysis (eleven definite APS and four highly likely), median age 44 (range: 13-71) years. Nine had polycythaemia vera and six, essential thrombocythaemia. Thirteen of the 15 patients (86.7%) had thrombotic APS (seven with initial venous events and six arterial) and two (13.3%) had obstetric APS. Nine patients were single-positive, and six double-positive for aPL. None were triple aPL-positive. Four patients at our centre had recurrent thrombotic/obstetric events, including while on anticoagulation/antiplatelet treatment.
Topics: Adolescent; Adult; Aged; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Cohort Studies; Female; Humans; Male; Middle Aged; Polycythemia Vera; Pregnancy; Recurrence; Thrombocytosis; Thrombosis; Young Adult
PubMed: 34192956
DOI: 10.1177/09612033211021154 -
Hematology (Amsterdam, Netherlands) Dec 2023Polycythemia vera (PV) is classically thought to be associated with low erythropoietin (EPO) levels. Here, we present a review of the utility of using EPO levels in...
OBJECTIVES
Polycythemia vera (PV) is classically thought to be associated with low erythropoietin (EPO) levels. Here, we present a review of the utility of using EPO levels in diagnosing polycythemia.
METHODS
We conducted a systematic literature review of the Medline data through Pubmed and Google Scholar. We included the articles which described confirmed PV associated with elevated EPO level. Our search strategy included the following terms in Pubmed (((polycythemia vera[MeSH Terms]) OR (jak2 protein tyrosine kinase[MeSH Terms])) OR (Myeloproliferative Disorders[MeSH Terms])) AND (Erythropoietin[MeSH Terms]), and 'polycythemia vera with erythropoietin' in Google Scholar.
RESULTS
Our research yielded four cases of PV with elevated EPO levels. The most common symptom was a headache. Thrombotic phenomena happened in a single case in the form of Budd-Chiari syndrome. The mean Hb level was 20.2 gm/dl, and the EPO level was 213 mlU/mL.
DISCUSSION
Although PV is usually associated with low EPO levels, high levels do not exclude this diagnosis. Workup should include testing for JAK2 mutation and bone marrow biopsy in the presence of suggestive signs and symptoms. Novel biomarkers are also being proposed to aid in the diagnosis.
CONCLUSION
Although elevated EPO levels suggest secondary causes of polycythemia, cases where elevated EPO levels were associated with an underlying PV are reported in the literature, and we have summarized a review of them. Workup for polycythemia should include JAK2 mutation testing if signs and symptoms suggest PV even if EPO is elevated.
Topics: Humans; Polycythemia; Polycythemia Vera; Janus Kinase 2; Bone Marrow; Erythropoietin
PubMed: 37843428
DOI: 10.1080/16078454.2023.2269510 -
Blood Advances May 2024Cytoreductive therapy is not routinely recommended for younger patients with polycythemia vera (PV) due to concern that treatment toxicity may outweigh therapeutic... (Meta-Analysis)
Meta-Analysis
Cytoreductive therapy is not routinely recommended for younger patients with polycythemia vera (PV) due to concern that treatment toxicity may outweigh therapeutic benefits. However, no systematic data support this approach. To support objective risk/benefit assessment of cytoreductive drugs in patients with PV aged <60 years (PV<60), this systematic review and meta-analysis was conducted to evaluate toxicity and disease-related complications in PV<60 treated with interferon alfa (rIFN-α) or hydroxyurea (HU). A search of PubMed, Scopus, Web of Science and Embase identified 693 unique studies with relevant keywords, of which 14 met inclusion criteria and were selected for analysis. The weighted average age of patients treated with rIFN-α was 48 years (n = 744 patients; 12 studies) and for HU was 56 years (n = 1397; 8 studies). The weighted average duration of treatment for either drug was 4.5 years. Using a Bayesian hierarchical model, the pooled annual rate of discontinuation due to toxicity was 5.2% for patients receiving rIFN-α (n = 587; 95% confidence interval [CI], 2.2-8.2) and 3.6% for HU (n = 1097; CI, 1-6.2). The average complete hematologic response for rIFN-α and HU was 62% and 52%, respectively. Patients experienced thrombotic events at a pooled annual rate of 0.79% and 1.26%; secondary myelofibrosis at 1.06% and 1.62%; acute myeloid leukemia at 0.14% and 0.26%; and death at 0.87% and 2.65%, respectively. No treatment-related deaths were reported. With acceptable rates of nonfatal toxicity, cytoreductive treatment, particularly with disease-modifying rIFN-α, may benefit PV<60. Future randomized trials prioritizing inclusion of PV<60 are needed to establish a long-term benefit of early cytoreductive treatment in these patients.
Topics: Humans; Polycythemia Vera; Treatment Outcome; Interferon-alpha; Hydroxyurea; Adult; Middle Aged; Cytoreduction Surgical Procedures; Age Factors
PubMed: 38507746
DOI: 10.1182/bloodadvances.2023012459 -
American Journal of Hematology Jun 2014Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases including polycythemia vera (PV), essential thrombocythemia (ET), and primary(idiopathic)... (Meta-Analysis)
Meta-Analysis Review
Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases including polycythemia vera (PV), essential thrombocythemia (ET), and primary(idiopathic) myelofibrosis (PMF). In this systematic review, we provide a comprehensive report on the incidence and prevalence of MPNs across the globe. Electronic databases (PubMed, EMBASE, MEDLINE, and Web of Science) were searched from their inception to August 2012 for articles reporting MPN incidence or prevalence rates. A random effects meta-analysis was undertaken to produce combined incidence rates for PV, ET, and PMF. Both heterogeneity and small study bias were assessed. Thirty-four studies were included. Reported annual incidence rates ranged from 0.01 to 2.61, 0.21 to 2.27, and 0.22 to 0.99 per 100,000 for PV, ET, and PMF, respectively. The combined annual incidence rates for PV, ET, and PMF were 0.84, 1.03, and 0.47 per 100,000. There was high heterogeneity across disease entities (I(2) 97.1-99.8%) and evidence of publication bias for ET and PMF (Egger test, P = 50.007 and P ≤ 0.001, respectively).The pooled incidence reflects the rarity of MPNs. The calculated pooled incidence rates do not reflect MPN incidence across the globe due to the high unexplained heterogeneity. Improved, widespread registration of MPNs would provide better information for global comparison of the incidence and prevalence of MPNs.
Topics: Humans; Incidence; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential
PubMed: 24971434
DOI: 10.1002/ajh.23690 -
BMC Cancer Jun 2019Research into Philadelphia-negative chronic myeloproliferative neoplasms is heterogeneous. In addition, no systematization of studies of polycythemia vera (PV),... (Meta-Analysis)
Meta-Analysis
Systematization of analytical studies of polycythemia vera, essential thrombocythemia and primary myelofibrosis, and a meta-analysis of the frequency of JAK2, CALR and MPL mutations: 2000-2018.
BACKGROUND
Research into Philadelphia-negative chronic myeloproliferative neoplasms is heterogeneous. In addition, no systematization of studies of polycythemia vera (PV), essential thrombocythemia (ET) or primary myelofibrosis (PMF) have been carried out. The objective of this review is to characterize studies on BCR-ABL1-negative chronic myeloproliferative neoplasms and to compare the frequency of JAK2, MPL and CALR mutations in PV, ET and PMF.
METHOD
A systematic review of the scientific literature was conducted, as was meta-analysis with an ex-ante selection of protocol, according to phases of the PRISMA guide in three interdisciplinary databases. To guarantee reproducibility in the pursuit and retrieval of information, the reproducibility and methodological quality of the studies were evaluated by two researchers.
RESULTS
Fifty-two studies were included, the majority having been carried out in the United States, China, Brazil and Europe. The frequency of the JAK2V617F mutation ranged from 46.7 to 100% in patients with PV, from 31.3 to 72.1% in patients with ET, and from 25.0 to 85.7% in those with PMF. The frequency of the MPL mutation was 0% in PV, from 0.9 to 12.5% in ET, and from 0 to 17.1% in PMF. The CALR mutation occurred at a frequency of 0.0% in PV, whereas in ET, it ranged from 12.6 to 50%, and in PMF, it ranged from 10 to 100%. The risk of this mutation presenting in PV is 3.0 times that found for ET and 4.0 times that found for PMF.
CONCLUSION
Given the specificity and reported high frequencies of the JAK2V617F, MPL and CALR mutations in this group of neoplasms, the diagnosis of these diseases should not be made on clinical and hematological characteristics alone but should include genetic screening of patients.
Topics: Biomarkers, Tumor; Calreticulin; Genetic Heterogeneity; Genetic Testing; Humans; Janus Kinase 2; Mutation Rate; Oncogene Proteins, Fusion; Polycythemia Vera; Primary Myelofibrosis; Receptors, Thrombopoietin; Reproducibility of Results; Thrombocythemia, Essential
PubMed: 31208359
DOI: 10.1186/s12885-019-5764-4 -
The Cochrane Database of Systematic... Apr 2013Polycythaemia vera and essential thrombocythaemia are chronic Philadelphia-negative myeloproliferative neoplasms that increase the risk of arterial and venous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycythaemia vera and essential thrombocythaemia are chronic Philadelphia-negative myeloproliferative neoplasms that increase the risk of arterial and venous thrombosis, as well as bleeding. In addition to the different therapeutic strategies available, an antiplatelet drug is often used to reduce thrombotic risk.
OBJECTIVES
To quantify the benefit and harm of antiplatelet drugs for long-term primary and secondary prophylaxis of arterial and venous thrombotic events in patients with polycythaemia vera or essential thrombocythaemia.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library (Issue 1 2012), MEDLINE (1966 to 2012), and EMBASE (1980 to 2012), as well as online registers of ongoing trials and conference proceedings. The date of the last search was October 2012.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing long-term (>6 months) use of an antiplatelet drug versus placebo or no treatment in participants with polycythaemia vera or essential thrombocythaemia, as diagnosed by established international criteria, with data for at least one of the selected outcomes.
DATA COLLECTION AND ANALYSIS
Using a pre-defined extraction form, two review authors independently screened results, extracted data, and assessed quality. We planned to analyse the following outcomes: mortality from arterial and venous thrombotic events (primary efficacy outcome), mortality from bleeding episodes (primary safety outcome), fatal and non-fatal arterial thrombotic events, fatal and non-fatal venous thrombotic events, micro-circulation events, transient neurological and ocular manifestations, major and minor bleeding episodes, and all-cause mortality and any adverse events. We based quantitative analysis of outcome data on an intention-to-treat principle. We used the pooled odds ratio (OR) with 95% confidence interval (CI) with a fixed-effect model (Mantel-Haenszel) to estimate the overall treatment effect.
MAIN RESULTS
We identified no new studies from the updated searches. We included in this review two RCTs for a total of 630 participants. Both RCTs included participants with an established diagnosis of polycythaemia vera and with no clear indication or contraindication to aspirin therapy. We judged both studies to be of moderate quality. Published data from both studies were insufficient for a time-to-event data analysis and for some of the primary and secondary outcomes that we planned. The use of low-dose aspirin, compared with placebo, was associated with a lower risk of fatal thrombotic events (although this benefit was not statistically significant (OR 0.20, 95% CI 0.03 to 1.14; P = 0.07). No data on mortality from bleeding episodes were available. A non-significant benefit of aspirin was shown for all-cause mortality (OR 0.46, 95% CI 0.21 to 1.01; P = 0.05). No increase in the risk of major bleeding was reported in participants taking aspirin compared with those given placebo (OR 0.99, 95% CI 0.23 to 4.36; P = 0.99), and a non-significant increase with aspirin treatment was shown for minor bleeding (OR 1.85, 95% CI 0.90 to 3.79; P = 0.09). No published studies have reported findings in participants with essential thrombocythaemia or in the study of other antiplatelet drugs.
AUTHORS' CONCLUSIONS
For patients with polycythaemia vera who have no clear indication or contraindication to aspirin therapy, available evidence suggests that the use of low-dose aspirin, when compared with no treatment, is associated with a statistically non-significant reduction in the risk of fatal thrombotic events and all-cause mortality, without an increased risk of major bleeding.
Topics: Anticoagulants; Aspirin; Humans; Platelet Aggregation Inhibitors; Polycythemia Vera; Randomized Controlled Trials as Topic; Thrombocythemia, Essential; Thrombosis
PubMed: 23633335
DOI: 10.1002/14651858.CD006503.pub3 -
The Cochrane Database of Systematic... Apr 2008Polycythaemia vera and essential thrombocythaemia are chronic Philadelphia-negative myeloproliferative disorders, which increase the risk of arterial and venous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycythaemia vera and essential thrombocythaemia are chronic Philadelphia-negative myeloproliferative disorders, which increase the risk of arterial and venous thrombosis as well as bleeding. In addition to the different therapeutic strategies available, aspirin is often used to prevent platelet aggregation.
OBJECTIVES
To quantify the benefit and harm of antiplatelet drugs for long-term primary and secondary prophylaxis of arterial and venous thrombotic events in patients with polycythaemia vera or essential thrombocythaemia.
SEARCH STRATEGY
Our searched included the CENTRAL (The Cochrane Library, issue 1 2007), MEDLINE (1966 to 2007) and EMBASE (1980 to 2007) databases, online registers of ongoing trials and conference proceedings. The date of the last search was March 2007.
SELECTION CRITERIA
All randomised controlled trials (RCTs) comparing long-term (>6 months) use of an antiplatelet drug versus placebo or no treatment in patients with polycythaemia vera or essential thrombocythaemia, diagnosed by established international criteria, with data for at least one of the selected outcomes, were included.
DATA COLLECTION AND ANALYSIS
Using a predefined extraction form, we collected and analysed the following data where appropriate: mortality from arterial and venous thrombotic events, mortality from bleeding episodes, fatal and non-fatal arterial thrombotic events, fatal and non-fatal venous thrombotic events, micro-circulation events, transient neurological and ocular manifestations, major and minor bleeding episodes, all-cause mortality and any adverse events. We based quantitative analysis of outcome data on an intention-to-treat principle. The overall treatment effect was estimated by the pooled odds ratio (OR) with 95% confidence interval (CI) using a fixed-effect model (Mantel-Haenszel).
MAIN RESULTS
Two RCTs that investigated 630 patients with an established diagnosis of polycythaemia vera, with no clear indication or contraindication to aspirin therapy, were included in this review. The use of aspirin, compared with placebo, was associated with a lower risk of fatal thrombotic events (although this benefit was not statistically significant (OR 0.20, 95% CI 0.03 to 1.14)) and did not increase the risk of major bleeding (OR 0.99, 95% CI 0.23 to 4.36). No studies have been published in patients with essential thrombocythaemia or studying other antiplatelet drugs.
AUTHORS' CONCLUSIONS
The available evidence suggests that the use of aspirin is associated with a statistically non-significant reduction in the risk of fatal thrombotic events, without an increased risk of major bleeding, when compared with no treatment in patients polycythaemia vera who have no clear indication or contraindication to aspirin therapy.
Topics: Anticoagulants; Aspirin; Humans; Platelet Aggregation Inhibitors; Polycythemia Vera; Randomized Controlled Trials as Topic; Thrombocythemia, Essential; Thrombosis
PubMed: 18425953
DOI: 10.1002/14651858.CD006503.pub2 -
Biomedicines Jan 2023The impact of primary arterial hypertension (HTN) in myeloproliferative neoplasms (MPNs) remains unclear, with scant literature available, mostly focusing on... (Review)
Review
The impact of primary arterial hypertension (HTN) in myeloproliferative neoplasms (MPNs) remains unclear, with scant literature available, mostly focusing on cardiovascular risk factors as a singular entity or on organ-specific HTN. Furthermore, available studies reporting findings on drug-induced HTN in MPNs report varying and contradictory findings. In consideration of the above, this study set out to systematically review the available literature and shed light on the occurrence of HTN in MPNs, its association with thrombosis, as well as the drugs used in MPN management that could increase blood pressure. The literature search yielded 598 potentially relevant records of which 315 remained after the duplicates ( = 283) were removed. After we screened the titles and the abstracts of these publications, we removed irrelevant papers ( = 228) and evaluated the full texts of 87 papers. Furthermore, 13 records did not meet the inclusion criteria and were excluded from the systematic review. Finally, a total of 74 manuscripts were entered into the qualitative synthesis and included in the present systematic review. Our systematic review highlights that HTN is the most common comorbidity encountered in MPNs, with an impact on both the occurrence of thrombosis and survival. Moreover, drug-induced HTN remains a challenge in the management of MPNs. Further research should investigate the characteristics of patients with MPNs and HTN, as well as clarify the contribution of HTN to the development of thrombotic complications, survival and management in MPNs. In addition, the relationship between clonal hematopoiesis of indeterminate potential, HTN, cardiovascular disease and MPNs requires examination in upcoming assessments.
PubMed: 36830925
DOI: 10.3390/biomedicines11020388 -
BMC Cancer Feb 2019Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematopoietic stem cell clonal diseases. Most patients with MPN... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematopoietic stem cell clonal diseases. Most patients with MPN are asymptomatic at diagnosis although some of them suffer from constitutional symptoms. Thrombosis and bleeding can also be one of the initial manifestations although the reported prevalence varied considerably across the studies. This systematic review and meta-analysis was conducted with the aims to better understand the prevalence and characteristics of thrombosis and bleeding among patients with newly-diagnosed MPN.
METHODS
Using a search strategy that included the terms for myeloproliferative neoplasms, thrombosis, and bleeding, two investigators independently searched for published articles indexed in the MEDLINE and EMBASE databases from inception to August 2018. The pooled prevalence was calculated using the DerSimonian-Laird random-effects model with a double arcsine transformation.
RESULTS
A total of 29 cohort studies (8 prospective and 21 retrospective) with 13,436 patients with MPN were included into this meta-analysis. At diagnosis, the pooled prevalence of overall thrombosis among patients with MPN was 20.0% (95% CI, 16.6-23.8%; I 96%), with the pooled prevalence of arterial thrombosis of 16.2% (95% CI, 13.0-20.0%; I 95%) and the pooled prevalence of venous thrombosis of 6.2% (95% CI, 4.9-7.8%; I 89%). Common thrombotic events included cerebrovascular disease/transient ischemic attack, coronary heart disease, and deep venous thrombosis. The pooled prevalence of hemorrhagic complications among patients who were newly diagnosed with MPN patients was 6.2% (95% CI, 5.0-7.8%; I 85%). Common sites of bleeding included gastrointestinal, mucosal, and cutaneous bleeding.
CONCLUSIONS
Thrombosis and bleeding are common initial manifestations of MPN. Investigations for MPN should be considered for patients who present with unexplained thrombosis or abnormal bleeding.
Topics: Hemorrhage; Humans; Myeloproliferative Disorders; Philadelphia Chromosome; Prevalence; Thrombosis
PubMed: 30819138
DOI: 10.1186/s12885-019-5387-9