Original Article
Efficacy and Safety of Low-Dose Aspirin in Polycythemia Vera
N Engl J Med 2004; 350:114-124January 8, 2004
- Abstract
Background
The use of aspirin for the prevention of thrombotic complications in polycythemia vera is controversial.
Methods
We enrolled 518 patients with polycythemia vera, no clear indication for aspirin treatment, and no contraindication to such treatment in a double-blind, placebo-controlled, randomized trial to assess the safety and efficacy of prophylaxis with low-dose aspirin (100 mg daily). The two primary end points were the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes. The mean duration of follow-up was about three years.
Results
Treatment with aspirin, as compared with placebo, reduced the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes (relative risk, 0.41; 95 percent confidence interval, 0.15 to 1.15; P=0.09) and the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (relative risk, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.03). Overall mortality and cardiovascular mortality were not reduced significantly. The incidence of major bleeding episodes was not significantly increased in the aspirin group (relative risk, 1.62; 95 percent confidence interval, 0.27 to 9.71).
Conclusions
Low-dose aspirin can safely prevent thrombotic complications in patients with polycythemia vera who have no contraindications to such treatment.
Media in This Article
Figure 1
Probability of Survival Free of Myocardial Infarction, Stroke, and Death from Cardiovascular Causes (Panel A) and Probability of Survival Free of Myocardial Infarction, Stroke, Death from Cardiovascular Causes, Pulmonary Embolism, and Deep Venous Thrombosis (Panel B).Figure 2
Probability of Survival Free of a Thrombotic Event.Article Activity
- Article
Polycythemia vera is a chronic disorder in which the clonal proliferation of hematopoietic precursors progressively increases the red-cell mass.1 This expansion causes hyperviscosity of the blood, a major determinant of circulatory disturbances in patients with polycythemia vera.2 Since thrombotic complications are a major cause of illness and death in untreated patients,3,4 chemotherapy and phlebotomy are often used in patients who are at high risk for thrombotic events.5
The efficacy and safety of antithrombotic drugs in patients with polycythemia vera are uncertain. Aspirin has long been avoided, because a trial conducted by the Polycythemia Vera Study Group reported a high incidence of gastrointestinal bleeding in patients who received a high dose of aspirin (900 mg daily).6 Recently, however, the use of aspirin in patients with polycythemia vera has been reconsidered, mainly because of its antithrombotic effects and evidence that the optimal benefit of aspirin can be achieved at doses considerably lower than the 900-mg daily dose that the study group tested.7
The increase in thromboxane synthesis that occurs in polycythemia vera8 suggests that thromboxane-dependent platelet activation is a major contributor to the increased risk of thrombosis among patients with the disease. In a pilot study, we found that low-dose aspirin effectively suppresses the production of thromboxane by platelets in patients with high platelet counts and is well tolerated.9 We now report the results of a multicenter trial of low-dose aspirin in patients with polycythemia, the European Collaboration on Low-Dose Aspirin in Polycythemia Vera (ECLAP) study.
Methods
International Network
A network of 94 hematologic centers in 12 countries was developed.10 The centers in each participating country were led by a national coordinator. The international coordinating center in Italy (Consorzio Mario Negri Sud) received all data forms and developed a centralized data base.
Of the 1638 patients included in the ECLAP project, 1120 were entered into a prospective, observational cohort study, and the other 518 (32 percent) were enrolled in our double-blind, placebo-controlled, randomized trial to assess the efficacy and safety of low-dose aspirin (100 mg daily in an enteric-coated formulation [Bayer]). The main reasons for excluding patients in the ECLAP project from this aspirin trial were an indication for antithrombotic therapy (742 patients [66 percent]), a contraindication to aspirin therapy (271 patients [24 percent]), and the patient's unwillingness to participate (197 patients [18 percent]).
Study Patients
Polycythemia vera was diagnosed on the basis of standard clinical and laboratory findings and criteria that have been described elsewhere.10 Patients were eligible if they had no clear indication for aspirin treatment and no clear contraindication to it, were able to provide written informed consent, and had no clinically significant coexisting conditions. There were no age limits.
A double-blind, placebo-controlled design was used. A total of 253 patients were randomly assigned to receive aspirin (100 mg daily), and 265 were randomly assigned to receive placebo. Randomization was centralized and was performed over the telephone. Patients were assigned to treatments with the use of a program based on the biased-coin algorithm, which allowed for stratification according to center. All patients who were recruited received other recommended treatments: phlebotomy, cytoreductive drugs, and standard cardiovascular drugs were given as required.
Data collection was recorded at follow-up visits at 12, 24, 36, 48, and 60 months. Compliance was monitored with the use of counts of aspirin or placebo pills and through attendance at follow-up visits.
Study End Points
The study had two primary combined efficacy end points: the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes. The secondary end points were fatal or nonfatal cerebrovascular events, fatal or nonfatal cardiac events, minor thrombotic complications (including atypical cerebral or visual symptoms of ischemia, erythromelalgia, and thrombophlebitis), and major and minor thrombotic complications as defined above. Additional analyses were performed for each component of the primary end points and for the main causes of death.
The safety of low-dose aspirin was assessed by analyzing rates of fatal and nonfatal major hemorrhage (any hemorrhage requiring transfusion, hospitalization, or both), minor hemorrhage, and any adverse event leading to the discontinuation of treatment.
Definition of Events
Events were defined and classified according to the International Classification of Diseases, Ninth Revision. Death from cardiovascular causes included death after a documented diagnosis of myocardial infarction or stroke in the absence of any other evident cause, sudden death, death from heart failure, and any other death classified as having cardiovascular causes. Nonfatal acute myocardial infarction was defined by at least two of the following findings: chest pain of typical intensity and duration; ST-segment elevation or depression of 1 mm or more in any limb lead on electrocardiography, of 2 mm or more in any precordial lead, or both; and at least a doubling of the levels of cardiac enzymes.
A diagnosis of nonfatal stroke required unequivocal signs or symptoms of a neurologic deficit with sudden onset and a duration of more than 24 hours. The diagnosis had to be confirmed with the use of computed tomography (CT), magnetic resonance imaging, or other objective means or on autopsy. These criteria were also used for the diagnosis of fatal stroke. Alternatively, we used the diagnosis reported in the hospital records or on the death certificate. A transient ischemic attack was defined as the abrupt onset of unilateral motor or sensory disturbance, speech defect, homonymous hemianopia, constructional apraxia, or transient monocular blindness (defined as the abrupt onset of a unilateral decrease in visual acuity involving a portion or the entirety of the visual field) that resolved completely in less than 24 hours.
Pulmonary embolism was defined by a positive pulmonary angiogram, a ventilation–perfusion scan or CT scan indicating a high probability of pulmonary embolism, or evidence of pulmonary embolism on autopsy. Deep venous thrombosis was defined by a typical clinical picture with positive results on investigation involving such techniques as phlebography, ultrasonography, impedance plethysmography, or CT.
The validation of the clinical events included in the primary end points was ensured by an ad hoc committee of expert clinicians who were unaware of the treatment-group assignments. Each event was validated independently by two evaluators, and disagreement between the evaluators was assessed by the chairman of the study.
The study protocol conformed to good clinical practice for trials and to the 2000 revision of the Declaration of Helsinki regarding medical research in humans. We obtained the approval of each local ethics committee before the start of the trial. All patients provided written informed consent. The study was conceived, conducted, and analyzed by the independent investigators under the aegis of the steering committee.
Planned Sample Size and Early Termination
On the basis of the information that was available at the time the study was planned, the rate of events included in the first (more conservative) of the two primary end points over a five-year follow-up period was estimated to be about 14 percent. To test for a beneficial effect of aspirin (a 30 percent rate reduction) at a convincing level of statistical significance (two-tailed α=0.05, and 1–β=0.80), we planned to recruit 940 patients per group.
After a planned interim safety analysis (in December 2000), the steering committee was informed that fewer centers than expected were recruiting effectively; that after the planned two years of recruitment, the rate of randomization was reduced to nearly zero; that an impractically long follow-up period would be required in order to accumulate the number of events needed to reach the predefined rate of end points; and that no additional support for the trial could be obtained. For these reasons, the study was stopped, and follow-up of the patients who had undergone randomization was completed during the next 12 months. These decisions were made with the advice and consent of the data and safety monitoring board and were communicated to the investigators, who were monitored to ensure that they conducted a final follow-up visit. We obtained updated follow-up information after September 1, 2001, for 92 percent of the patients who had undergone randomization, for a total duration of follow-up of 1478 person-years.
Statistical Analysis
Analyses were performed according to the intention-to-treat principle. We analyzed data with the use of Kaplan–Meier survival curves and the log-rank test. The efficacy of treatment was assessed by fitting base-line values for the risk-stratification variables into Cox regression models that were adjusted for the confounding effects of relevant prognostic indicators. Events included in the composite end points were analyzed hierarchically; that is, if the patient was alive at the end of the study, we determined whether a nonfatal event had occurred. We used the Kruskal–Wallis test for continuous variables. All reported P values are two-sided. All analyses were performed with the use of the SAS statistical software package (SAS Institute).
Results
Base-Line Characteristics of the Patients
Table 1Table 1
Base-Line Characteristics of the Patients with Polycythemia Vera. summarizes the base-line demographic and clinical characteristics of the patients. A total of 26 percent of the patients were 70 years of age or older. There were significantly more current smokers in the placebo group than in the aspirin group. The hematocrit was maintained at a median value of 46 percent during follow-up, with levels higher than 48 percent in 25 percent of patients. The platelet count was maintained at a median level of 321,000 per cubic millimeter during follow-up; 25 percent of patients had levels higher than 460,000 per cubic millimeter.Efficacy
Table 2Table 2
Rates and Relative Risks of Major Study End Points in the Two Groups. summarizes the thrombotic events in the two groups of patients. The 59 percent reduction in the risk of the combined primary end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes in the aspirin group, as compared with the placebo group, was not statistically significant, whereas the 60 percent decrease in the risk of the combined primary end point of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes was significant (95 percent confidence interval, 9 to 82 percent; P=0.03) (Figure 1AFigure 1Probability of Survival Free of Myocardial Infarction, Stroke, and Death from Cardiovascular Causes (Panel A) and Probability of Survival Free of Myocardial Infarction, Stroke, Death from Cardiovascular Causes, Pulmonary Embolism, and Deep Venous Thrombosis (Panel B). and Figure 1B).Secondary analyses showed a significant reduction in the rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, deep venous thrombosis, or death from any cause (relative risk reduction, 53 percent; 95 percent confidence interval, 9 to 75; P=0.02) and reductions in the rates of minor thrombosis and any thrombosis, with relative risk reductions of 53 percent (P=0.049) and 58 percent (P=0.003), respectively (Table 2 and Figure 2Figure 2
Probability of Survival Free of a Thrombotic Event.). The rates of major cerebrovascular events, nonhemorrhagic stroke, transient ischemic attack, peripheral thrombosis, deep venous thrombosis, and pulmonary embolism in the aspirin group were not significantly different from the rates of these complications in the placebo group.The results of additional subgroup analyses confirmed the consistency of the effects of aspirin on the risk of death from cardiovascular causes and the risk of major arterial or venous thrombotic events among patients with various characteristics at base line (Figure 3Figure 3
Effect of Aspirin on the Risk of a Major Arterial or Venous Event or Death from Cardiovascular Causes in Various Subgroups.). All analyses were repeated with the use of multivariate models with adjustment for smoking status and the use or nonuse of digoxin or for major potential confounding factors (i.e., age, sex, duration of disease, smoking status, previous thrombotic and hemorrhagic events, digoxin use, hypertension, diabetes, congestive heart failure, angina pectoris, phlebotomy, and cytoreductive treatment). In the fully adjusted model, the rate of the combined primary end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes was reduced by 77 percent (P=0.02) and the rate of the primary combined end point of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, deep venous thrombosis, or death from cardiovascular causes was reduced by 71 percent (P=0.008).Safety
Table 3Table 3
Rates and Relative Risks of Bleeding Episodes in the Two Groups. shows the rates and relative risks of episodes of bleeding in the two groups. In the aspirin group, there were nonsignificant increases in the risks of any bleeding episode, a major bleeding episode, and a minor bleeding episode. Almost all the excess in the incidence of bleeding in the aspirin group was due to the 83 percent increase in the rate of minor bleeding episodes.At the completion of the study, 24.5 percent of the patients in the aspirin group and 30.6 percent of those in the placebo group had stopped taking the study drug. Side effects were reported as the reason for the discontinuation of therapy in 7.1 percent of the patients in the aspirin group and 6.4 percent of those in the placebo group. Overall, gastrointestinal intolerance and bleeding were the most frequently reported side effects (reported in 2.8 percent and 4.4 percent, respectively, of the patients in the aspirin group and 4.5 percent and 1.5 percent, respectively, of the patients in the placebo group). Adverse events or side effects resulted in the discontinuation of use of the study drug in 28 patients in the aspirin group (11.1 percent) and in 27 patients in the placebo group (10.2 percent). There was no significant difference in the rate of any other adverse event.
Discussion
The rationale for this trial was based on three considerations: the increased synthesis of platelet thromboxane in polycythemia,8 the fact that 100 mg of aspirin daily effectively suppresses this abnormality,8 and the finding in a preliminary trial involving patients with polycythemia that the prolonged administration of low-dose aspirin was well tolerated.9
The design of our study allowed us to exclude patients who were considered to have a clear indication for aspirin therapy. For this reason, we disqualified 45 percent of the potential enrollees, most of whom had a history of thrombosis. The patients who were enrolled had no contraindication to aspirin therapy, and most of them had no history of a thrombotic event. They account for about one third of the patients with polycythemia vera enrolled in our collaborative study of the disease. The present study can therefore be considered a primary prevention trial of aspirin in patients with polycythemia vera.
We had calculated that for such a study, a large sample or a very long duration of follow-up would be required to detect a 30 percent reduction in the risk of the defined end points with the use of aspirin.10 The ECLAP hematologic network recruited, in about two years, approximately one fourth of the number of patients that was originally projected. Despite this major limitation, the trial demonstrated a beneficial effect of aspirin; the risk reduction in the aspirin group (as great as 50 to 60 percent) was larger than that reported in any previous primary or secondary prevention trial involving subjects who did not have polycythemia vera.11-17 Our results should be interpreted cautiously, however, because of the wide confidence intervals surrounding the point estimates. The relatively small number of events accounted for the fact that differences between the aspirin group and the placebo group reached statistical significance only for the second primary end point.
The overall strength of the results, however, is supported by their internal consistency. The effect of aspirin was detectable after approximately 180 days and appeared to be consistent for various arterial and venous vascular complications and in various subgroups.
In primary prevention trials that did not involve patients with polycythemia vera, aspirin had no statistically significant effects on the incidence of stroke or the rate of death, even though its use reduced by approximately 30 percent the risk of nonfatal myocardial infarction, the most frequent event in those studies.12-17 In our trial, there was a higher incidence of stroke than of myocardial infarction, and aspirin was effective in reducing the risk of all thrombotic events, including those affecting the cerebrovascular circulation.
Patients with polycythemia vera have an increase in the synthesis of thromboxane by a factor of approximately 10, as compared with age- and sex-matched controls.8 This abnormality can be largely suppressed with the use of low-dose aspirin.8 Aside from patients with polycythemia vera, only patients with acute coronary syndromes have increases in thromboxane synthesis of this magnitude18,19; in such patients, low-dose aspirin therapy reduces the risk of major vascular events by 50 to 60 percent.20 Thus, the apparently unusual size of the effect of aspirin in patients with polycythemia vera, as compared with its antithrombotic effect in other prevention trials,12-17 might reflect the increased synthesis of thromboxane, which we believe is the primary target of aspirin in platelets.7
An important finding in our trial was the moderate increase in the risk of bleeding episodes associated with the long-term use of aspirin in polycythemia vera. The relative risk of major bleeding complications of 1.62 is consistent with the estimates from five primary prevention trials involving subjects who did not have polycythemia.12-17 The occurrence of a limited number of events precludes the precise estimation of the risk of bleeding, but the safety of prophylactic antiplatelet therapy in patients with polycythemia vera is corroborated by the results of the epidemiologic cohort study of the ECLAP project (unpublished data). We believe that the risk of aspirin-induced bleeding in patients with this disease has been overemphasized.21 We recommend the use of aspirin to prevent thrombotic complications in patients with polycythemia vera who have no contraindication to this treatment.
Supported by a grant (ERBBMH4CT961433) from the Biomed 2 Program of the European Union and by unrestricted grants from Bayer and Bayer Italia.
We are indebted to Daniela Basilico for her assistance in the preparation of the manuscript.
Source Information
From the Catholic University School of Medicine, Rome (R.L.); the Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy (R.M., G.T.); Sahlgrenska Hospital, Göteborg, Sweden (J.K.); the Department of Hematology and Blood Coagulation, University of Vienna, Vienna, Austria (H.G.); the University of Rome La Sapienza, Rome (C.P.); and the Ospedali Riuniti, Bergamo, Italy (T.B.).
Address reprint requests to Dr. Landolfi at the Istituto di Medicina Interna e Geriatria, Università Cattolica, Largo Gemelli 8, 00168 Rome, Italy, or at rlandolfi@rm.unicatt.it.
The European Collaboration on Low-Dose Aspirin in Polycythemia Vera (ECLAP) Investigators are listed in the Appendix.
Appendix
Investigators in the ECLAP trial included the following persons: Writing committee — R. Landolfi, R. Marchioli, J. Kutti, H. Gisslinger, G. Tognoni, C. Patrono, T. Barbui; Principal ECLAP investigators (recruiting 20 or more patients): Vienna, Austria — Department of Hematology and Blood Coagulation (36): H. Gisslinger; Bergamo, Italy — Ospedali Riuniti (41): T. Barbui, G. Finazzi, S. Pusterla, A. Falanga, M. Galli; Göteborg, Sweden — Sahlgrenska Hospital (22): J. Kutti, H. Wadenvik. Other ECLAP investigators included the following (numbers in parentheses are the numbers of patients recruited): Austria: Innsbruck — Universitäts Klink f. Innere Medizin (5): G. Gastl, C. Ludescher; Linz — Krankenhause der Elisabethinen (1): D. Lutz, M. Girschikofsky; Krankenhaus der Barmherzigen Schwetern (4): G. Michlmayr, E. Rechberger. Wr. Neustadt — Krankenhaus Wr. Neustadt (1): H. Niessner, E. Ivansich; France: Paris — Hôpital Saint Louis (7): J.D. Rain, C. Chommienne-Thomas; Germany: Mannheim — Klinikum Der Stadt Mannheim (4): R. Hehlmann, G. Engelich; Ulm — Universitäts-Kinderklinik Ulm (2): E. Kohne, A. Kramer; Greece: Thessaloniki — Theagenion Cancer Center (9): J.I. Christakis, M. Papaioannou, G. Gerotziafas; Ireland: Dublin — Beaumont Hospital (4): R. O'Donnell; Israel: Afula — Haemek Medical Center (3): M. Bennett; Ashkelon — Barzilai Medical Center (7): G. Lugassy; Kfar Saba — Meir Hospital (6): M. Ellis; Tel Aviv — Tel Aviv Souraski Medical Center (17): A. Eldor (deceased), E. Naparstek, R. Marilus; Italy: Ancona — Ospedale Nuovo di Torrette (18): P. Leoni, S. Rupoli, A.R. Scortechini, V. Agostini; Avellino — Ospedale S Giuseppe Moscati (12): E. Volpe, F. Calmieri, A. Volpe, G. Storti, A. Ciampa; Bari — Università degli Studi, Policlinico (6): F. Dammacco, V.M. Lauta, G. Ranieri, R. Rizzi; Bologna — Policlinico S. Orsola (7): S. Tura, C. Finelli, G. Marino; Brescia — Spedali Civili di Brescia (8): G. Rossi, C. Almici, A. Capucci, F. Zanetti; Catania — Ospedale Ferrarotto (1): R. Giustolisi, R.R. Cacciola, E. Cacciola; Catanzaro — Azienda Ospedaliera Pugliese–Ciaccio (9): A. Peta, D. Magro; Como — Ospedale Valduce (5): G. Frigerio, F. Alberio, A. Beretta; Cuneo — Azienda Ospedaliera S. Croce e Carle (2): M. Bonferroni, A. Raviolo; Firenze — Policlinico di Careggi (9): P.L. Rossi Ferrini, A. Grossi, A. Fabbri; Latina — Ospedale Civile (6): S. Nardelli, A. Centra; Messina — Policlinico Universitario di Messina (7): C. Musolino, G. Bellomo, O. Trincali, G. Spatari; Milan — Azienda Ospedaliera Ospedale S. Paolo (6): P. Foa, G. Gerli, M.C. Carraro; Policlinico Ospedale Maggiore (6): A. Zanella, A. Lurlo, F. Barraco; Modena — Clinica Medica II, Policlinico (5): G. Torelli, M. Marietta; Monza — Ospedale S. Gerardo (6): E. Pogliani, I.R. Miccolis, A. La Rocca; Montebelluna — Ospedale di Montebelluna (4): A. Puglisi, G. Sardeo; Naples — Facoltà di Medicina Università Federico II (1): B. Rotoli, V. Martinelli, R. Ciancia; Azienda Ospedaliera A. Cardarelli (4): R. Cimino, A. Fasanaro; Padova — Università II Padova, Dip. Scienze Mediche e Chirurgiche (10): M.L. Randi; Parma — Cattedra di Ematologia, Università di Parma (4): V. Rizzoli, C. Caramatti, L. Gaeta; Pavia — Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Università di Pavia (10): M. Lazzarino, F. Passamonti, M. Lazzola, L. Malabarba; Pescara — Ospedale Civile (13): D. Natale, S. Pulini, G. Daví; Reggio Emilia — Ospedale di Reggio Emilia (15): L. Gugliotta, F. Ilariucci; Rome — Università Cattolica del Sacro Cuore (4): R. Landolfi, E. De Candia; Ospedale S. Eugenio, Università Tor Vergata (7): S. Amadori, F. Buccisano; Università la Sapienza (8): F. Mandelli, E. Montefusco, M.C. Petti, A. Spadea; S. Giovanni Rotondo — Ospedale Casa Sollievo Della Sofferenza (6): M. Carotenuto (deceased), A. Morelli, M. Nobile; Sassari — Università di Sassari (4): M. Longinotti, S.M. Pardini; Siena — Ospedale di Siena (5): F. Lauria, A. Buccalossi, S. Gentili; Taranto — Ospedale Nord (4): P. Mazza, M. Cervellera, A. Maggi; Teramo — Ospedale Civile G. Mazzini (1): A. Di Francesco, E. Pasqualoni; Venice — USL 12 Veneziana, Ospedale S. Giovanni e Paolo (16): T. Chisesi, A. Polacco; Venezia-Mestre — Ospedale Umberto I (17): T. Chisesi, G. Capnist; Vicenza — Ospedale di Vicenza (1): F. Rodeghiero, M. Ruggeri; Spain: Barakaldo (Vizcaya) — Hospital de Cruces (8): B. Arrizabalaga; Barcelona — Hospital Santa Creu Y San Pau (2): A. Remacha; Burgos — Hospital General Yagüe (7): B. Pérez De Mendiguren; La Laguna (Santa Cruz de Tenerife) — Hospital Universitario de Canarias (4): L. Hernández-Nieto, M.T. Hernández-García, G. González-Brito, P. Machado; León — Hospital de León (2): G. Garcia; Madrid — Hospital Universitario S. Carlos (4): A. Villegas, A. Peña, A. González Fernández; Valencia — Hospital General Universitario (2): F. Carbonell; Hospital Peset (3): A. Del Arco; Sweden: Borås — Borås Hospital (4): H. Bäck; Danderyd — Danderyd Hospital (1): L. Stenke; Eksjö — Höglands Hospital (2): S. Hansen; Kristianstad — Kristianstad Hospital (8): G. Larsson; Kungälv — Kungälv Hospital (3): G. Strömblad; Luleå — Luleå Hospital (2): B. Lauri; Motala — Motala Hospital (1): B.O. Ryden; Örebro — Örebro Medical Centre Hospital (3): O. Linder; Örnsköldsvik — Örnsköldsvik Hospital (1): B.G. Lundholm; Säffle — Säffle Hospital (9): O. Lannemyr; Sundsvall — Sundsvall Hospital (6): M. Strandberg; Uddevalla — Uddevalla Hospital (8): B. Andréasson, D. Stockelberg; Västerås — Västerås Hospital (6): F. Pasquariello; Switzerland: Basel — Kantonsspital Basel (1): A. Tichelli; Oldenburg (3): B. Otremba, H.F. Hinrichs; Schweiz (1): W. Weber-Stadelmann; United Kingdom: Birmingham — City Hospital NHS Trust (9): D. Bareford; Bournemouth — The Royal Bournemouth Hospital (1): D.G. Oscier, N. Bowey; South Yorks — District General Hospital (1): P.C. Taylor; Steering committee — R. Landolfi (chair, Università Cattolica del Sacro Cuore, Rome), T. Barbui (Ospedali Riuniti, Bergamo), G. de Gaetano (Università Cattolica del Sacro Cuore, Campobasso), R. Marchioli (Consorzio Mario Negri Sud, Santa Maria Imbaro), Y. Najean (Hospital S. Luis, Paris), C. Patrono (Università di Roma La Sapienza, Rome), T.C. Pearson (London); Scientific and organizing secretariat — R. Marchioli (coordinator), A. Di Blasio, S. Atashkar, G. Finazzi, H. Gisslinger, E. Mari, D. Tamayo, G. Tognoni; Data management and analysis — G. Borrelli, B. Ferri, R.M. Marfisi, M. Olivieri, A. Polidoro, R. Spoltore; Event adjudicating committee — R. Landolfi (chair), G. Levantesi, R. Di Mascio, G. Finazzi, G. Miceli, G. Sperti; Safety and data monitoring committee — E. Correale (chair), J. Vermjlen, R. Collins.
- References
References
1
Tefferi A . Pathogenetic mechanisms in chronic myeloproliferative disorders: polycythemia vera, essential thrombocytopenia, agnogenic myeloid metaplasia, and chronic myelogenous leukemia. Semin Haematol 1999;36:Suppl:3-8
Web of Science | Medline2
Landolfi R ,Marchioli R ,Patrono C . Mechanisms of bleeding and thrombosis in myeloproliferative disorders. Thromb Haemost 1997;78:617-621
Web of Science | Medline3
Chievitz E ,Thiede T . Complications and causes of death in polycythemia vera. Acta Med Scand 1962;172:513-523
CrossRef | Web of Science | Medline4
Gruppo Italiano Studio Policitemia
CrossRef | Web of Science | Medline5
Berk PD ,Goldberg JD ,Donovan PB ,Fruchtman SM ,Berlin NI ,Wasserman LR . Therapeutic recommendations in polycythemia vera based in Polycythemia Vera Study Group protocols. Semin Hematol 1986;23:132-143
Web of Science | Medline6
Tartaglia A ,Goldberg J ,Berk PD ,Wasserman LR . Adverse effects of antiaggregating platelet therapy in the treatment of polycythemia vera. Semin Hematol 1986;23:172-176
Web of Science | Medline7
Patrono C . Aspirin as an antiplatelet drug. N Engl J Med 1994;330:1287-1294
Full Text | Web of Science | Medline8
Landolfi R ,Ciabattoni G ,Patrignani P , et al. Increased thromboxane biosynthesis in patients with polycythemia vera: evidence for aspirin-suppressible platelet activation in vivo. Blood 1992;80:1965-1971
Web of Science | Medline9
Gruppo Italiano Studio Policitemia
CrossRef | Web of Science | Medline10
Landolfi R ,Marchioli R . European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP): a randomized trial. Semin Thromb Hemost 1997;23:473-478
CrossRef | Web of Science | Medline11
Antithrombotic Trialists' Collaboration
CrossRef | Web of Science12
Peto R ,Gray R ,Collins R , et al. Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J (Clin Res Ed) 1988;296:313-316
CrossRef | Web of Science | Medline13
Steering Committee of the Physicians' Health Study Research Group
Full Text | Web of Science | Medline14
Thrombosis Prevention Trial: randomised trial of low intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. Lancet 1998;351:1755-1762
CrossRef | Web of Science | Medline15
Hansson L ,Zanchetti A ,Carruthers SG , et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998;351:1755-1762
CrossRef | Web of Science | Medline16
de Gaetano G . Low dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet 2001;357:89-95
CrossRef | Web of Science | Medline17
Hayden M ,Pignone M ,Phillips C ,Mulrow C . Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002;136:161-172
Web of Science | Medline18
Fitzgerald DJ ,Roy L ,Catella F ,FitzGerald GA . Platelet activation in unstable coronary disease. N Engl J Med 1986;315:893-899
Full Text | Web of Science | Medline19
Vejar M ,Fragasso G ,Hackett D , et al. Dissociation of platelet activation and spontaneous myocardial ischemia in unstable angina. Thromb Haemost 1990;63:163-168
Web of Science | Medline20
The RISC Group
CrossRef | Web of Science | Medline21
Streiff MB ,Smith B ,Spivak JL . The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of American Society of Hematology members' practice patterns. Blood 2002;99:1144-1149
CrossRef | Web of Science | Medline
- Citing Articles (171)
Citing Articles
1
Lori Cooper. 2012. Case 55. , 180-184.
CrossRef2
Giovanni Barosi, Letizia Lupo, Vittorio Rosti. (2012) Management of Myeloproliferative Neoplasms: From Academic Guidelines to Clinical Practice. Current Hematologic Malignancy Reports
CrossRef3
T Barbui. (2012) How I manage children and young adults with myeloproliferative neoplasms. Leukemia
CrossRef4
Wendy Osborne, Gail L Jones, Graham H Jackson, Helen Marr. (2012) Myeloproliferative disorders in older people. Reviews in Clinical Gerontology1-11
CrossRef5
Brian Lima, Edward Soltesz. (2012) Management of Extensive Intracardiac Thombosis in a Patient with Polycythemia Vera Undergoing Coronary Artery Bypass Grafting. Journal of Cardiac Surgeryno-no
CrossRef6
Francesco Passamonti, Margherita Maffioli, Domenica Caramazza. (2012) New generation small-molecule inhibitors in myeloproliferative neoplasms. Current Opinion in Hematology1
CrossRef7
Raoul Tibes, Ruben Mesa. (2011) JAK2 inhibitors in the treatment of myeloproliferative neoplasms: rationale and clinical data. Clinical Investigation 1:12, 1681-1693
CrossRef8
F. Cervantes. (2011) Management of Essential Thrombocythemia. Hematology 2011:1, 215-221
CrossRef9
H Reikvam, R V Tiu. (2011) Venous thromboembolism in patients with essential thrombocythemia and polycythemia vera. Leukemia
CrossRef10
G Finazzi. (2011) How to manage essential thrombocythemia. Leukemia
CrossRef11
Tiziano Barbui. (2011) How to manage thrombosis in myeloproliferative neoplasms. Current Opinion in Oncology 23:6, 654-658
CrossRef12
Angel Lanas, Ping Wu, Jennie Medin, Edward J. Mills. (2011) Low Doses of Acetylsalicylic Acid Increase Risk of Gastrointestinal Bleeding in a Meta-Analysis. Clinical Gastroenterology and Hepatology 9:9, 762-768.e6
CrossRef13
A. Tefferi, A. Pardanani. (2011) JAK inhibitors in myeloproliferative neoplasms: Rationale, current data and perspective. Blood Reviews 25:5, 229-237
CrossRef14
Y. Benhamou, I. Marie, N. David, X. Gbaguidi, N. Cailleux, C. Peillon, D. Plissonnier, H. Lévesque. (2011) Les thromboses veineuses profondes des membres supérieurs. La Revue de Médecine Interne 32:9, 567-574
CrossRef15
Ayalew Tefferi, Pierre Noel, Curtis A. Hanson. (2011) Uses and Abuses of JAK2 and MPL Mutation Tests in Myeloproliferative Neoplasms. The Journal of Molecular Diagnostics 13:5, 461-466
CrossRef16
J. Hoekstra, E. L. Bresser, J. H. Smalberg, M. C. W. Spaander, F. W. G. Leebeek, H. L. A. Janssen. (2011) Long-Term Follow-Up of Patients With Portal Vein Thrombosis and Myeloproliferative Neoplasms. Journal of Thrombosis and Haemostasisno-no
CrossRef17
Raoul Tibes, Ruben A. Mesa. (2011) Myeloproliferative neoplasms 5 years after discovery of JAK2V617F: what is the impact of JAK2 inhibitor therapy?. Leukemia & Lymphoma 52:7, 1178-1187
CrossRef18
Daniel Lechner, Heinz Gisslinger. (2011) Philadelphia-negative myeloproliferative Neoplasien. Wiener klinische Wochenschrift Education 6:1-2, 35-48
CrossRef19
Raffaele Landolfi, Leonardo Gennaro, Maria Anna Nicolazzi, Igor Giarretta, RosaMaria Marfisi, Roberto Marchioli. (2011) Polycythemia vera: gender-related phenotypic differences. Internal and Emergency Medicine
CrossRef20
Erik Vakil, Ayalew Tefferi. (2011) BCR-ABL1—Negative Myeloproliferative Neoplasms: A Review of Molecular Biology, Diagnosis, and Treatment. Clinical Lymphoma Myeloma and Leukemia 11, S37-S45
CrossRef21
D. Bhadauria, R. K. Sharma, A. Kaul, N. Prasad, A. Gupta, D. Gurjar, A. Jain. (2011) A rare clinical syndrome of refractory secondary hypertension, renal artery stenosis and erythrocytosis. NDT Plus 4:3, 175-177
CrossRef22
Ombeline Fagniez, Gérard Tertian, Marie Dreyfus, Denis Ducreux, David Adams, Christian Denier. (2011) Hematological disorders related cerebral infarctions are mostly multifocal. Journal of the Neurological Sciences 304:1-2, 87-92
CrossRef23
Ruben A. Mesa, Ayalew Tefferi. 2011. Myeloproliferative Neoplasms. , 47-61.
CrossRef24
Robyn Scherber, Ruben A. Mesa. (2011) Future Therapies for the Myeloproliferative Neoplasms. Current Hematologic Malignancy Reports 6:1, 22-27
CrossRef25
Ayalew Tefferi. (2011) Annual Clinical Updates in Hematological Malignancies: A Continuing Medical Education Series: Polycythemia vera and essential thrombocythemia: 2011 update on diagnosis, risk-stratification, and management. American Journal of Hematology 86:3, 292-301
CrossRef26
Tiziano Barbui, Guido Finazzi. (2011) Special Issues in Myeloproliferative Neoplasms. Current Hematologic Malignancy Reports 6:1, 28-35
CrossRef27
Animesh Pardanani, Ayalew Tefferi. (2011) Targeting myeloproliferative neoplasms with JAK inhibitors. Current Opinion in Hematology 18:2, 105-110
CrossRef28
Claire Harrison, Tiziano Barbui. (2011) Aspirin in low-risk essential thrombocythemia, not so simple after all?. Leukemia Research 35:3, 286-289
CrossRef29
P. A. Beer, W. N. Erber, P. J. Campbell, A. R. Green. (2011) How I treat essential thrombocythemia. Blood 117:5, 1472-1482
CrossRef30
Jonathan S. Bleeker, William J. Hogan. (2011) Thrombocytosis: Diagnostic Evaluation, Thrombotic Risk Stratification, and Risk-Based Management Strategies. Thrombosis 2011, 1-16
CrossRef31
Brady L. Stein, Alfred Rademaker, Jerry L. Spivak, Alison R. Moliterno. (2011) Gender and Vascular Complications in the JAK2 V617F-Positive Myeloproliferative Neoplasms. Thrombosis 2011, 1-8
CrossRef32
Sigurdur Yngvi Kristinsson, Magnus Björkholm, Sam Schulman, Ola Landgren. (2011) Hypercoagulability in Multiple Myeloma and Its Precursor State, Monoclonal Gammopathy of Undetermined Significance. Seminars in Hematology 48:1, 46-54
CrossRef33
Soo-Mee Bang, Ho Young Kim, Hyo Jung Kim, Hee-Jin Kim, Jong Ho Won, Bong Seog Kim, Chul-Won Jung, Hyun-Sook Chi, . (2011) Diagnostic and therapeutic guideline for myeloproliferative neoplasm. Journal of the Korean Medical Association 54:1, 112
CrossRef34
Philip Lanzkowsky. 2011. Polycythemia. , 257-271.
CrossRef35
Ruben A. Mesa, Srdan Verstovsek. 2010. Philadelphia Chromosome-Negative Myeloproliferative Neoplasms. , 362-372.
CrossRef36
Emmanouil Papadakis, Ron Hoffman, Benjamin Brenner. (2010) Thrombohemorrhagic complications of myeloproliferative disorders. Blood Reviews 24:6, 227-232
CrossRef37
Peter J Campbell, Anthony R Green. 2010. Myeloproliferative Neoplasms. , 686-709.
CrossRef38
Raffaele Landolfi, Maria Anna Nicolazzi, Angelo Porfidia, Leonardo Di Gennaro. (2010) Polycythemia vera. Internal and Emergency Medicine 5:5, 375-384
CrossRef39
Monica Carpenedo, Enrico Maria Pogliani. (2010) From Vaquez to Dameshek through JAK…2 much for polycythemia vera to be feared?. Internal and Emergency Medicine 5:5, 371-373
CrossRef40
Elena Mishchenko, Ayalew Tefferi. (2010) Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shunt. European Journal of Haematology 85:3, 192-199
CrossRef41
F Passamonti, E Rumi, D Pietra, C Elena, E Boveri, L Arcaini, E Roncoroni, C Astori, M Merli, S Boggi, C Pascutto, M Lazzarino, M Cazzola. (2010) A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia 24:9, 1574-1579
CrossRef42
A. Alvarez-Larran, F. Cervantes, A. Pereira, E. Arellano-Rodrigo, V. Perez-Andreu, J.-C. Hernandez-Boluda, R. Ayats, C. Salvador, A. Muntanola, B. Bellosillo, V. Vicente, L. Hernandez-Nieto, C. Burgaleta, B. Xicoy, C. Besses. (2010) Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood 116:8, 1205-1210
CrossRef43
Elena Crisà, Ermanno Venturino, Roberto Passera, Marco Prina, Piercarla Schinco, Alessandra Borchiellini, Valentina Giai, Maria Ausilia Ciocca Vasino, Mario Bazzan, Antonella Vaccarino, Mario Boccadoro, Dario Ferrero. (2010) A retrospective study on 226 polycythemia vera patients: impact of median hematocrit value on clinical outcomes and survival improvement with anti-thrombotic prophylaxis and non-alkylating drugs. Annals of Hematology 89:7, 691-699
CrossRef44
Bruce D. Adams, Russell Baker, J. Abraham Lopez, Susan Spencer. (2010) Myeloproliferative Disorders and the Hyperviscosity Syndrome. Hematology/Oncology Clinics of North America 24:3, 585-602
CrossRef45
Alessandro M. Vannucchi. (2010) Insights into the pathogenesis and management of thrombosis in polycythemia vera and essential thrombocythemia. Internal and Emergency Medicine 5:3, 177-184
CrossRef46
Ayalew Tefferi. 2010. Myeloproliferative Neoplasms: Essential Thrombocythemia, Polycythemia Vera, and Primary Myelofibrosis. , 147-156.
CrossRef47
Claire N. Harrison, David Bareford, Nauman Butt, Peter Campbell, Eibhlean Conneally, Mark Drummond, Wendy Erber, Tamara Everington, Anthony R. Green, Georgina W. Hall, Beverley J. Hunt, Christopher A. Ludlam, Richard Murrin, Catherine Nelson-Piercy, Deepti H. Radia, John T. Reilly, Jon Van der Walt, Bridget Wilkins, Mary F. McMullin, . (2010) Guideline for investigation and management of adults and children presenting with a thrombocytosis. British Journal of Haematology 149:3, 352-375
CrossRef48
D. Wolf, R. Stauder. 2010. Management of Myeloproliferative Diseases in Senior Patients. , 72-81.
CrossRef49
Patrick J. Brown, Matthew J. Zirwas, Joseph C. English. (2010) The Purple Digit. American Journal of Clinical Dermatology 11:2, 103-116
CrossRef50
Maria Caterina Putti, Maria Luigia Randi. (2010) Thrombotic complications in children with haematologic malignacies. Thrombosis Research 125, S151-S154
CrossRef51
A. Dragani, S. Pascale, A. Recchiuti, D. Mattoscio, S. Lattanzio, G. Petrucci, L. Mucci, E. Ferrante, A. Habib, F. O. Ranelletti, G. Ciabattoni, G. Davi, C. Patrono, B. Rocca. (2010) The contribution of cyclooxygenase-1 and -2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: implications for antiplatelet therapy. Blood 115:5, 1054-1061
CrossRef52
Matthew A. Fieldwalker, Shannon C. Jackson, Douglas Seal. (2010) High Transoxygenator Pressure Gradient in a Patient With Polycythemia Vera. Journal of Cardiothoracic and Vascular Anesthesia 24:1, 104-108
CrossRef53
Alessandro M. Vannucchi. (2010) JAK2 Mutation and Thrombosis in the Myeloproliferative Neoplasms. Current Hematologic Malignancy Reports 5:1, 22-28
CrossRef54
Fabrizio Fabris, Maria Luigia Randi. (2009) Essential thrombocythemia: past and present. Internal and Emergency Medicine 4:5, 381-388
CrossRef55
Bruce D. Adams, Russell Baker, J. Abraham Lopez, Susan Spencer. (2009) Myeloproliferative Disorders and the Hyperviscosity Syndrome. Emergency Medicine Clinics of North America 27:3, 459-476
CrossRef56
Alessandro M. Vannucchi, Paola Guglielmelli, Alessandro Rambaldi, Costanza Bogani, Tiziano Barbui. (2009) Epigenetic therapy in myeloproliferative neoplasms: evidence and perspectives. Journal of Cellular and Molecular Medicine 13:8a, 1437-1450
CrossRef57
C. PATRONO, B. ROCCA. (2009) Aspirin, 110 years later. Journal of Thrombosis and Haemostasis 7, 258-261
CrossRef58
María José Moreno, María Luisa Lozano, Francisca Ferrer, Beatriz Bellosillo, Carlos Besses, Vicente Vicente, Constantino Martínez. (2009) ABO blood group does not increase the risk of thrombosis in Philadelphia-negative myeloproliferative disorders. Blood Coagulation & Fibrinolysis 20:5, 390-392
CrossRef59
Edward N. Libby, Agnes Y. Lee. 2009. Anticoagulants in Cancer. , 221-236.
CrossRef60
G. Barosi, G. Birgegard, G. Finazzi, M. Griesshammer, C. Harrison, H. C. Hasselbalch, J.-J. Kiladjian, E. Lengfelder, M. F. McMullin, F. Passamonti, J. T. Reilly, A. M. Vannucchi, T. Barbui. (2009) Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood 113:20, 4829-4833
CrossRef61
Laurie D. DeLeve, Dominique-Charles Valla, Guadalupe Garcia-Tsao. (2009) Vascular disorders of the liver. Hepatology 49:5, 1729-1764
CrossRef62
Gianfranco Lessiani, Alfredo Dragani, Angela Falco, Francesca Fioritoni, Francesca Santilli, Giovanni Davì. (2009) Soluble CD40 ligand and endothelial dysfunction in aspirin-treated polycythaemia vera patients. British Journal of Haematology 145:4, 538-540
CrossRef63
Giovanni Barosi, Vittorio Rosti. (2009) Novel strategies for patients with chronic myeloproliferative disorders. Current Opinion in Hematology 16:2, 129-134
CrossRef64
Alessandro M Vannucchi, Paola Guglielmelli, Lisa Pieri, Elisabetta Antonioli, Alberto Bosi. (2009) Treatment options for essential thrombocythemia and polycythemia vera. Expert Review of Hematology 2:1, 41-55
CrossRef65
M. F. McMullin. (2009) Idiopathic erythrocytosis: a disappearing entity. Hematology 2009:1, 629-635
CrossRef66
Hans Carl Hasselbalch. (2009) Myelofibrosis with myeloid metaplasia: The advanced phase of an untreated disseminated hematological cancer. Leukemia Research 33:1, 11-18
CrossRef67
Ashkan Emadi, Jerry L Spivak. (2009) Anagrelide: 20 years later. Expert Review of Anticancer Therapy 9:1, 37-50
CrossRef68
Francesco Passamonti. (2009) New and old prognostic factors in polycythemia vera. Current Hematologic Malignancy Reports 4:1, 19-24
CrossRef69
Francesca Palandri, Emanuela Ottaviani, Federica Salmi, Lucia Catani, Nicola Polverelli, Mauro Fiacchini, Giovanni Martinelli, Michele Baccarani, Nicola Vianelli. (2009) JAK2 V617F mutation in essential thrombocythemia: correlation with clinical characteristics, response to therapy and long-term outcome in a cohort of 275 patients. Leukemia & Lymphoma 50:2, 247-253
CrossRef70
P. A. Beer, A. R. Green. (2009) Pathogenesis and management of essential thrombocythemia. Hematology 2009:1, 621-628
CrossRef71
Gunnar Birgegård. (2009) Long-term management of thrombocytosis in essential thrombocythaemia. Annals of Hematology 88:1, 1-10
CrossRef72
S.W. Krause, A. Mackensen. (2008) Chronische myeloproliferative Erkrankungen. Der Internist 49:12, 1452-1457
CrossRef73
Jie Bai, Yangping Xue, Lei Ye, Jianfeng Yao, Chunlin Zhou, Zonghong Shao, Linsheng Qian, Renchi Yang, Haiyan Li, Hongyun Zhang, Yizhou Zheng. (2008) Risk factors of long-term incidences of thrombosis, myelofibrosis and evolution into malignance in polycythemia vera: a single center experience from China. International Journal of Hematology 88:5, 530-535
CrossRef74
C H M Jamieson, C F Barroga, W P Vainchenker. (2008) Miscreant myeloproliferative disorder stem cells. Leukemia 22:11, 2011-2019
CrossRef75
Massimo Franchini, Pier Mannuccio Mannucci. (2008) Venous and arterial thrombosis: Different sides of the same coin?. European Journal of Internal Medicine 19:7, 476-481
CrossRef76
R Landolfi, L Di Gennaro, A Falanga. (2008) Thrombosis in myeloproliferative disorders: pathogenetic facts and speculation. Leukemia 22:11, 2020-2028
CrossRef77
J.-J. Kiladjian, B. Cassinat, S. Chevret, P. Turlure, N. Cambier, M. Roussel, S. Bellucci, B. Grandchamp, C. Chomienne, P. Fenaux. (2008) Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood 112:8, 3065-3072
CrossRef78
R. L. Levine, D. G. Gilliland. (2008) Myeloproliferative disorders. Blood 112:6, 2190-2198
CrossRef79
Guido Finazzi. (2008) Aspirin in asymptomatic patients with confirmed positivity of antiphospholipid antibodies? No. Internal and Emergency Medicine 3:3, 197-200
CrossRef80
G Finazzi, T Barbui. (2008) Evidence and expertise in the management of polycythemia vera and essential thrombocythemia. Leukemia 22:8, 1494-1502
CrossRef81
Regina Kunz, Benjamin Djulbegovic, Holger J. Schunemann, Martin Stanulla, Paula Muti, Gordon Guyatt. (2008) Misconceptions, Challenges, Uncertainty, and Progress in Guideline Recommendations. Seminars in Hematology 45:3, 167-175
CrossRef82
Naseema Gangat, Ayalew Tefferi. (2008) Pharmacotherapy of essential thrombocythemia. Expert Opinion on Pharmacotherapy 9:10, 1679-1685
CrossRef83
A. Ugur Ural, Turker Cetin, Ferit Avcu. (2008) Antithrombotic Challenges after Coronary Artery Surgery in Patients with Polycytemia Vera. Journal of Cardiac Surgery 23:4, 410-410
CrossRef84
Naseema Gangat, Jacob J. Strand, Terra L. Lasho, Chin-Yang Li, Animesh Pardanani, Ayalew Tefferi. (2008) Pruritus in polycythemia vera is associated with a lower risk of arterial thrombosis. American Journal of Hematology 83:6, 451-453
CrossRef85
Ayalew Tefferi. (2008) Essential thrombocythemia, polycythemia vera, and myelofibrosis: Current management and the prospect of targeted therapy. American Journal of Hematology 83:6, 491-497
CrossRef86
F. Santilli, M. Romano, A. Recchiuti, A. Dragani, A. Falco, G. Lessiani, F. Fioritoni, S. Lattanzio, D. Mattoscio, R. De Cristofaro, B. Rocca, G. Davi. (2008) Circulating endothelial progenitor cells and residual in vivo thromboxane biosynthesis in low-dose aspirin-treated polycythemia vera patients. Blood 112:4, 1085-1090
CrossRef87
F Cervantes, F Passamonti, G Barosi. (2008) Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders. Leukemia 22:5, 905-914
CrossRef88
Ayalew Tefferi, Naseema Gangat, Alexandra P. Wolanskyj, Susan Schwager, Animesh Pardanani, Terra L. Lasho, Ruben Mesa, Rebecca F. McClure, Chin-Yang Li, Curtis A. Hanson. (2008) 20+ yr without leukemic or fibrotic transformation in essential thrombocythemia or polycythemia vera: predictors at diagnosis. European Journal of Haematology 80:5, 386-390
CrossRef89
Ernst Rechberger, Gerald Webersinke, Andreas L. Petzer. (2008) Chronische Myeloproliferative Erkrankungen (CMPE). Wiener klinische Wochenschrift Education 3:1, 59-77
CrossRef90
Alessandro Squizzato, Erica Romualdi, Saskia Middeldorp, Alessandro Squizzato. 2008. Antiplatelet drugs for polycythaemia vera and essential thrombocythaemia. .
CrossRef91
F. Stegelmann, H. M. Kvasnicka, M. Griesshammer. (2008) Chronische myeloproliferative Erkrankungen. best practice onkologie 3:2, 24-32
CrossRef92
V Guerini, V Barbui, O Spinelli, A Salvi, C Dellacasa, A Carobbio, M Introna, T Barbui, J Golay, A Rambaldi. (2008) The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2V617F. Leukemia 22:4, 740-747
CrossRef93
Henry G Watson, Yen Lin Chee. (2008) Aspirin and other antiplatelet drugs in the prevention of venous thromboembolism. Blood Reviews 22:2, 107-116
CrossRef94
Ruben A Mesa. (2008) New insights into the pathogenesis and treatment of chronic myeloproliferative disorders. Current Opinion in Hematology 15:2, 121-126
CrossRef95
M. Ruggeri, F. Rodeghiero, A. Tosetto, G. Castaman, F. Scognamiglio, G. Finazzi, F. Delaini, C. Mico, A. M. Vannucchi, E. Antonioli, V. De Stefano, T. Za, L. Gugliotta, A. Tieghi, M. G. Mazzucconi, C. Santoro, T. Barbui, . (2008) Postsurgery outcomes in patients with polycythemia vera and essential thrombocythemia: a retrospective survey. Blood 111:2, 666-671
CrossRef96
A Tefferi. (2008) The history of myeloproliferative disorders: before and after Dameshek. Leukemia 22:1, 3-13
CrossRef97
DP McLornan, MF McMullin. (2008) How would I manage a case of essential thrombocythaemia presenting with an ischaemic toe. Hematological Oncology 26:1, 3-7
CrossRef98
B. S. Wilkins, W. N. Erber, D. Bareford, G. Buck, K. Wheatley, C. L. East, B. Paul, C. N. Harrison, A. R. Green, P. J. Campbell. (2008) Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease subtypes. Blood 111:1, 60-70
CrossRef99
Ayalew Tefferi. (2007) JAK2 Mutations and Clinical Practice in Myeloproliferative Neoplasms. The Cancer Journal 13:6, 366-371
CrossRef100
Guido Finazzi, Tiziano Barbui. (2007) Expertise-Based Management in Essential Thrombocythemia and Polycythemia Vera. The Cancer Journal 13:6, 372-376
CrossRef101
Guido Finazzi. (2007) Unanswered questions in polycythaemia vera. European Journal of Haematology 79:s68, 18-21
CrossRef102
J. J. Michiels, S. Commandeur, G. J. Hoogenboom, J. J. Wegman, L. Scholten, R. H. Rijssel, H. Raeve. (2007) JAK2V617F positive early stage myeloproliferative disease (essential thrombocythemia) as the cause of portal vein thrombosis in two middle-aged women: therapeutic implications in view of the literature. Annals of Hematology 86:11, 793-800
CrossRef103
Giuseppe Curigliano, Alessandra Balduzzi, Anna Cardillo, Raffaella Ghisini, Giulia Peruzzotti, Laura Orlando, Rosalba Torrisi, Silvia Dellapasqua, Loredana Lunghi, Aron Goldhirsch, Marco Colleoni. (2007) Low-dose aspirin for the prevention of venous thromboembolism in breast cancer patients treated with infusional chemotherapy after insertion of central vein catheter. Supportive Care in Cancer 15:10, 1213-1217
CrossRef104
Elizabeth O Hexner. (2007) JAK2 V617F: implications for thrombosis in myeloproliferative diseases. Current Opinion in Hematology 14:5, 450-454
CrossRef105
A M Vannucchi, E Antonioli, P Guglielmelli, G Longo, A Pancrazzi, V Ponziani, C Bogani, P R Ferrini, A Rambaldi, V Guerini, A Bosi, T Barbui. (2007) Prospective identification of high-risk polycythemia vera patients based on JAK2V617F allele burden. Leukemia 21:9, 1952-1959
CrossRef106
Naseema Gangat, Jacob Strand, Chin-Yang Li, Wenting Wu, Animesh Pardanani, Ayalew Tefferi. (2007) Leucocytosis in polycythaemia vera predicts both inferior survival and leukaemic transformation. British Journal of Haematology 138:3, 354-358
CrossRef107
Mary Frances McMullin. (2007) A review of the therapeutic agents used in the management of polycythaemia vera. Hematological Oncology 25:2, 58-65
CrossRef108
A Squizzato, E Romualdi, S Middeldorp, Alessandro Squizzato. 2007. Antiplatelet drugs for polycythemia vera and essential thrombocythaemia. .
CrossRef109
Brian J. Zikmund-Fisher, Angela Fagerlin, Peter A. Ubel. (2007) Mortality versus survival graphs: Improving temporal consistency in perceptions of treatment effectiveness. Patient Education and Counseling 66:1, 100-107
CrossRef110
G. Finazzi, T. Barbui. (2007) The treatment of polycythaemia vera: an update in the JAK2 era. Internal and Emergency Medicine 2:1, 13-18
CrossRef111
C. A. Weber, A. C. Matzdorff, T. Gerriets, T. Villmow, E. Stolz. (2007) Circulating microemboli in patients with myeloproliferative disorders. European Journal of Neurology 14:2, 199-205
CrossRef112
Ruben A. Mesa, Joyce Niblack, Martha Wadleigh, Srdan Verstovsek, John Camoriano, Sunni Barnes, Angelina D. Tan, Pamela J. Atherton, Jeff A. Sloan, Ayalew Tefferi. (2007) The burden of fatigue and quality of life in myeloproliferative disorders (MPDs). Cancer 109:1, 68-76
CrossRef113
A. M. Vannucchi, T. Barbui. (2007) Thrombocytosis and Thrombosis. Hematology 2007:1, 363-370
CrossRef114
Myoung Ok Park, Hyun Jeong Baek, Seo Young Song. (2007) A Case of Polycythemia Vera Combined with Focal Segmental Glomerulosclerosis. The Korean Journal of Hematology 42:1, 58
CrossRef115
Marcello Di Nisio, Tiziano Barbui, Leonardo Di Gennaro, Giovanna Borrelli, Guido Finazzi, Raffaele Landolfi, Giuseppe Leone, RosaMaria Marfisi, Ettore Porreca, Marco Ruggeri, Anne W. S. Rutjes, Gianni Tognoni, Alessandro M. Vannucchi, Roberto Marchioli, . (2007) The haematocrit and platelet target in polycythemia vera. British Journal of Haematology 136:2, 249-259
CrossRef116
R. A. Mesa. (2007) Navigating the Evolving Paradigms in the Diagnosis and Treatment of Myeloproliferative Disorders. Hematology 2007:1, 355-362
CrossRef117
Carlo Patrono, Bianca Rocca. (2007) Drug Insight: aspirin resistance—fact or fashion?. Nature Clinical Practice Cardiovascular Medicine 4:1, 42-50
CrossRef118
Craig M. Kessler, Jan Jacques Michiels. 2007. Thrombocytosis: Essential Thrombocythemia and Reactive Causes. , 295-318.
CrossRef119
Harry L. A. Janssen, Frank W. G. Leebeek. (2006) JAK2 mutation: The best diagnostic tool for myeloproliferative disease in splanchnic vein thrombosis?. Hepatology 44:6, 1391-1393
CrossRef120
Hans Carl Hasselbalch, Caroline H. Riley. (2006) Statins in the treatment of polycythaemia vera and allied disorders: An antithrombotic and cytoreductive potential?. Leukemia Research 30:10, 1217-1225
CrossRef121
Tiziano Barbui, Guido Finazzi. (2006) Evidence-based management of polycythemia vera. Best Practice & Research Clinical Haematology 19:3, 483-493
CrossRef122
Raffaele Landolfi, Maria Celeste Cipriani, Linda Novarese. (2006) Thrombosis and bleeding in polycythemia vera and essential thrombocythemia: Pathogenetic mechanisms and prevention. Best Practice & Research Clinical Haematology 19:3, 617-633
CrossRef123
Claire N. Harrison, Anthony R. Green. (2006) Essential thrombocythaemia. Best Practice & Research Clinical Haematology 19:3, 439-453
CrossRef124
A. Manoharan, R. Gemmell, T. Hartwell. (2006) Use of whole blood platelet lumi-aggregometry to optimize anti-platelet therapy in patients with chronic myeloproliferative disorders. American Journal of Hematology 81:9, 676-683
CrossRef125
Ayalew Tefferi. (2006) The diagnosis of polycythemia vera: New tests and old dictums. Best Practice & Research Clinical Haematology 19:3, 455-469
CrossRef126
Guido Finazzi, Xylina T. Gregg, Tiziano Barbui, Josef T. Prchal. (2006) Idiopathic erythrocytosis and other non-clonal polycythemias. Best Practice & Research Clinical Haematology 19:3, 471-482
CrossRef127
Ruben A Mesa. (2006) Practical management of classical myeloproliferative disorder patients: a clinician’s guide. Future Oncology 2:4, 515-524
CrossRef128
Richard T. Silver. (2006) Long-term effects of the treatment of polycythemia vera with recombinant interferon-α. Cancer 107:3, 451-458
CrossRef129
David Dingli, Ayalew Tefferi. (2006) Hydroxyurea: The drug of choice for polycythemia vera and essential thrombocythemia. Current Hematologic Malignancy Reports 1:2, 69-74
CrossRef130
Naseema Gangat, Alexandra P. Wolanskyj, Susan M. Schwager, Ruben A. Mesa, Ayalew Tefferi. (2006) Estrogen-based hormone therapy and thrombosis risk in women with essential thrombocythemia. Cancer 106:11, 2406-2411
CrossRef131
I. Marie, F. Hervé. (2006) Mutation de la protéine kinase JAK2 au cours de la polyglobulie de Vaquez : nouvelles perspectives physiopathologiques et thérapeutiques. La Revue de Médecine Interne 27:6, 473-477
CrossRef132
S. Moncada. (2006) Adventures in vascular biology: a tale of two mediators. Philosophical Transactions of the Royal Society B: Biological Sciences 361:1469, 735-759
CrossRef133
Jan Jacques Michiels, Zwi Berneman, Wilfried Schroyens, Peter J. Koudstaal, Jan Lindemans, Huub H.D.M. van Vliet. (2006) Platelet-mediated thrombotic complications in patients with ET: Reversal by aspirin, platelet reduction, and not by coumadin. Blood Cells, Molecules, and Diseases 36:2, 199-205
CrossRef134
F Cervantes, A Alvarez-Larrán, E Arellano-Rodrigo, M Granell, A Domingo, E Montserrat. (2006) Frequency and risk factors for thrombosis in idiopathic myelofibrosis: analysis in a series of 155 patients from a single institution. Leukemia 20:1, 55-60
CrossRef135
Gustav Born, Carlo Patrono. (2006) Antiplatelet drugs. British Journal of Pharmacology 147:S1, S241-S251
CrossRef136
KAZUYA SHIMODA. (2006) Nihon Naika Gakkai Zasshi 95:10, 2060-2066
CrossRef137
Hideyuki Inoue, Shigekazu Nakada, Tomomi Ishikawa, Hiroshi Miyawaki, Kimio Saitou, Jun Kimura. (2006) Essential thrombocythemia complicated with pulmonary hypertension.. Nihon Naika Gakkai Zasshi 95:1, 133-135
CrossRef138
Elisabeth I Penninga, Ole W Bjerrum. (2006) Polycythaemia Vera and Essential Thrombocythaemia. Drugs 66:17, 2173-2187
CrossRef139
Patrono, Carlo, García Rodríguez, Luis A., Landolfi, Raffaele, Baigent, Colin, . (2005) Low-Dose Aspirin for the Prevention of Atherothrombosis. New England Journal of Medicine 353:22, 2373-2383
Full Text140
R. Baz, L. Li, K. Kottke-Marchant, G. Srkalovic, B. McGowan, E. Yiannaki, M. A. Karam, B. Faiman, R. A. Jawde, S. Andresen, J. Zeldis, M. A. Hussein. (2005) The Role of Aspirin in the Prevention of Thrombotic Complications of Thalidomide and Anthracycline-Based Chemotherapy for Multiple Myeloma. Mayo Clinic Proceedings 80:12, 1568-1574
CrossRef141
Massimo Breccia, Salvatore Giacomo Morano, Mariella D'Andrea, Eleonora Russo, Gianna Maria D'Elia, Giuliana Alimena. (2005) Budd-Chiari syndrome as the first manifestation of polycythemia vera in young women with inherited thrombophilic state: an aggressive form of myeloproliferative disorder requiring multidisciplinary management. European Journal of Haematology 75:5, 396-400
CrossRef142
Claire N Harrison. (2005) Anagrelide for control of thrombocytosis due to myeloproliferative disorders. Future Oncology 1:5, 609-618
CrossRef143
Ayalew Tefferi, Jerry L. Spivak. (2005) Polycythemia Vera: Scientific Advances and Current Practice. Seminars in Hematology 42:4, 206-220
CrossRef144
Guido Finazzi, Claire Harrison. (2005) Essential Thrombocythemia. Seminars in Hematology 42:4, 230-238
CrossRef145
Roberto Marchioli, Guido Finazzi, Rosa Maria Marfisi, Gianni Tognoni, Tiziano Barbui. (2005) Clinical Trials in Myeloproliferative Disorders: Looking Forward. Seminars in Hematology 42:4, 259-265
CrossRef146
Guido Finazzi, Tiziano Barbui. (2005) Risk-adapted therapy in essential thrombocythemia and polycythemia vera. Blood Reviews 19:5, 243-252
CrossRef147
A. Tefferi, T. Barbui. (2005) bcr/abl-Negative, Classic Myeloproliferative Disorders: Diagnosis and Treatment. Mayo Clinic Proceedings 80:9, 1220-1232
CrossRef148
Barbui, Tiziano, Finazzi, Guido, . (2005) When and How to Treat Essential Thrombocythemia. New England Journal of Medicine 353:1, 85-86
Full Text149
Harrison, Claire N., Campbell, Peter J., Buck, Georgina, Wheatley, Keith, East, Clare L., Bareford, David, Wilkins, Bridget S., van der Walt, Jon D., Reilly, John T., Grigg, Andrew P., Revell, Paul, Woodcock, Barrie E., Green, Anthony R., . (2005) Hydroxyurea Compared with Anagrelide in High-Risk Essential Thrombocythemia. New England Journal of Medicine 353:1, 33-45
Full Text150
Claire N. Harrison. (2005) Essential thrombocythaemia: challenges and evidence-based management. British Journal of Haematology 130:2, 153-165
CrossRef151
Mary F. McMullin, D. Bareford, P. Campbell, A. R. Green, Claire Harrison, Beverley Hunt, D. Oscier, M. I. Polkey, J. T. Reilly, E. Rosenthal, Kate Ryan, T. C. Pearson, Bridget Wilkins, . (2005) Guidelines for the diagnosis, investigation and management of polycythaemia/erythrocytosis. British Journal of Haematology 130:2, 174-195
CrossRef152
Bjorn Andreasson, Eva Lofvenberg, Jan Westin. (2005) Management of patients with polycythaemia vera: results of a survey among Swedish haematologists. European Journal of Haematology 74:6, 489-495
CrossRef153
Brian J. Zikmund-Fisher, Angela Fagerlin, Peter A. Ubel. (2005) What's Time Got to Do with It? Inattention to Duration in Interpretation of Survival Graphs. Risk Analysis 25:3, 589-595
CrossRef154
Claire Harrison. (2005) Pregnancy and its management in the Philadelphia negative myeloproliferative diseases. British Journal of Haematology 129:3, 293-306
CrossRef155
Rosemarie A Reiter, Bernd Jilma. (2005) Platelets and new antiplatelet drugs. Therapy 2:3, 465-502
CrossRef156
E Joanna Baxter, Linda M Scott, Peter J Campbell, Clare East, Nasios Fourouclas, Soheila Swanton, George S Vassiliou, Anthony J Bench, Elaine M Boyd, Natasha Curtin, Mike A Scott, Wendy N Erber, Anthony R Green. (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. The Lancet 365:9464, 1054-1061
CrossRef157
Josef T Prchal. (2005) Polycythemia vera and other primary polycythemias. Current Opinion in Hematology 12:2, 112-116
CrossRef158
H. Cario. (2005) Childhood polycythemias/erythrocytoses: classification, diagnosis, clinical presentation, and treatment. Annals of Hematology 84:3, 137-145
CrossRef159
M. A. Elliott, A. Tefferi. (2005) Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. British Journal of Haematology 128:3, 275-290
CrossRef160
Christian Opherk, Roland Brüning, Hannah L. Pellkofer, Martin Dichgans, Gerhard F. Hamann. (2005) Subarachnoid Hemorrhage and Diplopia as Initial Presentation of Polycythemia vera. Cerebrovascular Diseases 19:4, 279-280
CrossRef161
David Dingli, Ayalew Tefferi. (2005) A critical review of anagrelide therapy in essential thrombocythemia and related disorders. Leukemia & Lymphoma 46:5, 641-650
CrossRef162
Michael Steurer, Guenther Gastl, Wieslaw-Wiktor Jedrzejczak, Robert Pytlik, Werner Lin, Ernst Schl
gl, Heinz Gisslinger. (2004) Anagrelide for thrombocytosis in myeloproliferative disorders. Cancer 101:10, 2239-2246
CrossRef163
J. Gracia Colldeforns, D. Hernández Maraver, R. de Paz Arias, F. Hernández Navarro. (2004) Síndromes mieloproliferativos crónicos. Medicine - Programa de Formación Médica Continuada Acreditado 9:21, 1332-1346
CrossRef164
F. Gundling, F. Kreth, M. Tr
CrossRef165
Alessandro M. Vannucchi, Alberto Grossi, Alessandro Pancrazzi, Elisabetta Antonioli, Paola Guglielmelli, Francesca Balestri, Monica Biscardi, Simona Bulgarelli, Giovanni Longo, Claudio Graziano, Luigi Gugliotta, Alberto Bosi. (2004) PRV-1 , erythroid colonies and platelet Mpl are unrelated to thrombosis in essential thrombocythaemia. British Journal of Haematology 127:2, 214-219
CrossRef166
Ellinor I. B. Peerschke, Richard T. Silver, Babette Weksler, Sage E. Grigg, Naphtali Savion, David Varon. (2004) Ex vivo evaluation of erythrocytosis-enhanced platelet thrombus formation using the cone and plate(let) analyzer: effect of platelet antagonists. British Journal of Haematology 127:2, 195-203
CrossRef167
David Dingli, Ayalew Tefferi. (2004) Anagrelide: an update on its mechanisms of action and therapeutic potential. Expert Review of Anticancer Therapy 4:4, 533-541
CrossRef168
(2004) Low-Dose Aspirin in Polycythemia Vera. New England Journal of Medicine 350:16, 1683-1685
Full Text169
Schafer, Andrew I., . (2004) Thrombocytosis. New England Journal of Medicine 350:12, 1211-1219
Full Text170
Spivak, Jerry, . (2004) Daily Aspirin — Only Half the Answer. New England Journal of Medicine 350:2, 99-101
Full Text171
Thomas Bachleitner-Hofmann, Elke Grumbeck, Heinz Gisslinger. (2003) Oral anticoagulants as secondary prophylaxis of thrombosis in patients with polycythemia vera: a retrospective analysis of 15 patients. Thrombosis Research 112:4, 229-232
CrossRef
- Letters
