RESUMEN
Hyperviscosity syndrome is a clinical condition characterized by the slowing of blood flow through the vessels and it may be associated with several diseases. The nosographic classification of primary hyperviscosity conditions (Wells classification 1970) divided the primary hyperviscosity syndromes in polycythaemic, sclerocytemic and sieric. Recent and personal laboratory observations have highlighted an unexpected behaviour of the erythrocyte deformability observed in some haematological disorders such as polycythemia vera, multiple myeloma and monoclonal gammopathy of undetermined significance. The interest of this observation depends on the fact that up to now, according to the Wells classification, the hemorheological alteration present in PV was related to the increase of RBC mass while that present in MM and MGUS was attributable to the abnormality of plasma or serum viscosity only. Through an extensive research among the literature, using MEDLINE/PubMed to identify all published reports on the hyperviscosity syndromes, issues that until now have been dealt with separately will therefore be analyzed in a unique paper, allowing a global view. The aim of this paper is to provide some suggestions for reflection and emphasizing the need of a nosographic framework of hyperviscosity that, probably, deserves to be reviewed.
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Viscosidad Sanguínea , Deformación Eritrocítica , Gammopatía Monoclonal de Relevancia Indeterminada/fisiopatología , Mieloma Múltiple/fisiopatología , Policitemia Vera/fisiopatología , Animales , Humanos , Modelos Cardiovasculares , Gammopatía Monoclonal de Relevancia Indeterminada/sangre , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Mieloma Múltiple/sangre , Mieloma Múltiple/diagnóstico , Policitemia Vera/sangre , Policitemia Vera/diagnósticoRESUMEN
OBJECTIVES: Pregnancies in women with polycythemia vera (PV) are associated with an increased risk of PV-related maternal complications and often result in miscarriage. Recommendations for the management of PV pregnancies are mainly based on studies with a small number of patients. A correlation between pregnancy outcome and postpartum course has been reported for essential thrombocythemia, but corresponding data for PV are lacking so far. METHODS: In 41 PV pregnancies, the pregnancy outcome, the use of PV-specific therapies (ie, acetylsalicylic acid, low-molecular weight heparin and/or interferon-alpha), and the postpartum PV course were investigated. RESULTS: A live birth rate of 51.2% (21/41 pregnancies) was observed. 43.9% of pregnancies ended in spontaneous abortion and 4.9% in stillbirth. A significantly increased live birth rate occurred in pregnancies with PV-specific therapies compared to standard antenatal care (69.0% vs. 8.3%; P < .0019). The use of PV-specific therapy significantly increased the number of maternal hemorrhages (P = .021) without increasing the risk of fetal complications. During the median postpartum follow-up period of 1.2 years (range 0.1-13.7), complicated postpartum PV occurred significantly more often after miscarriages (P = .035). CONCLUSIONS: According to our analysis, PV-specific therapy improved the live birth rate. Significantly more complicated postpartum PV courses were observed after miscarriages.
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Hemorragia/etiología , Policitemia Vera/fisiopatología , Policitemia Vera/terapia , Complicaciones del Embarazo/fisiopatología , Complicaciones del Embarazo/terapia , Aborto Espontáneo , Adolescente , Adulto , Femenino , Heparina de Bajo-Peso-Molecular , Humanos , Policitemia Vera/complicaciones , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , Trombocitemia Esencial/terapia , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Polycythemia vera (PV), a Philadelphia chromosome-negative myeloproliferative neoplasm, is characterized by panmyelosis, pancytosis, and a JAK2 mutation. Patients are at increased risk of thrombohemorrhagic events, and progression to myelofibrosis or acute leukemia. Current treatments include aspirin, phlebotomy, and cytoreductive drugs (most commonly hydroxyurea). Givinostat is a potent, class I/II histone deacetylase (HDAC) inhibitor that is in phase I/II clinical trials in PV. Givinostat was well tolerated and yielded promising clinico-hematological responses. A phase III study of givinostat versus hydroxyurea in high-risk PV patients is planned. AREAS COVERED: We present an overview of PV, current treatment guidelines, and the putative mechanism(s) of action of givinostat. We discuss the preclinical and clinical studies of givinostat in PV and briefly review approved and investigational competitor compounds. EXPERT OPINION: HDAC inhibitors have long been known to be active in PV, but chronic toxicities can be challenging. Givinostat, however, is active and well tolerated, and is entering a pivotal Phase III randomized trial. Givinostat offers the possibility of replacing hydroxyurea as the standard first-line cytoreductive choice for PV patients. This would completely change the current therapeutic paradigm and guidelines for PV management. Although surrogate clinical study endpoints may suffice for regulatory purposes, thrombosis reduction and prevention of disease progression remain most important to patients and clinicians.
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Carbamatos/administración & dosificación , Inhibidores de Histona Desacetilasas/administración & dosificación , Policitemia Vera/tratamiento farmacológico , Animales , Carbamatos/efectos adversos , Carbamatos/farmacología , Progresión de la Enfermedad , Inhibidores de Histona Desacetilasas/efectos adversos , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Hidroxiurea/administración & dosificación , Hidroxiurea/efectos adversos , Hidroxiurea/farmacología , Janus Quinasa 2/genética , Mutación , Policitemia Vera/genética , Policitemia Vera/fisiopatologíaRESUMEN
INTRODUCTION: Current treatment for polycythemia vera (PV) is limited and primarily targets thrombosis risk. Agents targeting distinct mechanisms of action within myeloproliferation are undergoing clinical evaluation to optimize efficacy, improve tolerance and augment long term disease complications. AREA COVERED: This article reviews the current data from completed early phase clinical trials in PV, either as monotherapy or in combination with the few currently approved agents. EXPERT OPINION: There remains an opportunity in PV management to improve efficacy and decrease risk of disease progression. Evolving data from use of long acting interferons are serving to clarifying the potential front line role of this therapy. JAK2 inhibition has made a significant impact on decreasing morbidity in patients with hydroxyurea resistant/refractory disease. New approaches may soon expand options including histone deactylase inhibitors (HDACi), either as monotherapy or combination therapy, which showed promising activity and symptomatic control of pruritus. Drugs targeting new molecular pathways (mammalian target of rapamycin, insulin receptor substrates 1/2, MDM2 protein) or the iron metabolism pathway are in early phase trial. Further translational studies assessing efficacy, long term complications, survival, and constitutional symptom control could pave a way for future success in PV drug development either as monotherapy or in combination.
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Desarrollo de Medicamentos , Terapia Molecular Dirigida , Policitemia Vera/tratamiento farmacológico , Animales , Progresión de la Enfermedad , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Hidroxiurea/uso terapéutico , Janus Quinasa 2/antagonistas & inhibidores , Policitemia Vera/fisiopatologíaRESUMEN
INTRODUCTION: Polycythemia vera (PV) is the most common myeloproliferative neoplasm (MPN). PV is characterized by erythrocytosis, leukocytosis, thrombocytosis, increased hematocrit, and hemoglobin in the peripheral blood. Splenomegaly and myelofibrosis often occur in PV patients. Almost all PV patients harbor a mutation in the JAK2 gene, mainly represented by the JAK2V617F point mutation. AREAS COVERED: This article examines the recent in vitro and in vivo available models of PV and moreover, it offers insights on emerging biomarkers and therapeutic targets. The evidence from mouse models, resembling a PV-like phenotype generated by different technical approaches, is discussed. The authors searched PubMed, books, and clinicaltrials.gov for original and review articles and drugs development status including the terms Myeloproliferative Neoplasms, Polycythemia Vera, erythrocytosis, hematocrit, splenomegaly, bone marrow fibrosis, JAK2V617F, Hematopoietic Stem Cells, MPN cytoreductive therapy, JAK2 inhibitor, histone deacetylase inhibitor, PV-like phenotype, JAK2V617F BMT, transgenic JAK2V617F mouse, JAK2 physiologic promoter. EXPERT OPINION: Preclinical models of PV are valuable tools for enabling an understanding of the pathophysiology and the molecular mechanisms of the disease. These models provide new biological insights on the contribution of concomitant mutations and the efficacy of novel drugs in a 'more faithful' setting. This may facilitate an enhanced understanding of pathogenetic mechanisms and targeted therapy.
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Janus Quinasa 2/genética , Terapia Molecular Dirigida , Policitemia Vera/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Desarrollo de Medicamentos , Humanos , Ratones , Mutación Puntual , Policitemia Vera/genética , Policitemia Vera/fisiopatología , Mielofibrosis Primaria/tratamiento farmacológico , Mielofibrosis Primaria/etiología , Esplenomegalia/tratamiento farmacológico , Esplenomegalia/etiologíaRESUMEN
La eritrocitaféresis terapéutica (ET) es una estrategia más eficiente que la flebotomía en la reducción del hematocrito en las eritrocitosis primarias y secundarias. Objetivo: Analizar la tasa de respuesta y seguridad de la ET en policitemia vera (PV) y eritrocitosis secundaria (ES). Pacientes y método: Revisión retrospectiva de los pacientes con PV o ES tratados con ET, ante el fracaso a flebotomías o con comorbilidades que impedían cambios importantes de volemia. Resultados: Se realizaron 127 sesiones de ET (48 PV y 79 ES) en 20 pacientes (12 ES y 8 PV). La respuesta se obtuvo en el 87,5% de PV y en el 50% de ES. La tasa de complicaciones fue del 7,08%. Conclusiones: A pesar del tamaño de nuestra muestra y la heterogeneidad clínica de nuestra serie, podemos postular que la ET reduce de manera segura los valores de hematocrito en menor tiempo que la flebotomía, especialmente en pacientes con PV y en casos seleccionados de ES en quienes se prevé intolerancia hemodinámica a la flebotomía o en quienes falla este método
Therapeutic erythrocytapheresis (TE) is a more efficient strategy compared to phlebotomy to deplete levels of haematocrit in primary and secondary erythrocytosis. Objective: To analyse response rate and safety profile of TE in polycythemia vera (PV) and secondary erythrocytosis (SE). Patients and method: Retrospective review of all patients with PV or SE treated with TE, due to phlebotomy failure, or comorbidities that prevented changes of blood volumen. Results: 217 TE sessions (48 PV and 79 SE) corresponding to 20 patients (12 ES and 8 PV). Response were achieved in 87.5% of PV patients and in 50% of SE patients. Adverse effects related to TE performance occurred in 7.08%. Conclusion: Despite our small sample size and the heterogeneous nature of the patients included, we can postulate that TE is a secure strategy that can achieve haematocrit depletion in a shorter time than phlebotomy, specifically in PV patients and in selected cases of SE with expected haemodynamic intolerance to phlebotomies or in patients who fail to respond to phlebotomies
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Citaféresis/métodos , Policitemia/terapia , Policitemia Vera/terapia , Citaféresis/estadística & datos numéricos , Policitemia/fisiopatología , Policitemia Vera/fisiopatología , Estudios Retrospectivos , Insuficiencia del Tratamiento , Flebotomía/métodosRESUMEN
A 7-year-old male castrated cat was presented because of an acute onset of lethargy and vestibular ataxia. The cat was diagnosed with polycythemia vera. Later the patient developed additional clinical signs including orofacial twitching, aggressivity, hypersalivation, circling and a head tilt. A magnetic resonance imaging was performed and revealed hippocampal alterations compatible with hippocampal sclerosis. The presented case report describes the clinical signs and hematologic findings in a cat with polycythemia vera and the response of treatment. Another part is the discussion about the hypothesis that the hippocampal alterations were due to a cerebral hypoperfusion caused by the polycythemic condition.
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Hipocampo , Policitemia Vera , Esclerosis , Animales , Enfermedades de los Gatos/diagnóstico por imagen , Enfermedades de los Gatos/fisiopatología , Gatos , Hipocampo/diagnóstico por imagen , Hipocampo/fisiopatología , Imagen por Resonancia Magnética/veterinaria , Masculino , Policitemia Vera/complicaciones , Policitemia Vera/fisiopatología , Policitemia Vera/veterinaria , Esclerosis/diagnóstico por imagen , Esclerosis/etiología , Esclerosis/fisiopatología , Esclerosis/veterinariaAsunto(s)
Aspirina/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Policitemia Vera/tratamiento farmacológico , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológico , Adulto , Antiinflamatorios no Esteroideos/uso terapéutico , Anticoagulantes/uso terapéutico , Manejo de la Enfermedad , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Policitemia Vera/fisiopatología , Embarazo , Complicaciones Neoplásicas del Embarazo/etiología , Complicaciones Neoplásicas del Embarazo/patología , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To investigate the intensity of burdensome symptoms using self-assessment MPN-SAF TSS in patientswith radiation-associated and spontaneous myeloproiliferative neoplasms (MPNs). MATERIALS AND METHODS: The study included 89 patients with radiation-associated and spontaneous MPNs, the bur-densome symptoms of MPN were determined using MPN-SAF TSS. RESULTS: The average score for complaints in patients with radiation-associated MPNs was significantly higher thanin patients with spontaneous MPNs - 43.46 and 25.04 points, respectively (p = 0.003). MPN patients classified bysubtypes also showed differences regarding intensity of burdensome MPN symptoms, demonstrating significantlyhigher average score of complaints among primary myelofibrosis patients (35.60), compared to polycythemia vera(29.60) and essential thrombocythemia (18.05) patients, (p = 0.005). Our study did not reveal any influence of theJAK2 V617F mutation on MPN burdensome symptoms intensity in MPN patients. CONCLUSIONS: We demonstrated a higher intensity of the MPN burdensome symptoms determined by the optimizedself-assessment MPN-SAF TSS in patients with radiation-associated, and in primary myelofibrosis patients, indicat-ing increased severity of patient's general conditions at the stage of diagnosis verification. It is advisable to usethe optimized MPN-SAF TSS at the moment of molecular genetic testing during the diagnosis of MPN for selectionor modifying treatment strategies in order to achieve better quality of life for patients.
Asunto(s)
Accidente Nuclear de Chernóbil , Exposición a Riesgos Ambientales/efectos adversos , Policitemia Vera/fisiopatología , Mielofibrosis Primaria/fisiopatología , Exposición a la Radiación/efectos adversos , Trombocitemia Esencial/fisiopatología , Adulto , Anciano , Femenino , Expresión Génica , Humanos , Janus Quinasa 2/genética , Masculino , Persona de Mediana Edad , Mutación , Policitemia Vera/etiología , Policitemia Vera/genética , Policitemia Vera/psicología , Mielofibrosis Primaria/etiología , Mielofibrosis Primaria/genética , Mielofibrosis Primaria/psicología , Calidad de Vida/psicología , Dosis de Radiación , Radiación Ionizante , Autoevaluación (Psicología) , Índice de Severidad de la Enfermedad , Trombocitemia Esencial/etiología , Trombocitemia Esencial/genética , Trombocitemia Esencial/psicología , UcraniaRESUMEN
RATIONALE: Spinal cord infarction is rarely caused by hypercoagulable states. Polycythemia vera (PV) is a myeloproliferative neoplasm that can contribute to thrombotic events due to increased blood viscosity. We report a case of spinal cord infarction due to extensive aortic thrombosis caused by PV. PATIENT CONCERNS: A 56-year-old man presented with acute paraplegia and urinary retention during heavy physical exertion. DIAGNOSES: Imaging studies revealed spinal cord infarction at the T9 to T12 levels and aortoiliac occlusive disease. PV was diagnosed during workup for elevated hemoglobin level INTERVENTIONS:: The patient received intravenous hydration and anticoagulation for spinal cord infarction. PV was managed with phlebotomy and hydroxyurea. Courses of inpatient and outpatient rehabilitation programs were also given. OUTCOMES: The patient became urinary catheter-free 5 months after disease onset, and was able to walk with walker. The American Spinal Injury Association Impairment scale also improved from C at diagnosis to D during last follow-up. LESSONS: Etiologic workup is important for patients with spinal cord infarction to direct specific treatment strategies. Physical exertion may act as a trigger for infarction in patients at risk for thrombotic events, and monitoring of neurologic status during and after periods of exercise is warranted.
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Enfermedades de la Aorta/complicaciones , Arteriopatías Oclusivas/complicaciones , Arteria Ilíaca/fisiopatología , Infarto/etiología , Esfuerzo Físico/fisiología , Policitemia Vera/complicaciones , Médula Espinal/irrigación sanguínea , Aorta/fisiopatología , Enfermedades de la Aorta/fisiopatología , Arteriopatías Oclusivas/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Policitemia Vera/fisiopatologíaRESUMEN
Very important developments related to polycythemia vera (PV) have occurred during the last two decades. The discovery of Janus kinase (JAK) 2 mutations has changed both the diagnosis and clinical management of PV. Currently JAK2 molecular testing is essential in the diagnostic work-up and JAK2 mutation positivity is a major diagnostic criterion. The discovery of JAK2 mutations suggested that abnormal JAK-STAT signaling was a pivotal feature in the pathogenesis of Philadelphia-negative myeloproliferative neoplasms. This idea led to the development of JAK inhibitors. Currently ruxolitinib, a JAK1/JAK2 inhibitor, is also approved for PV patients with hydroxyurea resistance or intolerance. International collaborations have made it possible to describe disease characteristics and evolution better. Presently it is possible to quantify the symptomatic burden of the disease and to estimate prognosis. In spite of these developments, management of PV still largely depends on estimation of thromboembolic risk and trying to decrease the risk with or without cytoreductive medications. Different approaches have been proposed by international disease experts for the diagnosis, thromboembolic risk estimation, and drug selection. This paper aims to review clinical aspects of PV and propose a management algorithm. The authors also point to still unresolved questions and unmet needs in diagnosis and management.
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Policitemia Vera , Manejo de la Enfermedad , Progresión de la Enfermedad , Humanos , Janus Quinasa 2/antagonistas & inhibidores , Janus Quinasa 2/genética , Mutación/genética , Policitemia Vera/diagnóstico , Policitemia Vera/genética , Policitemia Vera/fisiopatología , Policitemia Vera/terapia , PronósticoAsunto(s)
Janus Quinasa 2/genética , Mutación Missense , Dolor , Policitemia Vera , Sustitución de Aminoácidos , Humanos , Masculino , Persona de Mediana Edad , Dolor/diagnóstico por imagen , Dolor/enzimología , Dolor/genética , Dolor/fisiopatología , Policitemia Vera/diagnóstico por imagen , Policitemia Vera/enzimología , Policitemia Vera/genética , Policitemia Vera/fisiopatologíaAsunto(s)
Janus Quinasa 2/genética , Leucemia Eritroblástica Aguda/genética , Anciano , Humanos , Janus Quinasa 2/metabolismo , Leucemia , Leucemia Eritroblástica Aguda/fisiopatología , Masculino , Mutación , Policitemia Vera/complicaciones , Policitemia Vera/genética , Policitemia Vera/fisiopatología , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
OPINION STATEMENT: Polycythemia vera (PV) is the most common myeloproliferative neoplasm (MPN), the ultimate phenotype of the JAK2 V1617F mutation, the MPN with the highest incidence of thromboembolic complications, which usually occur early in the course of the disease, and the only MPN in which erythrocytosis occurs. The classical presentation of PV is characterized by erythrocytosis, leukocytosis, and thrombocytosis, often with splenomegaly and occasionally with myelofibrosis, but it can also present as isolated erythrocytosis with or without splenomegaly, isolated thrombocytosis or isolated leukocytosis, or any combination of these. When PV is present, the peripheral blood hematocrit (or hemoglobin) determination will not accurately represent the actual volume of red cells in the body, because in PV, in contrast to other disorders causing erythrocytosis, when the red cell mass increases, the plasma volume usually increases. In fact, unless the hematocrit is greater than 59%, true erythrocytosis cannot be distinguished from pseudoerythrocytosis due to plasma volume contraction. Usually, the presence of splenomegaly or leukocytosis or thrombocytosis establishes the diagnosis. However, when a patient presents with isolated thrombocytosis and a positive JAK2 V617F assay, particularly a young woman, the possibility of PV must always be considered because of plasma volume expansion. The WHO PV diagnostic guidelines are not helpful in this situation, since the hematocrit is invariably normal and a bone marrow examination will not distinguish ET from PV. Only a direct measurement of both the red cell mass and plasma volume can establish the correct diagnosis. In managing a PV patient, it is important to remember that PV is an indolent disorder in which life span is usually measured in decades, even when myelofibrosis is present, that chemotherapy is futile in eradicating the disease but does increase the incidence of acute leukemia and that hydroxyurea is not safe in this regard nor is it antithrombotic. Phlebotomy to a sex-specific normal hematocrit is the cornerstone of therapy and there now exist safe remedies for controlling leukocytosis, thrombocytosis, and extramedullary hematopoiesis and symptoms due to inflammatory cytokines when this is necessary.
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Leucocitosis/complicaciones , Policitemia Vera/etiología , Policitemia/complicaciones , Esplenomegalia/complicaciones , Trombocitosis/complicaciones , Tromboembolia/complicaciones , Hematócrito , Humanos , Janus Quinasa 2/genética , Policitemia Vera/genética , Policitemia Vera/fisiopatologíaRESUMEN
Ruxolitinib was well tolerated and superior to best available therapy (including interferon [IFN]) in controlling hematocrit without phlebotomy eligibility, normalizing blood counts, and improving polycythemia vera-related symptoms in the Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care (RESPONSE) studies. This ad hoc analysis focuses on ruxolitinib in relation to IFN in the RESPONSE studies, with attention on the following: (1) safety and efficacy of ruxolitinib and best available therapy in patients who received IFN before study randomization, (2) safety and efficacy of IFN during randomized treatment in best available therapy arm, and (3) use of ruxolitinib after crossover from best available therapy in IFN-treated patients. IFN exposure before randomization had little effect on the efficacy or safety of ruxolitinib. In the randomized treatment arms, ruxolitinib was superior to IFN in efficacy [hematocrit control (RESPONSE = 60% of ruxolitinib vs 23% of IFN patients; RESPONSE-2 = 62% of ruxolitinib vs 15% of IFN patients)] and was tolerated better in hydroxyurea-resistant or hydroxyurea-intolerant patients. After crossing over to receive ruxolitinib, patients who had initially received IFN and did not respond had improved hematologic and spleen responses (62% of patients at any time after crossover) and an overall reduction in phlebotomy procedures. Rates and incidences of the most common adverse events decreased after crossover to ruxolitinib, except for infections (primarily grade 1 or 2). These data suggest that ruxolitinib is efficacious and well tolerated in patients who were previously treated with IFN. The RESPONSE (NCT01243944) and RESPONSE-2 (NCT02038036) studies were registered at clinicaltrials.gov .
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Antineoplásicos/uso terapéutico , Interferones/uso terapéutico , Quinasas Janus/antagonistas & inhibidores , Policitemia Vera/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/uso terapéutico , Adulto , Anciano , Antineoplásicos/efectos adversos , Venodisección/efectos adversos , Terapia Combinada/efectos adversos , Estudios Cruzados , Monitoreo de Drogas , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Femenino , Humanos , Hidroxiurea/efectos adversos , Hidroxiurea/uso terapéutico , Interferones/efectos adversos , Quinasas Janus/metabolismo , Masculino , Persona de Mediana Edad , Nitrilos , Policitemia Vera/metabolismo , Policitemia Vera/fisiopatología , Policitemia Vera/terapia , Pautas de la Práctica en Medicina , Inhibidores de Proteínas Quinasas/efectos adversos , Pirazoles/efectos adversos , Pirimidinas , Reproducibilidad de los Resultados , Esplenomegalia/etiología , Esplenomegalia/prevención & controlRESUMEN
RATIONALE: This case report describes the progression of primary myelofibrosis (PMF) to polycythemia vera (PV), and discuss its potential mechanisms. PATIENT CONCERNS: The patient was admitted because of abdominal discomfort and enlarged spleen for 19 months. DIAGNOSIS: A case of PMF progressed to PV was retrospectively analyzed. There were 19 months between the diagnosis of PMF and PV. The JAK2 V617F mutation was positive before and after the diagnosis of PV; however, new chromosomal abnormalities were detected during the progression. INTERVENTIONS: For treatment of PMF, the danazol, calcitriol, and thalidomide were given. Then, the use of thalidomide and calcitriol was stopped, and hydroxyurea was started. For treatment of PV, interferon treatment was given, whereas hydroxyurea was continued. OUTCOMES: After 30 months of the progression (at the recent follow-up), this patient had no obvious symptoms or thrombosis. LESSONS: PMF rarely progresses to PV, however, the progression will significantly improve the quality of life and prognosis.
Asunto(s)
Policitemia Vera/fisiopatología , Mielofibrosis Primaria/fisiopatología , Progresión de la Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Policitemia Vera/diagnóstico , Policitemia Vera/tratamiento farmacológico , Policitemia Vera/genética , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/tratamiento farmacológico , Mielofibrosis Primaria/genéticaRESUMEN
BACKGROUND AND OBJECTIVE: Data from the literature indicate the relationship between the bone marrow microvessel density and the blood parameters of angiogenesis. The aim of this study was to evaluate selected parameters of angiogenesis (VEGF-A, sVEGFR-1, and sVEGFR-2) and their correlations with white blood cells, platelets, and red blood cells. MATERIALS AND METHODS: The study included 72 patients (mean age, 61.84 years) with myeloproliferative neoplasms (MPNs): essential thrombocythemia (ET) (n=46), polycythemia vera (PV) (n=19), and primary myelofibrosis (PMF) (n=7). Serum VEGF-A, sVEGFR-1, and sVEGFR-2 were determined using the ELISA assay. RESULTS: We observed a significantly higher level of VEGF-A and reduced concentrations of sVEGFR-1 and sVEGFR-2 in the whole group of patients with MPNs as compared to controls. Detailed analysis confirmed significantly higher level of VEGF-A and lower concentration of sVEGFR-2 in each subgroups of MPNs patients. However, sVEGFR-1 concentrations were significantly lower only in PV and ET patients. CONCLUSIONS: The study showed an increased level of VEGF-A, which may indicate the intensity of neoangiogenesis in the bone marrow. Decreased sVEGFR-1 and sVEGFR-2 in the blood of patients with MPNs may reflect consumption of these soluble receptors.
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Neovascularización Patológica/sangre , Policitemia Vera/fisiopatología , Mielofibrosis Primaria/fisiopatología , Trombocitemia Esencial/fisiopatología , Factor A de Crecimiento Endotelial Vascular/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Receptor 2 de Factores de Crecimiento Endotelial Vascular/sangre , Anciano , Recuento de Células Sanguíneas , Médula Ósea/irrigación sanguínea , Médula Ósea/patología , Análisis Mutacional de ADN , Femenino , Fibrinógeno/análisis , Proteínas de Fusión bcr-abl/genética , Humanos , Masculino , Persona de Mediana Edad , Policitemia Vera/diagnóstico , Policitemia Vera/genética , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/genética , Estadísticas no Paramétricas , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/genéticaRESUMEN
In this cross-sectional study of 45 patients with myeloproliferative neoplasms, we found no evidence of secondary osteoporosis. INTRODUCTION: Patients with essential thrombocythemia (ET) and polycythaemia vera (PV) are at increased risk of fractures but the underlying mechanisms have not been settled. We conducted a study to assess bone mineral density, microarchitecture, estimated bone strength and global bone turnover in 45 patients with ET or PV. METHODS: Patients were evaluated in a cross-sectional study with dual energy X-ray absorptiometry (DXA) at the hip and spine; high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia; and biochemical markers of bone turnover including pro-collagen type 1 N-terminal pro-peptide, osteocalcin, C-terminal cross-linking telopeptide of type 1 collagen and bone-specific alkaline phosphatase. Also, 45 healthy comparisons, matched on age, height and weight with each patient were included as control subjects. RESULTS: Patients and comparisons had almost identical BMDs: 0.96 (IQR: 0.85-1.07) g/cm2 and 0.96 g/cm2 (IQR: 0.86-1.05 g/cm2), respectively. As well all microarchitecture and estimated bone strength measures were highly similar in the two groups. Levels of bone turnover markers were within reference values in patients. CONCLUSION: These results reveal no evidence of secondary osteoporosis among patients with ET or PV. The mechanism behind the increased fracture risk in ET or PV patients remains unknown.