RESUMEN
By definition, idiopathic erythrocytosis (IE) applies to a group of patients characterised by having a measured RCM above their predicted normal range (an absolute erythrocytosis) and following investigation do not have a form of primary or secondary erythrocytosis. Patients with IE are heterogenous. The possibilities include physiological variation, 'early' polycythaemia vera (10-15% develop clear features of PV over a few years), unrecognized congenital erythrocytosis, unrecognized or unrecognizable secondary acquired erythrocytosis or a currently undescribed form of primary or secondary erythrocytosis. Patients are more commonly male with a median age at presentation of 55-60 years. Approximately half of the patients present with vascular occlusive complications. Retrospective evidence indicates that vascular occlusion occurs less frequently when the PCV is controlled at normal levels. Venesection is the treatment of choice to lower the PCV. As a general approach to management, all patients with a PCV above 0.54 should be venesected to a PCV less than 0.45. This target PCV should also apply to patients with lesser degrees of raised PCV who have additional other risk factors for vascular occlusion.
Asunto(s)
Policitemia , Anciano , Arteriopatías Oclusivas/etiología , Médula Ósea/patología , Clorambucilo/efectos adversos , Clorambucilo/uso terapéutico , Diagnóstico Diferencial , Enfermedades del Sistema Endocrino/complicaciones , Volumen de Eritrocitos , Células Precursoras Eritroides/patología , Eritropoyetina/sangre , Predisposición Genética a la Enfermedad , Humanos , Hipoxia/complicaciones , Enfermedades Renales/complicaciones , Leucemia/inducido químicamente , Leucemia Inducida por Radiación/etiología , Persona de Mediana Edad , Radioisótopos de Fósforo/efectos adversos , Radioisótopos de Fósforo/uso terapéutico , Policitemia/clasificación , Policitemia/congénito , Policitemia/diagnóstico , Policitemia/etiología , Policitemia/terapia , Policitemia Vera/diagnóstico , Receptores de Eritropoyetina/deficiencia , Receptores de Eritropoyetina/genética , Eliminación de Secuencia , Fumar/sangre , Accidente Cerebrovascular/etiologíaAsunto(s)
Trombocitosis/terapia , Adolescente , Adulto , Anciano , Humanos , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The term 'erythrocytosis' has advantages over 'polycythaemia' to describe patients with a raised haematocrit (PCV) and deserves to be more widely used. Measurement of red cell mass (RCM) and its relation to that expected for an individual's height and weight permits initial subdivision of erythrocytosis into absolute (increased RCM) or apparent normal RCM. Absolute erythrocytosis may be primary (intrinsically abnormal marrow erythropoiesis) or secondary (increased erythropoietin drive in response to pathological events outside the bone marrow). Both primary and secondary erythrocytosis may be either congenital or acquired. Idiopathic erythrocytosis is a third, probably heterogenous, group within the absolute erythrocytoses. Familial abnormalities of the erythropoietin receptor underlie the primary congenital subgroup. Polycythaemia vera (PV), the clonal myeloproliferative disorder, is so far, the only primary acquired disorder. Newer diagnostic investigations such as serum erythropoietin estimation, improved karyotypic analysis, in vitro culture of erythroid colonies and estimation of spleen size before splenomegaly is palpable, have permitted some modification of the traditional diagnostic criteria of polycythaemia vera. This may allow more confident diagnosis and, together with improved testing for causes of secondary erythrocytosis, may reduce the number of patients so far unsatisfactorily consigned to the idiopathic erythrocytosis group.
Asunto(s)
Policitemia , Humanos , Policitemia/clasificación , Policitemia/diagnósticoRESUMEN
Detection of non-palpable early splenic enlargement may aid diagnosis of primary polycythaemia (PP) and primary thrombocythaemia (PT). In this study linear spleen sizing by ultrasound has been compared with spleen volume estimation by single photon emission computerized tomography (SPECT) in 26 patients. Spleen length by ultrasound correlated well with SPECT volume estimation. Ultrasound spleen length was also measured in 60 normal control subjects where the upper limit of the 95% reference range was 11.6 cm. Changes in spleen length with both age and body weight were substantial and overshadowed the imperfect reproducibility of this method. Therefore, interpretation of an individual's measured spleen length should be in relation to that predicted for adults of the same age and weight, particularly at the extremes of the younger, heavier patients and also the older, lighter patients. Ultrasound spleen lengths of different patient groups (21 PP, 26 PT, 17 idiopathic erythrocytosis, 12 secondary polycythaemia, nine apparent polycythaemia) were compared both using the measured overall reference range and the differences from the values predicted for their age and weight. The comparison showed that almost all patients with PP whose spleens were not palpable had spleen lengths greater than the upper limit for the normal control group, but separation from the other patient groups was incomplete. Detection of non-palpable splenomegaly by ultrasound length should remain a 'minor' criterion amongst the 'proposed modified diagnostic criteria' of PP.
Asunto(s)
Policitemia/patología , Bazo/patología , Trombocitemia Esencial/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Policitemia/diagnóstico por imagen , Bazo/diagnóstico por imagen , Esplenomegalia/diagnóstico por imagen , Esplenomegalia/patología , Trombocitemia Esencial/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , UltrasonografíaRESUMEN
Polycythaemia may complicate or be the presenting feature of a wide variety of different pathologies. Early diagnosis and treatment of primary polycythaemia will significantly reduce the morbidity and mortality associated with this condition. Patients with a raised packed cell volume are divided into those with a raised red cell mass (absolute polycythaemia), and those with a red cell mass within their normal range (apparent polycythaemia). A standard investigative approach of an absolute polycythaemia enables patients with primary and secondary polycythaemia to be identified, leaving a group termed idiopathic erythrocytosis. There are a number of physiological situations and pathological events associated with idiopathic erythrocytosis and apparent polycythaemia. Careful follow-up of both groups of these patients is essential to identify possible causative mechanisms.
Asunto(s)
Policitemia/diagnóstico , Sondas de ADN , Humanos , Policitemia/sangre , Policitemia/orinaRESUMEN
There is no single diagnostic marker for polycythaemia vera (PV). The Polycythemia Vera Study Group established diagnostic criteria more than twenty years ago. Since some new laboratory and clinical investigations have developed, these criteria can now be updated. It is proposed that the overall pattern of major and minor criteria should remain. A raised red cell mass (greater than 25% above the patient's mean normal predicted value based on surface area) and absence of a cause of secondary polycythaemia are essential criteria. Then either palpable splenomegaly or the presence of a marker of clonal haemopoiesis would support the diagnosis of PV. In the absence of both of these latter major criteria, at least two minor criteria must be present to secure the diagnosis. These are: platelet count > 400 x 10(9)/l; neutrophil count > 10 x 10(9)/l; splenomegaly demonstrated by a scanning technique; characteristic BFU-E growth or reduced serum erythropoietin value.
Asunto(s)
Policitemia Vera/diagnóstico , Fosfatasa Alcalina/sangre , Biomarcadores , Recuento de Células Sanguíneas , Médula Ósea/patología , Células Clonales/patología , Diagnóstico Diferencial , Compensación de Dosificación (Genética) , Volumen de Eritrocitos , Células Precursoras Eritroides/patología , Eritropoyetina/análisis , Femenino , Humanos , Masculino , Oxígeno/sangre , Policitemia Vera/sangre , Policitemia Vera/complicaciones , Policitemia Vera/patología , Esplenomegalia/etiologíaRESUMEN
Plethora ('a morbid condition due to excess of red corpuscles') has been recognized since antiquity as a manifestation of disease. The use of leeches and blood letting, which was for centuries the mainstay of therapy in many clinical situations, reflected the importance then attached to having too much blood. Greater knowledge has achieved greater precision, so that measurement of packed cell volume (PCV) or hematocrit now defines polycythemia (> 0.51 in men and > 0.48 in women, when blood is sampled without venous occlusion). Clinical and laboratory investigations, mainly in the last 30 years, have enabled the subdivision of polycythemia into different subtypes of radically different etiology which will be described in this Chapter. The last decade, however, has seen the advancing edge of research in this field passing from clinical and routine laboratory testing to studies of cellular proliferation at the molecular level. Detailed understanding is, however, as always elusive, with each new finding revealing deeper layers which in turn need elucidation. The field of polycythemia is nevertheless moving slowly into the molecular era.
Asunto(s)
Policitemia/fisiopatología , Médula Ósea/metabolismo , Eritrocitos/metabolismo , Eritropoyetina/metabolismo , Hematócrito , Hemoglobinas/metabolismo , Humanos , Oxígeno/metabolismo , Policitemia/clasificación , Policitemia/diagnósticoRESUMEN
Some patients with an early or latent myeloproliferative disorder (MPD) present with Budd-Chiari syndrome (BCS, hepatic vein thrombosis). Cell culture analysis of erythroid progenitors (BFU-E) can be used to discriminate primary from secondary MPD and examination of X-chromosome inactivation (in females) can be used to demonstrate clonality in neoplastic tissues. The present study used these techniques to examine whether a group of 7 female patients who presented with BCS had evidence to support a diagnosis of MPD. Unilateral X-inactivation and therefore clonality can be studied in females heterozygous for X-linked restriction fragment length polymorphisms (RFLP) by differences in methylation between active and inactive chromosomes. Probes for two polymorphic loci, phosphoglycerate kinase (PGK, at Xq13.3 [BstX1 RFLP]) and M27 beta (an anonymous locus DXS255 at Xp11.22 [Pst1 RFLP]) were used to study methylation patterns. All 7 patients were heterozygous using M27 beta and 2/7 were also heterozygous using the PGK probe. Polyclonal patterns of X-inactivation in granulocytes were demonstrated in 3/7, a skewed/monoclonal pattern in 1/7 and aberrant patterns in 3/7 using M27 beta. Two patients who had aberrant patterns of X inactivation with M27 beta demonstrated a skewed/monoclonal pattern with PGK. The results of BFU-E growth patterns and clonality were entirely concordant in 5/6 patients. Thus X-chromosome inactivation patterns, in conjunction with erythroid colony studies, can be used to assist in the diagnosis of an underlying MPD in BCS.
Asunto(s)
Síndrome de Budd-Chiari/complicaciones , Trastornos Mieloproliferativos/diagnóstico , Biomarcadores , Síndrome de Budd-Chiari/patología , Células Cultivadas , Células Clonales , Compensación de Dosificación (Genética) , Eritropoyesis , Femenino , Humanos , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
Estimations of serum erythropoietin level by enzyme immunoassay (EIA) kit were made in 42 patients with primary polycythaemia, and in a comparison group consisting of 41 patients with secondary polycythaemia and 47 patients with idiopathic erythrocytosis. The majority of patients with primary polycythaemia were undergoing treatment by venesection and therefore had Hb levels in the normal range at the time of erythropoietin estimation. In primary polycythaemia, 64% of the first samples taken from each patient were below the reference range for serum erythropoietin in normal individuals. When two samples were taken from each patient 72% had low values in one or both samples. In the comparison group, analysis of those patients who had two samples taken showed only one individual with secondary polycythaemia and none with idiopathic erythrocytosis who had a serum erythropoietin level below the reference range. The finding of low serum erythropoietin in patients with primary polycythaemia, even when Hb levels are normal due to venesection, is of high diagnostic specificity (few false positive results) and useful diagnostic sensitivity (28% false negative results). It is proposed that future diagnostic criteria of primary polycythaemia should include the finding of a serum erythropoietin level below the lower limit of normal in at least one of two serum samples taken on different occasions.
Asunto(s)
Eritropoyetina/sangre , Hemoglobinas/metabolismo , Policitemia/diagnóstico , Adulto , Femenino , Humanos , Masculino , Policitemia/sangre , Valor Predictivo de las PruebasRESUMEN
25 patients with idiopathic erythrocytosis (absolute increase in red cell mass without conventional criteria of primary polycythaemia or known underlying cause) have been further studied for evidence of primary or secondary polycythaemia. Additional non-conventional criteria used were: platelet distribution width, platelet nucleotide ratio, serum erythropoietin, clinical evidence of ischaemic vascular disease and erythroid culture variables in serum-free system. All had been used in an earlier study in score form to assist in the diagnosis of primary polycythaemia. These patients were also newly assessed for the presence of hypoxia (supine oximeter values, history suggestive of sleep apnoea), for renal lesions and for splenic enlargement (impalpable) by ultrasound or computerized tomography. 7 patients had erythroid culture scores suggesting primary polycythaemia but the addition of non-culture criteria did not result in any scores more strongly predictive of primary polycythaemia. Supine oximeter values < 92% suggested hypoxaemia as the mechanism of polycythaemia in 3 patients in whom it had not previously been suspected. Some splenic enlargement (impalpable) was demonstrated in 6 patients, only 1 of whom had erythroid culture scores suggesting primary polycythaemia. 12 patients had confirmed, raised erythropoietin levels. We conclude that idiopathic erythrocytosis refers to a heterogenous group of patients. Features of primary or secondary polycythaemia may be demonstrated in some of them by additional new study techniques. The raised erythropoietin values found in half the patients were unexpected.
Asunto(s)
Policitemia/sangre , Adolescente , Adulto , Anciano , Plaquetas/química , Plaquetas/patología , Células Cultivadas , Células Precursoras Eritroides/patología , Eritropoyetina/análisis , Eritropoyetina/metabolismo , Femenino , Humanos , Hígado/diagnóstico por imagen , Masculino , Métodos , Persona de Mediana Edad , Policitemia/genética , Policitemia/patología , Radioinmunoensayo , UltrasonografíaRESUMEN
Traditional diagnostic criteria for primary thrombocythaemia (PT) remain essentially negative, aiming to exclude other myeloproliferative disorders and causes of reactive thrombocytosis (RT). It would be useful to have positive markers. We have examined several parameters to see how well they discriminate between PT and RT. Three groups of patients were studied: new, untreated PT (17), treated PT (12) and RT (17). Data consisted of: ESR, plasma fibrinogen, factor VIIIC, von Willebrand factor antigen (vWF:Ag), PDW, platelet nucleotide ratio (ATP:ADP) serum erythropoietin (Epo), ristocetin cofactor (vWF:RiCoF), multimeric structure of vWF, interleukin-6, evidence of clinical ischaemia and erythroid colony formation. Erythroid colonies were assayed in a serum-free system with the addition of Epo, IL3 or alpha-IFN to produce a discriminant function (DF) successfully used in the diagnosis of primary polycythaemia in an earlier study. Acute phase reactants (ESR, fibrinogen, VIIIC, vWF:Ag) and IL6 were the best discriminants, while PDW and serum Epo were less so. ATP:ADP and clinical ischaemia were nondiscriminatory in this study. Reduction in vWF:RiCof and in high molecular weight multimers were clearly associated with PT. Endogenous erythroid colonies were nondiscriminatory, but half the PT group and only one patient in the RT group obtained a DF suggestive of myeloproliferative disorder. Judicious use of a battery of tests may provide support for diagnosis of PT in difficult cases.
Asunto(s)
Trombocitemia Esencial/diagnóstico , Trombocitosis/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de PlaquetasRESUMEN
Patients with polycythaemia and normal controls have been studied to establish and subsequently test non-conventional criteria for the diagnosis of primary polycythaemia (primary proliferative polycythaemia, polycythaemia vera) as compared with conventional Polycythaemia Vera Study Group (PVSG) assessment. One criterion was erythroid colony formation from peripheral blood in a serum-free system, assayed alone and with the addition of recombinant human erythropoietin (Epo), interleukin 3 (IL3), or alpha interferon (alpha-IFN) (Dudley et al. 1990). The remaining criteria were non-culture associated and comprised platelet distribution width (PDW), platelet nucleotide ratio (ATP:ADP), serum erythropoietin and clinical evidence of ischaemic vascular disease. The combination of culture associated and non-culture associated variables, by use of a simple additive scoring system, gave no false positive and only 6% false negative results in distinguishing primary polycythaemia from other polycythaemias and normal controls in those (34 patients Group A) used in its derivation. Testing the scoring system in a newly presenting group (25 patients Group B) was highly satisfactory with no false positives and only a few false negative results (14%). Use of these non-conventional criteria should allow more confident diagnosis of primary polycythaemia, where conventional clinical and laboratory assessment is inconclusive.
Asunto(s)
Eritrocitos/efectos de los fármacos , Policitemia Vera/diagnóstico , Policitemia/diagnóstico , Adenosina Difosfato/sangre , Adenosina Trifosfato/sangre , Adulto , Biomarcadores/sangre , Plaquetas/fisiología , Células Cultivadas , Ensayo de Unidades Formadoras de Colonias , Diagnóstico Diferencial , Eritropoyetina/sangre , Eritropoyetina/farmacología , Femenino , Humanos , Interferón Tipo I/farmacología , Interleucina-3/farmacología , Isquemia/diagnóstico , Masculino , Policitemia/sangre , Policitemia Vera/sangre , Proteínas Recombinantes/farmacología , Valores de Referencia , Trombosis/diagnósticoRESUMEN
The term "apparent polycythaemia" is applied to a group of patients who have a raised PCV (> 0.51 in males, > 0.48 in females) but a normal red cell mass (less than 25% above their predicted mean normal value). Some have additionally a marked reduction in plasma volume and can be defined as a subgroup: relative polycythaemia. Smoking, hypertension and to a lesser extent obesity, excessive alcohol, low-dose diuretic therapy and hypoxaemia have all been associated with apparent polycythaemia but the mechanism is both uncertain and likely to be complex. This group of patients is unlikely to be uniform in pathogenesis and may well include some normal individuals. Investigation requires exclusion of factors associated with other types of polycythaemia. The possibility of an increased vascular occlusive risk is uncertain in these patients except at the higher PCV values. Reduction of PCV by venesection is sensible at PCV > 0.54 or where there is perceived to be an increased risk of vascular occlusion. The remaining patients should be managed by regular observation to detect further rise in PCV or evolution to absolute polycythaemia (raised red cell mass). In some, the PCV returns to normal.
Asunto(s)
Policitemia , Volumen de Eritrocitos , Femenino , Hematócrito , Humanos , Masculino , Policitemia/sangre , Policitemia/complicaciones , Policitemia/diagnóstico , Policitemia/terapia , Enfermedades Vasculares/etiologíaAsunto(s)
Encéfalo/irrigación sanguínea , Circulación Cerebrovascular , Compuestos de Organotecnecio , Oximas , Policitemia/diagnóstico por imagen , Policitemia/fisiopatología , Encéfalo/diagnóstico por imagen , Hematócrito , Humanos , Policitemia/terapia , Cintigrafía , Exametazima de Tecnecio Tc 99mAsunto(s)
Policitemia/diagnóstico , Anciano , Venodisección , Hematócrito , Humanos , Persona de Mediana Edad , Policitemia/terapiaAsunto(s)
Oxígeno/sangre , Policitemia/sangre , Adulto , Anciano , Volumen de Eritrocitos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sueño/fisiologíaRESUMEN
Thirty four consecutive patients (31 male, 3 female) with raised PCV (males greater than 0.51, females greater than 0.47) and normal red cell mass (apparent polycythaemia) and with normal red cell mass but a low plasma volume (relative polycythaemia) were studied retrospectively. Male sex, smoking, hypertension and diuretic therapy were found to be associated factors while obesity and excessive alcohol consumption were less clearly linked. Only three patients (all males) were negative for all these factors. Approximately 15% of patients had arterial hypoxaemia. There was no difference in the incidence of these factors in the two sub-groups. Possible mechanisms relating these factors to the raised PCV are discussed. Preliminary follow-up data show that in approximately one third of the patients the PCV returns to normal and that this is most likely in those patients with a normal recumbent PCV (at the time of the blood volume study). In one third the PCV continues to be raised, and the remainder have only intermittently raised PCV. As a result of this study, prospective studies of the incidence of hypoxaemia in these patients and of the PCV outcome with and without correction of associated factors are planned.