POLYCYTHEMIA VERA—Peripheral Vascular Manifestations

The presenting manifestations of polycythemia vera are often complications involving the vascular system. These include myocardial infarction, cerebro-vascular accidents and ischemic changes in the extremities.The concept of increased atherogenesis in cases of polycythemia vera has been questioned. A possible mechanism by which small, otherwise subclinical atheromatous plaques produce ischemic symptoms in patients with polycythemia vera is discussed. The blood in polycythemic patients has been shown to have an increased viscosity resulting in a prolonged circulation time. If a small atheromatous plaque is present in association with increased blood viscosity, this combination may well produce ischemic symptoms. This explains why treatment of polycythemia vera, with restoration of blood to normal viscosity, often reverses the patient''s ischemic symptoms.Two cases of polycythemia vera here reported, in which the presenting manifestations were gangrenous extremities, emphasize the need for prompt diagnosis and treatment of polycythemia vera. In the first case, early recognition and treatment of polycythemia vera successfully reversed the ischemic changes in the extremities, while failure of early recognition and treatment in the second case resulted in two major amputations.     

Conversion of polycythemia vera to refractory anemia with hyperplastic bone marrow.

Clinical and morphologic findings in the conversion of treated polycythemia vera to pancytopenia with hyperplastic bone marrow (refractory anemia or pancytopenia with hyperplastic bone marrow) are described in light of our own observation. The nomenclature associated with this condition (pancytopenia, chronic erythroleukemia, preleukemia) is not uniform, whereas the morphologic findings are virtually identical. Some patients subsequently develop acute leukemia. The prognosis in cases of refractory anemia with hyperplastic bone marrow following polycythemia vera is, independent of the subsequent acute leukemia, invariably terminal.     

对比不同静脉放血方法治疗真性红细胞增多症的临床效果*

摘要目的：观察四种不同的静脉放血方法治疗真性红细胞增多症的临床疗效,对比分析不同疗法所用的时间及管道填塞率,从 而探讨治疗真性红细胞增多症的有效方法。方法：选取2009 年5 月至2012 年5 月我院收治的真性红细胞增多症患者50 名,随机 采取密闭式放血袋法、注射器法、胃肠减压器法和球形负压引流袋法对上述患者进行治疗,观察并比较不同方法治疗的过程中, 患者管道的填塞率及操作时间。结果：密闭式放血袋法在放血过程中穿刺成功率高,操作时间短,管道的填塞率低。结论：密闭式 放血袋操作简便,省时、省力、无并发症发生,可在临床广泛推广使用。     

Megakaryocyte precursors (pro- and megakaryoblasts) in bone marrow tissue from patients with reactive thrombocytosis, polycythemia vera and primary (essential) thrombocythemia. An immunomorphometric study

To determine the number of megakaryocyte precursors (pro- and megakaryoblasts), an immunomorphometric study was performed on paraffin-embedded trephine biopsies of the bone marrow using a monoclonal antibody against platelet glycoprotein IIIa. Eighteen control specimens from patients with no evidence of any hematological disorder and a normal platelet count were selected and assessed together with the same number of specimens from patients with reactive thrombocytosis, polycythemia vera rubra (P. vera) or primary (essential) thrombocythemia (PTH). A strikingly proportionate increase in early megakaryocytes occurred in all patients enrolled in this study, compared with the controls. Moreover, there were no significant correlations between counts for precursors or total megakaryocytes per square millimeter of bone marrow with the corresponding values for platelets. This indicates that despite an orderly increase in immature forms in the bone marrow, the number of platelets circulating in the blood is influenced by other additional factors, such as the expanded platelet pool in the enlarged spleen. The non-disproportionate expansion of megakaryocyte precursors extends previous findings on progenitor cells of this lineage in vitro, particularly in PTH. Histological evaluation of the bone marrow of patients with P. vera and PTH indicated that megakaryopoiesis proceeded to the production of appropriate mature forms with no obvious excess of very small or blastic elements.     

Monoclonal gammopathy in chronic myeloproliferative disorders

The incidence of monoclonal gammopathy in 61 patients with chronic myeloproliferative disorders (CMPD) was studied. The distribution of patients among the CMPD subgroups was: chronic myelocytic leukemia, 24 patients; myelofibrosis, 11; polycythemia vera, 15; essential thrombocythemia, 7; unclassified MPD, 4 patients. Monoclonal gammopathy was found in 5 patients (8.2%). Two of these patients (1 IgA/k and 1 IgM/k) had myelofibrosis and 3 (2 IgG/k and 1 IgG/lambda) polycythemia vera. The presence of monoclonal gammopathy indicates an involvement of the lymphoplasmatic system in CMPD.     

A contribution to the cytostatic long-term chemotherapy of polycythemia vera (author's transl)

From 1967 to 1978 38 patients with polycythemia vera received a long term cytostatic chemotherapy. The results of 14 patients who were given Procarbacin (Natulan) during a mean treatment time of 9 1/2 years are communicated. Two patients showed secondary tumors after 9 or 11 years respectively. The advantages and disadvantages of the various therapeutic approaches in the management of polycythemia in the literature are discussed together with our own experiences.     

对比不同静脉放血方法治疗真性红细胞增多症的临床效果

目的：观察四种不同的静脉放血方法治疗真性红细胞增多症的临床疗效,对比分析不同疗法所用的时间及管道填塞率,从而探讨治疗真性红细胞增多症的有效方法。方法：选取2009年5月至2012年5月我院收治的真性红细胞增多症患者50名,随机采取密闭式放血袋法、注射器法、胃肠减压器法和球形负压引流袋法对上述患者进行治疗,观察并比较不同方法治疗的过程中,患者管道的填塞率及操作时间。结果：密闭式放血袋法在放血过程中穿刺成功率高,操作时间短,管道的填塞率低。结论：密闭式放血袋操作简便,省时、省力、无并发症发生,可在临床广泛推广使用。     

Primary (essential) thrombocythemia versus polycythemia vera rubra. A histomorphometric analysis of bone marrow features in trephine biopsies

A morphometric analysis of bone marrow biopsies was performed in 25 patients each with clinical diagnoses of primary (essential) thrombocythemia (PTH) and polycythemia vera rubra (P. vera) according to the rigid diagnostic criteria of the Polycythemia Vera Study Group to reveal significant differences in the histomorphologic features between these disorders. In comparison with control specimens of patients without any hematologic disease, megakaryocyte proliferation was most prominent in PTH, even exceeding that of P. vera with concomitant thrombocythemia (11 of 25 cases with a platelet count greater than 600 X 10(9)/L). Moreover, in P. vera there were wide ranges of megakaryocyte sizes, consisting of micro-megakaryocytes as well as giant forms with highly segmented nuclei (four nuclear lobes), which gave the cells a pleomorphic appearance. As compared with the normal bone marrow, the amount of neutrophilic granulopoiesis and erythropoiesis was not significantly increased in PTH, in contrast to P. vera. Similar results were obtainable regarding the density of reticulin (argyrophilic) fibers: a normal content was encountered in the control specimens and PTH, whereas P. vera displayed a minimal-to-slight increase. Finally, the bone marrow of P. vera was totally devoid of stainable iron while hemosiderin deposits were detected in about two-thirds of the patients without hematologic disorders and in PTH. The characteristic differences revealed by this morphometric study may lead to an improvement of the controversial histologic diagnosis in these disorders.     

Chromosomal study of polycythemia during different stages of the disease

A cytogenetic analysis of blood and bone marrow cells of 15 polycythemia vera patients was carried out at different stages of disease during the G-banding technique. Chromosome aberrations of single character were noted before treatment only in one case, i.e. with the patient at stage II of disease. Cell clones with marker chromosomes were revealed in 6 of 9 patients examined in the course of treatment at stages II and III. The cytogenetic analysis was applied to the terminal stage of polycythemia (blast crisis) in one case, when 3 aberrant clones with multiple quantitative and structural chromosome rearrangements were discovered in blood cell cultures with and without PHA. No preferential involvement of definite chromosomes in aberrations was noticed in all the cases examined, no deletion of the 20q --chromosome being discovered. The role of the treatment in the induction of chromosome aberrations is discussed in addition to its dependence on the stage of disease. It is possible that all the clones of pathological character may appear during the long-termed course of polycythemia in patients treated at more serious stages of the disease.     

JAK2V617F 点突变与骨髓增殖性疾病的临床相关性研究

目的:研究JAK2V617F点突变与骨髓增殖性疾病(myeloproliferative disease,MPD)的临床相关性,为MPD的基因学诊断及靶向治疗提供理论依据。方法:应用等位基因特异性聚合酶链反应(AS-PCR)检测JAK2V617F点突变。结果:102例的MPD患者中包括慢性粒细胞白血病(CML)患者9例、真性红细胞增多症(PV)患者21例、原发性血小板增多症(ET)患者37例、特发性骨髓纤维化(IMF)患者16例和分类不明的骨髓增殖性疾病(uMPD)患者19例,JAK2V617F突变阳性率依次为11%、71.4%、51.4%、75.0%、78.9%。结论:JAK2V617F点突变有助于不同类型MPD的诊断,在MPD疾病的诊断中起重要作用。     

Late-onset porphyrias: what are they?

Porphyrias are inherited disorders of heme biosynthesis. ALA dehydratase porphyria (ADP) and congenital erythropoietic porphyria (CEP) are autosomal recessive porphyrias, and are typically expressed at birth or in childhood. However, a few cases of late-onset recessive porphyrias have been reported. Recently we encountered a late-onset ADP patient who developed symptoms of acute porphyria when he was 63 years old. This was accompanied by polycythemia vera. It was concluded that he developed the porphyria because an abnormal ALAD allele was clonally expanded by polycythemia vera. Upon reviewing the literature, a few cases of late-onset CEP were found to be also associated with hematologic abnormalities suggestive of myelodysplastic syndrome (MDS), another clonal disorder. These findings suggest that these late-onset porphyrias may be heterozygous for their gene defects, but clinical expression may be elicited if there is a loss of heterozygosity, either by a clonal expansion of the porphyric allele or by a loss of function mutation in the other allele.     

Thrombocytosis in young people: evaluation of 57 cases diagnosed before the age of 40

Over the past 13 years 57 cases of primary thrombocytosis in young people have been studied. Only patients with a platelet count over 500 x 10(9)/liter and a follow-up longer than 2 years were considered. Thrombocytosis in young people represents approximately 25% of total cases referred to our department during this period. The most common causes are essential thrombocythemia (20 cases) and secondary thrombocytosis (22 cases). The highest platelet counts are found in essential thrombocythemia patients. Most of our patients were discovered by a fortuitous hematological examination. In contrast, 5 out of the polycythemic patients were recognized after a thrombosis. The same was true for 2 out of 20 essential thrombocythemia subjects. Four subjects (2 essential thrombocythemia and 2 secondary thrombocytosis) were diagnosed after hemorrhages. The overall survival was very good except for leukemic patients and thrombocytosis secondary to neoplasms. Vascular complications after diagnosis were scarce: 2 polycythemia vera patients showed bleedings during antiaggregating therapy. None of our patients developed epithelial cancer, malignant lymphoma or myelofibrosis. Vascular traumata seem more frequent in polycythemia vera regardless of age. Therefore, it seems useful to treat polycythemic patients, while no therapy seems to be indicated in other forms of thrombocytosis.     

A fluorescent dye which recognizes mature peripheral erythrocytes of myeloproliferative disorders

Based on the previous finding that erythrocytes from patients with chronic myelogenous leukemia stain with the fluorescent dye merocyanine 540, erythrocytes from patients with other myeloproliferative disorders were examined for their ability to bind the membrane probe. As assessed by both fluorescence staining and a quantitative dye removal assay, all samples of erythrocytes from patients with chronic myelogenous leukemia, polycythemia vera, myelofibrosis with myeloid metaplasia and essential thrombocythemia bound more dye than did erythrocytes from normal, healthy individuals. Erythrocytes from three of six patients with acute myelogenous leukemia also showed increased affinity for the dye. In contrast, erythrocytes from three patients with acute lymphocytic leukemia and one with unclassifiable leukemia bound only normal amounts of dye. The procedures described may be useful as a supplemental aid to diagnosis of myeloproliferative disorders or for investigation of hematological diseases where multilineage involvement is suspected.     

Hemoglobin abnormalities in neoplastic hematological disorders

Fetal hemoglobin (F) and hemoglobin A₂ were estimated in 35 patients with malignant hematological disorders. In 9 out of 10 patients with morphological and cytochemical features of acute myeloblastic leukemia the hemoglobin F was greater than 2%. Of the other 25 patients investigated only one patient with polycythemia rubra vera had a hemoglobin F level of more than 2%. Estimation of fetal hemoglobin may be of value in the classification of acute leukemias and the increased level observed probably reflects disturbed hemoglobin synthesis in the acute myeloblastic type.     

Multiple cytogenetically abnormal clones in two polycythemia vera patients

Summary Multiple abnormal karyotypes representing apparently unrelated clones were observed in initial bone marrow samples from two polycythemia vera patients. Serial sampling demonstrated a selective advantage in proliferation of one clone over the others. The predominance of the single clone was associated with progression of the disease.     

Chorea complicating polycythemia rubra vera

A patient with polycythemia rubra vera and chorea is described and the literature on this rare combination is reviewed. This is the first report of the association of chorea and polycythemia in a male patient.The contrasting features of other forms of diffuse cerebral pathology which may be accompanied by chorea, namely disseminated lupus erythematosus, Henoch-Schönlein purpura and rheumatic chorea, are discussed.     

Clinical presentation of a patient with congenital polycythemia

The authors describe a 19 year old male with an isolated but absolute erythrocytosis with iron deficiency without evidence for polycythemia vera as well as another causes of erythrocytosis. The polycythemia was due to a recently described von Hippel-Lindau (VHL) mutation. By stopping iron therapy there was no more requirements for phlebotomy in this patient.     

Usefulness of the assessment of erythroid progenitors growth for differential diagnosis of primary and secondary polycythemias

Erythropoietic progenitors from bone marrow of patients with polycythemia vera (PV), secondary polycythemia (SP) and healthy subjects (HS) were cultured in plasma clot diffusion chambers in vivo. The chambers were inserted into the peritoneal cavities of rats, which 24 and 2 h before implantation received an injection of phenylohydrazine. Control experiments were done without erythropoietin (Epo) stimulation. Colonies after 2 and 7 days of culture were considered to be formed by mature erythropoietic progenitors (CFU-D-E) and burst forming cells (BFU-D-E), respectively. PV-erythroid progenitors, both BFU-D-E and CFU-D-E produced markedly more colonies than those from SP and HS, especially in experiments without Epo stimulation (p less than 0.01). The plating efficiency in SP was comparable to that noted in HS (p greater than 0.05). These results have led us to postulate that the study of erythroid progenitor clonal proliferation in plasma clot diffusion chamber can be helpful in the differential diagnosis of PV and SP, when other clinical and laboratory findings are not sufficiently convincing.     

Burst-promoting activity in anemia and polycythemia

Burst-promoting activity (BPA) in the sera of patients with various types of anemia and polycythemia was compared with that of normal subjects by an in vitro method using mouse bone marrow cells. The control culture contained normal human AB serum instead of sample materials. Results were expressed as a percentage of burst numbers in control cultures. Serum erythropoietin (Epo) levels were determined by a radioimmunoassay. Serum BPA in patients with aplastic anemia (155.4 +/- 56.7%, mean +/- SD) was significantly higher than that in normal subjects (112.1 +/- 29.1%, Wilcoxon's rank sum test, P less than 0.05). However, serum BPA in patients with uremic anemia (122.2 +/- 26.5%), polycythemia vera (101.9 +/- 19.5%) and stress polycythemia (115.5 +/- 25.6%) was not significantly different from normal subjects. There was a correlation between serum BPA and Epo titers in patients with aplastic anemia and paroxysmal nocturnal hemoglobinuria (r = 0.81, t test, P less than 0.001).