Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have shown rIFN alpha to be an effective agent in the management of polycythemia vera. Red cell mass can be controlled within 6 to 12 months, eliminating the need for phlebotomy in up to 70% of cases. In addition, significant improvement in the platelet counts, iron status, pruritus scores and the degree of splenomegaly have been reported. Most patients require between 9 and 25 x 10(6)U/week, although once the disease is under control it may be possible to reduce both the dose and frequency of administration. Side-effects remain a significant problem, occurring in over 30% of patients, and may be related to the high mean age of the patients. Long-term studies are now indicated to determine if the natural history of the disease is altered and whether, in particular, the incidence of myelofibrosis and/or leukaemic transformation is reduced.
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PMID:Interferon treatment in polycythaemia vera. 895 85

"Autonomous" development of erythroid colonies in erythropoietin (EPO)-free semi-solid culture has been used as an in vitro assay for diagnosis of polycythemia vera (PV). These colonies, however, are small and poorly hemoglobinized, rendering the assay in many cases unreliable. We report here on the use of a novel assay; it combines a modified culture procedure that maximizes the growth of EPO-independent erythroid cells, and immunofluorescence flow cytometry for their detection and quantitation. Peripheral blood mononuclear cells are cultured for 2-5 days in the presence of a combination of growth factors. During this phase, early erythroid committed progenitors, burst forming units (BFUe), proliferate and differentiate into colony forming units (CFUe)-like progenitors. In the second phase, the latter cells, in the presence of stem cell factor, hemin, and iron-saturated transferrin, continue to proliferate and mature into hemoglobin (Hb)-containing orthochromatic normoblasts. Neither phases contained EPO. The culture produced large, pure, and synchronized erythroid cell populations. The cells were then dually labeled with fluorescent probes, nuclear DNA with thiazole orange and intracellular hemoglobin (Hb) with phycoerythrin-conjugated monoclonal antibodies against human Hb. Cells positive for both labels were assigned as Hb-containing nucleated precursors. The presence of such cells in EPO-free cultures indicated "autonomous growth." None of the EPO-free cultures derived from normal donors or patients with secondary polycythemia contained such cells. Cultures derived from PV patients contained from 5 to 92% "autonomously grown" cells. These culture and analysis methods should minimize false negative results with PV patients and provide objective and quantitative data.
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PMID:Improved method for diagnosis of polycythemia vera based on flow cytometric analysis of autonomous growth of erythroid precursors in liquid culture. 898 Feb 60

Concentration of malonic dialdehyde (MDA) and activity of antioxidant enzymes G-6-PD, glutation peroxidase (GP), glutation reductase, catalase, superoxide dismutase were measured in red cells of patients with polycythemia vera. Plasmic ions Fe3+ were estimated by means of electron-paramagnetic resonance. MDA concentration and antioxidant enzymes (except GP) in polycythemia red cells were found increased, while the activity of selenium-dependent GP was reduced, the inhibition being greatest in severe iron deficiency. It is suggested that GP activity in red cells depends on both selenium levels in the body and concentrations of non-hematic iron.
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PMID:[Erythremia: the activity of erythrocyte antioxidant enzymes and the association with iron deficiency]. 921 64

Eighteen patients with polycythemia vera who were less than 60 years old received human leukocyte interferon-alpha subcutaneously at a starting dose of 3 MU three times a week. The interferon dose was escalated to 6 MU three times a week if it was well tolerated and disease was not controlled after 3 months of treatment at the lower dose. Hematologic response was defined as complete if the hematocrit was maintained at less than 45% in the absence of phlebotomy and partial if the hematocrit was kept at 45% to 50%, associated with a 50% or greater reduction of phlebotomy requirements; no response was defined as a response less than a partial response. Complete disease control was achieved in 11 patients, with partial control in a further six cases. One patient failed to respond. Median duration of response was 16 months (range 5 to 43 months), with 15 patients still under treatment. Therapy with human leukocyte interferon-alpha significantly improved (p <.01) phlebotomy requirements, the degree of splenomegaly, pruritus scores, iron stores and mean red cell volume values, and platelet and leukocyte counts. Interferon treatment did not produce remarkable side effects and no patient withdrew from the study because of intolerance. We conclude that subcutaneous human leukocyte interferon-alpha is an effective and well-tolerated therapy in the management of polycythemia vera-associated myeloproliferation and pruritus in patients less than 60 years old.
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PMID:Role of human leukocyte interferon-alpha in the treatment of patients with polycythemia vera. 953 37

Long-term survival of patients with polycythemia vera (PV) is essentially determined by the ability to reduce the risk of thromboembolic complications resulting from the altered rheological conditions by the high red blood cell (RBC) mass of these patients. RBC depletion to normal hematocrit (Hct) values is the first line therapy and should be preferred to chemotherapy (or P32) because of the long-term risk of acute leukemia or other secondary malignancies. RBC depletion is accomplished much more effectively and rapidly by erythrocytapheresis (EA) than by repeated phlebotomies and has been shown to be well tolerated and accepted by the patients (8). The main indications for EA for a PV patient (often newly diagnosed) are high risk Hct values of >55-60% that can be reduced to the normal range within 1-2 h. The long-lasting effect (median interval between 2 EA treatments: ca. 6 months) is partially the result of the massive loss of iron, a growth factor for erythropoesis. This has been shown by in vitro studies in erythroid progenitor cells of PV patients before and after EA (11). The advantages and possible disadvantages of EA treatment are discussed.
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PMID:Advantages of isovolemic large-volume erythrocytapheresis as a rapidly effective and long-lasting treatment modality for red blood cell depletion in patients with polycythemia vera. 1022 58

Differentiation of an elevated hemoglobin/hematocrit level warrants not only the determination of relevant laboratory values, including erythropoietin, but also an elaborate evaluation of bone marrow histopathology. Particularly in the initial stages of polycythemia vera (PV), when not all stringent clinical criteria are completely fulfilled, a more refined analysis of morphological features helps to distinguish autonomous (PV) from spurious or secondary erythrocytosis - polyglobuly (PG). PV is characterized by a panmyelosis, i.e., a trilinear proliferation of all cell lineages, whereas in PG erythropoiesis predominates. Megakaryopoiesis exerts a significant impact on differentiation, because in PV there is a conspicuous grouping associated with a strikingly expressed pleomorphous appearance. This peculiar feature implicates assemblies of small- to medium-sized megakaryocytes lying adjacent to giant cells with extensively lobulated, staghorn-like nuclei. A further discriminating parameter is presented by the interstitial lesions frequently occurring in PG. These, according to the usually underlying inflammatory cause (chronic bronchitis-recurrent bronchopneumonias), include iron-laden macrophages, a prominent perivascular plasmacytosis, phagocytosis of cell debris by histiocytic reticular cells and often an in- crease in the number of eosinophils. Comparable findings are not, or only to a minor ex-tent, detectable in PV. In conclusion, by regarding hematopoiesis and the myeloid stroma initial stages of PV may be definitively distinguished from PG.
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PMID:[ Polyglobuly versus polycythemia vera]. 1066 66

Differentiation of an elevated, repeatedly determined platelet count (> or =500x10(9)/l) includes the discrimination between reactive causes generated by a variety of underlying conditions and a neoplastic myeloproliferative disorder (CMPD). In addition to clinical findings, the evolution of laboratory data during follow-up and histology of the bone marrow exerts a significant diagnostic impact. Characteristic features are not only expressed by hematopoiesis, but also by the myeloid stromal compartment. While the megakaryocyte-rich subtype of chronic myeloid leukemia (CML) and the 5q(-) syndrome (MDS) are dominated by abnormal micromegakaryocytes, in polycythemia vera (PV) this cell lineage reveals a pleomorphous appearance. In essential thrombocythemia (ET), a prevalence of giant megakaryocytes with deeply lobulated (staghorn-like) nuclei may be encountered. A clear-cut discrimination of ET from early (hypercellular) stages of idiopathic (primary) myelofibrosis (IMF) presenting with thrombocythemia becomes possible, provided the conspicuous atypical features of megakaryopoiesis characterizing the latter entity are taken into account. Moreover, CML displays a predominance of the granulocytic lineage whereas PV shows a panmyelosis or trilineage proliferation, involving erythropoiesis, in particular. In contrast, erythropoiesis is markedly reduced in CML and to a lesser degree also in IMF. In CMPDs extreme values of iron deposits may be found, ranging from a total lack (PV) to minor amounts (CML) and a normal staining reaction (ET). Similar results are exhibited regarding reticulin fibrosis, which is usually not present in ET, rarely observed in PV and detectable to a variable degree in CML and IMF.
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PMID:[Thrombocytosis versus thrombocythemia--differential diagnosis of elevated platelet count]. 1066 67

Iron deficiency affects 30% of the world's population. Iron metabolism is tightly regulated, with both gut transport and storage being coordinated. Hereditary haemochromatosis due to mutations in the HFE gene leads to increased absorption of iron and multiple end-organ damage. Myelodysplastic disorders are acquired clonal stem-cell disorders that cause ineffective erythropoiesis. Aplastic anaemia is caused by an intrinsic defect of haemopoietic stem cells; both inherited and acquired forms occur. Primary polycythaemia is a myeloproliferative disorder, a non-malignant stem-cell disease.
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PMID:Red cells II: acquired anaemias and polycythaemia. 1096 23

Therapeutic erythrocytapheresis (TEA) has been used in different diseases such as polycythemia vera (PV), secondary erythrocytosis or hemochromatosis as a process of the less cumbersome but more expensive phlebotomy. TEA is preferred in emergency conditions such as thrombocytosis or in conditions such as porphyria cutanea tarda (PCT) or erythropoietic porphyria when plasma exchange (PEX) is often combined with TEA to reduce extracellular levels of uroporphyrin which contribute to plasma hyperviscosity. TEA is often combined with drug therapy that varies from etoposide in PV to EPO and desferoxamine which are used to mobilize and reduce iron stores in hemochromatosis. Benefits from this combination may be more long lasting than expected. Nonetheless for TEA, there is no standard protocol and, clinical experience with this therapy remains highly anecdotal. Therapeutic red cell-exchange (TREX) has been used with much interest over the years, starting with the management of hemolytic disease of the newborn and later used to correct severe anemia in thalassemia patients thereby preventing iron overload. It has also been used for the management of complications of sickle cell disease such as priapism, chest syndrome, stroke, retinal, bone, splenic and hepatic infarction or in preparation for surgery by reducing HbS to less than 30%. Automated apheresis has also favored the use of TREX in conditions such as paroxysmal nocturnal hemoglobinuria and aniline poisoning, arsenic poisoning, Na chlorate intoxications and CO intoxications, hemoglobinopathies, autoimmune hemolytic anemia, reactions due to ABO incompatibility, in preparation for ABO incompatible bone marrow transplantation or for preventing anti-D immunization after the transfusion of D(+) cells to D(-) recipients. Another field of application has been in the emergency management of intraerythrocytic parasite infections such as malaria and babesiosis. Application of TREX may be wide but its real use remains limited. In our personal experience, in 16 years, only 167 TREX procedures have been carried out in a total of 13,747 therapeutic procedures. This represents only 1.21% of the total.
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PMID:Clinical application of therapeutic erythrocytapheresis (TEA). 1083 21

We report a case of adult T-cell leukemia (ATL) accompanied by polycythemia vera (PV) in which rapid development of myelofibrosis and clinical features of hemophagocytic syndrome (HPS) were observed at the terminal stage. The patient, a 53-year-old man who was born in Oita Prefecture, Japan, was diagnosed as having PV in 1996. He had undergone venesection but had not received any chemotherapy. In June 1997, he showed systemic lymphadenopathy with positivity for serum HTLV-1 antibody (x 10,240). Pathological findings and Southern blotting analysis for detection of monoclonal integration of HTLV-1 provirus DNA in a lymph node biopsy sample revealed that he also had acute-type ATL. Although several courses of chemotherapy were transiently effective, high fever, pancytopenia, increased serum LDH, hypoproteinemia and hyperferritinemia appeared, all of which were compatible with the clinical features of HPS. In addition, cytomegalovirus infection became evident. He died of multiple organ failure with rapid progression of myelofibrosis in May 1998. Detection of both increased CD68-positive histiocytes by immunohistochemistry and iron-stained phagocytic cells in marrow biopsy specimens appeared to be helpful for diagnosis of HPS in this patient, whose marrow showed myelofibrosis with hypocellularity.
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PMID:[Rapidly progressive fibrosis and increased CD68-positive cells in the bone marrow at the terminal stage of adult T-cell leukemia accompanied by polycythemia vera]. 1120 Nov 50


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