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)

Thrombotic and hemorrhagic disorders are common complications of the myeloproliferative disorders. Endothelial cells release both procoagulant and profibrinolytic factors, which may contribute to these hemorrhagic or thrombotic complications. The pre- and postvenous stasis levels of the procoagulant and profibrinolytic factors produced by endothelial cells were correlated with the occurrence of complications in polycythemia rubra vera (PRV) patients (n = 29) and essential thrombocythemia (ET) patients (n = 17) compared with normal patients (n = 17). Tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor (PAI) activity, von Willebrand's factor (vWF) activity and antigen (vWF:Ag), and factor VIII activity were measured. The resting tPA activity was significantly higher in the two disease groups compared with normal controls, but no difference between the levels of tPA and either complication within the disease groups was observed. Significantly elevated tPA following venous stasis was observed in the patients of both disease groups who had bleeding complications. Significant decreases, compared with the normal group, in both resting and postvenous stasis levels of PAI were observed in the disease groups regardless of complication history. The subjects from both disease groups with thrombotic complications had significantly elevated resting vWF and both resting and postvenous stasis vWF:Ag levels compared with normal controls. The endothelial cell is likely to be responding to abnormal hemostasis rather than being primarily involved in the genesis of a hyper- or hypocoaguable state.
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PMID:Relationship of thrombohemorrhagic complications to endothelial cell function in patients with chronic myeloproliferative disorders. 150 83

Bleeding and thrombosis are frequent complications in myeloproliferative disorders (MPD) and are associated with severe organ damage and a high mortality. Elevated platelet count, elevated hematocrit, and patient age are regarded as risk factors for bleeding and thromboembolic events in MPD, although the significance of these parameters was not confirmed by clinical studies. We retrospectively analyzed vascular complications in 260 patients with MPD and tried to identify parameters predictive for bleeding and thrombembolic events. Our cohort consisted of 115 patients with chronic myeloid leukemia (CML), 84 patients with polycythemia vera (PV), 26 with essential thrombocythemia (ET), 25 with osteomyelofibrosis (OMF), and 10 patients with unclassifiable MPD. During a median follow-up period of 31 months, 126 patients with chronic MPD suffered bleeding or thrombotic events. Bleeding was observed in 57% of patients with OMF, 23% with PV, 20% with chronic phase CML, and 16% with ET. Thrombotic events were most common in patients with PV (36% of patients), followed by ET, OMF, and chronic phase CML (20%, 17%, and 6% of patients, respectively). Recurrent thrombotic episodes frequently occurred in patients with PV and ET, whereas patients with OMF often had more than one bleeding event. Thirty patients died of thrombohemorrhagic complications during follow-up. Multivariate analysis, including all patients with chronic MPD, revealed that elevated red blood cell count, higher hemoglobin level, and increased percentage of segmented neutrophils at the time of diagnosis were associated with thrombosis, whereas patients with bleeding complications were characterized by low red cell count, lower hemoglobin, and a lower percentage of segmented neutrophils. However, when analyzed by MPD subgroup, none of these parameters retained a predictive value for bleeding or thrombotic events. Moreover, elevated platelet count and patient age were not risk factors for bleeding complications. Thrombotic events were less frequent in patients below the age of 40, and were increased in patients aged 70 and above. However, this was primarily due to the high percentage of elderly patients in subgroups mainly affected by thrombosis (PV and ET). In most MPD subgroups, the rate of bleeding and thrombosis was highest just before and during the first months after diagnosis, and declined thereafter. Thrombohemorrhagic complications were less frequent after phlebotomy in PV and after therapy with alkylating agents in CML. The institution of cytoreductive therapy soon after the diagnosis was made may explain the reduced incidence of complications later in the disease. We conclude that morbidity and mortality from thrombohemorrhagic complications are high in myeloproliferative disorders.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Incidence and clinical risk factors for bleeding and thrombotic complications in myeloproliferative disorders. A retrospective analysis of 260 patients. 191 29

Essential thrombocythaemia (ET) is a rare clonal myeloproliferative disorder characterized by a persistent increase in platelet count. The commonly used criteria for the diagnosis, except for the level of the increase in platelet count, are usually those fixed by the Polycythemia Vera Study Group. The average age of onset is around 60 years, both sexes being affected. The symptoms frequently present at diagnosis are related to microcirculatory disturbances (palms, soles, fingers). Neurological symptoms are often observed. Thrombotic complications of the large vessels are less frequent. Haemorrhagic problems are present in about 30% of patients. Bleeding time is normal in most cases, whereas platelet aggregation abnormalities are frequently found. Nil adrenaline aggregation is the most discriminative test. The clinical course is characterized by long intervals without any symptoms; thromboembolic or haemorrhagic episodes can, however, occur, mainly in uncontrolled ET. Development of terminal acute leukaemia has been reported in 34 cases. The expression of the influence of the treatments, 32P or alkylating agents, is very strong. The treatment of ET has to take in consideration the difficult compromise between balancing the necessity of preventing complications and the effects of drug toxicity. The use of recombinant alpha-interferon has recently been proposed and is under investigation. The pathogenesis of thrombocytosis in ET seems to involve an expansion in the megakaryocyte progenitor cell pool. Platelet membrane glycoprotein abnormalities and defective glycosylation of thrombospondin have been shown. Numerous other platelet abnormalities, including decreased alpha-adrenergic receptors, loss of PGD2 receptors and increased Fc receptors, have been reported. Arachidonic metabolism seems to be abnormal and lipoxygenase is defective. Most of the platelet abnormalities seem to be the result of intrinsic defects at the level of an abnormal clone of megakaryocytes. However, causal relationships between the platelet abnormalities and bleeding or thrombosis are not yet clearly demonstrated.
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PMID:Essential thrombocythaemia. 250 75

The association of erythrocyte disorders and thrombosis in polycythemia vera, paroxysmal nocturnal hemoglobinuria (PNH) and sickle cell anemia suggest that erythrocyte abnormality, could be involved in the genesis of thrombosis. A significant correlation between the hematocrit level and the incidence of thrombosis has been reported indicating the role of blood viscosity, but did to exclude an intrinsic red cell. Thrombotic episodes in sickle cell anemia might be explained by a decreased deformability and an increased adhesion of red cells to endothelium. The incidence of thrombosis is of 40 p. 100 in patient with PNH with a frequent sus-hepatic localization. In addition to abnormal erythrocyte adhesion, abnormal membrane lipid distribution was observed in PNH, suggesting that they could participate in the pathophysiology of thrombosis.
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PMID:[Role of erythrocytes in thromboembolism pathology]. 381 82

Nodular regenerative hyperplasia was found in nine patients who had hematological disease including polycythemia vera, agnogenic myeloid metaplasia, primary thrombocythemia, rheumatoid arthritis with thrombocytosis, multiple myeloma, and erythrocytosis associated with polycystic renal disease. Portal hypertension was suspected in three and features of hypersplenism were present in four. 2. Nodular regenerative hyperplasia occurred in livers which had widespread obliteration of portal vein radicals (obliterative portal venopathy). Morphometric analysis indicated that the portal vein lesions were predominately located in veins up to 0.2 mm in diameter and were significantly more frequent than similar lesions occurring in elderly persons. 3. The following pathogenesis of nodular regenerative hyperplasia is proposed: Thrombi, perhaps largely composed of platelet aggregates formed in the portal venous circulation or spleen, embolize to the liver and results in obliterative vascular lesions. Atrophy and regenerative nodule formation occur in response to the interruption of the portal blood supply.
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PMID:Nodular regenerative hyperplasia of the liver in hematologic disorders: a possible response to obliterative portal venopathy. A morphometric study of nine cases with an hypothesis on the pathogenesis. 743 53

Thrombotic accidents remain a major cause of morbidity and of fatal outcome in polycythemia vera (PV). High haematocrit which increases whole blood viscosity is the only identified predictive factor of thrombosis in PV. Neither high platelet count nor any abnormal platelet function have been found significantly linked to the thrombotic risk. There are recent development allowing to better characterize plasma hypercoagulability. The predictive value of these new tests has not yet been evaluated in PV.
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PMID:Laboratory investigations and prediction of thrombotic risk in polycythemia vera. 803 39

Thrombotic complications characterize the clinical course of polycythemia vera (PV) and represent the main cause of morbidity and mortality. However, uncertainty still exists as to the benefit/risk ratio of aspirin prophylaxis in this setting. In vivo platelet biosynthesis of thromboxane A2 is enhanced and can be suppressed by low-dose aspirin in PV, thus providing a rationale for assessing the efficacy and safety of a low-dose aspirin regimen in these patients. The Gruppo Italiano Studio Policitemia Vera has recently performed a pilot study on 112 patients randomized to receive aspirin, 40 mg daily, or placebo and followed for 16 +/- 6 months (mean +/- SD). This study showed that low-dose aspirin is well tolerated in PV patients, and that a large-scale efficacy trial is feasible in this setting. In this article we report the protocol of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study, which is a randomized trial designed to assess the risk/benefit ratio of low-dose aspirin in PV. To estimate the size and the follow-up duration required for the ECLAP trial, a retrospective analysis of the clinical epidemiology of a large PV population has recently been completed by the Gruppo Italiano Studio Policitemia Vera. On this basis, approximately 3500 patients will be enrolled in the ECLAP study with a follow-up of 3 to 4 years. The uncertainty principle will be used as the main eligibility criterion: Polycythemic patients of any age, having no clear indication for or contraindication to aspirin treatment, will be randomized in a double-blind fashion to receive oral aspirin (100 mg daily) or placebo. According to current therapeutic recommendations, the basic treatment of randomized patients should be aimed at maintaining the hematocrit value < or = 45% in subjects aged < or = 50, and hematocrit < 45% as well as platelet count < 400 x 10(9)/L in patients aged > 50. Randomization will be stratified by participating center. The study is funded by the European Union BIOMED 2 program.
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PMID:European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP): a randomized trial. 938 6

Polycythemia vera (PV) and essential thrombocythemia (ET) are two myeloproliferative disorders (MPDs) that result from an acquired mutation of a single hematopoietic stem cell that gives the progeny of the stem cell a growth advantage over their normal counterparts. The incidence of both diseases appears to be similar. From time to time, PV has an atypical presentation making it difficult to differentiate from ET and other MPDs. Identification of a patient as having PV or ET generally follows the observation of elevated hematocrit or elevated platelet count. Thrombotic complications are the major cause of morbidity and mortality in both groups of patients. In PV, the frequencies of venous and arterial thrombosis are about equal, whereas venous thrombosis is less common in ET. Accurate diagnosis of these disorders is essential for proper treatment. The prognosis for untreated, asymptomatic ET patients is generally good, but quite poor for untreated PV patients. Proper treatments have been shown to reduce complications and significantly extend the life span for both groups of patients.
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PMID:Diagnostic criteria and prognosis in polycythemia vera and essential thrombocythemia. 993 May 51

Thrombotic events are present in 20% to 50% of patients with polycythemia vera (PV) and essential thrombocythemia (ET) at diagnosis and involve major vessels and the microcirculation. Establishing the precise risk of thrombosis in ET and PV is difficult. However, estimates may be obtained from retrospective and prospective studies, and some risk factors have been defined. In ET, increasing age and previous thrombosis emerge as major factors. The level of the platelet count per se does not correlate with thrombotic incidence. However, there is substantial evidence that adequate control of the platelet count reduces the frequency of thrombosis. While aspirin is usually effective at relieving vasomotor and microvascular occlusive symptoms or signs, there is only limited evidence that its use reduces the risk of larger vessel thrombosis. Other suggested risk factors include apparent clonal hematopoiesis in younger patients, hypercholesterolemia, and cigarette smoking. In PV, the overall impression is that the incidence of thrombosis is greater than in ET. As in ET, increasing age and previous thrombosis are significant risk factors. In addition, adequate reduction of the hematocrit reduces the incidence of thrombosis. Identifying the risk associated with thrombocytosis in PV is confounded by the overall myeloproliferation usually found in these patients and the fact that the thrombocytosis is not usually as marked as in ET. However, by analogy with ET, one could argue that the risk associated with the thrombocytosis in ET is equally applicable to PV. In support of this, there is overwhelming evidence that patients treated with adequate myelosuppression with complete normalization of their blood counts have the lowest thrombotic incidence. Essential thrombocythemia and PV patients presenting with thrombosis should be investigated for other congenital or acquired prothrombotic conditions. Establishment of the presence of one or the other of these may alter the long-term management of these patients with the use of either aspirin or anticoagulation in addition to cytoreduction. Thrombotic risk has emerged as a major factor in stratifying patients with myeloproliferative disease. While some clear thrombotic risk factors have been defined, there is a need to identify further additive risk factors in patients considered to be at low risk of thrombosis.
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PMID:The risk of thrombosis in essential thrombocythemia and polycythemia vera. 1209 53

Thrombosis is a major cause of mortality and morbidity in polycythemia vera (PV). The wide range of thrombotic events reflects the complex picture in PV. There are multiple factors involved in thrombogenesis in this disease, including increased hematocrit, thrombocytosis, impaired fibrinolytic activity, platelet activation, leukocyte activation, endothelial damage, interactions between platelets and endothelium, various modalities of therapy, and increased in whole-blood viscosity. Among them, the increase in blood viscosity, and hence the impairment of blood flow, is the major factor. In this article, the role of hyperviscosity in PV is reviewed. A high hematocrit occurs under PV and many other conditions with abnormal red blood cell aggregation. The impaired capillary blood flow results in neurological manifestations and increased bleeding risk in PV. Thrombotic complications can also occur in both arteries and veins and manifest as stroke, myocardial infarction, deep vein thrombosis, or pulmonary embolism. The hemodynamic principle is aptly applied in the management of PV. The most important objective is the reduction of the patient's hematocrit.
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PMID:Hyperviscosity in polycythemia vera and other red cell abnormalities. 1463 44


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