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)

Recently new radioimmunoassay methods have been established to measure plasma concentrations of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4), platelet release products which are set free when platelets aggregate. Plasma concentrations of beta-TG and PF4 were investigated in disorders with increased thromboembolic risk. Extremely high concentrations of these platelet proteins were found in patients with venous thrombosis, pulmonary embolism, polycythemia vera, and chronic renal failure. Moderately increased beta-TG and PF4 levels were observed in patients with peripheral vascular disease, coronary artery disease, chronic rheumatoid arthritis, multiple myeloma, and diabetes mellitus. These data indicate, that plasma concentrations of beta-TG and PF4 are useful parameters for the evaluation of the "in vivo" platelet activity. By using these new methods for clinical applications special blood sampling conditions have been taken into account; moreover one has to consider that the plasma levels of the platelet "release products" are dependent from renal function.
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PMID:[Clinical significance of the radioimmunological determination of beta-thromboglobulin and platelet factor 4]. 9 43

It has been postulated that platelet-derived growth factor and platelet factor 4 (PF4) are involved in the imbalance of the mechanism of medullar stroma maintenance which triggers off the bone marrow myelofibrotic process. In this work we compare the PF4 and the beta-thromboglobulin (beta-TG) and mitogenic activity in platelet-poor plasma (PPP) and platelet extracts (PE) from patients with myeloproliferative disorders (MPD) with those of secondary thrombocytosis (ST) and normal volunteers. Statistically significant differences were found between MPD and ST patients or controls, but none between ST and controls in all the parameters studied. Maximal differences in platelet-derived factors (PDFs) between MPD and control groups were found in polycythemia vera patients. However, the relationship between the presence of myelofibrosis and abnormal levels of beta-TG, PF4 and mitogenic activity in PPP and PE was only observed in patients with agnogenic myeloid metaplasia (AMM). These results show that PDFs are specifically decreased in MPD platelets. Furthermore, no statistical correlation was found between PDFs and the number of platelets. However, other unknown factors or conditions would be necessary to develop myelofibrosis in MPD, which is present in AMM.
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PMID:Abnormal levels of platelet-specific proteins and mitogenic activity in myeloproliferative disease. 138 57

Platelet function and the clinical course of the disease were prospectively investigated in 29 patients with myeloproliferative disorders. Serial determinations (median: 5 investigations per patient within 17 months) of platelet aggregation, plasma and intraplatelet concentrations of beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), and of fibrinopeptide A (FPA) plasma levels were carried out. In the chronic phase of polycythaemia vera, patients with thrombohaemorrhagic complications during the study period had higher platelet count, more severe platelet aggregation defects, and increased plasma levels of beta TG and FPA compared to patients without complications. However, thrombohaemorrhagic complications were not predicted by changes in these parameters in the individual patient during the chronic disease phase. When patients with chronic myelogenous leukaemia entered blast crisis, bleeding complications were related to thrombocytopenia, impaired platelet function and low intraplatelet concentrations of beta TG and PF4. Cytoreduction by chemotherapy in the chronic phase of CML did not alter beta TG and PF4 plasma levels, whereas treatment of polycythaemia rubra vera by venesection favourably influenced platelet alpha-granule secretion and increased intraplatelet concentrations of beta TG and PF4.
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PMID:A prospective study of haemostatic parameters in relation to the clinical course of myeloproliferative disorders. 214 44

Bleeding and thrombosis are a major cause of morbidity and mortality in myeloproliferative disorders (MPD). This study evaluates the relation between thrombohemorrhagic complications and platelet abnormalities in different subgroups of MPD. In 57 MPD patients thrombohemorrhagic complications occurred in 71% of patients with polycythemia rubra vera and 50% of patients with osteomyelofibrosis and primary thrombocythemia but in only 29% of patients with chronic myelogenous leukemia. Increased beta-thromboglobulin and platelet factor 4 plasma levels, platelet aggregation defects, and increased dispersion of the platelet volume distribution curve were most frequent in those subgroups where most serious thrombohemorrhagic complications were observed, and multiple platelet-related abnormalities were often found simultaneously. Fibrinopeptide A plasma levels were rarely elevated, however. Our results indicate that platelet abnormalities associated with bleeding and thrombosis are primarily determined by the clinical subgroup of myeloproliferative disease.
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PMID:Bleeding and thrombosis in chronic myeloproliferative disorders: relation of platelet disorders to clinical aspects of the disease. 277 37

Simultaneous assays of platelet factor 4 (PF-4) and beta-thromboglobulin (beta TG) were performed in 192 cases of myeloproliferative syndromes (polycythaemia vera and primary thrombocytosis, as defined by the Polycythaemia Vera Study Group). The results led to the following conclusions: (I) both assays must be combined in order to avoid a poor interpretation due to marker release in vitro; (II) the 'normality' of the values must take the platelet number into account, even in the 'normal' range of this parameter; (III) the sensitivity of the beta TG assay is greater than that of PF-4 when considering the correlation of the marker values with arterial accidents; (IV) the predictive value of an excessive level of beta TG and/or PF-4 is difficult to define, since only 13 of the cases studied had a vascular accident during the 12-month follow-up period, and the levels of the markers in these patients were not statistically different from the levels in those patients not experiencing such accidents.
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PMID:The clinical significance of beta-thromboglobulin and platelet factor-4 in polycythaemic patients. 619 55

The vascular risk factors of patients with polycythemia rubra vera was assessed by reviewing the results of international therapeutic studies. The risk factors were: an age over 60, previous vascular problems, the quality of follow-up (maintenance of hematocrit below 50 p. cent and platelet count below (600.10(9)/l). The treatment is one of the most important factors: the risk of vascular complications was three times greater in patients treated by venesection, al other factors being equal. This counter-balanced the higher risk of leukemia in patients treated by myelo-depression. The use of platelet anti-agregant drugs remains controversial. Recent results question their efficacy in preventing thrombosis and emphasise the risk of hemorrhage. The results of platelet factor 4 (PF4) and beta-thromboglobin (beta TG) levels provide further information for judging the vascular risk of these patients, and may, in prospective studies, give a better assessment of the efficacy of platelet anti-agregant drugs in vivo.
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PMID:[Vascular complications of polycythemia]. 622 77

A 75-year-old Japanese woman with polycythemia vera was admitted to our hospital in January 2003 with suspected pulmonary thromboembolism. After administration of heparin, platelet count decreased from 1,694 x 10(9)/l on admission to 60 x 10(9)/l on hospital day 14. The patient developed acute limb embolism and transient cerebral ischemic attack on days 17 and 25, respectively. Signs and symptoms mimicked those of disseminated intravascular coagulation. Antibodies against heparin and platelet factor 4 complexes were detected in serum, and a diagnosis of heparin-induced thrombocytopenia and thrombosis was made. Argatroban treatment improved thrombocytopenia and hypercoagulable state.
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PMID:Heparin-induced thrombocytopenia and thrombosis in a patient with polycythemia vera. 1533 86

Microvascular disturbances in essential thrombocythemia (ET) and polycythemia vera (PV), including erythromelalgia, and atypical and typical transient cerebral, ocular, and coronary ischemic attacks, are caused by platelet-mediated transient and occlusive thrombosis in the end-arterial circulation. ET patients with microvascular disturbances have shortened platelet survival, increased beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), and thrombomodulin (TM) levels, and increased urinary thromboxane B2 (TXB2) excretion, indicating platelet-mediated thrombotic processes. Inhibition of platelet cyclooxygenase-1 by aspirin is followed by relief of microvascular disturbances; correction of shortened platelet survival; correction of increased plasma beta-TG, PF4, and TM levels; and correction of increased TXB2 excretion to normal. In PV associated with thrombocythemia, increased hematocrit and whole blood viscosity aggravate the platelet-mediated microvascular syndrome of thrombocythemia to produce major arterial and venous thrombotic complications. Correction of hematocrit to normal by phlebotomy will reduce the major arterial and venous thrombotic complications, but fails to prevent the platelet-mediated microvascular circulation disturbances in PV patients because thrombocythemia persists. Complete relief and prevention of microvascular and major thrombosis in ET and PV patients, in addition to phlebotomy, are obtained by treatment with aspirin and not with coumarin. The discovery of JAK2 V617F gain of function mutation in patients with myeloproliferative disorders (MPDs) expands our insights into the molecular etiology and biological features of ET, PV, and chronic idiopathic myelofibrosis (CIMF). The current concept is that heterozygous JAK2 V617F mutation with increased kinase activity is enough for megakaryocyte proliferation and increased hypersensitive platelets with no or slightly increased erythropoiesis in ET and in early PV mimicking ET. Homozygous JAK2 mutation with pronounced kinase activity is associated with trilinear megakaryocyte, erythroid, and granulocytic myeloproliferation, myeloid metaplasia, and secondary myelofibrosis (MF), with the most frequent clinical picture of classical PV complicated by major thrombosis in addition to the platelet-mediated microvascular thrombotic syndrome of thrombocythemia. The positive predictive value of a JAK2 V617F polymerase chain reaction test for the diagnosis of MPDs is high (near to 100%), but only half of ET and MF (sensitivity 50%) and the majority of PV (sensitivity 85 to 97%) are JAK2 V617F positive. Bone marrow histopathology, when used in combination with specific markers such as serum erythropoietin, PRV-1, endogenous erythroid colony formation, peripheral blood parameters and red cell mass, has a high sensitivity and specificity (near 100%) to detect the early and overt stages of the MPDs and to differentiate between ET, PV, and CIMF in both JAK2 V617F-positive and -negative MPDs.
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PMID:Clinical and laboratory features, pathobiology of platelet-mediated thrombosis and bleeding complications, and the molecular etiology of essential thrombocythemia and polycythemia vera: therapeutic implications. 1667 74

Patients with essential thrombocythemia (ET) and polycythemia vera (PV), complicated by microvascular ischemic or thrombotic events, have shortened platelet survival, increased beta-thromboglobulin, platelet factor 4, and thrombomodulin levels, and increased urinary thromboxane B2 excretion. These are all reversible by inhibition of platelet cyclooxygenase 1 with aspirin, and are therefore indicative of platelet activation and platelet-mediated thrombotic processes. The thrombotic tendency persists as long as platelet counts are above the upper limit of normal (400 x 10 (9)/L). Despite strong evidence of in vivo platelet activation, the ex vivo platelet function tests are impaired. Platelet dysfunction in ET and PV typically is characterized by a missing second-wave adrenaline aggregation, an increased adenosine diphosphate aggregation threshold, and reduced secretion products, but a normal arachidonic acid or collagen-induced aggregation. The proposed concept is that platelets in thrombocythemia (ET and PV) are hypersensitive. Due to the existing high shear stress in the microvasculature (end-arterial circulation), platelets spontaneously activate, secrete their products, form aggregates mediated by von Willebrand factor (vWF) that transiently plug the microcirculation, deaggregate, and then recirculate as exhausted defective platelets with secondary storage pool disease on ex vivo analysis. At increasing platelet counts from below to above 1000 x 10 (9)/L, the thrombotic condition changes into an overt spontaneous bleeding tendency as a result of a functional vWF deficiency that is caused by proteolysis of large vWF multimers. This is consistent with acquired type 2 von Willebrand syndrome (AvWS). AvWS is reversible by reduction of the platelet count to normal. The acquired JAK2 V617F gain of function mutation is the cause of trilinear myeloproliferative disease with the sequential occurrence of ET and PV. Heterozygous JAK2 V617F mutation with slightly increased kinase activity is enough for the induction of spontaneous megakaryopoiesis and erythropoiesis, and an increase of hypersensitive platelets is the cause of aspirin-sensitive, platelet-mediated microvascular ischemic and thrombotic complications in ET and early PV mimicking ET. Homozygous JAK2 mutation with pronounced increase of kinase activity is associated with pronounced trilinear megakaryocyte, erythroid, and granulocytic myeloproliferation, with the most frequent clinical picture of classical PV complicated by major thrombosis, in addition to the platelet-mediated microvascular thrombotic syndrome of thrombocythemia.
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PMID:The paradox of platelet activation and impaired function: platelet-von Willebrand factor interactions, and the etiology of thrombotic and hemorrhagic manifestations in essential thrombocythemia and polycythemia vera. 1697 69

Microvascular circulation disturbances including erythromelalgia, its microvascular ischemic complications, and migraine-like atypical or typical transient ischemic cerebral, ocular, and coronary ischemic attacks are specific clinical manifestations in patients with essential thrombocythemia (ET), and polycythemia vera (PV) associated with thrombocythemia. Thrombocythemia (ET and PV) patients with microvascular disturbances have shortened platelet survival, increased beta-thromboglobulin (beta-tg), platelet factor 4 (PF4), and thrombomoduline (TM) levels, and increased urinary thromboxane B2 (TxB2) excretion indicating platelet-mediated processes in vivo. Inhibition of platelet cyclooxygenase (COX 1) by aspirin is followed by relief of microvascular disturbances, correction of shortened platelet survival, and return of plasma levels of beta-tg, PF4, TM levels and TxB2 excretion to normal. The transient ischemic attacks and thrombotic complications in thrombocythemia are very likely caused by hypersensitive platelets produced by spontaneously proliferating enlarged megakaryocytes in the bone marrow of ET and PV patients. In contrast to normal platelets in healthy individuals the circulating hypersensitive thrombocythemic platelets spontaneously activate and secrete their products, thus forming aggregates that transiently plug the microcirculation, or result in occlusive platelet thrombi in arterioles or small arteries. Clear evidence is presented that the microvascular transient ischemic and occlusive thrombotic complications in thrombocythemia patients are relieved by treatment with aspirin and by reduction of platelet counts to normal (<400 x 109/l), but not by coumadin. In patients with thrombocythemia associated with PV, increased hematocrit and whole blood viscosity aggravate the platelet-mediated microvascular ischemic and thrombotic syndrome of thrombocythemia to major arterial and venous thrombotic complications. Correction of hematocrit and blood viscosity by phlebotomy significantly reduces the major arterial and venous thrombotic complications, but fails to prevent the platelet-mediated microvascular circulation disturbances in PV patients because thrombocythemia persists. Complete relief and prevention of microvascular and major thrombosis in PV patients are obtained by treatment with low-dose aspirin on top of phlebotomy or by treatment with the platelet lowering agents, anagrelide, interferon or hydroxyurea.
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PMID:Platelet-mediated erythromelalgic, cerebral, ocular and coronary microvascular ischemic and thrombotic manifestations in patients with essential thrombocythemia and polycythemia vera: a distinct aspirin-responsive and coumadin-resistant arterial thrombophilia. 1712 81


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