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)

Thirty-six patients with chronic myeloproliferative disorders (CMPD) were studied as regards blood coagulation and fibrinolysis. These studies revealed various mild abnormalities: activated thromboplastin time (APTT) tended to prolong and the level of factor V decreased significantly. In several cases, the levels of D-dimer, thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex were elevated compared to normal. These results suggest that abnormal coagulation system in the patients with CMPD is related to low grade disseminated intravascular coagulation. Many coagulation factors did not correlate with peripheral blood cell counts. Two patients with polycythemia vera were evaluated for several abnormalities of the coagulation system before and during treatment. Coagulation abnormalities persisted after hematologic control had been achieved. Our results suggest that patients with CMPD have a chronic state of abnormal blood coagulation system even after normalization of blood cell counts.
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PMID:[Abnormal blood coagulation and fibrinolysis in chronic myeloproliferative disorders]. 187 Feb 70

Subnormal platelet responses to thromboxane A2 (TXA2) were found in a patient with polycythemia vera, and the mechanism of this dysfunction was analyzed. The patient's platelets showed defective aggregation and release reaction to arachidonic acid, enzymatically generated TXA2 and synthetic TXA2 mimetics (STA2, U-46619). In contrast, they showed normal responses to thrombin. When the platelet TXA2 receptor was examined with both a 125I-labelled derivative of a TXA2 receptor antagonist ([125I]-PTA-OH) and a 3H-labelled TXA2 agonist ([3H]U-46619), the equilibrium dissociation rate constants (Kd) and the maximal concentrations of binding sites (Bmax) of the patient's platelets to both ligands were within normal ranges, suggesting that the binding capacity of their TXA2 receptor was normal. STA2 failed to induce normal elevation in the cytoplasmic free calcium ion concentration, phosphatidic acid formation and 40 kD protein phosphorylation in the patient's platelets, whereas these responses to thrombin were within normal ranges. 12-O-Tetradecanoyl-phorbol-13-acetate (TPA) also evoked normal response in the 40 kD protein phosphorylation in the patient's platelets. These results suggested that the patient's platelets had TXA2 receptor abnormalities which were characterized by defective transduction of the binding signal to postreceptor reactions after normal TXA2 binding.
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PMID:Hemorrhagic thrombocytopathy with platelet thromboxane A2 receptor abnormality: defective signal transduction with normal binding activity. 295 39

Essential thrombocythemia is a myeloproliferative disorder characterized by frequent bleeding and thrombotic complications. On a molecular level, two abnormalities of platelet thrombospondin have been identified: abnormal glycosylation of the intact 185,000-dalton chain has been detected and a shortened form of the thrombospondin chain is present. We have used two monoclonal antibodies and Lens culinaris lectin to probe the structure of thrombospondin in the platelets from three patients with essential thrombocythemia; one patient with polycythemia vera and two patients with secondary thrombocytosis. The presence of abnormal thrombospondin fragments with molecular weights of 160,000 and 30,000 was detected in the intact platelets and in the supernatant from thrombin-treated platelets, in all of the individuals except one of the secondary thrombocytosis patients. Monoclonal antibody binding studies indicate that both fragments are produced by proteolysis at a single site, which results in the removal of a 30,000-dalton fragment from the NH2-terminal. Lens culinaris lectin-binding studies revealed that some of the carbohydrate moieties of thrombospondin are near this cleavage site. The results are consistent with the hypothesis that the abnormal thrombospondin fragments observed under conditions of increased platelet production are due to increased susceptibility to proteolysis which, in turn, may be due to defective glycosylation.
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PMID:Thrombospondin in essential thrombocythemia. 351 Jun 84

Patients with polycythemia vera have been described to have hemorrhagic as well as thrombotic tendencies. In a patient with polycythemia vera and angina pectoris, we observed markedly decreased platelet aggregation response to epinephrine but increased platelet and whole-blood thromboxane A2 generation compared with normal subjects. Electron microscopy mostly showed partially activated forms of platelets, which may account for decreased aggregation response in vitro and hemorrhagic tendencies. Young and large platelets found in this disease, however, can generate large amounts of vasoconstrictor and platelet proaggregatory prostanoid thromboxane A2 in response to endogenous thrombin, which may be a basis for thrombotic tendencies.
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PMID:Decreased platelet aggregation but increased thromboxane A2 generation in polycythemia vera. 401 70

We attempted to determine if a hypercoagulability state exists in patients with polycythemia vera (PV) and essential thrombocythemia (ET). We studied the hematocrit level, platelet count, use of any antiaggregant drugs, thrombotic or bleeding accidents and plasma levels of antithrombin III, protein C, total protein S, free protein S, vWF:Ag (Von Willebrand's factor related antigen), thrombin-antithrombin complexes, D-dimer, fibrinolytic activity, tissue plasminogen activator, plasminogen and PAI-1 in 33 patients (19 with ET and 14 with PV). PAI-1 plasma concentration was significantly higher in, both ET and PV patients than in the control group, and were higher in those patients with previous thrombotic episodes than in asymptomatic patients or with previous bleeding episodes. Increasing age was associated to more thrombotic episodes while younger patients presented with more hemorrhagic complications. A linear correlation between platelet count and PAI-1 levels in PV patients (r = 0.44, p < 0.05) and ET patients (r = 0.30, p < 0.05) was found. Fibrinolytic activity in patients with ET was significantly decreased when compared to the control group. A hypofibrinolytic state could be an additional factor which could be used as a predictive index of the thrombotic or bleeding tendency in each patient.
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PMID:High plasma levels of plasminogen activator inhibitor 1 (PAI-1) in polycythemia vera and essential thrombocythemia are associated with thrombosis. 799 52

A patient with colon carcinoma complicated by polycythemia vera (PV) who underwent a partial colectomy concomitant with prophylactic perioperative treatment resulting in successful outcome is herein described. Seven weeks after the cessation of the latest exacerbation of PV, a partial colectomy was performed. In order to prevent the development of disseminated intravascular coagulation and thrombotic complications, the following perioperative treatment was performed: administration of gabexate mesilate (2,000 mg/day), fresh frozen plasma (300 ml/day), heparin (5,000 IU/day) for 7 days and anti-thrombin-III for 4 days, and a potent antibiotic therapy for 12 days and graded elastic bandages around the bilateral lower extremities for 14 days. As a result, an uneventful postoperative course was achieved. The present case suggests that these treatments are useful in the perioperative management of PV patients.
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PMID:Prophylactic perioperative treatment in a patient with colon carcinoma complicated by polycythemia vera. 935 51

Because platelets interact with fibrinolysis in a complex manner, it can be expected that with abnormal platelet numbers and quality this interference can be even more profound. The aim of this work was to study the lysis-resistance of platelet-rich clots in diseases with high platelet counts: polycythemia vera (PV), essential thrombocythemia (ET) and to make comparison with polyglobulia (PG). Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were analyzed by an in vitro clot lysis test. Plasminogen activator inhibitor-1 (PAI-1) activity was measured in plasma and in the supernatants of the washed and gel-filtered platelets after activation by thrombin. The lysis showed decreased speed of PPP-clots in PV and ET. This phenomenon was even more marked in PRP-clots from PV and ET, but further increased lysis resistance after retraction was not observed in PV and ET, most likely due to abnormal platelet functions. Our results suggest that the fibrinolytic activity is reduced in PV and ET, and may play a role both in the increased aptitude for venous thrombosis and in the arterial complications. These are partly caused by higher plasmatic PAI-1 activity as well as by more active platelet PAI-1. The PAI-1 activity was significantly higher in the supernatants of the washed and gel-filtered platelets of PV after activation by thrombin compared with controls. Other factors might have influenced the reduced fibrinolysis.
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PMID:Reduced in vitro clot lysis and release of more active platelet PAI-1 in polycythemia vera and essential thrombocythemia. 968 57

The pathogenesis of polycythemia vera (PV), a disease involving a multipotent hematopoietic progenitor cell, is unknown. Thrombopoietin (TPO) is a newly characterized hematopoietic growth factor which regulates the production of multipotent hematopoietic progenitor cells as well as platelets. To evaluate the possibility that an abnormality in TPO-mediated signal transduction might be involved in the pathogenesis of PV, we examined TPO-induced protein tyrosine phosphorylation using platelets as a surrogate model system. Platelets were isolated from the blood of patients with PV as well as from patients with other chronic myeloproliferative disorders and control subjects. Impaired TPO-mediated platelet protein tyrosine phosphorylation was a consistent observation in patients with PV as well as those with idiopathic myelofibrosis (IMF), in contrast to patients with essential thrombocytosis, chronic myelogenous leukemia, secondary erythrocytosis, iron deficiency anemia, hemochromatosis, or normal volunteers. Thrombin-mediated platelet protein tyrosine phosphorylation was intact in PV platelets as was expression of the appropriate tyrosine kinases and their cognate substrates. However, expression of the platelet TPO receptor, Mpl, as determined by immunoblotting, chemical crosslinking or flow cytometry was markedly reduced or absent in 34 of 34 PV patients and also in 13 of 14 IMF patients. Impaired TPO-induced protein tyrosine phosphorylation in PV and IMF platelets was uniformly associated with markedly reduced or absent expression of Mpl. We conclude that reduced expression of Mpl is a phenotypic characteristic of platelets from patients with PV and IMF. The abnormality appears to distinguish PV from other forms of erythrocytosis and may be involved in the platelet function defect associated with PV.
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PMID:A novel thrombopoietin signaling defect in polycythemia vera platelets. 1101 90

Thrombohemorrhagic complications are a major cause of morbidity and mortality in patients with essential thrombocythemia (ET) and polycythemia vera (PV). The pathogenesis of these complications is not completely clarified. Several studies have described abnormalities of red blood cells and platelets in these patients. However, no studies are available on changes in the polymorphonuclear leukocytes (PMNs), which can play an important role in the activation of the hemostatic system. In patients with ET (n = 37) and PV (n = 34), a series of PMN activation parameters (PMN membrane CD11b and leukocyte alkaline phosphatase [LAP] antigen expression, cellular elastase content, plasma elastase, and myeloperoxidase levels) was evaluated simultaneously with the levels of plasma markers of endothelial damage (thrombomodulin and von Willebrand factor antigen) and hypercoagulation (thrombin-antithrombin complex, prothrombin fragment 1 + 2, and D-dimer). The results show the occurrence of PMN activation in both groups of patients compared with a control group of healthy subjects. An increase in CD11b and LAP expression by PMN membrane was observed, together with a significant increase in cellular elastase content, plasma elastase, and myeloperoxidase levels. In addition, patients had high plasma levels of endothelial and hypercoagulation markers compared with controls. For the first time, these data show that in ET and PV, 2 hematologic conditions that place patients at increased risk for thrombosis, an in vivo leukocyte activation occurs and is associated with laboratory signs of endothelium and coagulation system activation. (Blood. 2000;96:4261-4266)
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PMID:Polymorphonuclear leukocyte activation and hemostasis in patients with essential thrombocythemia and polycythemia vera. 1111 Jul

Recently, the asymmetric distribution of phospholipids in eukaryotic cell membranes has been appreciated and been found to be dependent on the activity of a number of enzymes. The expression of phosphatidylserine (PS), a negatively charged phospholipid, on the platelets of patients with polycythemia vera (P vera) and essential thrombocythemia (ET) was compared to that in normal individuals. The effect of platelet aggregation on PS expression was determined. Exposure of PS on platelets obtained from patients with P vera and ET and from age- and sex-matched healthy volunteers was measured by fluorescein-labeled Annexin V binding to platelets and by the platelets' thrombin-generating capacity determined by the prothrombinase assay. PLatelet prothrombinase activity (mean +/- standard deviation [SD]), as measured by thrombin generation, was 2.32+/-2.2 micro/mL in the P vera group and 1.55+/-1.0 micro/mL in the control group (p=0.3). PS expression as measured by Annexin V binding (mean +/- SD) was 2.6+/-2.4 % in the P vera group versus 1.55+/-1.2% among controls (p=0.03). In the ET group, prothrombinase activity (mean +/- SD) was 1.0+/-0.6 micro/mL and 2.1+/-0.9 micro/mL in the control group (p=0.006). Annexin V binding (mean +/- SD) was 4.8+/-4.2% in the ET group and 2.77+/-2.1% among control subjects (p=0.09). When the prothrombinase assay was performed after addition of adenosine diphosphate (ADP) to the platelets, there was a significant increase in thrombin generation in the myeloproliferative disorder (MPD) group (3.1+/-2.0 micro/mL) compared to the thrombin generated by unstimulated myeloproliferative disorder platelets (2.07+/-1.69 micro/mL) (p=0.0006). An increase in thrombin generation was seen in the ADP-stimulated platelet samples in all ten paired samples studied. Likewise, the addition of ADP to control platelets increased thrombin generation from 2.0+/-1.0 micro/mL in unstimulated platelets to 4.3+/-1.6 micro/mL in ADP-treated platelets (p=0.0006). Thrombin generation increased in all of the ADP-stimulated platelet samples compared to the untreated platelets. There was however, no difference in the increased thrombin generation when ADP-stimulated platelets from MPD patient and control subjects were compared (p=0.3). Results indicate that some patients with MPDs may show increased PS expression on platelet surface. When analyzed overall, there was a tendency toward greater PS expression in the P vera and ET patient groups; however, the increase did not reach statistical significance. This increase was noted in both the prothrombinase assay the Annexin V binding assay. We have also shown that stimulation of platelets by addition of the agonist ADP results in enhanced PS expression, which appears increase the thrombogenic potential of the platelets as demonstrated by the enhanced thrombin generation demonstrated by these platelets in the prothrombinase assay. There was no difference in the degree of PS expression in response to ADP stimulation between MPD and control platelets. Results show that PS expression and platelet-dependent thrombin generation is variable in patients with MPDs. This expression is increased after platelet aggregation occurs. The role of PS expression in the thromboembolic complications of MPD patients should be studied further.
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PMID:Phosphatidylserine expression on the platelet membrane of patients with myeloproliferative disorders and its effect on platelet-dependent thrombin formation. 1199 Dec 37


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