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)

In order to evaluate the role of proteolysis in acquired von Willebrand's disease (vWD) associated with the myeloproliferative syndrome, we have determined the relative quantity of von Willebrand factor (vWF) fragments as compared with the intact 225 kDa subunit in four patients. The plasma vWF of each individual lacked large multimers; each had a prolonged bleeding time; and both platelet and leukocyte counts were elevated. Plasma was obtained from blood drawn into 1 mmol/L leupeptin, 6 mmol/L N-ethylmaleimide, and 5 mmol/L EDTA to prevent in vitro proteolysis. vWF was isolated from plasma by immunoadsorbent chromatography, reduced, subjected to SDS-5% polyacrylamide gel electrophoresis, and immunoblotted with a mixture of 55 anti-vWF monoclonal antibodies. In three patients with essential thrombocytosis (ET) the 176 and 140 kDa fragments were increased in proportion to the intact 225 kDa subunit indicating increased proteolysis. Treatment of one ET patient with CCNU (Lomustine) decreased the platelet count and, to a lesser extent, the white blood cell count. This was associated with a correction of the bleeding time, a partial correction of the multimeric abnormality, and a lessening of vWF cleavage. In a patient with polycythemia rubra vera (PRV) the proportion of the 176 kDa fragment was increased to the upper limit of normal but there was no definite evidence of increased proteolysis. These studies provide evidence that proteolysis plays a role in the acquired von Willebrand's disease associated with the myeloproliferative syndrome. However, other mechanisms must also be considered.
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PMID:Subunit composition of plasma von Willebrand factor in patients with the myeloproliferative syndrome. 353 24

The clinical value of a new in vitro test of hemostasis, which we have called Filter Bleeding Time (FBT), was determined in 59 patients referred because of a suspected bleeding disorder. FBT is based on the progressive slowing of the drop rate of citrated blood through a filter of woven Dacron under constant pressure as platelet aggregates occlude the filter. The value for FBT is defined as the time when the blood drop interval has reached 1 minute. The Mayo modification of the Ivy bleeding time (IBT) was performed in all patients; platelet response to ADP, collagen, epinephrine and arachidonate was performed in 24 patients. In 30 normal volunteers FBT measured 1-3 hr after venipuncture was 2.8 +/- 1.5 (means +/- 1SD) min. The FBT was prolonged in 3 of 3 patients with Glanzmann's thrombasthenia, 2 with disseminated intravascular coagulation, 1 with chronic lymphocytic leukemia, 1 with myelofibrosis, and 1 who had taken aspirin. In 6 patients FBT was prolonged while IBT was normal: 4 after taking aspirin, 2 with polycythemia vera. All 6 had reduced platelet aggregation (PA) to ADP (5 microM), collagen (2 mg/ml), epinephrine (5 microM) and/or arachidonate (1.7 mM). In 3 patients FBT was normal while IBT was abnormal: 1 with disseminated intravascular coagulation, 2 undiagnosed; 1 of these 3 had abnormal PA. Of 6 patients with von Willebrand's disease, FBT was prolonged in 5 and borderline in 1; IBT was prolonged in 3, normal in 1, and not done in 2 infants.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical evaluation of a new test of hemostasis: the Filter Bleeding Time. 674 May 68

We report a case of 47-year-old patient with von Willebrand's disease (VWD) caused by polycythemia vera (PV) who underwent CABG surgery. The patient has been suffering of PV for 10 years and was admitted because of post infarction angina. On admission, she was found to have a decreased von Willebrand factor which was suggested by prolonged APTT. CABG was safely performed without undue bleeding with the use of Factor VIII concentrates. The appropriate control of polycythemic state before surgery and perioperative use of Factor VIII concentrates was considered to be important for successful open heart surgery associated with such complication.
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PMID:[A case of CABG in a patient complicated with von Willebrand's disease secondary to polycythemia vera]. 771 22

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

Patients with polycythemia vera and essential thrombocythemia have a hemostatic imbalance, the mechanisms of which are still elusive. Hemorrhagic tendency usually manifests in patients with high platelet count and reveals the clinical and laboratory features of acquired von Willebrand's disease. In most patients, however, the increased risk of arterial and venous thromboses constitutes the main therapeutic challenge. Data from large retrospective studies have recently allowed us to reassess the clinical epidemiology of these manifestations. Erythromelalgia and other peculiar microcirculatory disturbances are selectively sensitive to aspirin. This finding, and the thromboxane A2 hyperproduction existing in polycythemic and thrombocythemic subjects, provide the rationale for the use of low-dose aspirin in these patients. The efficacy and safety of this treatment in patients with polycythemia vera is being tested in a large scale, randomized trial. Appropriately designed clinical studies are also needed for defining the neoplastic risk of commonly used chemotherapic agents and the antithrombotic efficacy of alternative cytoreductive strategies.
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PMID:Bleeding and thrombosis in myeloproliferative disorders. 977 11

A qualitative abnormality of platelet function should be considered in patients with mucocutaneous bleeding in the absence of thrombocytopenia or von Willebrand disease. Antiplatelet drugs are the most common cause of acquired platelet disorders leading to bleeding. Uremia, hepatic cirrhosis, myeloma and related disorders, polycythemia vera, essential thrombocythemia, and cardiopulmonary bypass have long been recognized as clinical situations in which platelet dysfunction may contribute to bleeding. When an acquired platelet disorder is suspected, it is useful to examine platelet function by measuring the bleeding time, examining platelet-dependent closure time in a platelet function analyzer and performing platelet aggregometry. When a specific acquired platelet disorder is diagnosed, many treatment options are available including controlling the underlying disease, giving platelet transfusions and administering a hemostatic drug.
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PMID:Acquired disorders of platelet function. 1630 11

Myeloproliferative neoplasms (MPN) are associated with an increased risk of arterial and venous thrombosis. Pegylated-interferon alpha (IFN) and hydroxyurea (HU) are commonly used to treat MPN, but their effect on hemostasis has not yet been studied. The aim of our study was to determine whether IFN and HU impact the biological hemostatic profile of MPN patients by studying markers of endothelial, platelet, and coagulation activation. A total of 85 patients (50 polycythemia vera and 35 essential thrombocythemia) were included: 28 treated with IFN, 35 with HU, and 22 with no cytoreductive drug (non-treated, NT). Von Willebrand factor, shear-induced platelet aggregation, factor VIII coagulant activity (FVIII:C), fibrinogen, and thrombin generation with and without exogenous thrombomodulin were significantly higher in IFN-treated patients compared to NT patients, while protein S anticoagulant activity was lower. In 10 patients in whom IFN therapy was discontinued, these hemostatic biomarkers returned to the values observed in NT patients, strongly suggesting an impact of IFN therapy on endothelial and coagulation activation. Overall, our study shows that treatment with IFN is associated with significant and reversible effects on the biological hemostatic profile of MPN patients. Whether they could be associated with an increased thrombotic risk remains to be determined in further randomized clinical studies.
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PMID:Interferon Alpha Therapy Increases Pro-Thrombotic Biomarkers in Patients with Myeloproliferative Neoplasms. 3231 12