A role for changes in platelet production in the cause of acute coronary syndromes.
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Platelets are heterogeneous with respect to their size, density, and reactivity. Large platelets are more active hemostatically, and platelet volume has been found to be increased both in patients with unstable angina and with myocardial infarction. Furthermore, platelet volume is a predictor of a further ischemic event and death when measured after myocardial infarction. Platelets which are anucleate cells with no DNA are derived from their precursor, the megakaryocyte. Therefore, it is suggested that changes in platelet size are determined at thrombopoiesis in the megakaryocyte and that those changes might precede acute cardiac events. Understanding of the signaling system that controls platelet production may also further elucidate the cascade of events leading to acute vascular occlusion in some patients. (+info)
Patients with thrombocytosis have normal or slightly elevated thrombopoietin levels.
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BACKGROUND AND OBJECTIVE: The distinction between clonal and reactive thrombocytoses is a frequent problem and implies different therapeutic options. As thrombopoietin (TPO) is the main regulator of megakaryocytopoiesis and thrombopoiesis, we measured TPO levels in patients with thrombocytosis in an attempt to understand the regulation and potential utility of distinguishing thrombocytoses. DESIGN AND METHODS: Serum TPO levels, platelet counts, mean platelet volume, hemoglobin, erythrocyte sedimentation rate and age were evaluated in 25 patients with clonal thrombocytosis (15 with essential thrombocythemia, 6 with polycythemia vera and 4 with chronic myeloid leukemia) and in 50 patients with reactive thrombocytosis distributed in three groups: 1) patients in post-surgical states; 2) patients with solid tumors; and 3) patients with inflammatory diseases. RESULTS: TPO levels were slightly increased in patients with clonal (135+/-50 pg/mL) and reactive (147+/-58 pg/mL) thrombocytosis compared with controls (121+/-58 pg/mL). Analyzing the different groups, patients with essential thrombocythemia had the lowest TPO levels (120+/-28 pg/mL) and patients with solid tumors the highest levels (162+/-59 pg/mL). Patients with clonal thrombocytosis were older, had higher platelet counts, mean platelet volume and hemoglobin, and lower erythrocyte sedimentation rate than patients with reactive thrombocytosis. INTERPRETATION AND CONCLUSIONS: Minor differences were observed in TPO levels between patients with primary and secondary thrombocytoses. Erythrocyte sedimentation rate, but not TPO levels, may be a useful tool for discriminating both types of thrombocytoses. (+info)
Hydroxyurea in the management of the hematologic complications of chronic granulocytic leukemia.
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The effect of hydroxyurea in 35 patients with chronic granulocytic leukemia (CGL), who either had entered an accelerated phase of the disease or had experienced excessive myelosuppression following alkylating agents, was studied. By either intravenous or oral administration, the drug was successful in reducing peripheral leukocyte and blast counts in all cases and in reducing splenomegaly in 13 of 17 patients. The median duration of disease control was 75 days in myeloproliferative acceleration and 27 days in frank blastic transformation. Mild nausea and vomiting were experienced by most patients, but reversible bone marrow suppression occured in only three patients. The drug proved useful in 19 patients who demonstrated myeloproliferative acceleration, especially in controlling excessive leukocytosis and/or thrombocytosis. Rapid reduction of an elevated blast cell count was achieved in nine patients who presented in blastic crisis, in an attempt to eliminate the associated risk of cerebral vascular leukostasis. Five patients who required treatment for their disease following splenectomy in the chronic phase were also well controlled. Hydroxyurea appears to have a definite role in the management of these hematologic complications of CGL. (+info)
Mother cell of megakaryocyte.
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It was attempted to describe the morphology of the most immature cell of megakaryocytic series. The megakaryocytes were observed with the electron microscope in five cases, being traced back to their immature forms. In two cases the most immature cells of megakaryocytic series were considered to be the cells which were probably identified as lymphocytes under the light microscope, but they were not lymphocytes with the electron microscope. In other two cases it was presumed that neutrophilic and megakaryocytic series were derived from morphologically similar immature cells, since the most immature cells of neutrophilic and megakaryocytic series were not distinguished when they were traced back to their immature forms. These findings suggest that mother cells of megakaryocytes in the adult bone marrow may be identified as lymphoid cells with the light microscope. (+info)
Mechanism of platelet liberation.
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Megakaryocytes from 5 patients and 1 normal person were observed electronmicroscopically. In some pathologic states platelets seemed to be liberated without demarcation membrane system (DMS) and in a normal individual they seemed to be liberated independently of DMS. These findings suggest that DMS is not concerned with platelet liberation and that platelets are liberated through pseudopodia and bleb formation. In mature megakaryocytes vigorous amoeboid movement seems to exist and both pseudopodia and blebs may represent this movement. Structural similarity between surface connected system (SCS) of platelet and DMS of megakaryocyte suggests that the structure called DMS is transported as SCS into platelet. (+info)
Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients.
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In a 20-year period, 223 patients (median age, 64.8 years) with myelofibrosis with myeloid metaplasia (MMM) had therapeutic splenectomy at our institution. Primary indications for surgery were transfusion-dependent anemia (45.3%), symptomatic splenomegaly (39. 0%), portal hypertension (10.8%), and severe thrombocytopenia (4.9%). Operative mortality and morbidity rates were 9% and 31%, respectively. The 203 survivors of surgery had a median postsplenectomy survival time (PSS) of 27 months (range, 0-155). Among preoperative variables, thrombocytopenia (platelet count less than 100 x 10(9/)L) and nonhypercellular bone marrow were identified as independent risk factors for decreased PSS. Durable remissions in constitutional symptoms, transfusion-dependent anemia, portal hypertension, and severe thrombocytopenia were achieved in 67%, 23%, 50%, and 0% of the patients, respectively. Histologic or cytogenetic features of bone marrow obtained before splenectomy did not predict a response in cytopenias. After splenectomy, substantial enlargement of the liver and marked thrombocytosis occurred in 16.1% and 22.0% of the patients, respectively. The thrombocytosis was associated with an increased risk of perioperative thrombosis and decreased PSS. The rate of blast transformation (BT) was 16.3%, and the risk of BT was higher in the presence of increased spleen mass and preoperative thrombocytopenia. However, the PSS of patients with BT was not significantly different from that of patients without BT. We conclude that presplenectomy thrombocytopenia in MMM may be a surrogate for advanced disease and is associated with an increased risk of BT and inferior PSS. However, the development of BT after splenectomy may not affect overall survival and does not undermine the palliative role of the procedure for the other indications. (+info)
Artefactual serum hyperkalaemia and hypercalcaemia in essential thrombocythaemia.
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AIM: To investigate possible abnormalities of serum potassium and calcium levels in patients with essential thrombocythaemia and significant thrombocytosis. METHODS: 24 cases of essential thrombocythaemia with significant thrombocytosis (platelet count > 700 x 10(9)/litre) had serum potassium and calcium estimations performed at the time of maximum thrombocytosis before treatment, and at the time of low platelet count after treatment with cytoreductive drugs. Selected patients were further investigated with plasma sampling and estimation of ionised calcium and parathyroid hormone. RESULTS: At the time of maximum thrombocytosis six patients had serum hyperkalaemia (> 5.5 mmol/litre) and five had serum hypercalcaemia (> 2.6 mmol/litre). Following treatment and reduction of the platelet count, hyperkalaemia resolved in all cases and hypercalcaemia in four of the five cases. Mean serum potassium and calcium concentrations were raised (p < 0.0001) at maximum thrombocytosis compared with the values when the platelet count was low. Serum potassium and calcium values were significantly correlated at all stages. Measurements on plasma consistently corrected the hyperkalaemia but not the hypercalcaemia. Serum hypercalcaemia was associated with raised ionised calcium and normal parathyroid hormone concentrations. CONCLUSIONS: Essential thrombocythaemia with significant thrombocytosis is associated with serum hyperkalaemia and hypercalcaemia. The probable mechanism of hypercalcaemia is the secretion of calcium in vitro from an excessive number of abnormally activated platelets. It is thus likely that the hypercalcaemia is an artefact, as is the hyperkalaemia. (+info)
The physiology of platelet production.
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The production of platelets from the bone marrow megakaryocytes is a well-regulated process. Nearly 100 years ago, James Homer Wright described how platelets formed from megakaryocytes and entered the circulation. Subsequent clinical and animal studies have enumerated a number of principles of platelet physiology: the platelet count is constant in any one individual but varies greatly between individuals; an inverse relationship exists between the platelet count and platelet size; the body conserves the mass, not the number, of platelets; and megakaryocyte number, size and ploidy vary in response to changing demands for platelets. With the discovery of thrombopoietin (TPO), a number of additional physiological principles have emerged: TPO takes 24 h to rise maximally and has a maximal half-life of 45 min; TPO levels are inversely and exponentially proportional to the platelet mass; platelets bind and clear TPO from the circulation; and hepatic TPO product on is not altered by changes in the platelet mass. Using these principles, a model for the regulation of platelet production by TPO has been proposed in which the constitutive hepatic TPO produced is removed from the circulation by the platelet mass. Changes in the platelet mass or its ability to clear TPO produce changes in TPO levels resulting in an altered platelet production rate. Using this model, a number of pathological disorders of platelet production, such as essential thrombocythemia and idiopathic thrombocytopenic purpura, are analyzed. (+info)