Prognostic significance of bone marrow biopsy in essential thrombocythemia.
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BACKGROUND AND OBJECTIVE: The diagnostic and prognostic value of bone marrow biopsy (BMB) has been widely investigated in patients with chronic myeloproliferative disorders (CMPD). The present study is based on a review of the results of routine BMBs taken from 93 essential thrombocythemia (ET) patients at the time of diagnosis. DESIGN AND METHODS: The common BMB histologic parameters and clinico-hematologic variables were considered for diagnostic and prognostic purposes. Clinico-pathologic correlations were looked for univariately. Moreover, the diagnostic significance of the histologic findings was tested by means of cluster analysis. Overall survival and event-free survival were considered as prognostic endpoints. RESULTS: There were no correlations between the clinic and pathologic findings, and none of the histologic and clinical parameters was predictive of survival or the occurrence of major clinical events. Cluster analysis of the BMB findings revealed two distinct morphologic patterns: one was clearly myeloproliferative; the other had somewhat dysplastic features. The event-free and overall survival rates in the latter group were significantly worse (p = 0.0377 and p = 0.0162 respectively), with major ischemic events accounting for most of the difference in event-free survival. INTERPRETATION AND CONCLUSIONS: These results have no clearcut counterpart in the literature, but we feel that dysplastic BMB findings could be included in the definition of ET prognostic scores in order to allow therapeutic strategies to be adapted to the level of risk. (+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)
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)
Diagnosis of essential thrombocythemia at platelet counts between 400 and 600x10(9)/L. Gruppo Italiano Malattie Mieloproliferative Croniche(GIMMC).
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BACKGROUND AND OBJECTIVE: Diagnostic criteria for essential thrombocythemia (ET) remain essentially negative, that is, exclusion of other myeloproliferative diseases and causes of reactive thrombocytosis. A platelet count above 600x10(9)/L is still generally considered an absolute diagnostic criterion although new protocols for positive diagnostic criteria have recently been proposed, reducing the stringency of a definite platelet limit. This study demonstrates that a platelet count 600x10(9)/L is not a reliable diagnostic criterion for ET, especially in the early stages. DESIGN AND METHODS: An ongoing retrospective study by the GIMMC analyzed 2,316 ET patients diagnosed between 1986 and 1995. Of these 2,316 patients, diagnosed according to the PVSG criteria, 68 had a platelet count 600x10(9)/L and were analyzed separately; 37 out of 68 were excluded from this analysis because of a follow-up shorter than 2 years and/or because of treatment with myelosuppressive agents. The remaining 31 patients were the subjects of our study. RESULTS: After a median follow-up of 4.56 years (range 2-9.6 years) none of the 31 patients had a spontaneous decrease of platelets to the normal range. Transformation to a different chronic myeloproliferative disorders was never observed and no patient developed a condition known to produce reactive thrombocytosis. During follow-up, 23 patients (74%) were treated with anti-aggregating drugs, mainly aspirin. The disease did not evolve into acute leukemia in any patient, 1 had a thrombotic event and none presented hemorrhagic episodes. Median platelet count during follow-up was 534x10(9)/L (range 398-997x10(9)/L). INTERPRETATION AND CONCLUSIONS: Long term follow-up has documented that our 31 patients were correctly diagnosed as having ET, although platelet count was 600x10(9)/L. Our patients were probably in a early phase of their disease and following updated PVSG criteria would have been misdiagnosed leading to incomplete recognition of the natural history of the disease. Further, because an early diagnosis could also have a clinical relevance, our results outline the need for new criteria for the diagnosis of ET. The exclusion of patients with a platelet count between 400 and 600x10(9)/L may prevent patients, nevertheless at risk of vascular complications, from being treated. (+info)
Essential thrombocythemia transformed to acute myelogenous leukemia with t(3;17)(p24; q12), del(5)(q13q34) after treatment with carboquone and hydroxyurea.
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In 1991, a 52-year-old woman was diagnosed as having essential thrombocythemia (ET). She was doing well with continuous medication with carboquone (CQ) and subsequently hydroxyurea (HU). However, substantial leukocytosis with leukemic blast cells, anemia and thrombocytopenia developed in 1996. Analysis of peripheral blood showed 4.4 x 10(3)/microl white blood cells with 82% of leukemic blast cells. These blasts showed negative staining with myeloperoxidase by immunostaining, but the myeloperoxidase was positive by electron microscopic analysis. Cytogenetic analysis of bone marrow cells revealed a t(3;17)(p24; q12), del(5)(q13q34). On the basis of these findings, the leukemic blast cells were classified as acute myelogenous leukemia (AML:M0) in the FAB classification. The causative agent, CQ and HU in secondary leukemia from ET and chromosomal abnormality related to ET blastic crisis (BC) are discussed. (+info)
Relevance of bone marrow features in the differential diagnosis between essential thrombocythemia and early stage idiopathic myelofibrosis.
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BACKGROUND AND OBJECTIVES: Diagnosis of essential thrombocythemia (ET) remains a challenging problem and has been predominantly established by exclusion of other thrombocythemic disorders. In this context the updated diagnostic criteria of the Polycythemia Vera Study Group (PVSG) are generally accepted, although histopathologic features of the bone marrow were only marginally considered. DESIGN AND METHODS: A retrospective evaluation was performed of 168 patients presenting with ET in accordance with the criteria of the PVSG. Analysis was focused on the discriminating impact of bone marrow morphology. RESULTS: Histopathology revealed that our cohort of patients could be divided into three distinct groups (true ET, questionable ET and false ET). These groups were characterized by certain diagnostic constellations of clinical data on admission. True ET was found in 53 patients presenting with no or a borderline splenomegaly and no relevant anemia or leuko-erythroblastic blood picture. The other patients showed clinical signs and symptoms which were more compatible with initial-prefibrotic (52 patients) or early (68 patients) idiopathic-primary myelofibrosis (IMF) with severe thrombocythemia. In true ET no significant hypercellularity of the bone marrow including myeloid precursors or an increase in reticulin fibers was detectable. Most prominent were changes of megakaryopoiesis which revealed large to giant-sized cells lacking a definite maturation defect. Their appearance in true ET contrasted with the clusters of abnormally differentiated, often bizarre elements of this lineage in patients with initial and early IMF (questionable or false ET). Calculation of survival disclosed a relevant disparity with a non-significant loss in life expectancy of 10.9% in true ET compared to 29.6% in questionable and 51.3% in false ET. Follow-up studies and repeated bone marrow biopsies revealed no transition into myelofibrosis in true ET, whereas this did occur in 22 of 27 patients with questionable and false ET. In the latter cohort bone marrow changes were accompanied by increasing anemia, splenomegaly, tear-drop poikilocytosis and reduction of the platelet count consistent with IMF. INTERPRETATION AND CONCLUSIONS: A detailed evaluation of bone marrow features, in particular megakaryopoiesis is recommended to establish positive criteria for the diagnosis of ET and thus to accomplish a significant improvement of the PVSG postulates. In this context ongoing clinical trials on ET must regard pretreatment bone marrow biopsies as a major clue to diagnosis. (+info)
Isolated spleen agenesis: a rare cause of thrombocytosis mimicking essential thrombocythemia.
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Thrombocytosis is a common feature of myeloproliferative disorders but may also result from various conditions including chronic iron deficiency, hemorrhage, chronic inflammation and splenectomy. We report two cases of secondary thrombocytosis caused by isolated and congenital asplenia, mimicking essential thrombocythemia. These two adult cases of spleen agenesis were unexpected. We conclude that in thrombocytosis without clinical evidence of splenomegaly, attentive screening of blood in search of Howell-Jolly bodies and abdominal ultrasonography should always be performed not only to detect mild spleen enlargement but also to make sure of the presence of this organ. (+info)