Should a platelet limit of 600 × 10⁹/l be used as a diagnostic criterion in essential thrombocythaemia? An analysis of the natural course including early stages

Abstract

Summary. In order to evaluate the natural history of essential thrombocythaemia (ET), clinical data and prognostic factors of 143 patients with ET were retrospectively analysed (mean observation time 6·1 Ϯ 4·6 years). In 42 patients the early phase of the disease with initial platelet counts between 250 and 600 × 10 9 /l was assessed. In most early cases, ET was suggested by clinical symptoms (79%) and increased megakaryopoiesis (95%) with abnormal megakaryocytes in bone marrow histology (n ¼ 34) and cytology (n ¼ 5). Other myeloproliferative disorders and reactive thrombocytosis were excluded according to the diagnostic criteria of the Polycythemia Vera Study Group. During follow-up of the 38 early cases not treated cytoreductively at diagnosis, the platelet counts increased to >600 × 10 9 /l in 28 patients (74%) and remained between 450 and 600 × 10 9 /l in 10 patients (26%). In primarily asymptomatic patients (n ¼ 46) with initial platelet counts above (n ¼ 37) and below 600 × 10 9 /l (n ¼ 9) the rates of increase of symptomatic patients were similar at about 7% per year. No influence of the initial platelet count on survival was seen in multivariate analysis of prognostic factors which included all 143 cases. Survival was mainly influenced by the rate of ET-related complications during follow-up (P ¼ 0·002). Analysing the influence of cytoreductive therapy on symptom-free survival, platelet reduction benefited patients under 60 years (19 cytoreductively treated v 65 untreated patients, P ¼ 0·075). The results demonstrate the possible clinical relevance of the early stages of ET and suggest that the features of pathologic megakaryopoiesis in the bone marrow are a more reliable diagnostic criterion than a definite platelet limit. Therefore, further therapeutic studies should include all stages of the disease and all age groups.Keywords: myeloproliferative disorder, early essential thrombocythaemia, prognostic factors, diagnostic criteria, bone marrow histology.Due to the lack of a specific diagnostic marker, the diagnostic criteria of essential thrombocythaemia (ET) established by the Polycythemia Vera Study Group (PVSG) were directed primarily at the exclusion of other myeloproliferative disorders and of reactive thrombocytosis. For diagnosis of ET, a platelet count of 600 × 10 9 /l was considered as an absolute requirement (Murphy et al, 1986). For protocols involving myelosuppressive agents a platelet count of 1000 × 10 9 /l was determined to restrict the erroneous inclusion of cases with reactive thrombocytosis and to avoid possible overtreatment of cases with a mild course of ET (Murphy et al, 1986(Murphy et al, , 1997. In most of the following studies, patients with lower platelet counts were excluded according to the criteria of the PVSG. Such selectivity is acceptable for therapeutic studies. But in the evaluation of the natural course of ET the exclusion of early stages with moderate thrombocytosis below the limit of 600 × 10 9 /l may lead to incomplete recognition of characteristic features of the di...

Major vascular complications in essential thrombocythemia: a study of the predictive factors in a series of 148 patients

“…Actually, only one patient in the latter subgroup of 36 patients had a MVC during the follow-up period. These results are in accordance with those previously reported by others investigators, 5,9,10 and reinforce the appropriateness of a wait-and-see approach for young ET patients, as previously recommended. 21 In our series, a history of previous vascular complications or the presence of major ischemic events at the time of ET diagnosis were also strongly linked to the risk of subsequent vascular complications, as also pointed out by others.…”

“…In this sense, cigarette smoking has been related to a greater incidence of arterial ischemic complications in ET patients in some, 7 but not all studies, 5,10 whereas such an association has not been observed for diabetes and hypertension. 5,10 On the other hand, the lack of predictive value of platelet counts, in agreement with the results obtained in most Actuarial probability of appearance of major vascular complications (MVC) in 148 ET patients (a), and according to age group (b), the history or not of previous vascular complications at time of ET diagnosis (c), and the presence or absence of hypercholesterolemia (d). The dotted lines in each figure indicate the adjusted probability of developing MVC when the other significant covariates remain unchanged.…”

“…5,6,22 In addition, in the present series hypercholesterolemia was the only vascular risk factor related to the appearance of ischemic events, an association not previously reported. 5,10 On the contrary, no predictive value was observed for other vascular risk factors, such as cigarette smoking, diabetes and arterial hypertension. In this sense, cigarette smoking has been related to a greater incidence of arterial ischemic complications in ET patients in some, 7 but not all studies, 5,10 whereas such an association has not been observed for diabetes and hypertension.…”

“…1,[4][5][6][7][8][9][10][17][18][19][20] The frequency of thrombotic complications at presentation of ET in the different retrospective studies varies from 31 to 83%. 1 The arterial thrombotic manifestations of ET in 809 patients from 11 retrospective studies were described as microcirculatory disturbances in 41%, of which 24% involved the extremities and 17% the cerebral circulation.…”

“…Thus, although several risk factors, such as advanced age, 5 previous history of thrombosis 5,6 and existence of associated vascular risk factors, 7 have been identified, there are discrepancies between the different studies. [5][6][7][8][9][10] On the other hand, there is no universal agreement on the criteria for the selection of ET patients who need cytotoxic treatment, mainly because of the hazard associated with such a therapy. In this setting, a better knowledge of the variables associated with a higher thrombotic risk can be of help to make treatment decisions.…”