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Essential thrombocythemia and pregnancy: a report of six normal pregnancies in five untreated patients.

OBJECTIVE: To report our experience with essential thrombocythemia complicating pregnancy. METHODS: Over a 5-year period, we studied 21 women of reproductive age affected by essential thrombocythemia. Diagnoses were based on previously published Polycythemia Vera Study Group criteria. RESULTS: Five of our 21 patients became pregnant (total six pregnancies). All pregnancies were carried to term, with uncomplicated deliveries of normally formed infants. No thrombotic or hemorrhagic complications were encountered. CONCLUSION: Normal pregnancy and delivery is readily possible in patients with essential thrombocythemia.

Adult↗

Essential thrombocythemias. Clinical evolutionary and biological data.

This retrospective study reviewed 94 patients, aged 6 to 90 years, with thrombocythemia. The women/men ratio was 1.76. At onset or, less commonly, during the course of the disease, 45% of the patients presented hemorrhagic manifestations, 29% thrombotic complications, and only 14% the association of hemorrhage and thrombosis. The average platelet count was 1200 X 10(9)/1, with no difference according to sex or age. Platelet hypoaggregation was seen in practically all the cases (94%), although myelofibrosis was less frequent (54%). The frequency of hemorrhages increased when the platelet count was above 1000 X 10(9)/1 (P less than 0.01), but the occurrence of thrombosis was correlated neither with platelet count nor with thrombopathy. Survival time was lengthy: 80% of survival (standard error 6%) was observed at 100 months. Transformation to acute leukemia was observed in five patients. Because the disease course is most often prolonged, therapeutic measures must be conservative: anti-aggregating drugs in small doses, and chemotherapy beginning with nonalkylating agents.

Adolescent↗

Arterial thrombosis in essential thrombocythemia.

The course of essential thrombocythemia has been observed in ten patients, ages 46 to 83, of whom nine were followed for a period of 4 months to 9 years. In contrast to the experience with essential thrombocythemia recorded in the literature, manifestations of arterial thrombosis were far more common than hemorrhage. In six of the ten patients, the presenting complaints were ascribable to incipient gangrene of the toes and several of these patients additionally developed occlusion of tibial and larger arteries while under our observation. All patients with incipient gangrene showed marked clinical improvement accompanying busulfan-induced reduction and normalization of the platelet count. Relapses in five patients after 2 to 87 months responded well to retreatment with busulfan. No patient has shown evolution to another myeloproliferative disorder. Essential thrombocythemia should be considered in the differential diagnosis of occlusive arterial disease.

Aged↗

Bleeding and thrombosis in myeloproliferative disorders.

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.

Hemorrhage↗

[Treatment of essential thrombocythemia].

PURPOSE: Essential thrombocythemia (ET) is a myeloproliferative syndrome that rises many therapeutic problems. This affection is rarely life threatening, but hemorrhagic and thrombotic complications must be prevented when possible. The rarity of these complications makes difficult the assessment of treatment efficiency. Few randomised clinical trials were done, and treatment often rests on retrospective studies. The potential toxicity of treatments, their leukemogenicity in particular, rises a decisional problem for young patients. We propose to review available data in order to propose the most rational treatment for each patient. CURRENT KNOWLEDGE AND KEY POINTS: After numerous years when we only disposed of retrospective studies, non-randomised prospective studies or isolated case-reports, two randomised trials allows us to more precisely define ET treatment. The first trial proved the efficiency of the hydroxyurea-aspirin association in the prevention of thrombotic events in high-risk patients. The second trial signalled to our attention the increased risk of bleeding of the association anagrelide-aspirin, with also the possibility of increased appearance of myelofibrosis. FUTURE PROSPECTS AND PROJECTS: New perspectives in the treatment of ET will require to get more insights in the role of hydroxyurea and anagrelide in particular by longer follow-up. But not less important is a better definition of the thrombosis risks (who has to be treated?) and also of the diagnostic groups since ET can, in some particular cases, be misdiagnosed with polycythemia vera or idiopathic myelofibrosis.

Aspirin↗

Splenectomy after portal thrombosis in patients with polycythemia vera and essential thrombocythemia.

BACKGROUND AND OBJECTIVES: Polycythemia vera (PV) and essential thrombocythemia (ET) are two rare acquired myeloproliferative disorders (MPD) with frequent thrombotic and hemorrhagic complications. The occurrence of thrombosis in unusual sites, e.g. splanchnic vasculature, is a severe complication of these diseases. We describe a single-institution experience in patients with ET and PV, diagnosed in agreement with the Polycthemia Vera Study Group criteria, with portal vein thrombosis who did or did not undergo splenectomy. DESIGN AND METHODS: The medical records and the follow-up outcome of 16 MPD patients with portal thrombosis who underwent splenectomy (group A1) and 16 who did not (group A2) were evaluated. Their median follow-up was, respectively, 13.45 and 10.49 years. The overall survival of these patients was compared with that of a population of 32 patients with MPD and no portal thrombosis (group B) matched for sex, age, diagnosis and duration of follow-up. RESULTS: In group A1, 2 patients developed deep vein thrombosis, 1 patient had a surgical hemorrhage and 2 patients died early, one from acute infection, the other from bone marrow aplasia. Among the survivors, one male had a deep vein thrombosis and 1 developed a new portal thrombosis. Four patients died during the follow-up (median 9.48 years, range 3.17-25.1; 1 stroke, 2 gastrointestinal bleedings, 1 leukemic conversion). No difference was observed in the incidence of thrombotic or hemorrhagic complications or in the rate of deaths when group A1 was compared to the other groups. The use of antiplatelets drugs was statistically increased in group A1 after splenectomy, because portal vein thrombosis induced per se an increased use of therapeutic agents. No statistical difference was observed in overall survival between the different groups. INTERPRETATION AND CONCLUSIONS: 1) Bleeding and thrombosis are the leading causes of morbidity and mortality in ET and PV patients with portal vein thrombosis both with or without splenectomy. 2) Portal vein thrombosis, and sometimes splenectomy, requires increased use of drugs which may enhance the risk of leukemic transformation. In spite of this, the patients who survive the first post-splenectomy period may have a long and safe life.

Adolescent↗

Primary thrombocythemia in the young patient.

Primary thrombocythemia is typically a disease of older patients and frequently is associated with thrombosis and hemorrhage. Seven female and two male patients younger than 30 years were evaluated because of platelet counts exceeding 1 million/mm3. No hemorrhagic or thrombotic problems existed before diagnosis or developed during the follow-up period of 14 months to 10 years. Platelet function studies done in six of the nine patients showed absent aggregation with epinephrine and variable aggregation with adenosine diphosphate, as are seen in other chronic myeloproliferative states. One patient had spontaneous aggregation. Secondary causes of thrombocytosis were excluded. Only one patient received specific chemotherapy, which was given before 1973. Thus, thrombocythemia without a secondary cause appears to be much more benign in the young patient than in the older, and aggressive chemotherapy to lower the platelet count is not necessarily justified unless serious complications develop.

Adenosine Diphosphate↗

Thrombosis-free survival and life expectancy in 187 consecutive patients with essential thrombocythemia.

A total of 187 consecutive patients with essential thrombocythemia (ET) were diagnosed and followed by our Hematology Department in the period October 1980-November 1994. The overall follow-up was 773 patient-years. Thrombosis-free survival and overall survival were calculated for the whole cohort; the same parameters were then calculated after arbitrary division of the cohort into two groups, according to the median age at diagnosis (55 years). Fifty percent of the patients had at least one thrombotic episode within 9 years after diagnosis. The thrombosis-free survival curves calculated for patients younger or older than 55 years at diagnosis were comparable. About 85% of the patients were alive 10 years after diagnosis. The survival curves for patients younger and older than 55 years at diagnosis were not significantly different in the observation period, and the observed mortality (seven patients) among patients younger than 55 years at diagnosis was significantly higher than expected (1.68 cases). The relative risk of death was four times greater (SMR = 4.17, 95% C.I. 1.6-8.6, p<0.01) than for healthy, age-matched people living in the same area. Age at diagnosis, smoking, sex, hypercholesterolemia, peak number of platelets, hypertension, and diabetes were not significant prognostic cardiovascular risk factors in our cohort. In conclusion, our data show that ET has to be considered a serious disease that significantly decreases both quality of life (expected life without thrombosis) and life expectancy for younger patients.

Cohort Studies↗

Essential thrombocythemia: a retrospective study on the clinical course of 100 patients.

We report a study concerning 100 patients affected by essential thrombocythemia: 90 adult (age greater than 20 years) and 10 pediatric subjects. The diagnosis was made by chance (78%), because of hemorrhages (10%), thrombosis (9%), vasomotor symptoms (29%). In the adult group, single-agent chemotherapy was performed with good remission using pipobroman or interferon. Antiaggregant agents were used in all patients at diagnosis. During the clinical course only a few complications occurred.

Adolescent↗

Leukemia and myelodysplasia effect of multiple cytotoxic therapy in essential thrombocythemia.

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by increased risk of thrombosis and/or hemorrhages. Cytotoxic drugs are mostly used in patients at high risk for thrombotic complications, while their use is still debated in low risk patients because of the risk of leukemia or secondary neoplasm. We discuss the leukemic risk of available treatment strategies in a large cohort of patients. Over a 12 years period we treated 23 patients with busulfan (BU), 1 with pipobroman (Pi), 6 with 32P, 48 with hydroxyurea (HU) in 62 cases associated with acetyl salicylic acid (ASA) while 77 patients received ASA alone and 33 did not receive any therapy. We observed 2 cases of acute leukemia (AL) and 1 of myelodysplastic syndrome (MDS). One of these patients had been treated with 32P and Pi these after with and the other two with BU and HU. They represented 23% of all patients treated with more than 1 cytotoxic agent, 16.6% of 32P treated subjects, 4% of those with HU and 6.4% of those with BU. The case of MDS occurred in a 81 years old female and represents 4% of cases of ET over the 70 years of age. No cases of AL or MDS were observed in patients not receiving cytotoxic therapy (with or without ASA). According to our experience the use of more than one cytotoxic agent in ET confirms the increase in the risk of leukemia in these cases. However, none of the patients treated with HU alone, even for more than 10 years (12 cases) developed AL. No treatment or therapy with ASA alone may be the best choice in young patients with ET with a low risk of thrombotic complications.

Aged↗