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Effectiveness of anagrelide in the treatment of symptomatic patients with essential thrombocythemia.

We prospectively evaluated the effect of anagrelide on platelet counts and the clinical manifestations of microvascular circulation disturbances in 17 newly diagnosed patients with essential thrombocythemia. Ten patients had symptoms related to thrombocythemia, eight at the time of starting anagrelide treatment. The platelet counts before anagrelide treatment and during maintained remission of essential thrombocythemia by anagrelide were 980 (range, 610-2030) and 378 (range, 212-546) x 10(9)/L, respectively. Spontaneous platelet aggregation was found in 6 patients (35%), which disappeared on remission of essential thrombocythemia in five cases (P = 0.02). Essential thrombocythemia-related microvascular thrombotic and hemorrhagic symptoms disappeared with the normalization of platelet count in all cases during maintained remission of essential thrombocythemia by long term continuous anagrelide treatment with a follow-up period of between 2 and 6 years. However, ET-related symptoms reappeared in three patients, coinciding with increased platelet count up to 600 x 10(9)/L caused by anagrelide dose reduction. We conclude that reduction of increased platelet to normal (< 400 x 10(9)/L) in symptomatic patients with essential thrombocythemia through use of maintained anagrelide treatment is associated with the disappearance of spontaneous platelet aggregation and the complete relief of thrombotic and hemorrhagic manifestations.

Adult↗

[Thrombocythemias].

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Blood Platelet Disorders↗

Essential thrombocythaemia.

Essential thrombocythaemia (ET) is a rare clonal myeloproliferative disorder characterized by a persistent increase in platelet count. The commonly used criteria for the diagnosis, except for the level of the increase in platelet count, are usually those fixed by the Polycythemia Vera Study Group. The average age of onset is around 60 years, both sexes being affected. The symptoms frequently present at diagnosis are related to microcirculatory disturbances (palms, soles, fingers). Neurological symptoms are often observed. Thrombotic complications of the large vessels are less frequent. Haemorrhagic problems are present in about 30% of patients. Bleeding time is normal in most cases, whereas platelet aggregation abnormalities are frequently found. Nil adrenaline aggregation is the most discriminative test. The clinical course is characterized by long intervals without any symptoms; thromboembolic or haemorrhagic episodes can, however, occur, mainly in uncontrolled ET. Development of terminal acute leukaemia has been reported in 34 cases. The expression of the influence of the treatments, 32P or alkylating agents, is very strong. The treatment of ET has to take in consideration the difficult compromise between balancing the necessity of preventing complications and the effects of drug toxicity. The use of recombinant alpha-interferon has recently been proposed and is under investigation. The pathogenesis of thrombocytosis in ET seems to involve an expansion in the megakaryocyte progenitor cell pool. Platelet membrane glycoprotein abnormalities and defective glycosylation of thrombospondin have been shown. Numerous other platelet abnormalities, including decreased alpha-adrenergic receptors, loss of PGD2 receptors and increased Fc receptors, have been reported. Arachidonic metabolism seems to be abnormal and lipoxygenase is defective. Most of the platelet abnormalities seem to be the result of intrinsic defects at the level of an abnormal clone of megakaryocytes. However, causal relationships between the platelet abnormalities and bleeding or thrombosis are not yet clearly demonstrated.

Arachidonic Acid↗

Primary thrombocythaemia presenting as postpartum haemorrhage: a case report.

A young primigravida presented with postpartum haemorrhage with no apparent cause following a low forceps delivery. She was extremely pale with gross hepatosplenomegaly. Hysterectomy was performed following three episodes of disseminated intravascular coagulation. Investigations revealed an extremely high platelet count with poor aggregatory function. A diagnosis of primary thrombocythaemia was made.

Adult↗

Bilateral adrenal swelling as a cause of chest, back, and upper abdominal pain in essential thrombocythemia and polycythemia vera is due to microvascular ischemic thrombosis rather than to hemorrhage.

Bilateral massive adrenal swelling (BAS) on computed tomography (CT) scan with no enhancement after injection of intravenous contrast media has been observed in two completely different clinical settings. On the one hand, BAS is the result of ischemic necrosis and subsequent hemorrhagic infarction in patients with sepsis and hypotension in critically ill situations. On the other hand, BAS is the result of microvascular thrombosis, ischemia, and secondary inflammatory swelling in the setting of thrombotic conditions such as antiphospholipid syndrome (APS), heparin-induced thrombocytopenia and thrombosis (HITT), and thrombocythemia. In this study we present evidence that the etiology of unilateral or BAS in reported cases of essential thrombocythemia (ET) and polycythemia vera (PV) is similar to the etiology of microvascular circulation disturbances in thrombocythemia caused by platelet-mediated inflammation and thrombosis in the peripheral, cerebral, and/or coronary endarterial microvascular circulation.

Abdominal Pain↗

Propensity for hemorrhage and thrombosis in chronic myeloproliferative disorders.

Polycythemia vera (PV) and essential thrombocythemia (ET) are two myeloproliferative disorders (MPDs) with frequent thrombotic and hemorrhagic complications. Thrombosis is often the cause of mortality in PV and ET; hemorrhage occurs more commonly in idiopathic myelofibrosis patients, but is rarely fatal. Thromboses may occur in arteries or veins. Splanchnic, portal, hepatic, and splenic vein thromboses are not uncommon and thrombosis is also thought to cause placental vascular insufficiency and fetal wastage during pregnancies in MPD patients. These complications may result because of altered interactions between platelets, white blood cells, or endothelial cells, due to either altered receptor expression, receptor-ligand interactions, or signaling events. Age, leukocytosis, increased hematocrit, and a history of thrombotic events are risk factors for thrombosis. In determining a link between clonality and thrombosis using X-chromosome inactivation patterns in patients with ET, those who were polyclonal were less likely to experience thromboses. The search for hypercoagulability in these patients led to identification of changes in the expression patterns of coagulation proteins from the coagulation cascade. Mutations in factor V Leiden were examined and the incidence of mutations did not vary between normal and MPD patients. However, mutations in factor V Leiden were found to be risk factors for venous thrombotic events. Similarly, presence of a prothrombin gene mutation showed a higher risk for venous thromboembolic events. Proteolyzed thrombospondin appeared to contribute to hypercoagulability, and acquired von Willebrand factor disorder gave rise to hemorrhagic complications. These findings provide several potential reasons for thrombotic and hemorrhagic complications in MPD patients. Therefore, the best therapy for these patients is reduction of their platelet counts to less than 450,000/microL and close regulation of their hematocrits. The role of leukocytosis in bleeding or hemorrhage in this population remains to be elucidated.

Abortion, Spontaneous↗

Pregnancy in essential thrombocythaemia: treatment and outcome of 17 pregnancies.

OBJECTIVE: To evaluate treatment and outcome of 17 pregnancies in nine patients with essential thrombocythaemia (ET) seen at our institution from 1988 to 1998. METHODS: Treatment and outcome of 17 pregnancies in nine ET patients were retrospectively analyzed. RESULTS: Seventeen pregnancies in nine patients with ET resulted in 11 (65%) live births and ended in six (35%) spontaneous abortions. Abortion could not be predicted from ET-associated complications before (p= 0.23) or during (p = 0.39) pregnancy. Maternal complications occurred during six pregnancies (35%): Three major bleedings in two patients with an acquired von Willebrand disease and two minor bleedings in patients treated with low-dose acetylsalicylic acid (ASA) were observed during pregnancy or at term; one patient suffered from transient visual loss while pausing low-dose ASA. Platelet counts prior to pregnancy were significantly higher as compared to the platelet nadir observed during pregnancy (p = 0.0017). Postpartum clinical course was uneventful in all patients. No specific treatment was given during 11 pregnancies. Six women received low-dose ASA during pregnancy followed by low-molecular-weight heparin until the end of the sixth week postpartum in five cases. This treatment was correlated with a favourable outcome (live birth versus abortion) when compared to no treatment (p=0.04). CONCLUSION: Pregnancy in ET can be complicated by first trimester abortion and/or maternal haemorrhage. Our limited observation suggest a positive impact of low-dose ASA during pregnancy followed by low-molecular-weight heparin postpartum on pregnancy outcome in ET; nevertheless, confirmation by prospective documentation is mandatory.

Abortion, Spontaneous↗

[A case of acute exacerbation of chronic pulmonary thromboembolism with essential thrombocythemia during treatment for hemoptysis].

An 89-year-old woman with essential thrombocythemia and chronic respiratory failure was admitted for treatment of hemoptysis. She stopped taking aspirin and was given tranexamic acid. Though her hemoptysis improved, respiratory failure suddenly worsened. As a result of various examinations and laboratory findings, acute exacerbation of chronic pulmonary thromboembolism was diagnosed. Though there was the risk of recurrence of hemoptysis, she started taking aspirin again. Her respiratory failure improved but hemoptysis did not reappear. Thrombosis and hemorrhage are common complications of essential thrombocythemia, however, pulmonary thromboembolism is a rare complication. There is a possibility that the exacerbation of this case was caused by tranexamic acid as well as rest and cessation of aspirin. If a patient with essential thrombocythemia bleeds, we should be careful when using tranexamic acid.

Aged, 80 and over↗

[Thrombocythemia].

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Bone Marrow Cells↗

[Chronic subdural hematoma associated with primary thrombocythemia; report of an operated case, using plateletpheresis].

Primary thrombocythemia is a chronic proliferative disorder of the bone marrow in which either thrombotic or paradoxically hemorrhagic symptoms or both may occur due to the pathological increase in the number of platelets. The mechanism of hemorrhagic diathesis in this disorder is not fully defined. We presented a rare case of primary thrombocythemia developing chronic subdural hematoma which was surgically managed with the use of plateletpheresis. It was believed that plateletpheresis was useful in controlling hemorrhagic complications during surgery associated with primary thrombocythemia. A 62-year-old man was admitted to the hospital for evaluation of motor weakness on the right side. The patient had no episode of head trauma. CT scan demonstrated the presence of subdural hematoma in the left frontotemporal region with significant ventricular shift and deformity. No definite abnormalities were disclosed on laboratory examination except for the hemogram in which platelet count was extremely elevated and read 109 x 10(4)/mm3. Examination of bone marrow smears disclosed an abnormal increase in megakaryocytes. Despite the increase in the number of the platelets, other coagulation studies gave normal results. Prior to surgery plateletpheresis was attempted in hopes of reducing the number of peripheral platelets and eventually avoiding the risk of hemorrhagic complications during surgery. As a result surgery for aspiration of the hematoma was successfully performed. The postoperative course remained uneventful as the patient continuously underwent two courses of plateletpheresis and chemotherapy. The patient was discharged with no neurological deficits and the peripheral platelets remained reduced in number at 50 x 10(4)/mm3 two months after discharge.

Chronic Disease↗

[Management of patients with coagulation disorder in oral and maxillofacial surgery. I. Management of patients with hypocoagulation caused by primary thrombocytopathy].

Any oral and maxillo-facial surgical treatment, however urgent it may be, must not include pathological states in which the patient's life may be particularly at risk as, for example, with Disseminated Intravascular Coagulation (DIC) or throm-botic thrombocytopenic purpura. In this article the authors present the result of studies carried out on the nosology of thrombocytopathy from an odontostomatological point of view. Thrombocytopathy can be divided into two groups: the first including the pathologies with a predominant defective number of thrombocytes (i.e.: thrombocytopenia, thrombocythemia, thrombocyto-sis), the second including forms with predominant qualitative defects (commonly known as thrombocytopathies). The authors, after having presented in short the physiopathologic functions of thrombocytes, illustrate the clinical and therapeutic aspects of the most important thrombocytopathies. Morbus Maculosus Werhofii, Glanzmann's disease, Bernard-Soulier syndrome, thrombocytopathies from defective reaction of release, Thrombocytopathies from defective procoagulant activity of blood plaques, thrombocytopathies in linkage to other genetic anomalies, von Willebrand's pseudodisease and a lot of acquired thrombocytopathies are identified. In the last part the authors illustrate the most opportune clinical steps corresponding to the most important thrombocytopathies. The results obtained suggest the necessity of keeping to the management that was described, Actually a low percentage of accidents occurred only when the above-mentioned clinical processes were completely performed.

Blood Loss, Surgical↗