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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Essential thrombocythemia is a clonal myeloproliferative disorder, characterized predominantly by a markedly elevated platelet count without known cause. We report a case that was recognized during investigation of a transient ischemic attack, and review the neurologic findings in 33 patients with unequivocal essential thrombocythemia under prospective study by the Polycythemia Vera Study Group. Twenty-one patients had neurologic manifestations at some point during their course, including headache (13 patients), paresthesiae (10), posterior cerebral circulatory ischemia (9), anterior cerebral circulatory ischemia (6), visual disturbances (6) and epileptic seizures (2). All patients with neurologic symptoms responded satisfactorily to treatment, although continuous or repeated treatment was often required. Therapeutic recommendations include plateletpheresis for major thrombo-hemorrhagic phenomena, or megakaryocyte suppression with radioactive phosphorus, alkylating agents (such as melphalan), or hydroxyurea; minor symptoms may respond to platelet antiaggregating agents.
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PMID:Neurologic manifestations of essential thrombocythemia. 668 92

The clinical features and progress of a patient with a fatal myeloproliferative disease are reported. Her care required frequent transfusions of red cell products and components. These transfusions were followed, after varying intervals, by fever, arthralgia, myalgia, headache and pericarditis. These reactions could be avoided by transfusing plasma-free products, and were ameliorated by systemic steroids. This patient, then, is the first reported case of delayed, serum sickness-like transfusion reactions. During the course of her illness she was demonstrated to have antibodies to immunoglobulins. The role of these antibodies, if any, is uncertain.
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PMID:Delayed serum sickness-like transfusion reactions in a multiply transfused patient. 733 79

We report on our treatment experience in Germany with anagrelide, a novel platelet lowering agent, in 48 patients (27 females, 21 males) with essential thrombocythaemia. Their age was between 19 and 79 yr when anagrelide therapy was initiated. Sixteen patients were previously untreated, 15 pretreated with hydroxyurea and 17 had multiple pretreatments. Forty-one of the 48 patients had either microvascular, thromboembolic or bleeding complications. About 50% received low dose acetylsalicylic acid as an adjunct. Their platelet count prior to therapy ranged from 850,000/microl to 3,100,000/microl. Eighty-seven per cent of the patients treated with anagrelide were complete hematological responders, while 13% responded only partially or failed to respond. Twelve of our patients (25%) developed short-term (from a few days to a maximum of 4 wk) side effects including headache (most frequent), palpitations, tachycardia or nausea. Eight patients reported long-term (more than 1 month) adverse effects. However, in only 5 of all 48 patients (10%) were these side effects not acceptable so that treatment had to be discontinued. We have now treated patients for up to 7 yr (median maintenance dose 2.5 mg/d). Preliminary evidence suggests that anagrelide mediated platelet count reduction also prevents recurrence of thromboembolic complications. Hence, anagrelide has the potential to become the first-line platelet-lowering treatment in myeloproliferative disorders with high platelet counts.
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PMID:Anagrelide, a novel platelet lowering option in essential thrombocythaemia: treatment experience in 48 patients in Germany. 971 17

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of anagrelide are reviewed. Anagrelide is a selective thrombocytopenic agent with FDA-approved labeling for the treatment of essential thrombocythemia. Clinical trials have shown that the drug may have a role in the treatment of other chronic myeloproliferative disorders, including polycythemia vera, chronic myeloid leukemia, and agnogenic myeloid metaplasia. The mechanism by which anagrelide reduces platelet count is not yet clear. The current hypothesis is that anagrelide affects the late (postmitotic) phases of megakaryocyte development. Anagrelide has a large volume of distribution and is extensively metabolized; less than 1% is recovered unchanged in the urine. Plasma half-life after a 0.5-mg dose is 1.3 hours. Anagrelide's efficacy and safety have been evaluated in open-label, noncomparative trials, in which the response rate was 60-93%. Adverse effects include headache, diarrhea, edema, palpitations, and abdominal pain. Patients with renal or hepatic dysfunction need to be closely monitored for signs of toxicity. The recommended starting dosage is 0.5 mg four times a day or 1 mg twice a day, with dosage adjustment to the lowest effective amount required to reduce and maintain platelet count below 600 x 10(9)/L. The wholesale acquisition price for 0.5-mg capsules is $350 per 100. Whether anagrelide will replace hydroxyurea as first-line therapy in some or all patients remains to be determined. Anagrelide is effective in the treatment of essential thrombocythemia and may have a role in the treatment of other myeloproliferative disorders.
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PMID:Anagrelide, a selective thrombocytopenic agent. 978 84

Essential thrombocythaemia (ET) is usually considered a disease of the middle-aged but, with the advent of automated platelet counting, ET is diagnosed with increasing frequency in young adults and, even more rarely, in children. We report five paediatric patients (four girls and one boy, mean age 89 months) diagnosed with ET in agreement with Polycythaemia Vera Study Group criteria. The patients had a persistent thrombocytosis over 900 x 10(9)/l and, at the time of diagnosis, their platelet count ranged between 1,112 and 3,178 x 10(9)/l. A 9-month-old girl had thrombosis of the inferior cava vein, two children had headaches and two others remained asymptomatic throughout the follow-up period. Megakaryocytes in the bone marrow were increased in number. The chromosomal analysis was normal, and bcr rearrangement was always negative. None of the patients had spontaneous BFU-E or altered levels of serum erythropoietin and thrombopoietin. Two patients showed alteration of platelet aggregation, and all had decreased levels of intraplatelet serotonin. In spite of the diagnosis of ET in our patients, we are not sure that the cases reported here are really myeloproliferative disorders. The features could suggest that the cases observed may be affected by an 'idiopathic thrombocytosis' without myeloproliferation. Possible variants of ET are described in young adults, and the heterogeneous nature of ET is also suggested by our paediatric patients. Only careful long-term follow-up of patients such as these will clarify the natural history of these disorders and suggest therapeutic management.
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PMID:Features of essential thrombocythaemia in childhood: a study of five children. 1120 8

Anagrelide hydrochloride (Agrylin, Roberts Pharmaceutical Corp.) is an oral imidazoquinazoline agent that has been shown to reduce elevated platelet counts and the risk of thrombosis in patients with thrombocythaemia in various myeloproliferative disorders (MPD). It is currently approved by the FDA as oral treatment for essential thrombocythaemia (ET) and thrombocythaemia associated with polycythaemia vera (PV). Anagrelide selectively suppresses bone marrow megakaryocytes by interfering with the maturation process and decreasing platelet production without affecting the erythroid and myeloid progenitor cells. Other medications indicated for the treatment of thrombocythaemia, including interferon alpha (IFN-alpha), alkylating agents and hydroxyurea, suppress all cell lines. Anagrelide is known to inhibit platelet cyclic adenosine monophosphate (cAMP) phosphodiesterase at concentrations that exceed those achieved at doses used to treat ET. Anagrelide is extensively metabolised in the liver and its metabolites are primarily excreted in the urine. Adverse effects associated with the use of anagrelide are primarily caused by the drugs' direct vasodilating and positive inotropic effects. These include headache, hypotension and diarrhoea. It has also been known to cause fluid retention, tachycardia, nausea, abdominal pain and arrhythmias. The starting dose of anagrelide ranges from 0.5 mg q.i.d. to 1 mg b.i.d. with a maximum dose of 2.5 mg q.i.d. Adequate responses have been maintained with a median dose of 2-2.5 mg/day. Platelet counts begin to decrease in 7-10 days, however, they return to pre-treatment levels within 4-8 days if therapy is stopped. Anagrelide 2 mg/day for one year costs approximately US$6439, and treatment must continue indefinitely [1].
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PMID:Anagrelide: a novel agent for the treatment of myeloproliferative disorders. 1124 36

Extreme thrombocytosis is a frequent feature in myeloproliferative disorders which can predispose a person to thrombotic complications. As opposed to other myeloproliferative disorders, symptomatic thrombocytosis is rare in chronic myeloid leukemia. We describe a second case report of chronic myeloid leukemia (Ph chromosome positive) in a patient in chronic phase on hydroxyurea who presented with sudden onset digital cyanosis of the left hand, giddiness, headache and malaise due to extreme thrombocytosis. A 67% global reduction in the platelet count from 1553 x 10(9)/L to 513 x 10(9)/L after two therapeutic plateletpheresis procedures was seen. There was simultaneous improvement in all symptoms except cyanosis on the tip of the middle finger that progressed to dry gangrene. Dramatic reduction in the platelet count and ablation of symptoms by therapeutic plateletpheresis is an effective therapy and should begin as soon as possible.
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PMID:Therapeutic plateletpheresis in a case of symptomatic thrombocytosis in chronic myeloid leukemia. 1566 50

Essential thrombocythaemia (ET), the most often occurring myeloproliferative disorder is a clonal malignant disorder arising from stem cell. The course of the disease is complicated by some severe thrombotic events and far less commonly by haemorrhagic phenomena. Treatment of ET consist of antiplatelet drugs (e.g. aspirin) and lowering platelet count (hydroxyurea or interferon alpha). Anagrelide (anagrelide hydrochloride) is an imidazoquinazoline derivative which lowers platelet count probably by inhibiting thrombopoiesis and reduces platelet aggregation. The aim of the study was to evaluate the efficacy and side effects of anagrelide in patients with ET refractory to prior treatment with hydroxyurea. Anagrelide (Agrylin or Thromboreductin) was used in 40 patients with ET from Jan. 1999 to June. 2003. Out of 40 patients, there were 29 females and 11 males, (median age 52.0 +/- 14.25 years; range, 21-72). Median follow up was 23 months (range, 8 to 54 months). Anagrelide in the average dose of 2,0 mg (range, 1,0-3,5 mg) reduced platelet count in all patients. Median time of response was 3-4 weeks. Complete remission (platelet count < or =450 G/l) achieved 22 persons (55%) and partial remission 17 persons, and only one patient had platelet count slightly above 600 G/l (627 G/l). There was a significant (p < 0.05) reduction in platelet count from a mean of 1136.05 +/- 295.09 G/l to 480.98 +/- 72.26 G/l (56%) Despite platelet count reduction <500 G/l in 3 patients reappeared symptoms of low extremities deep venous thrombosis and in one transient ischaemic cerebral stroke was found. Hemoglobin level in a single case was lower than 12 g/dL (10.8 g/dL), and neither leukopenia nor disturbances of hepatic or renal function were observed. During the first two months of treatment with anagrelide some mild and transient side effects were noticed, eg. headache in 10 (25%), fluid retention in 8 (20%), palpitations in 4 (10%), and diarrhoea in 2 (5%) patients, but all of them continued therapy. Achieved platelet count reduction allowed in 2 ET patients safe performance of planned surgery (cholecystectomy, partial thyroidectomy) and in 1 balloon coronary angioplasty. Anagrelide proved to be an effective drug for of ET patients refractory to hydroxyurea.
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PMID:[Anagrelide in the treatment of thrombocythemia essential (ET)]. 1596 9

Chronic myeloid leukemia is a myeloproliferative disorder characterized by the presence of the Philadelphia chromosome, t(9:22). Extramedullary blast crisis is a rare event. Imatinib mesylate has become the treatment of choice, especially for patients for whom allogenic stem cell transplantation is not an option. Imatinib produces complete cytogenetic responses in excess of 80%. However, the penetration of the drug and its metabolites into the CNS (Central Nervous System) is poor. Hence for patients who are on prolonged imatinib therapy and continue to have complete cytogenetic responses, the central nervous system may become a sanctuary site. We report a patient who had a complete hematologic and cytogenetic response and presented with headache and vomiting. The MRI showed meningeal enhancement and the CSF (Cerebro Spinal Fluid) examination was positive for blasts. He was started on cranial radiotherapy and triple intrathecal chemotherapy. He showed good symptomatic improvement and cleared the blasts in the CSF. At the end of radiation, he was in complete hematological remission but had 50% marrow metaphases positive for Philadelphia chromosome. As he did not have a matched sibling donor, the dose of imatinib was increased to 600 mg daily. He continues to be in complete hematologic remission at the time of this report.
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PMID:Isolated central nervous system blast crisis in chronic myeloid leukemia. 1599 75

Essential thrombocythemia (ET) is a clonal myeloproliferative disorder characterized by sustained thrombocytosis, isolated hyperplasia of megakaryocytic lineage, and association with thrombotic or bleeding episodes. It is extremely rare in childhood and frequently presents without evident clinical signs. We describe a 3-year-old girl with severe headache and dizziness suffering from ET, who was treated with Interferon-alpha-2a (IFN) based on the potent effect of this agent to inhibit myeloid colonies induced by phytohemagglutinin A stimulated leukocyte conditioned medium (PHA-LCM). Bone-marrow-derived mononuclear cells of this patient did not exhibit spontaneous colony formation but responded to recombinant human (rh) erythropoietin (EPO), rh granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, and stem-cell factor in addition to PHA-LCM. After 65 months of in vivo IFN treatment, the patient experienced a sustained partial remission with platelet counts varying between 400 and 600 x 10(3)/microl.
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PMID:Long-lasting partial remission by Interferon-alpha treatment in a child with essential thrombocythemia. 1642 12


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