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International Journal of Hematology Jul 2020Anagrelide is widely used for cytoreductive therapy in patients with essential thrombocythemia who are at high risk for thrombosis. The recommended starting dose in the... (Comparative Study)
Comparative Study
Comparison of starting doses of anagrelide as a first-line therapy in patients with cytoreductive therapy-naïve essential thrombocythemia: difference between starting at 0.5 and 1.0 mg/day.
Anagrelide is widely used for cytoreductive therapy in patients with essential thrombocythemia who are at high risk for thrombosis. The recommended starting dose in the package insert of anagrelide varies by country. A high starting dose leads to an early onset of action, but causes a higher incidence of adverse events. This relationship indicates that both the onset of action and side effects of anagrelide are dose dependent. We retrospectively compared the efficacy and safety of anagrelide as a first-line drug between patients with essential thrombocythemia who started at 0.5 or 1.0 mg/day. Incidence of total adverse events and anagrelide-related palpitation, discontinuation rates, and the median daily dose of anagrelide were lower in the 0.5 mg/day group than in the 1.0 mg/day group; however, comparable platelet-lowering effects were achieved in both groups. These data suggest that a low starting dose of anagrelide followed by dose escalation may result in fewer adverse events and lower discontinuation rates, while providing desirable platelet-lowering effects. Initiating anagrelide at a lower dose may be a useful approach in actual clinical practice.
Topics: Adult; Aged; Aged, 80 and over; Cytoreduction Surgical Procedures; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Quinazolines; Retrospective Studies; Safety; Thrombocythemia, Essential; Treatment Outcome; Young Adult
PubMed: 32328973
DOI: 10.1007/s12185-020-02876-z -
In Vivo (Athens, Greece) 2021This work aimed to prospectively evaluate the clinical significance of circulating microparticles (MPs) in relation to thrombotic risk factors and thrombotic...
BACKGROUND/AIM
This work aimed to prospectively evaluate the clinical significance of circulating microparticles (MPs) in relation to thrombotic risk factors and thrombotic complications in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN).
PATIENTS AND METHODS
In a cohort of 206 patients with MPN, MPs' procoagulant activity was measured by the Zymuphen functional assay in 429 samples, while platelet- and erythrocyte-MPs were enumerated by flow cytometry in 558 samples.
RESULTS
MPN patients had higher MP levels than the control group. The levels of MPs were higher in male patients, smokers, and those who were older than 60 years, and in the presence of JAK2 mutation, history of thrombosis, platelets >400×10/l, hematocrit >45%, or leukocytes >10×10/l. Cytoreductive treatment reduced MP levels, with anagrelide being associated with lower MP levels than hydroxyurea.
CONCLUSION
The relationship with thrombotic risk factors indicates a possible role of MPs in the complex thrombotic mechanism, though cytoreductive treatment seems to affect this role through reducing MP levels.
Topics: Blood Platelets; Cell-Derived Microparticles; Humans; Male; Myeloproliferative Disorders; Neoplasms; Thrombosis
PubMed: 34697168
DOI: 10.21873/invivo.12632 -
International Medical Case Reports... 2022Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN) which could complicate surgical procedures due to thrombosis and spontaneous bleeding. However,...
INTRODUCTION
Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN) which could complicate surgical procedures due to thrombosis and spontaneous bleeding. However, currently, there is neither concrete guideline nor prerequisite for ET patients who underwent operations.
CASE REPORT
A 48 year-old-female was admitted to the emergency unit on 21 February 2020 due to vomiting and inability to pass gas/stool. The patient previously had an operation for uterine myoma two weeks before which showed thrombocyte count of 688,000/mm. The patient was previously diagnosed with essential thrombocythemia with positive JAK2V617 point mutation on 24 June 2019. Laboratory examination showed thrombocyte 1,134,000/mm and leukocyte 22,700/mm suggestive of neutrophilia. CT scan showed fluid collection with blood density in the abdomen and pelvis. She was then diagnosed with obstructive ileus due to abdominal abscess and intestine adhesion. Adhesiolysis by laparoscopy was performed on 29 February 2020 with thrombocyte count of 727,000/mm. Patient was able to pass flatus and defecate three days post-surgery. However, a decrease of hemoglobin to 8.2 g/dL on 3 March 2020 with thrombocyte count of 700,000/mm was suggestive of internal bleeding. She was discharged three weeks post-surgery after improvement of clinical condition with thrombocyte count of 850,000/mm. She was given hydroxyurea 1000 mg once every two days, aspirin 80 mg OD, anagrelide 1 mg OD, and amlodipine 10 mg OD.
CONCLUSION
Myeloproliferative disease patients with high thrombocyte count are subjected to increased risk of thrombotic complications in perioperative settings, thus perioperative management and risk assessment are important to improve quality of life and prevent complications. Surgery in MPN patients with elevated thrombocytes may be considered if the benefits outweigh the risks. More studies in this field should be conducted in-order to provide more data for a guideline or systematic review/meta-analyses.
PubMed: 36120702
DOI: 10.2147/IMCRJ.S375777 -
European Journal of Case Reports in... 2024Anagrelide is a medication primarily used to manage thrombocytosis, an abnormal increase in platelet levels in the blood. It is often prescribed for patients with...
UNLABELLED
Anagrelide is a medication primarily used to manage thrombocytosis, an abnormal increase in platelet levels in the blood. It is often prescribed for patients with myeloproliferative disorders, such as essential thrombocythaemia (ET). Given the heightened susceptibility to thromboembolism associated with this condition, the primary emphasis in treatment revolves around reducing the risk of thrombotic events through the administration of cytotoxic agents. While anagrelide is generally effective in reducing platelet counts, it comes with potential side effects, including an increased risk of certain thrombotic events. Anagrelide acts by inhibiting megakaryocyte maturation and platelet release, thereby reducing platelet production. However, this platelet-lowering effect may be accompanied by an increase in platelet activation and reactivity, which could contribute to a prothrombotic state. We present a case of a 60-year-old female with a history of ET, managed with anagrelide and hydroxyurea therapy, who experienced an acute ST-elevation myocardial infarction.
LEARNING POINTS
The dual role of anagrelide: although anagrelide is effective in lowering platelet levels in essential thrombocythaemia, it can increase platelet activation, raising thrombotic risk. Clinicians need to monitor patients closely for thrombotic events.Balancing efficacy and side effects: the risk of severe side effects such as myocardial infarction, as seen in this case report, necessitates a balanced approach in using anagrelide, weighing its benefits against potential risks.
PubMed: 38455691
DOI: 10.12890/2024_004340 -
Therapeutic Advances in Neurological... 2022Cerebrovascular events, especially ischemic stroke, are common complications of essential thrombocythemia (ET). Compared to JAK2V617 F mutation, CALR mutation is...
Cerebrovascular events, especially ischemic stroke, are common complications of essential thrombocythemia (ET). Compared to JAK2V617 F mutation, CALR mutation is considered as a lower risk factor of thrombosis in ET. Until now stroke in ET with CALR mutation has rarely been reported. We retrospectively investigated patients diagnosed with stroke and ET in Xijing hospital of Air Force Medical University, from 2015 to 2021. Clinical characteristics (including medical history, physical and auxiliary examination and prognosis) were recorded and associated literature was reviewed. Among the 19 patients diagnosed with both stroke and ET we retrieved, two cases were positive for CALR mutation. In case 1, a 71-year-old man developed the first ischemic event under the treatment of anagrelide, followed by a hemorrhagic stroke after receiving aspirin and clopidogrel for 4 months. Ischemic stroke reccurred and the neurological function deteriorated progressively. In case 2, a 44-year-old man presented with hypoxic-ischemic encephalopathy due to serious myocardial infarction and subsequent brain imaging indicated three times of ischemic stroke events. The patient gradually got improved through cytoreductive and antiplatelet therapy and rehabilitation. Literature review showed that cerebrovascular event is the most serious neurological complication of ET and may be the presenting symptom. Most of reported cases with ET accompanied by stroke were positive for JAK2 V617 F mutation, but with rare CALR mutation. ET with CALR mutation can cause both hemorrhagic and ischemic stroke. Identification of such rare causes of stroke is of great importance to provide precise and individualized prevention and therapy.
PubMed: 35498365
DOI: 10.1177/17562864221092093 -
Journal of Clinical Medicine May 2024Essential thrombocythemia (ET) is a myeloproliferative neoplasm that overproduces platelets and is associated with life-threatening thrombosis. Medical cytoreduction...
Essential thrombocythemia (ET) is a myeloproliferative neoplasm that overproduces platelets and is associated with life-threatening thrombosis. Medical cytoreduction either with hydroxyurea (HU) or anagrelide (AG) is widely used, but drug intolerance or resistance are major concerns. Low-dose combination of HU and AG as an alternative strategy has been explored in various studies. It showed comparable response with acceptable toxicity in second-line settings for patients who experienced side effects from prior monotherapy. In this study, we evaluated the efficacy and safety of upfront combination for ET patients. From January 2018 to June 2022, a total of 241 ET patients with intermediate to high risk were enrolled. We identified 21 patients with initial drug combinations and compared treatment outcomes and adverse events (AEs) between combination and monotherapy groups. The median age was 62 years old (range, 26-87) and median platelet count was 912 × 10/L (range, 520-1720). Overall treatment response did not exhibit significant differences between the groups, although there was a trend towards a lower response rate in patients treated with AG alone at 3 months post-treatment (AG + HU, 85.7% vs. AG alone, 75.4%, = 0.068). AEs of any grade occurred in 52.3% of the combination group, 44.3% of the HU monotherapy group, and 43.4% of the AG single group, respectively. Of note was that the HU plus AG combination group suffered a lower incidence of grade 3-4 AEs compared to the other two groups, with statistical significance ( = 0.008 for HU monotherapy vs. combination therapy and < 0.01 for AG monotherapy vs. combination therapy). Our findings demonstrated that the upfront low-dose combination approach showed feasible clinical outcomes with significantly lower severe AEs compared to conventional monotherapy. These results may offer valuable insights to clinicians for future prospective investigations.
PubMed: 38792442
DOI: 10.3390/jcm13102901 -
Medicine Jul 2020Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension. It is often underdiagnosed or misdiagnosed as idiopathic pulmonary arterial...
INTRODUCTION
Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension. It is often underdiagnosed or misdiagnosed as idiopathic pulmonary arterial hypertension (PAH). Inappropriate treatment may cause worsening of symptoms which may lead to fatal outcomes. Anesthetic considerations and management for pulmonary hypertension are well described, but few anesthesiologists are aware of the entity of PVOD and its management.
PATIENT CONCERNS
We report a case of PVOD in a 73-year-old female who was on concurrent aspirin and anagrelide, requiring emergent open femoral hernia repair.
DIAGNOSIS
PVOD and incarcerated femoral hernia INTERVENTION:: Combined spinal-epidural (CSE) was performed to enable the surgery.
OUTCOME
Surgery was completed successfully under central neuraxial anesthesia and the patient remained stable and comfortable throughout, avoiding the need for general anesthesia. Due to the concurrent aspirin and anagrelide therapy, significant bleeding from the CSE puncture site was observed immediately post-operatively. This was resolved with external manual compression and withholding the aspirin and anagrelide. Patient remained well without neurological deficit and was discharged postoperative day seven.
LESSONS
It is important to differentiate PVOD from PAH due to the controversial use of pulmonary vasodilators in PVOD. Pulmonary vasodilator is commonly used to treat acute pulmonary hypertension in PAH but its usage may lead to pulmonary edema in patients with PVOD. Hence, with no ideal treatment available, the avoidance of general anesthesia is crucial to prevent acute pulmonary hypertensive crisis in patient with PVOD. However, this needs to be weighed against the elevated risk of central neuraxial bleeding when performing a CSE in a patient on concurrent aspirin and anagrelide therapy. Calculated decision-making considering the risks and benefits of all alternatives should be carried out in such a scenario, and measures should be taken in anticipation of the potential consequences of the eventual decision.
CONCLUSION
It is important to differentiate PVOD from PAH. PVOD has unique anesthetic considerations due to the controversial use of pulmonary vasodilators. This case also emphasizes the importance of active anticipation of potential issues and adequate follow up.
Topics: Aged; Anesthesia, Epidural; Anesthesia, Spinal; Female; Hernia, Femoral; Herniorrhaphy; Humans; Intraoperative Complications; Pulmonary Veno-Occlusive Disease
PubMed: 32791767
DOI: 10.1097/MD.0000000000021517 -
European Journal of Haematology Aug 2019This study aimed to retrospectively assess the efficacy and safety of anagrelide in cytoreduction therapy-naïve essential thrombocythemia (ET) patients in a real-world...
OBJECTIVE
This study aimed to retrospectively assess the efficacy and safety of anagrelide in cytoreduction therapy-naïve essential thrombocythemia (ET) patients in a real-world setting.
METHOD
Data from 53 ET patients who received anagrelide as a first-line therapy were reviewed for patient characteristics, antiplatelet status, cytoreduction status, therapeutic effects, adverse events, thrombohemorrhagic event development, progression to myelofibrosis or acute leukemia, and cause of death.
RESULTS
The rate of achieving a platelet count of <600 × 10 /L during anagrelide monotherapy was 83.0%. Adverse events occurred in 32 of 53 patients, and tended to be slightly more severe in patients with cardiac failure; however, they were mostly tolerable. The therapeutic effect of anagrelide was consistent, regardless of genetic mutation profiles. The incidence of anemia as an adverse event was significantly higher in the CALR mutation-positive group. Favorable platelet counts were also achieved in patients for whom hydroxyurea was introduced as a replacement for anagrelide or in addition to anagrelide because of unresponsiveness or intolerance to treatment.
CONCLUSION
In Japanese cytoreduction therapy-naïve ET patients, anagrelide administration as a first-line therapy demonstrated favorable effects in reducing platelet counts, and its safety profile that was generally consistent with those in previous reports.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Disease Progression; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mutation; Platelet Aggregation Inhibitors; Platelet Count; Quinazolines; Risk Factors; Thrombocythemia, Essential; Treatment Outcome; Young Adult
PubMed: 31107982
DOI: 10.1111/ejh.13265 -
Dermatologic Therapy Feb 2022
Topics: Humans; Prednisolone; Quinazolines; Thrombocythemia, Essential; Toes; Ulcer
PubMed: 34846771
DOI: 10.1111/dth.15221 -
Molecular and Clinical Oncology Sep 2023Chronic myeloproliferative neoplasms (MPN) include polycythemia vera (PV), primary myelofibrosis, essential thrombocythemia (ET) and chronic myeloid leukemia (CML)....
Chronic myeloproliferative neoplasms (MPN) include polycythemia vera (PV), primary myelofibrosis, essential thrombocythemia (ET) and chronic myeloid leukemia (CML). Overlapping MPNs are rare; however, they can occur in the same individual. The present case report describes a patient with both triple-negative ET and CML. A 64-year-old woman was followed-up at our hematology clinic at Feist Weiller Cancer Center, Louisiana State University Health Shreveport (Shreveport, LA, USA) since 2000 after she was diagnosed with JAK2V617F-negative ET. The patient remained stable on hydroxyurea until 2012, when they underwent a bone marrow biopsy for progressively increasing white blood cell counts, and the pathology was consistent with CML; PCR for BCR-ABL was positive for both P210 and P190 transcripts. The patient was then initiated on dasatinib. After dasatinib, they were given a trial of imatinib, and were later transitioned to nilotinib and finally to bosutinib (2019) due to unchanged thrombocytosis. Next-generation sequencing from a bone marrow biopsy in 2019 demonstrated an EZH2 mutation that may be associated with triple-negative ET. CML was in major molecular response at that time. The patient was continued on bosutinib with hydroxyurea, after which hydroxyurea was changed to anagrelide due to worsening anemia and persistent thrombocytosis. However, bosutinib and anagrelide were discontinued due to worsening pulmonary hypertension. The patient was noted to have peripheral blasts of 14% by flow cytometry, after which they underwent a repeat bone marrow biopsy in 2022, which showed extensive myelofibrosis. BCR-ABL transcripts were undetectable. Given their accelerated myelofibrosis, the patient was started on a hypomethylating agent, decitabine/cedazuridine, along with darbepoetin for anemia in June 2022. Given their persistent thrombocytosis, the patient was also started on peginterferon α. Most studies reporting two clonal processes in the same patient have been for PV and CML. To the best of our knowledge, this is the first reported case of triple-negative ET with double transcript CML in the same individual.
PubMed: 37614369
DOI: 10.3892/mco.2023.2663