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Internal Medicine (Tokyo, Japan) Nov 2022Anagrelide is used worldwide to treat essential thrombocythemia (ET) by reducing platelet counts. Cardiomyopathy and heart failure (HF) are rare but serious... (Review)
Review
Anagrelide is used worldwide to treat essential thrombocythemia (ET) by reducing platelet counts. Cardiomyopathy and heart failure (HF) are rare but serious complications associated with anagrelide use, although no cases were reported during Japanese Phase I to III studies. A 46-year-old, otherwise healthy, Japanese ET patient developed HF with reduced ejection fraction after 18 months of treatment with 1.0-3.5 mg of anagrelide daily. HF was stabilized with anagrelide withdrawal and guideline-directed HF therapy. The cardiac function returned to normal after six months. This case suggests that anagrelide can cause cardiomyopathy and HF in ET patients, regardless of nationality, comorbid cardiovascular conditions, or therapy duration.
Topics: Humans; Middle Aged; Thrombocythemia, Essential; Platelet Aggregation Inhibitors; Cardiomyopathies; Heart Failure
PubMed: 35342135
DOI: 10.2169/internalmedicine.9090-21 -
South Dakota Medicine : the Journal of... Nov 2021Anagrelide is a drug used for treatment of essential thrombocytosis especially when conventional therapy is insufficient. Adverse effects associated with anagrelide are...
BACKGROUND
Anagrelide is a drug used for treatment of essential thrombocytosis especially when conventional therapy is insufficient. Adverse effects associated with anagrelide are palpitation, liver toxicity, renal failure and in few cases pericardial effusion. We here report a rare case of anagrelide induced pericardial effusion.
CASE PRESENTATION
A 76-year-old male with past medical history of hypertension, hyperlipidemia, chronic obstructive pulmonary disease, and myeloproliferative disorder presented to the emergency department with dyspnea on rest and exertion. He was initially treated with hydroxyurea for thrombocytosis but was later switched to anagrelide. On examination patient had muffled heart sounds. Lab investigations identified hyperkalemia and transaminitis. Transthoracic echocardiogram identified a moderate sized pericardial effusion. The pericardial effusion and transaminitis were attributed to anagrelide toxicity as other causes were ruled out. Pericardiocentesis was performed and anagrelide was discontinued. Patient was discharged in a well-compensated state with outpatient follow-up in two to three weeks.
CONCLUSION
Anagrelide is considered to be very effective treatment for essential thrombocytosis. It is, however, associated with serious adverse effects such as pericardial effusion, liver toxicity and palpitations. The mechanisms of these adverse drug reactions are still not completely understood. We suggest that patient taking anagrelide presenting with shortness of breath should have a transthoracic echocardiogram performed to rule out pericardial effusion. Liver enzymes should also be monitored closely and anagrelide discontinued immediately if the above-mentioned adverse events are noted.
Topics: Aged; Humans; Male; Myeloproliferative Disorders; Platelet Aggregation Inhibitors; Thrombocytosis; Treatment Outcome
PubMed: 35008135
DOI: No ID Found -
Expert Review of Hematology Sep 2021Chronic myeloproliferative neoplasm (MPNs) are clonal malignant bone marrow (BM) diseases, arising from a hematopoietic stem cell. All therapies for these neoplasms... (Review)
Review
Chronic myeloproliferative neoplasm (MPNs) are clonal malignant bone marrow (BM) diseases, arising from a hematopoietic stem cell. All therapies for these neoplasms have peculiar effects on the bone marrow, but little evidence has been described in the literature. This review examines BM morphological changes following the main treatments in Philadelphia-negative MPNs. Hydroxyurea can reduce the cellularity of the erythroid and megakaryocyte lineages but has minimal impact on fibrotic evolution. There is general agreement on its dysplastic effects, with a high incidence of acute myeloid leukemia and myelodysplastic syndrome. Interferon treatment can reduce or normalize BM cellularity, improve erythropoiesis, and reduce the number and atypicality of megakaryocytes. Most data describe reduction or complete resolution of marrow fibrosis; dysplastic effects are not reported. Anagrelide may induce an increase in the number of BM megakaryocytes, especially immature megakaryocytes or precursors, and a worsening of marrow fibrosis or increased transformation of essential thrombocythemia into myelofibrosis. Ruxolitinib can improve or stabilize BM fibrosis and reduces the frequency and dense clustering of megakaryocytes. Since previous therapy can modify BM features, it is essential to obtain information on previous or current therapies and to collect complete clinical information.
Topics: Bone Marrow; Humans; Myeloproliferative Disorders; Neoplasms; Primary Myelofibrosis; Thrombocythemia, Essential
PubMed: 34384330
DOI: 10.1080/17474086.2021.1967138 -
Journal of Hematology Jun 2021Essential thrombocythemia (ET) is one of the "classic" Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms characterized by sustained thrombocytosis,...
BACKGROUND
Essential thrombocythemia (ET) is one of the "classic" Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms characterized by sustained thrombocytosis, increased megakaryopoiesis and high risk of vascular complications. ET is very rare in childhood. The annual incidence is approximately 1 per 10,000,000 in children less than 14 years, and about 60 times lower than adults. The genetic landscape and clonal features in childhood ET has not been well defined. There is no evidence-based guidance on the diagnosis of childhood ET.
METHODS
Medical records of 28 pediatric patients (age ≤ 14 years at diagnosis) with ET were reviewed and evaluated to characterize the different mutation profiles and to evaluate the treatment modalities used and the potential long-term outcome.
RESULTS
More than half of the patients were found to have positive history of parental consanguinity (57.1%) whereas positive family history was documented for more than a quarter of our patients (28.6%). Janus kinase 2 gene () V617F mutation was positive in two of 26 patients (7.7%). Myeloproliferative leukemia virus oncogene () exon 10 and calreticulin () mutations were tested in eight patients, which were negative for all of them. Treatment included low-dose aspirin (LDA) in seven patients (50%), combination of LDA with hydroxyurea in three patients (21.4%), hydroxyurea in two patients (14.3%), combination of platelets apheresis with LDA and anagrelide in one patient each (7.1%). During the treatment, two patients experienced stroke (7.1%), one patient developed Budd-Chiari syndrome (3.6%) and one patient developed azoospermia (3.6%).
CONCLUSIONS
The incidence of ET in children is extremely low in Saudi Arabia. Most of the children with ET were asymptomatic, and thrombocytosis was often discovered incidentally. V617F mutation has no known impact on the prognosis or on the outcome of the disease in the pediatric age group that is in contrast to the adult ET. Children less than 1 year are at high risk for complications particularly during acute precipitating infectious episode. The potential complications and clinical course of pediatric ET are unpredictable.
PubMed: 34267847
DOI: 10.14740/jh822 -
European Journal of Haematology Oct 2020We report an extension study of patients with essential thrombocythaemia (ET) in the Hungarian Myeloproliferative Neoplasm (HUMYPRON) Registry, which demonstrated that...
OBJECTIVE
We report an extension study of patients with essential thrombocythaemia (ET) in the Hungarian Myeloproliferative Neoplasm (HUMYPRON) Registry, which demonstrated that over 6 years anagrelide significantly decreased the number of patients experiencing minor arterial and minor venous thrombotic events (TEs) vs hydroxyurea+aspirin.
METHODS
Data on patients with ET were collected through completion of a questionnaire developed according to 2008 WHO diagnostic criteria and with regard to Landolfi, Tefferi and IPSET criteria for thrombotic risk. Data were entered into the registry from 14 haematological centres. TEs, secondary malignancies, disease progression and survival were compared between patients with ET treated with anagrelide (n = 116) and with hydroxyurea+aspirin (n = 121).
RESULTS
Patients were followed for (median) 10 years. A between-group difference in the number of patients with TEs was observed (25.9% anagrelide vs 38.0% hydroxyurea+aspirin; P = .052). Minor arterial events were more frequently reported in the hydroxyurea+aspirin group (P < .001); there were marginally more reports of major arterial events in the anagrelide group (P = .049). TE prior to diagnosis was found to significantly influence TE incidence (P > .001). Progression-free survival (P = .004) and survival (P = .001) were significantly increased for the anagrelide group vs hydroxyurea+aspirin.
CONCLUSIONS
Anagrelide reduced TEs, and increased progression-free and overall survival vs hydroxyurea+aspirin over (median) 10 years.
Topics: Aspirin; Drug Therapy, Combination; Health Care Surveys; Humans; Hungary; Hydroxyurea; Quinazolines; Registries; Thrombocythemia, Essential; Thrombosis; Treatment Outcome
PubMed: 32557810
DOI: 10.1111/ejh.13459 -
International Journal of Hematology Oct 2022In Japan, anagrelide has been approved for use in patients with essential thrombocythemia. Here, the safety and efficacy of anagrelide was assessed in clinical practice...
Safety and efficacy of anagrelide in Japanese post-marketing surveillance, with subgroup analyses on the effect of previous cytoreductive therapies, age, and starting dose.
BACKGROUND
In Japan, anagrelide has been approved for use in patients with essential thrombocythemia. Here, the safety and efficacy of anagrelide was assessed in clinical practice as post-marketing surveillance. Subgroup analyses were conducted to compare patients (1) with or without a history of cytoreductive therapy (CRT), (2) <60 or ≥60 years of age, and (3) with an anagrelide starting dose of ≤0.5 mg/day or 1.0 mg/day.
METHODS
Data were collected for all patients who received anagrelide, with an observation period of 12 months after treatment initiation.
RESULTS
Of the 648 patients, 54.3% experienced adverse drug reactions (ADRs). The most commonly reported ADRs were headaches, palpitations, and anemia. No significant difference was observed in overall ADRs across patient subgroups. A significantly higher incidence of headaches was observed in patients < 60 years versus those ≥ 60 years (P < 0.001). The incidence of anemia and serious ADRs were significantly higher in patients ≥ 60 years, and those with a history of CRT (P < 0.05). The discontinuation rate at 6 months was significantly lower in patients started at the lower anagrelide dose (P < 0.05). Platelet counts decreased in all analyzed groups.
CONCLUSIONS
This surveillance showed that anagrelide has a tolerable safety and efficacy profile.
Topics: Cytoreduction Surgical Procedures; Headache; Humans; Japan; Platelet Aggregation Inhibitors; Product Surveillance, Postmarketing; Quinazolines
PubMed: 35624199
DOI: 10.1007/s12185-022-03380-2 -
Leukemia Research Aug 2022Anagrelide (ANA) is a platelet-specific cytoreductive agent utilized in the guideline-directed management of high-risk essential thrombocythemia. In the context of...
Anagrelide (ANA) is a platelet-specific cytoreductive agent utilized in the guideline-directed management of high-risk essential thrombocythemia. In the context of polycythemia vera (PV), ANA is occasionally employed in clinical practice, although data has not consistently demonstrated a benefit to targeting a platelet goal as a therapeutic endpoint. The aim of the current study was to delineate the patterns of ANA use in PV, and to describe outcomes and toxicities. Within a multi-center cohort of 527 patients with PV, 48 received ANA (9 excluded for absent data). 27 (69.2%) had high-risk PV, 10 (25.6%) had prior thrombosis, and none had extreme thrombocytosis, acquired von Willebrand disease, and/or documented resistance to hydroxyurea. While ANA effectively lowered median platelet count, 43.5% of patients had an unresolved thrombocytosis at time of ANA discontinuation. Treatment-emergent adverse events-including headaches, cardiac palpitations and arrhythmias, nausea, vomiting and/or diarrhea-led to ANA discontinuation in 76.9% of patients. Further, three patients experienced arterial thromboses during a median duration of 27.5 months of ANA therapy. In conclusion, this study highlights ANA's restrictive tolerability profile which, compounded by the absence of clear advantage to strict platelet control in PV, suggests the use of ANA should be limited in this setting.
Topics: Cytoreduction Surgical Procedures; Humans; Polycythemia Vera; Quinazolines; Thrombocythemia, Essential; Thrombocytosis; Thrombosis
PubMed: 35717689
DOI: 10.1016/j.leukres.2022.106903 -
Cureus Mar 2021Treatment modalities for polycythemia vera (PV) have evolved over time. Phlebotomy and low-dose aspirin suffice in low-risk patients, but cytoreductive therapies are... (Review)
Review
Treatment modalities for polycythemia vera (PV) have evolved over time. Phlebotomy and low-dose aspirin suffice in low-risk patients, but cytoreductive therapies are indicated in all high-risk patients (age ≥ 65 years or those with a history of PV-related thrombotic event) and may be considered for low-risk patients with progressively increasing splenomegaly, progressively increasing leucocyte and platelet counts, and for those who do not tolerate phlebotomy. Hydroxyurea/hydroxycarbamide or interferons can be used as first-line drugs. Hydroxyurea may not be tolerated by some patients, and it also carries risk of myelosuppression. Interferon alfa is especially useful for PV symptoms, and the newer preparation, ropeginterferon alfa-2b, has lesser incidence of flu-like reactions. Ruxolitinib reduces the JAK2V617F mutation burden and is used as a second-line drug. Anagrelide reduces platelet production and can be used in conjunction with hydroxyurea in patients with excessive thrombocytosis. The alkylating agent, busulfan, can also be used as a last resort in patients with a limited life expectancy. Prospective future treatments include givinostat, a histone deacetylase inhibitor, and idasanutlin, a murine double minute 2 antagonist.
PubMed: 33936902
DOI: 10.7759/cureus.14193 -
Future Oncology (London, England) Sep 2022Patients diagnosed with high-risk essential thrombocythemia (ET) have limited treatment options to reduce the risk of thrombosis and lessen the progression of the...
Patients diagnosed with high-risk essential thrombocythemia (ET) have limited treatment options to reduce the risk of thrombosis and lessen the progression of the disease by targeting the molecular source. Hydroxyurea is the recommended treatment, but many patients experience resistance or intolerance. Anagrelide is an approved second-line option for ET, but concerns of a higher frequency of disease transformation may affect its role as a suitable long-term option. Interferons have been evaluated in myeloproliferative neoplasms for over 30 years, but early formulations had safety and tolerability issues. SURPASS-ET (NCT04285086) is a phase III, open-label, multicenter, global, randomized, active-controlled trial that will evaluate the safety, efficacy, tolerability and pharmacokinetics of ropeginterferon alfa-2b compared with anagrelide as second-line therapy in high-risk ET.
Topics: Clinical Trials, Phase III as Topic; Humans; Hydroxyurea; Multicenter Studies as Topic; Quinazolines; Randomized Controlled Trials as Topic; Thrombocythemia, Essential
PubMed: 35924546
DOI: 10.2217/fon-2022-0596 -
Wiener Klinische Wochenschrift Jan 2021According to the World Health Organization (WHO) classification, essential (primary) thrombocythemia (ET) is one of several Bcr-Abl negative chronic myeloproliferative...
According to the World Health Organization (WHO) classification, essential (primary) thrombocythemia (ET) is one of several Bcr-Abl negative chronic myeloproliferative neoplasms (MPN). The classical term MPN covers the subcategories of MPN: ET, polycythemia vera (PV), primary myelofibrosis (PMF), and prefibrotic PMF (pPMF). ET is marked by clonal proliferation of hematopoietic stem cells, leading to a chronic overproduction of platelets. At the molecular level a JAK2 (Janus Kinase 2), calreticulin, or MPL mutation is found in the majority of patients. Typical ongoing complications of the disease include thrombosis and hemorrhage. Primary and secondary prevention of these complications can be achieved with platelet function inhibitors and various cytoreductive drugs including anagrelide, hydroxyurea and interferon. After a long follow up, in a minority of ET patients the disease transforms into post-ET myelofibrosis or secondary leukemia. Overall, life expectancy with ET is only slightly decreased.
Topics: Austria; Humans; Mutation; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential
PubMed: 33215234
DOI: 10.1007/s00508-020-01761-3