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Cureus Jun 2022Anagrelide is an inhibitor of the phosphodiesterase-3 (PDE-3) enzyme that suppresses megakaryocytes; hence it is used in the treatment of essential thrombocythemia....
Anagrelide is an inhibitor of the phosphodiesterase-3 (PDE-3) enzyme that suppresses megakaryocytes; hence it is used in the treatment of essential thrombocythemia. Anagrelide can cause positive inotropic and chronotropic effects on the cardiovascular system. Its cardiovascular side effects are rare and include palpitations, tachyarrhythmias, cardiomyopathy, angina, and heart failure. We report the case of a 71-year-old female who presented with sudden onset chest pain. Her only outpatient medications included anagrelide and aspirin. She was found to have supraventricular tachycardia (SVT) with aberrancy that responded to beta-blockers. The chest X-ray, computed tomography angiogram (CTA), and echocardiogram were unremarkable. Her arrhythmia may be attributed to the anagrelide in the absence of any cardiovascular findings.
PubMed: 35747119
DOI: 10.7759/cureus.26119 -
American Society of Clinical Oncology... 2015The groundbreaking discovery of the Janus-associated kinase 2 (JAK2) V617F mutation 10 years ago resulted in an unprecedented intensive basic and clinical research in... (Review)
Review
The groundbreaking discovery of the Janus-associated kinase 2 (JAK2) V617F mutation 10 years ago resulted in an unprecedented intensive basic and clinical research in Philadelphia-negative myeloproliferative neoplasms (MPNs). During these years, many new potential targets for therapy were identified that opened the era of targeted therapy for these diseases. However, only one new drug (ruxolitinib) has been approved during the past 40 years, and, although promising new therapies are evaluated, the armamentarium to treat MPN still relies on conventional drugs, like cytotoxic agents and anagrelide. The exact role of interferon (IFN) alfa still needs to be clarified in randomized studies, although it has been shown to be effective in MPNs for more than 25 years. The current therapeutic strategy for MPNs is based on the risk of vascular complication, which is the main cause of mortality and mortality in the medium term. However, the long-term outcome may be different, with an increasing risk of transformation to myelodysplastic syndrome or acute leukemia during follow-up times. Medicines able to change this natural history have not been clearly identified yet, and allogeneic stem cell transplantation currently remains the unique curative approach, which is only justified for patients with high-risk myelofibrosis or for patients with MPNs that have transformed to myelodysplasia or acute leukemia.
Topics: Anemia; Antineoplastic Agents; Female; Forecasting; Hematopoiesis, Extramedullary; Humans; Janus Kinases; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Myeloproliferative Disorders; Phlebotomy; Polycythemia Vera; Pregnancy; Pregnancy Complications, Hematologic; Primary Myelofibrosis; Risk Assessment; Splenomegaly; Stem Cell Transplantation; Thrombocythemia, Essential
PubMed: 25993201
DOI: 10.14694/EdBook_AM.2015.35.e389 -
Therapeutic Advances in Hematology Jun 2015The new World Health Organization (WHO) diagnostic criteria for essential thrombocythemia (ET) issued in 2008 made an important distinction between true ET and early... (Review)
Review
The new World Health Organization (WHO) diagnostic criteria for essential thrombocythemia (ET) issued in 2008 made an important distinction between true ET and early myelofibrosis (MF), which has helped to identify a more homogenous population for the diagnosis with longer survival and much less transformation to overt MF. The recent finding of a new mutation (CALR), which is mutually exclusive with JAK2 and MPL mutations, adds to the characterization of ET patients, since there are important phenotypic differences between the mutation types. CALR patients are younger, have lower white blood cell counts (WBC) and a lower thrombosis incidence. A growing field of interest is the state of hypercoagulation due to dysfunction of hemostatic systems, cell-cell interaction and hereditary prothrombotic traits. Activation of platelets, WBC and endothelial cells has been found, making the whole intravascular milieu prothrombotic. Several risk score models, based on retrospective studies, have been developed lately, distinguishing patient groups with graded risk for complications and death. Even if these may be helpful in evaluating patients, they have not been validated in prospective studies and there are not enough data to support their use as a basis for treatment algorithms. The traditional risk factors age, previous thrombosis and platelets >1500 × 10(9)/l are still recommended for the distinction between high risk and low risk ET and the decision to give cytoreductive therapy. However, cardiovascular (CV) risk factors add to thrombosis risk and should be considered both for specific treatment in any risk group and for upgrading low risk patients with high CV risk to an intermediary group where active therapy with aspirin and cytoreduction may be considered. First-line cytoreductive therapy differs with age; in younger patients interferon (IFN) or anagrelide are preferable, in older patients hydroxycarbamide (HC). Second-line therapy for younger patients is HC, for older patients IFN or anagrelide (ANA). JAK2 inhibitors may be suitable in rare cases with symptoms not responding to other therapy.
PubMed: 26137205
DOI: 10.1177/2040620715580068 -
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 -
International Journal of Clinical... Oct 2012Headache is frequently reported as one of the neurological manifestations of essential thrombocythaemia (ET) and other myeloproliferative neoplasms. It is associated... (Review)
Review
Headache is frequently reported as one of the neurological manifestations of essential thrombocythaemia (ET) and other myeloproliferative neoplasms. It is associated with considerable morbidity; yet, it is a frequently under-recognised symptom. In patients with ET, headaches may be attributable to the disease, to the prescribed ET treatment, or unrelated to ET. The majority of headaches in ET are self-limiting and can be managed with standard headache therapies such as paracetamol, but it is vital that the clinician managing these conditions is able to recognise the headaches with a more sinister pathology. In this article, we will review the incidence and management of headaches in ET, whether they are primarily related to the disease or a result of its treatment. Identification of specific headache types in patients with ET may enable physicians to employ the most effective headache medication. This would enhance the patient-physician relationship, increasing patient compliance and thus reducing the risk of adverse outcomes.
Topics: Alkylating Agents; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Headache Disorders; Humans; Hydroxyurea; Immunologic Factors; Interferon-alpha; Phosphorus Radioisotopes; Platelet Aggregation Inhibitors; Quinazolines; Radiopharmaceuticals; Risk Factors; Thrombocythemia, Essential
PubMed: 22889110
DOI: 10.1111/j.1742-1241.2012.02986.x -
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 -
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 -
Current Hematologic Malignancy Reports Oct 2016Anagrelide (ANA) is a drug with specific platelet-lowering activity, used primarily in ET, registered as a second-line drug in essential thrombocythemia (ET) in Europe... (Review)
Review
Anagrelide (ANA) is a drug with specific platelet-lowering activity, used primarily in ET, registered as a second-line drug in essential thrombocythemia (ET) in Europe and in some countries as first-line therapy, in USA licensed by FDA for thrombocythemia in myeloproliferative neoplasms (MPN). The platelet-lowering efficacy is similar to that of hydroxycarbamide (HC), around 70 % complete response and 90 % partial response. Side effects are common, especially headache and tachycardia, but usually subside or disappear within a few weeks. Around 20 % of patients stop ANA therapy due to side effects or insufficient response. Studies of treatment patterns in Europe show that ANA is preferentially given to younger patients, probably because of the concern for a possible leukemogenic effect of the common first-line drug, HC. Only two randomized studies have compared the efficacy of ANA and HC in preventing thrombosis and haemorrhage, the larger of them showing a slightly better efficacy of HC, the other showing non-inferiority of ANA to HC. A recent observational 5-year study of 3600 patients shows a low and basically similar efficacy of ANA and other cytoreductive therapies in ET. ANA does not appear to inhibit fibrosis development, and probably due to its anticoagulation properties, the combination of ASA and ANA produces an increased rate of haemorrhage. Combination of ANA with HC or interferon (IFN) is feasible and effective in patients with insufficient platelet response to mono-therapy.
Topics: Age Factors; Bone Marrow; Cardiovascular Diseases; Humans; Interferon-alpha; Myeloproliferative Disorders; Platelet Aggregation Inhibitors; Quinazolines; Tachycardia; Thrombocythemia, Essential
PubMed: 27497846
DOI: 10.1007/s11899-016-0335-0 -
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 -
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