Inhibition of Platelet Production Induced by an Antiplatelet Drug, Anagrelide, in Normal Volunteers

Wa, Andes; Noveck, Robert J.; Fleming, John

doi:10.1055/s-0038-1661206

Cited by 51 publications

(37 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mean autologous platelet life span, however, was unchanged (7.9 Ϯ 0.8 days), indicating that anagrelide exerts its effect by inhibiting platelet production rather than by increasing platelet destruction. The finding that platelet survival was unaffected by anagrelide is in agreement with previous results obtained in healthy individuals 8 and in a limited number of patients (n ϭ 3). 10 It is noteworthy that the platelet function studies revealed a persistent defect in platelet function as measured by aggregation after temporary discontinuation of the drug.…”

Section: Discussionsupporting

confidence: 92%

“…Before treatment, platelet aggregation was invariably defective among patients with essential thrombocythemia, including the absent response to epinephrine and diminished aggregation with either ADP, collagen, or both (data are not shown) 7,8 The results showed the persistence of the platelet aggregation defect.…”

Section: Platelet Aggregation Studiesmentioning

confidence: 95%

“…7 In vivo, anagrelide inhibits platelet production in a dosedependent manner without affecting the production of other marrow elements. 3,8 However, the mechanism by which anagrelide induces thrombocytopenia has not yet been defined. 9 In vitro, anagrelide inhibits the formation of megakaryocyte (MK) colonies, but only at concentrations higher than those achieved in vivo.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of anagrelide on in vivo megakaryocyte proliferation and maturation in essential thrombocythemia

Tomer

2002

Blood

View full text Add to dashboard Cite

To define the mechanism by which anagrelide normalizes the platelet count in essential thrombocythemia, we studied in vivo megakaryocytopoiesis in 10 newly diagnosed patients prior to and while on anagrelide therapy. Using flow cytometric analysis of aspirated marrow, megakaryocytopoiesis was quantified and correlated with the autologous platelet production rate. Megakaryocytes were identified by CD41a expression and enumerated in relation to the nucleated marrow erythroid precursors. Megakaryocyte diameters were directly measured by timeof-flight technique, and cell ploidy was measured by DNA staining. Two to 3 thousand megakaryocytes were analyzed in each sample. In the 10 patients, the platelet count was 1063 ؎ 419 ؋ 10 9 platelets/L (mean ؎ 1 SD) with markedly in-

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Platelet Aggregation Studiesmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of anagrelide on in vivo megakaryocyte proliferation and maturation in essential thrombocythemia

Tomer

2002

Blood

View full text Add to dashboard Cite

show abstract

“…At therapeutic concentrations, anagrelide does not appear to shorten platelet survival or to inhibit the proliferation of CFU-M in vivo. These observations, including the lack of effect of anagrelide on platelet survival in normal subjects (Abe Andes et al, 1984) and the concentrationdependent effect of anagrelide on human megakaryocytopoiesis (Mazur et al, 1992), have been recognized by other investigators.…”

Section: Discussionmentioning

confidence: 94%

The effects of anagrelide on human megakaryocytopoiesis

Solberg

Tefferi²,

Oles³

et al. 1997

Br J Haematol

View full text Add to dashboard Cite

Summary.Anagrelide, an inhibitor of platelet aggregation, decreases the number of platelets in normal subjects and in patients with myeloproliferative disorders. We describe studies aimed at discovering the general mechanism(s) by which anagrelide acts. We examined three hypotheses:(1) anagrelide shortens platelet survival, (2) anagrelide inhibits the proliferation of megakaryocytic-committed progenitor cells (CFU-M), and (3) anagrelide inhibits maturation of megakaryocytes. We observed that anagrelide did not shorten platelet survival. Proliferation of CFU-M in vivo was not affected by anagrelide, although high concentrations of anagrelide inhibited CFU-M in vitro. In-vivo and in-vitro anagrelide altered the maturation of megakaryocytes, causing a decrease in their size and changing other morphometric features. We conclude that anagrelide decreases the number of platelets primarily by interfering with the maturation of megakaryocytes.

show abstract

“…17 ANA received its primary marketing authorization in the USA in 1997 for ET and subsequently for other MPNs. It was initially developed as an inhibitor of platelet aggregation 20 but found to have value as a platelet-lowering agent for the treatment of ET. 21,22 Unlike many other treatments used in MPN, ANA is non-mutagenic, has no effect on angiogenesis and does not increase risks of leukemia, which make it a particularly useful drug for young patients with a longer natural history of ET.…”

mentioning

confidence: 99%

Spotlight on anagrelide hydrochloride for the treatment of essential thrombocythemia

Sarma¹,

McLornan²,

Harrison³

2017

ODRR

View full text Add to dashboard Cite

Anagrelide (ANA) hydrochloride is an oral imidazoquinazoline registered as an orphan drug in Europe. It is indicated as a second-line agent for the reduction of thrombocytosis in high-risk essential thrombocythemia (ET) in Europe and in any myeloproliferative neoplasmassociated thrombocytosis and for the amelioration of thrombo-hemorrhagic events in the context of myeloproliferative neoplasm in the USA and Japan. The compound has been in clinical use for almost two decades with approval in the European Union (EU) for over a decade. The licensed indication encompasses the apparently specific action of the drug to reduce the platelet count; however, the precise mode of action of ANA remains unclear. Here, we review the current data from two large phase 3 studies, PT-1 and ANAHDRET, and a phase 4 post-approval observational study EXELS. All of these studies were conducted in the EU and therefore pertain to ET as the only licensed indication. Data from these studies suggest that ANA is on the whole as effective as the most commonly used agent hydroxycarbamide (HC). Although ANA, when compared to HC, appears to be slightly less effective in preventing arterial thrombosis and myelofibrotic transformation, it is associated with lower risk of venous thrombosis. Since the initial data from the PT-1 study, a caution has been recommended for the combined use of ANA and aspirin as this may provoke excess hemorrhage. ET is a clinically and biologically heterogeneous condition, and these biological variations may in part explain some of the clinical differences observed in various studies in response to specific treatments. No new toxicities of ANA have emerged in the past decade, which means that clinicians and patients can be reassured about the efficacy and safety of this agent, which is of particular importance in a chronic condition such as ET.

show abstract

Inhibition of Platelet Production Induced by an Antiplatelet Drug, Anagrelide, in Normal Volunteers

Cited by 51 publications

References 10 publications

Effects of anagrelide on in vivo megakaryocyte proliferation and maturation in essential thrombocythemia

Effects of anagrelide on in vivo megakaryocyte proliferation and maturation in essential thrombocythemia

The effects of anagrelide on human megakaryocytopoiesis

Spotlight on anagrelide hydrochloride for the treatment of essential thrombocythemia

Contact Info

Product

Resources

About