Antiplatelet therapy versus observation in low-risk essential thrombocythemia with a CALR mutation

Alvarez‐Larrán, Alberto; Pereira, Arturo; Guglielmelli, Paola; Hernández‐Boluda, Juan Carlos; Arellano‐Rodrigo, Eduardo; Ferrer‐Marín, Francisca; Alimam, Samah; Grießhammer, Martin; Kerguelen, Ana; Andréasson, Björn; Burgaleta, Carmen; Schwarz, Jiřı́; García‐Gutiérrez, Valentín; Ayala, Rosa; Barba, Pere; Gómez‐Casares, María Teresa; Paoli, Chiara; Drexler, Beatrice; Zweegman, Sonja; McMullin, Mary Frances; Samuelsson, Jan; Harrison, Claire; Cervantes, Francisco; Vannucchi, Alessandro M.; Besses, Carlos

doi:10.3324/haematol.2016.146654

Cited by 123 publications

(117 citation statements)

References 17 publications

(16 reference statements)

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“…21 In a retrospective study evaluating nonpregnant patients, patients with the CALR mutation had excessive bleeding and no reduction in thrombotic risk with ASA for primary prevention. 44 It is reassuring that the number of bleeding events in the antepartum and postpartum periods is comparable or lower with the total bleeding rates reported in randomized trials evaluating prophylactic LMWH and ASA during pregnancy or in the postpartum period in women without ET. [45][46][47][48] It is further reassurance that there was no antepartum bleeding reported in women with ET who received a combination of ASA and LMWH during their pregnancies.…”

Section: Discussionmentioning

confidence: 99%

Risk of venous thromboembolism in pregnant women with essential thrombocythemia: a systematic review and meta-analysis

Skeith

Carrier

Robinson

et al. 2017

Blood

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We performed a meta-analysis to evaluate the risk of venous thromboembolism (VTE) in pregnant women with essential thrombocythemia. Twenty-one trials and 756 pregnancies met inclusion criteria. The absolute VTE risk in the antepartum period is not above a threshold where low-molecular-weight heparin (LMWH) prophylaxis is clearly indicated or below a threshold where LMWH should be withheld (2.5%; 95% CI, 1.3-4.3). Postpartum, the absolute VTE risk is above a threshold where postpartum LMWH prophylaxis should be considered (4.4%; 95% CI, 1.2-9.5).

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Section: Discussionmentioning

confidence: 99%

Risk of venous thromboembolism in pregnant women with essential thrombocythemia: a systematic review and meta-analysis

Skeith

Carrier

Robinson

et al. 2017

Blood

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“…The results of this study are difficult to interpret because: i) the proportion of patients treated with antiplatelet therapy in CALR - vs JAK2 -mutated patients is unknown, ii) a multivariable model for risk of bleeding was not reported, and iii) cytoreduction was started much earlier in CALR - vs. JAK2 -mutated patients mostly to control the higher platelet count. 103 …”

Section: Discussionmentioning

confidence: 99%

Assessing the thrombotic risk of patients with essential thrombocythemia in the genomic era

2017

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The molecular characterization of myeloproliferative neoplasms, including essential thrombocythemia (ET), has enabled deeper understanding of their pathogenesis. A driver lesion, namely, Janus kinase (JAK)2V617F, calreticulin (CALR) or myeloproliferative leukemia (MPL) gene mutation can be identified in the vast majority of patients. Each of these mutations is associated with distinct clinical features and may modulate the patients’ clinical course, risk of complications, including vascular events, and survival. JAK2V617F appears to be a risk-modifying mutation and has been shown to increase the likelihood of thrombotic events in patients with ET across studies. As such, it has been included in prognostic models and its presence may influence treatment decisions. The association of CALR and MPL mutations with the incidence of vascular events has been less clear. Even more limited information is available on the contribution of additional non-driver lesions to the thrombotic risk. In this review we discuss the available evidence on the role of recurrent mutations in the risk of thrombotic complications in patients with ET and how these mutations weigh into modern prognostic scores.

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“…A recent retrospective study has shown that in patients with low-risk CALR-mutant ET, low-dose aspirin does not reduce the risk of thrombosis and may increase the risk of bleeding. 42 This observation suggests a genotype-based approach to antiplatelet therapy in low-risk patients, and observation alone appears a reasonable option for those with CALR-mutant ET without concomitant cardiovascular risk factors and without microvascular symptoms.…”

Section: Distinguishing Familial Et From Hereditary Thrombocytosismentioning

confidence: 99%

“…4,40,41 A more recent work has evaluated the benefit-to-risk ratio of low-dose aspirin in 433 low-risk ET patients who were on antiplatelet therapy or observation only. 42 In JAK2 (V617F)-mutated patients, low-dose aspirin was associated with a reduced incidence of venous thrombosis with no effect on the risk of bleeding. By contrast, in CALR-mutated patients, antiplatelet therapy did not affect the risk of thrombosis whereas it was associated with a higher incidence of bleeding.…”

Section: How We Treat Patients With Et According To Their Individual mentioning

confidence: 99%

How I treat essential thrombocythemia

Rumi

Cazzola

2016

Blood

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Essential thrombocythemia (ET) is an indolent myeloproliferative neoplasm that may be complicated by vascular events, including both thrombosis and bleeding. This disorder may also transform into more aggressive myeloid neoplasms, in particular into myelofibrosis. The identification of somatic mutations of JAK2, CALR, or MPL, found in about 90% of patients, has considerably improved the diagnostic approach to this disorder. Genomic profiling also holds the potential to improve prognostication and, more generally, clinical decision-making because the different driver mutations are associated with distinct clinical features. Prevention of vascular events has been so far the main objective of therapy, and continues to be extremely important in the management of patients with ET. Low-dose aspirin and cytoreductive drugs can be administered to this purpose, with cytoreductive treatment being primarily given to patients at high risk of vascular complications. Currently used cytoreductive drugs include hydroxyurea, mainly used in older patients, and interferon α, primarily given to younger patients. There is a need for disease-modifying drugs that can eradicate clonal hematopoiesis and/or prevent progression to more aggressive myeloid neoplasms, especially in younger patients. In this article, we use a case-based discussion format to illustrate our approach to diagnosis and treatment of ET.

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Antiplatelet therapy versus observation in low-risk essential thrombocythemia with a CALR mutation

Cited by 123 publications

References 17 publications

Risk of venous thromboembolism in pregnant women with essential thrombocythemia: a systematic review and meta-analysis

Risk of venous thromboembolism in pregnant women with essential thrombocythemia: a systematic review and meta-analysis

Assessing the thrombotic risk of patients with essential thrombocythemia in the genomic era

How I treat essential thrombocythemia

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