Venous thromboembolism in patients with chronic lymphocytic leukemia

Šimkovič, Martin; Vodárek, Pavel; Motyčková, Monika; Belada, David; Vrbacky, Filip; Зак, Павел; Smolej, Lukáš

doi:10.1016/j.thromres.2015.05.010

Cited by 20 publications

(17 citation statements)

References 44 publications

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“…Our data supported that, in patients treated with ibrutinib, the rate of thrombosis was low (3·9%) and the cumulative incidence of VTE was lower than expected as compared to historical controls (0·6 per 100 person‐years in our study compared to 1·5 per 100 person‐years in prior studies of CLL patients) (Whittle et al , ; Simkovic et al , )’. However, many patients in our study received concomitant antiplatelet agents or AC (39·6% and 8·3%, respectively), which may have reduced the risk of thrombosis even though the median overlap was short.…”

Section: Thrombosis Types and Treatment During Ibrutinibsupporting

confidence: 89%

“…Ibrutinib also inhibits other tyrosine kinases which may be responsible for its well‐established toxicities of atrial fibrillation (AF) and bleeding as well as increased risk of haemorrhage when combined with anticoagulation (AC) or antiplatelet agents (Byrd et al , ; Berglof et al , ; Lipsky et al , ). The population most likely to be exposed to ibrutinib is at higher risk for thrombosis given the presence of a maligiancy, such as chronic lymphocytic leukaemia (CLL), where the risk of venous thrombosis (VTE) was ~1·5 per 100 patients years, as well increased age where VTE risk is higher (Whittle et al , ; Heit, ; Simkovic et al , ). Additionally, arterial thrombosis risk also increases with age and in malignancy, and ibrutinib increases risk of AF, which may increase stroke (Leong et al , ; Wiczer et al , ).…”

Section: Thrombosis Types and Treatment During Ibrutinibmentioning

confidence: 99%

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Venous and arterial thrombosis in patients with haematological malignancy during treatment with ibrutinib

et al. 2019

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Section: Thrombosis Types and Treatment During Ibrutinibsupporting

confidence: 89%

Section: Thrombosis Types and Treatment During Ibrutinibmentioning

confidence: 99%

Venous and arterial thrombosis in patients with haematological malignancy during treatment with ibrutinib

et al. 2019

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“…CLL has not been associated with a high incidence of thrombosis. However, recent studies have shown incidence rates may be as high as other leukemias – 5%–11% 105,106. The risk factors for VTE is these studies were age >60 years, advanced stage of CLL, CLL treatment, and inherited thrombophilia.…”

Section: Coagulation Disorders In Chronic Lymphocytic Leukemiamentioning

confidence: 82%

Complications and management of coagulation disorders in leukemia patients

Lad

Jain

Varma

2017

BLCTT

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Abstract:Patients with leukemia are predisposed to various coagulation abnormalities. Thrombosis and bleeding continue to be a major cause of morbidity and mortality in leukemias. The pathophysiology of these disorders is unique, and not only the disease but also the treatment and other factors play a role. There has been an increase in the understanding of these disorders in leukemias. However, it is still difficult to predict when and which patients will have these complications. The evidence for the management of coagulation abnormalities in leukemias is still evolving and not as established as in solid malignancies. The management of these disorders is complex, and making clinical decisions is often challenging. In the era of specialization, where there are different hematologists looking after benign-and malignant-hematology patients, opinions of thrombosis experts are often sought by leukemia specialists. This review aims to bridge the gap in the knowledge of these disorders between these specialists.

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“…Because targeting miRs has proved beneficial in humans and animal studies [29,66], miR-15a-5p may be a potential therapeutic target in disorders of hemostasis or thrombosis. For example, although numerous mechanisms may be at play in the relatively frequent venous thromboembolisms seen in CLL [67], reduced miR-15a-5p could contribute to this complication by enhancing signaling through GPVI, in which case in vivo administration of miR-15a-5p may be a potential therapeutic. Alternatively, miR-15a-5p appears to be overexpressed in infectious and inflammatory disorders [51] and may contribute to platelet dysfunction, bleeding and vascular permeability [68], such that anti-miR therapy could have a useful role in these pathophysiologies.…”

Section: Discussionmentioning

confidence: 99%

miR‐15a‐5p regulates expression of multiple proteins in the megakaryocyte GPVI signaling pathway

Basak

Bhatlekar

Manne

et al. 2019

Journal of Thrombosis and Haemostasis

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BACKGROUND.-Megakaryocytes (MKs) invest their progeny platelets with proteins and RNAs. MicroRNAs (miRs), which inhibit mRNA translation into protein, are abundantly expressed in MKs and platelets. Although platelet miRs have been associated with platelet reactivity and disease, there is a paucity of information on the function of miRs in human MKs. OBJECTIVE.-To identify MK miRs that regulate the GPVI signaling pathway in the MKplatelet lineage. METHODS.-Candidate miRs associated with GPVI-mediated platelet aggregation were tested for functionality in cultured MKs derived from cord blood. RESULTS.-An unbiased, transcriptome-wide screen in 154 healthy donors identified platelet miR-15a-5p as significantly negatively associated with CRP-induced platelet aggregation. Platelet agonist dose-response curves demonstrated activation of αIIbβ3 in suspensions of cord bloodderived cultured MKs. Overexpression and knockdown of miR-15a-5p in these MKs reduced and enhanced, respectively, CRP-induced αIIbβ3 activation, but did not alter thrombin or ADP stimulation. FYN, SRGN, FCER1G, MYLK and PRKCQ, genes involved in GPVI signaling, were identified as miR-15a-5p targets and were inhibited or de-repressed in MKs with miR-15a-5p overexpression or inhibition, respectively. Lentiviral overexpression of miR-15a-5p also inhibited GPVI-FcRγ-mediated phosphorylation of Syk and PLCγ2, GPVI downstream signaling molecules, but effects of miR-15a-5p on αIIbβ3 activation did not extend to other ITAM-signaling receptors (FcγRIIa and CLEC-2). CONCLUSION.-Cord blood-derived MKs are a useful human system for studying the functional effects of candidate platelet genes. miR-15a-5p is a potential "master-miR" for

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Venous thromboembolism in patients with chronic lymphocytic leukemia

Cited by 20 publications

References 44 publications

Venous and arterial thrombosis in patients with haematological malignancy during treatment with ibrutinib

Venous and arterial thrombosis in patients with haematological malignancy during treatment with ibrutinib

Complications and management of coagulation disorders in leukemia patients

miR‐15a‐5p regulates expression of multiple proteins in the megakaryocyte GPVI signaling pathway

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