The tyrosine kinase inhibitor, nilotinib potentiates a prothrombotic state

Alhawiti, Naif M.; Burbury, Kate; Kwa, Faith A.A.; O’Malley, Cindy J.; Shuttleworth, Peter; Alzard, Mohamad; Hamadi, Abdullah; Grigg, Andrew; Jackson, Denise E.

doi:10.1016/j.thromres.2016.07.019

Cited by 63 publications

(62 citation statements)

References 37 publications

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“…Nilotinib also interferes with endothelial cell migration, cell proliferation, and promotes a pro-atherogenic phenotype by increasing the expression of cell surface adhesion molecules 7. A recent paper revealed multiple pathways through which Nilotinib encourages a prothrombotic state 8. Nilotinib potentiates PAR1 mediated release of platelet alpha granules and also increases platelet thrombus volume.…”

Section: Discussionmentioning

confidence: 99%

Republished: Tyrosine kinase inhibitor induced rapidly progressive vasculopathy after intracranial stent placement

Chen

Sorace

Shakeri

et al. 2018

J NeuroIntervent Surg

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Tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) has been associated with progressive peripheral arterial disease and, more recently, rare cases of intracranial vascular stenosis have been reported. We report the fourth case of TKI treatment associated intracranial vasculopathy and rapid progression of intracranial vascular stenosis following intracranial stent placement. This was a 49-year-old woman who developed right-sided weakness, paresthesias, numbness, and speech difficulties 7 years following TKI treatment for CML. Cerebral catheter angiography demonstrated 90% stenosis of the left supraclinoid internal carotid artery, for which the patient underwent intracranial stent placement with no residual stenosis and improved distal blood flow. Approximately 1 month following the procedure, the patient returned with similar symptoms. Catheter angiography demonstrated 70% and 50% stenosis just distal and proximal to the stent construct, respectively. Rapid disease progression and non-atherosclerotic vasculopathy may argue against endovascular therapy.

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Section: Discussionmentioning

confidence: 99%

Republished: Tyrosine kinase inhibitor induced rapidly progressive vasculopathy after intracranial stent placement

Chen

Sorace

Shakeri

et al. 2018

J NeuroIntervent Surg

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“…Systemic hypertension is more common with ponatinib . A study assessing the impact of imatinib, dasatinib and nilotinib on thrombus generation on immobilised collagen demonstrated accelerated thrombus formation after exposure to nilotinib in vitro and ex vivo . Nilotinib and ponatinib are reported to inhibit endothelial proliferation and survival in vitro, which may affect vascular regeneration, repair and re‐perfusion .…”

Section: Ischaemic Events With Tki Therapymentioning

confidence: 99%

“…Nilotinib and ponatinib are reported to inhibit endothelial proliferation and survival in vitro, which may affect vascular regeneration, repair and re‐perfusion . Nilotinib induces increased platelet adhesion and activation, whereas dasatinib inhibits platelet aggregation and is associated with a small increase in clinically significant bleeding . More work is needed to understand better the impact of TKIs on vascular risk.…”

Section: Ischaemic Events With Tki Therapymentioning

confidence: 99%

“…20 A study assessing the impact of imatinib, dasatinib and nilotinib on thrombus generation on immobilised collagen demonstrated accelerated thrombus formation after exposure to nilotinib in vitro and ex vivo. 21 Nilotinib and ponatinib are reported to inhibit endothelial proliferation and survival in vitro, which may affect vascular regeneration, repair and re-perfusion. 22,23 Nilotinib induces increased platelet adhesion and activation, whereas dasatinib inhibits platelet aggregation and is associated with a small increase in clinically significant bleeding.…”

Section: Incidence Of Cerebrovascular Complications Is Around 1% or Lmentioning

confidence: 99%

“…22,23 Nilotinib induces increased platelet adhesion and activation, whereas dasatinib inhibits platelet aggregation and is associated with a small increase in clinically significant bleeding. 21,24 More work is needed to understand better the impact of TKIs on vascular risk.…”

Section: Incidence Of Cerebrovascular Complications Is Around 1% or Lmentioning

confidence: 99%

See 2 more Smart Citations

Chronic myeloid leukaemia and tyrosine kinase inhibitor therapy: assessment and management of cardiovascular risk factors

Ross

Arthur

Burbury

et al. 2018

Internal Medicine Journal

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Several BCR-ABL1 tyrosine kinase inhibitors (TKIs) are approved for the first-line treatment of chronic phase chronic myeloid leukaemia (CML). Disease control is achieved in the vast majority of patients and disease-specific survival is excellent. Consequently, there is now emphasis on managing comorbidities and minimising treatment-related toxicity. Second-generation TKIs have cardiovascular risks that are greater than with imatinib treatment, but these risks must be balanced against the superior CML responses encountered with more potent TKIs. Cardiovascular risk should be assessed at baseline using a locally validated model based on the Framingham risk equation. Clinicians involved in the care of CML patients should be aware of the vascular complications of TKIs and manage cardiovascular risk factors early to mitigate treatment-related risks. Reversible risk factors, such as dyslipidaemia, smoking, diabetes and hypertension, should be addressed. We summarise the available data on cardiovascular complications in CML patients treated with TKIs. Using the latest evidence and collective expert opinion, we provide practical advice for clinicians to assess, stratify and manage cardiovascular risk in people with CML receiving TKI therapy.

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