Atorvastatin-related thrombocytopenic purpura

Narayanan, Deepa

doi:10.1136/bcr.01.2010.2614

Cited by 8 publications

(8 citation statements)

References 12 publications

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“…Given these associations were not observed for PCSK9, another lipid-lowering medication target, the effects of statins on these haematological traits were likely independent of LDL-C lowering. In particular, our analysis uncovered genetic associations between HMGCR inhibition and various platelet-related indices, including a lower platelet count, which corroborates previous case reports of thrombocytopenia following statin treatments [70][71][72]. Depressed individuals exhibit increased platelet activity [73], which is reduced after antidepressant treatment [74,75].…”

Section: Discussionsupporting

confidence: 86%

Statins and antidepressants induce similar in vitro gene expression responses

Jiang

Shah

2022

Preprint

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Cholesterol-lowering statins, which are widely prescribed for treating and preventing cardiovascular diseases, have previously been reported to show anti-depressive properties. However, there is conflicting evidence on the association of statins with depression, and the molecular mechanisms that govern their potential anti-depressive effects remain largely veiled. We evaluated the anti-depressive activities of statins using a combined approach of transcriptomic signature matching and genetic association analysis. We interrogated pre-compiled Connectivity Map (CMap) perturbational gene expression signatures and found that compounds with highly similar signatures to statins (average connectivity score > 90) were enriched for antidepressants (p < 1E-05). Genes perturbed in the same direction by both statins and antidepressants were significantly enriched for various immune pathways, while genes perturbed in the opposite direction were enriched for lipid metabolism pathways. Using publicly available expression quantitative trait loci (eQTL) and genome-wide association summary data, we performed Mendelian randomisation analysis to infer association of genetically predicted statin target inhibition with various depression, immune and disease traits. Genetically proxied HMGCR inhibition was significantly associated with extensive changes in immune cell traits, particularly platelet-related indices, and while we observed no genetic association between HMGCR expression and depression risk (p = 0.21), we found nominal association with depression-related worrying symptoms (p = 0.042). Our analyses provide genomic evidence for the association between statins and extensive alterations in immune-related processes, which have been linked to depression. Our findings carry clinical relevance, both for treating the increasing prevalence of individuals with comorbid cardiovascular diseases and depression, and for exploring the potential of repurposing statins for modulating depression symptoms.

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Section: Discussionsupporting

confidence: 86%

Statins and antidepressants induce similar in vitro gene expression responses

Jiang

Shah

2022

Preprint

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“…Patients are exposed to the implicated medication for at least a week before developing clinical signs of thrombocytopenia [ 16 ]. DIT is suggested by rapid recovery following discontinuation of the implicated medication and the temporal relationship between symptom onset and medication exposure [ 7 ]. It is common practice to discontinue the medication and treat with steroid, and IVIG and plasma exchange may be considered for refractory cases [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…Myopathy, rhabdomyolysis, and liver enzyme abnormalities are rare, but major side effects seen with statin use [5,6]. A few case reports of statin-induced thrombocytopenia, specifically with atorvastatin, rosuvastatin, and simvastatin [7][8][9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin-Induced Refractory Thrombocytopenia

Ghuman¹,

Manasewitsch²,

Ghuman³

et al. 2021

Cureus

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Drug-induced thrombocytopenia is rarely associated with statin medications. We describe the case of a 69-year-old woman who developed refractory thrombocytopenia following atorvastatin use. To our knowledge, this is the fourth reported case of atorvastatin-induced thrombocytopenia and the first reported case of atorvastatin-induced refractory thrombocytopenia. Additionally, we summarize the cases of statin-induced thrombocytopenia reported in the medical literature.

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“…55 However, there are still case reports regarding ATinduced thrombocytopenia. [56][57][58][59] Therefore, a clinical trial will be more convincing and provide further evidence of the therapeutic effects and safety of AT in patients with ITP.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin restores imbalance of cluster of differentiation 4 (CD4)⁺ T cells in immune thrombocytopenia in vivo and in vitro

Zhao

et al. 2021

Br J Haematol

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Immune thrombocytopenia (ITP) is an autoimmune haemorrhagic disease, in which the overactivation of T cells is crucial in the pathogenesis. Atorvastatin (AT), a lipid-lowering medicine, has shown promising immunomodulatory effects in certain inflammatory conditions. However, the immunoregulatory role of AT in ITP remains elusive. To investigate the effect of AT in the treatment of ITP, cluster of differentiation 4 (CD4) + T cells were isolated from patients with ITP and cultured with different dosages of AT. We found that AT significantly inhibited cell proliferation, led to cell cycle arrest, induced apoptosis, and repressed the activation of CD4 + T cells in vitro. ITP murine models were then established, and results showed that AT treatment led to faster recovery of the platelet count to normal and exhibited comparable immunomodulatory function. Furthermore, we found the phosphorylation of mammalian target of rapamycin (mTOR), protein kinase B (AKT) and extracellular signal-regulated kinase (ERK), as well as activation of rat sarcoma virus (RAS) were all reduced dramatically after AT treatment in vitro. In conclusion, our present study demonstrated that AT could reinstate the functions of CD4 + T cells by inhibiting the excessive activation, proliferation, and survival of CD4 + T cells in ITP via the RAS/mitogen-activated protein kinase kinase (MEK)/ ERK and the mTOR/phosphatidylinositol-3 kinase (PI3K)/AKT pathway. Therefore, we propose that AT could be used as a potential therapeutic option for ITP by restoring the over-activated cellular immunity.

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Atorvastatin-related thrombocytopenic purpura

Cited by 8 publications

References 12 publications

Statins and antidepressants induce similar in vitro gene expression responses

Statins and antidepressants induce similar in vitro gene expression responses

Atorvastatin-Induced Refractory Thrombocytopenia

Atorvastatin restores imbalance of cluster of differentiation 4 (CD4)⁺ T cells in immune thrombocytopenia in vivo and in vitro

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Atorvastatin-related thrombocytopenic purpura

Cited by 8 publications

References 12 publications

Statins and antidepressants induce similar in vitro gene expression responses

Statins and antidepressants induce similar in vitro gene expression responses

Atorvastatin-Induced Refractory Thrombocytopenia

Atorvastatin restores imbalance of cluster of differentiation 4 (CD4)+ T cells in immune thrombocytopenia in vivo and in vitro

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Product

Resources

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Atorvastatin restores imbalance of cluster of differentiation 4 (CD4)⁺ T cells in immune thrombocytopenia in vivo and in vitro