Atorvastatin-Induced Refractory Thrombocytopenia

Ghuman, Jasmine; Manasewitsch, Nicholas T; Ghuman, Joban; Antwi‐Amoabeng, Daniel; Chahal, Gurpreet Singh

doi:10.7759/cureus.12502

Cited by 5 publications

(6 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 86%

Statins and antidepressants induce similar in vitro gene expression responses

Jiang

Shah

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…The rest of the general physical and systemic examinations were unremarkable. The drop in the patient’s platelet count after discontinuation of treatment with oral steroids and IVIG suggests that she has a refractory case of DIT [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, atorvastatin appears to be the most common one to cause this complication. Of all the cases of DIT due to atorvastatin use, only one reported refractory thrombocytopenia [ 8 ]. It is also interesting to note that in all these previously reported cases, patients were elderly (mean age = 64yrs), but our study includes a young female of 22 years.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Statin-Induced Thrombocytopenia in a Young Female: A Case Report and Literature Review

Shehryar¹,

Ashraf²,

Ahmad³

et al. 2021

Cureus

View full text Add to dashboard Cite

The causal relationship of thrombocytopenia with statin intake has been described in many research articles. Our case discusses the refractory nature of thrombocytopenia in a 22-year-old female, one month following a daily intake of 20 mg atorvastatin. This is the first case ever of drug-induced refractory thrombocytopenia reported in a young patient. We will also discuss previously reported cases of drug-induced thrombocytopenia (DIT) in our manuscript.

show abstract

Atorvastatin-Induced Refractory Thrombocytopenia

Cited by 5 publications

References 19 publications

Statins and antidepressants induce similar in vitro gene expression responses

Statins and antidepressants induce similar in vitro gene expression responses

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

Statin-Induced Thrombocytopenia in a Young Female: A Case Report and Literature Review

Contact Info

Product

Resources

About

Atorvastatin-Induced Refractory Thrombocytopenia

Cited by 5 publications

References 19 publications

Statins and antidepressants induce similar in vitro gene expression responses

Statins and antidepressants induce similar in vitro gene expression responses

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

Statin-Induced Thrombocytopenia in a Young Female: A Case Report and Literature Review

Contact Info

Product

Resources

About

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