Thrombocytopenia defined as the presence of low platelet counts can be either idiopathic (immune thrombocytopenic purpura) or secondary to other causes like drug-induced thrombocytopenia (quinidine, sulphamethoxazole/trimethoprim, pencillamine, valproic acid, indomethacin, ibuprofen, carbamazepine, quinine); pregnancy; autoimmune conditions (eg, systemic lupus erythematosus); viral infections (eg, HIV, hepatitis, infectious mononucleosis), vaccinations( influenza vaccinations, MMR and DPT vaccinations); chronic liver disease; malignancy( lymphoproliferative disorders like non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia); myelodysplasia; or congenital causes of thrombocytopenia like Von Willibrand’s disease.1
There are two plausible causative agents for thrombocytopenia in our patient: atorvastatin and the flu vaccination. There are well-documented cases of thrombocytopenic purpura as a consequence of the flu vaccination2
and after immunisation in children.3,4
This is certainly a possibility in our patient. Although a atorvastatin re-challenge was not done, the fact that the patient has remained well with no further episodes of thrombocytopenic purpura with further flu vaccinations is highly suggestive of atorvastatin-induced thrombocytopenic purpura.
Statins are inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase: the main rate-limiting enzyme in cholesterol synthesis. Statins represent one of the most important pharmacological advances in the prevention of cardiovascular disease. Both primary prevention studies (WOSCOPS, AFCAPS/TexCAPS) and secondary prevention studies (4S, CARE, LIPID) with statins have shown a marked decrease in mortality and morbidity related to cardiovascular causes. Statins are generally divided into two groups: lipophilic and hydrophilic statins. Simvastatin, atorvastatin, fluvastatin are lipophilic, and rosuvastatin and pravastatin are hydrophilic.
Atorvastatin is one of the HMG-CoA reductase inhibitors that is approved for the use of both primary and secondary cardiovascular risk prevention. It has been in use for more than two decades now. The common side effects observed with atorvastatin are flatulence, myalgia, dyspepsia, constipation, diarrhoea, headache, asthenia and abnormalities in liver function tests. Atorvastatin was found to be well-tolerated with <2% of the treated patients having drug-related adverse events.5
Thrombocytopenia infrequently can occur as an idiosyncratic adverse reaction to a large number of drugs. Drug-induced thrombocytopenia and idiopathic (immune) thrombocytopenic purpura have identical clinical presentations. Therefore, diagnosis of drug-induced thrombocytopenia is made by rapid symptomatic recovery of the patient after discontinuation of the offending drug and the temporal relation between the onset of symptoms and drug challenge. But is has also been shown that a positive temporal relation between the onset of symptoms and drug challenge may not always be seen.6
A clinical trial on drug-induced thrombocytopenia in 309 patients did not identify statins as the culprit,6
but there certainly have been case reports related to simvastatin and atorvastatin-induced thrombocytopenic purpura.7,8
Statins have pleiotropic effects, including immunomodulatory, anti-inflammatory and antiproliferative properties.9
Statins affect coagulation by decreasing platelet aggregation, adhesion and its activity by its actions through nitric oxide synthase (NOS) activity and also by direct inhibition of platelets.10
A retrospective cohort study by Ray et al
found a 22% relative risk reduction in the incidence of deep venous thromboses with statins in a select group of patients over 65 years of age.11
In a recent randomised trial, use of 20 mg rosuvastatin in apparently healthy people reduced the occurrence of venous thromboembolism.12
It is well-known that the effects of statins on platelet function is time and dose dependent and is more likely to occur soon after the initiation of statin treatment.6
Our patient had been on atorvastatin for at least 6 months prior to the development of thrombocytopenia and rosuvastatin was initiated with no exacerbation of thrombocytopenia, which points to an idiosyncratic reaction being the most likely cause.
- Statins are generally considered to have a good safety profile.
- The benefits of statins extend beyond just lowering of the low density lipoprotein cholesterol concentrations because of its pleiotropic effects.
- These rarer side effects should by no means be inhibitive in a patient meriting lipid lowering treatment.
- Further management to achieve low density lipoproteins targets is at the discretion of the treating physician.