Phenytoin-Induced Severe Thrombocytopenia: A Case Report.

Phenytoin is a commonly prescribed antiepileptic medication for the prevention and treatment of tonic-clonic or partial seizures. Thrombocytopenia is a rare and serious adverse effect of phenytoin. This case report presents the case of a patient with severe thrombocytopenia induced by phenytoin for the treatment of tonic-clonic seizures. A 63-year-old male received 300 mg/day of phenytoin for the treatment of tonic-clonic seizures. Seven days after receiving the first dose of phenytoin, he was diagnosed with severe thrombocytopenia (platelet count 44 x 109/L) without hemorrhage. Phenytoin was discontinued, and seizures were controlled with levetiracetam. Seven days after stopping phenytoin, his daily platelet count improved from 44 to 177 x 109/L. The Naranjo algorithm score of 7 was at a probable level for phenytoin-induced thrombocytopenia. Thrombocytopenia is a serious adverse drug reaction that can result in life-threatening bleeding. Phenytoin-induced thrombocytopenia commonly begins 1-90 days after administration, and the recovery time is 3-21 days. The potential mechanism of phenytoin-induced thrombocytopenia is drug-induced immune thrombocytopenia. Drugs that enhance the concentration of phenytoin epoxide may be a contributing factor in phenytoin-induced thrombocytopenia. Phenytoin-induced thrombocytopenia is a rare but serious hematological complication. It should be recognized early, particularly in patients with a high risk of hemorrhage or concurrently with medications that increase phenytoin epoxide. Regularly consecutive complete blood count tests may be essential in order to detect an early decrease in platelet count in these patients.

HLA-B*15:21 and carbamazepine-induced Stevens-Johnson syndrome: pooled-data and in silico analysis.

HLA-B*15:02 screening before carbamazepine (CBZ) prescription in Asian populations is the recommended practice to prevent CBZ-induced Stevens-Johnson syndrome (CBZ-SJS). However, a number of patients have developed CBZ-SJS even having no HLA-B*15:02. Herein, we present the case of a Thai patient who had a negative HLA-B*15:02 screening result but later developed CBZ-SJS. Further HLA typing revealed HLA-B*15:21/B*13:01. HLA-B*15:21 is a member of the HLA-B75 serotype and is commonly found in Southeast Asian populations. Based on this case, we hypothesised that if all HLA-B*15:02 carriers were prevented from CBZ prescription, another common HLA-B75 serotype marker would show its association with CBZ-SJS. To test this hypothesis, we pooled data from previous association studies in Asian populations, excluded all cases with HLA-B*15:02, and analysed the association significance of HLA-B75 serotype markers. A significant association was found between CBZ-SJS and HLA-B*15:21 and HLA-B*15:11. We also applied an in silico analysis and found that all HLA-B75 serotype molecules shared similar capability in binding the CBZ molecule. In summary, this report provides the first evidence of a positive association between HLA-B*15:21 and CBZ-SJS and the first in silico analysis of CBZ binding sites and details of the molecular behaviour of HLA-B75 molecule to explain its molecular action.