Carbamazepine‐induced thrombocytopenia and carbamazepine‐10,11‐epoxide: A case report

Abstract

The case of a patient who developed thrombocytopenia during treatment with carbamazepine (CBZ) is described. The platelet count recovered soon after discontinuation of CBZ, Lymphocyte stimulation test with carbamazepine-10, 11-epoxide (CBZ-10, 11-EPOX), a major metabolite of CBZ, was positive, although with CBZ it was negative. These findings suggest that CBZ-10, 11-EPOX was possibly causative in the pathogenesis of CBZ-induced thrombocytopenia in this case.

Severe, isolated thrombocytopenia under polytherapy with carbamazepine and valproate

“…Bone marrow suppression results in blood cell dyscrasias, including agranulocytosis, hemolytic and aplastic anemia, bicytopenia, pancytopenia or rarely thrombocytopenia, which usually is mild 4 . Blood dyscrasia may be serious only in rare cases 2,3 . The risk for blood cell dyscrasia due to CBZ increases with age 3 .…”

“…4 Blood dyscrasia may be serious only in rare cases. 2,3 The risk for blood cell dyscrasia due to CBZ increases with age. 3 Thrombocytopenia due to CBZ usually occurs within 2-4 weeks of initiation of treatment and is followed by a rapid recovery after discontinuation.…”

“…Side‐effects of CBZ include weight gain, bone marrow suppression, liver and renal dysfunction, water intoxication, skin rashes, and ocular lens opacities 2,3 . Bone marrow suppression results in blood cell dyscrasias, including agranulocytosis, hemolytic and aplastic anemia, bicytopenia, pancytopenia or rarely thrombocytopenia, which usually is mild 4 .…”

Relation of blood platelet count during carbamazepine and oxcarbazepine treatment with daily dose, and serum concentrations of carbamazepine, carbamazepine-10, 11-epoxide, and 10-hydroxycarbazepine

“…Anti-IgG CBZ-dependent platelet reactive antibodies have been identifi ed in blood 6,17 ; however, no plasma antibodies against platelet GP IIb/ IIIa or Ib in the presence or absence of CBZ were found in another study, without any defi nitive evidence for an immune-mediated-mechanism 3 . In one patient who developed thrombocytopenia during CBZ treatment, the lymphocyte stimulation test with CBZE was positive, but not with CBZ, suggesting that this CBZ metabolite was the compound involved in the pathogenesis of the CBZinduced thrombocytopenia 4 . With regard to the possible eff ect of administering OXCBZ on the platelet number, this has been studied in much less detail, and only recently has one case of OXCBZ-induced thrombocytopenia been described 9 .…”

“…Unlike CBZ, phenobarbital or phenytoin, the OXCBZ metabolism is not induced or inhibited via cytochrome P-450, because the formation of MHCBZ from the parent drug occurs through a reduction of the carbonyl group by means a nonmicrosomal and noninducible ketoreductase 1 ; however, OXCBZ has a signifi cant inducing eff ect on the cytochrome system, although it is about 46 % lower than that of CBZ 2 . CBZ occasionally causes thrombocytopenia with generalized petechiae and ecchymoses, which most frequently appear 2 weeks after starting treatment [3][4][5] , although some cases are asymptomatic and unexpectedly found by routine laboratory testing 6,7 ; however, the pathophysiological mechanism is not well understood 3 . A decrease in blood platelets is not considered a major side eff ect of OXCBZ 8 ; nevertheless, Mahmud et al 9 recently described a case of thrombocytopenia secondary to OXCBZ administration, and these authors recommend that physicians prescribing this drug should carry out blood-profi le monitoring for the patients treated.…”