Lacosamide-Induced Thrombotic Thrombocytopenic Purpura

Lacosamide (Vimpat) is an antiepileptic drug approved for focal epilepsy. ¹ Undesirable hematological effects have rarely been reported. We report a probable case of thrombotic thrombocytopenic purpura (TTP) after lacosamide initiation.

A 34-year-old woman with temporal lobe epilepsy was switched from lamotrigine monotherapy to lacosamide because of uncontrolled seizures. Other medications included calcium, vitamin D, and birth control pills, which she had been taking for years. Five days after lacosamide (200 mg/d) was introduced, she developed abdominal pain, extensive bruising, and petechiae. The initial complete blood count showed a platelet count of 8 × 10⁹/L (reference value, 145-470 × 10⁹/L), leukocyte count of 9.2 × 10⁹/L (reference value, 4.5-11 × 10⁹/L), and hemoglobin count of 105 g/L (reference value, 120-160 g/L). In comparison, the last blood work done 3 months before the introduction of lacosamide had shown a platelet count of 240 × 10⁹/L, with normal hemoglobin and leukocytes. Lacosamide was stopped and replaced with pregabalin. A microangiopathic episode was confirmed with the presence of schistocytes on blood smear and positive hemolytic parameters (high lactate dehydrogenase, undetectable haptoglobin). Renal function and coagulation parameters remained normal, and direct antiglobulin test was negative. Two units of plasma were transfused followed by daily plasma exchanges. Rapid improvement of the platelet count occurred after the third procedure (178 × 10⁹/L), and plasmapheresis was stopped after the fourth (257 × 10⁹/L). At presentation, anti-ADAMTS13 antibody was positive (IgG 1/32), and ADAMTS13 activity was low (<10%). The antibody persisted almost 3 months later (IgG 1/8 and activity <10%). Despite the persistence of the antibody, the platelet count remained normal during this period. Long-term follow-up demonstrated the disappearance of the anti-ADAMTS13 antibody at 6 months and normalization of ADAMTS13 activity at 9 months.

Clinical presentation, laboratory findings, and response to treatment of this case support a diagnosis of TTP, probably caused by lacosamide (score of 7 on the Naranjo scale, a widely accepted and validated questionnaire to evaluate the likelihood that an adverse drug reaction is caused by the drug). ² The presence of anti-ADAMTS13 antibodies and their persistence over time without recurrent microangiopathic activity and without any treatment after initial plasmapheresis procedures (except lacosamide discontinuation) also support a causal link with lacosamide, possibly in antibody activation for microangiopathic activity. To our knowledge, this is the first report of TTP induced by lacosamide.

We identified in the literature 3 prior cases of lacosamide-induced severe thrombocytopenia, none of which had evidence of microangiopathic activity. Gavatha et al ³ mentioned that a patient developed anemia, thrombocytopenia, and granulocytopenia after adjunctive lacosamide treatment. However, he had had similar disturbances in blood counts prior to lacosamide initiation and when restarted on it, no problems occurred. Jones et al ⁴ reported a child on valproic acid who developed hyperammonemic encephalopathy, leukopenia, and thrombocytopenia after introduction of lacosamide. The authors suggested that lacosamide was responsible for inducing valproic acid bone marrow toxicity, and both drugs were discontinued. Finally, in a study of 32 patients treated with lacosamide, a patient developed thrombocytopenia after 13 doses. ⁵ No additional information was, however, provided.

In conclusion, clinicians should be aware that the use of lacosamide may induce TTP as a rare complication.