From the FDA Drug Label
The frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose-related. In a clinical trial of divalproex sodium as monotherapy in patients with epilepsy, 34/126 patients (27%) receiving approximately 50 mg/kg/day on average, had at least one value of platelets ≤ 75 x 109/L. Approximately half of these patients had treatment discontinued, with return of platelet counts to normal. In the remaining patients, platelet counts normalized with continued treatment In this study, the probability of thrombocytopenia appeared to increase significantly at total valproate concentrations of ≥ 110 μg/mL (females) or ≥ 135 μg/mL (males)
Yes, VPA can cause thrombocytopenia.
- The probability of thrombocytopenia appears to increase significantly at total valproate concentrations of ≥ 110 μg/mL (females) or ≥ 135 μg/mL (males) 1.
- In a clinical trial, 27% of patients receiving approximately 50 mg/kg/day on average had at least one value of platelets ≤ 75 x 10^9/L 1 1.
From the Research
Yes, valproic acid (VPA) can cause thrombocytopenia, which is a reduction in platelet count below normal levels, as evidenced by a study published in 2020 2. This is a well-recognized adverse effect that occurs in approximately 5-40% of patients taking VPA, though clinically significant thrombocytopenia (platelets <50,000/μL) is less common. The risk appears to be dose-dependent and more likely with higher serum VPA concentrations, particularly above 100 μg/mL, as supported by a study from 1994 3. Thrombocytopenia typically develops within the first months of treatment but can occur at any time. The mechanism involves both decreased platelet production and increased peripheral destruction. VPA may suppress megakaryocyte development in the bone marrow and can also induce immune-mediated platelet destruction. Some key factors that increase the risk of thrombocytopenia in patients taking VPA include:
- Lower baseline platelet counts (<200 × 10^9/L) 2
- Longer use of VPA (more than 3 days) 2
- Higher daily dose of VPA (more than 1000 mg/d) 2
- Concurrent use of VPA with other antiepileptic drugs 2
- Infection 2
- Use of mechanical ventilation 2 Patients taking VPA should have baseline platelet counts checked before starting therapy and monitored periodically thereafter, especially during dosage adjustments. If thrombocytopenia develops, dose reduction may be sufficient in mild cases, but medication discontinuation may be necessary in severe cases. The condition is usually reversible upon dose reduction or discontinuation of VPA. It is essential to weigh the benefits of VPA therapy against the potential risks of thrombocytopenia and to closely monitor patients for signs of this adverse effect. In clinical practice, the decision to use VPA should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history. Overall, the use of VPA requires careful consideration of the potential risks and benefits, and patients should be closely monitored for signs of thrombocytopenia.