From the FDA Drug Label
Because of reports of thrombocytopenia (see ), inhibition of the secondary phase of platelet aggregation, and abnormal coagulation parameters, (e.g., low fibrinogen), platelet counts and coagulation tests are recommended before initiating therapy and at periodic intervals. In an study, valproate increased the unbound fraction of warfarin by up to 32. 6%. The therapeutic relevance of this is unknown; however, coagulation tests should be monitored if valproic acid therapy is instituted in patients taking anticoagulants.
Valproate may affect blood coagulation by increasing the risk of thrombocytopenia, inhibiting platelet aggregation, and altering coagulation parameters.
- Monitoring is recommended: Platelet counts and coagulation tests should be performed before starting valproate therapy and at regular intervals.
- Interaction with anticoagulants: Valproate may increase the unbound fraction of warfarin, and coagulation tests should be monitored in patients taking anticoagulants.
- Clinical significance is unknown: The therapeutic relevance of valproate's effect on warfarin is unknown, and the clinical significance of these interactions is not fully understood 1.
From the Research
Valproate can negatively affect blood coagulation, but the most recent and highest quality study suggests that it does not significantly impair hemostasis when used within the therapeutic range. The study published in 2015 2 found no statistically significant differences in coagulation tests and primary hemostasis between patients taking valproate and controls. However, other studies have reported that valproate can cause thrombocytopenia, impair platelet function, and decrease levels of fibrinogen and von Willebrand factor, potentially increasing bleeding risk in patients 3, 4, 5, 6.
- Key points to consider:
- Valproate may cause dose-dependent decreases in platelet count, with significant thrombocytopenia occurring in approximately 5-40% of patients.
- Patients taking valproate should have baseline complete blood counts before starting therapy and periodic monitoring thereafter, particularly during the first few months of treatment.
- Clinicians should be especially vigilant with patients on higher doses (>50 mg/kg/day), those with polypharmacy, and individuals with pre-existing coagulation disorders.
- If significant thrombocytopenia develops (platelets <50,000/μL) or if bleeding complications occur, dose reduction or medication discontinuation may be necessary.
- For patients requiring surgery, valproate levels should be checked preoperatively, and clinicians should consider additional coagulation studies if the patient is on high doses or has been on long-term therapy.
- The mechanism behind valproate's effect on platelets involves direct bone marrow suppression and immune-mediated destruction of platelets, as well as inhibition of the arachidonate cascade and decreased synthesis of thromboxane A2 4.
- Despite the potential risks, the most recent study suggests that valproate does not significantly impair hemostasis when used within the therapeutic range, and therefore, routine coagulation monitoring may not be necessary for all patients taking valproate 2.