Published: 2 September 2021
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Consider blood cell wellbeing during valproate therapy
Published: 2 September 2021
Prescriber Update 42(3): 38–40
September 2021
The Centre for Adverse Reactions Monitoring (CARM) has recently received
two reports (CARM IDs 138863 and 138579) of patients being treated with
sodium valproate who experienced thrombocytopenia and pancytopenia,
respectively.
This article is a reminder of the haematological adverse reactions associated with sodium valproate treatment, which can range from minor bruising and bleeding to severe reactions such as haemorrhagic stroke or pancytopenia.1
Sodium valproate and thrombocytopenia – a common adverse reaction
Thrombocytopenia (low platelet count) has been estimated to occur in 5 to 60 percent of patients taking sodium valproate.2 Thrombocytopenia is listed as common (frequency rating ≥1/100 and <1/10) in the Epilim data sheet.3
The time to onset of thrombocytopenia varied in different studies, from the second week of treatment until 16 months after initiation. Risk factors for thrombocytopenia are female gender and older age. The risk is larger when higher doses are used.1
The exact mechanism by which sodium valproate can cause thrombocytopenia is unclear. Two possible explanations which have been suggested are:2,4
- peripheral platelet destruction due to formation of autoantibodies against platelets
- decreased production of platelets due to a dose-dependent direct bone marrow toxicity.
Thrombocytopenia is generally reversible with dose reduction or discontinuation of sodium valproate.1
Uncommon reactions affecting the blood
Pancytopenia (low red blood cells, white blood cells and platelets) and leukopenia (low white blood cells) with or without bone marrow depression are uncommon blood reactions (frequency rating ≥1/1000 and <1/100 in the data sheet).3 Neutropenia (low neutrophils) has been reported infrequently and mostly within the first weeks of treatment.1,2
Direct suppression of the bone marrow by an idiosyncratic mechanism has been proposed as a mechanism for the most severe haematological adverse reactions (eg, pancytopenia).5
New Zealand case reports
Up to 30 June 2021, CARM had received 937 case reports associated with sodium valproate treatment.
Table 1 details some of the reactions reported when sodium valproate was a suspect medicine.
Table 1: Overview of reports of haematological adverse reactions suspected to be caused by sodium valproate
| Reaction* | Total No. | Age group (years) | Gender | ||||||
|---|---|---|---|---|---|---|---|---|---|
| 0–20 | 21–40 | 41–60 | 61–80 | >81 | Unknown | F | M | ||
| Thrombocytopenia | 26 | 8 | 7 | 6 | 3 | 1 | 1 | 16 | 10 |
| Neutropenia | 24 | 4 | 4 | 9 | 4 | 1 | 2 | 14 | 10 |
| Pancytopenia | 7 | - | 1 | 2 | 1 | 2 | 1 | 4 | 3 |
| Leukopenia | 6 | - | 2 | 4 | - | - | - | 3 | 3 |
* Note: more than one reaction may have been reported for the same patient.
Keep track of the blood cells
Blood tests (full blood cell count and coagulation tests) are recommended for patients taking sodium valproate:3
- before starting sodium valproate therapy
- periodically during treatment
- before surgery
- in case of spontaneous bruising or bleeding.
Spontaneous bruising, bleeding or evidence of a haemostasis/coagulation disorder is an indication for dose reduction or withdrawal of sodium valproate whilst the cause of the coagulation disorder is being investigated.
More information
See the following Prescriber Update article for more information on sodium valproate and thrombocytopenia:
- Drug-induced immune thrombocytopenia (March 2018).
References
- UpToDate. Valproate: Drug information Topic 10035 Version 454.0. URL: uptodate.com/contents/valproate-drug-information (accessed 2 July 2021).
- Verrotti A, Scaparrotta A, Grosso S, et al. 2014. Anticonvulsant drugs and hematological disease. Neurological Sciences 35(7): 983–93. DOI: 10.1007/s10072-014-1701-0 (accessed 2 July 2021).
- Sanofi-Aventis NZ Limited. 2021. Epilim New Zealand Data Sheet 3 May 2021. URL: medsafe.govt.nz/profs/datasheet/e/Epilimtabsyrliqiv.pdf (accessed 2 July 2021).
- Buoli M, Serati M, Botturi A, et al. 2018. The risk of thrombocytopenia during valproic acid therapy: A critical summary of available clinical data. Drugs in R & D 18(1): 1–5. DOI: 10.1007/s40268-017-0224-6 (accessed 2 July 2021).
- Acharya S, Bussel JB. 2000. Hematologic toxicity of sodium valproate. Journal of Pediatric Hematology/Oncology 22(1): 62–5. DOI: 10.1097/00043426-200001000-00012 (accessed 2 July 2021).
