Pancytopenia and Valproic Acid: A Dose‐related Association

Oluboka, Oloruntoba; Haslam, David; Gardner, Don

doi:10.1111/j.1532-5415.2000.tb02668.x

Cited by 12 publications

(4 citation statements)

References 10 publications

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“…It is worthy to mention that the individuals were asymptomatic. This collaborates to the statement of Oluboka et al that is essential for physicians to clinically monitor for and inform patients about the signs and symptoms of reduced blood cell lineages (5). Moreover, both subjects had a full recovery in a month and this fact could suggest that pancytopenia secondary to VPa could be reversible on discontinuation of the drug (2).…”

Section: Introductionsupporting

confidence: 65%

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Valproic acid-associated pancytopenia: A dose-dependent adverse effect

Rissardo¹,

Caprara²,

Silveira³

2019

Ro J Neurol.

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Pancytopenia (PCP) is a life-threatening condition which is rarely associated with valproic acid (VPA). We present a case of an adult female with epilepsy that was seizure-free for the last three years. She was in use of VPA 500 mg bid. The subject reported that she recently had new seizures. VPA dose was increased to 500mg tid. One-month later, she was asymptomatic and seizure-free. Laboratory tests showed PCP. VPA dose was decreased to 500mg bid and maintained. One-month later, the complete blood cell count was normal. After one-year, the patient reported new episodes of convulsion. VPA was increased to 500 mg tid. One-month later, the laboratory tests revealed PCP. Valproic acid was discontinued. Carbamazepine 200 mg tid was started. After two-months, the laboratory tests were normal. The subject was seizure-free and asymptomatic for the last year.

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Section: Introductionsupporting

confidence: 65%

“…In this way, VPa hematological side effects are frequent, and among these, the thrombocytopenia and macrocytosis are the most common (4). Pancytopenia is a less commonly reported adverse effect, but it is a life-threatening condition and fatalities have been described (4,5).…”

Section: Introductionmentioning

confidence: 99%

Valproic acid-associated pancytopenia: A dose-dependent adverse effect

Rissardo¹,

Caprara²,

Silveira³

2019

Ro J Neurol.

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“…Kishi et al (1994) have shown that a high plasma VPA concentration is associated with in vivo and in vitro bone marrow suppression. While the VPA concentration‐dependent thrombocytopenia could be explained by the mechanism of bone marrow suppression, the rare occurrence of pancytopenia suggests that other mechanisms must be involved that renders the platelet cell lineage more vulnerable to VPA suppression or damage (Robinson et al, 1995; Oluboka et al, 2000). It is possible that both immune‐mediated peripheral destruction and VPA concentration‐dependent suppression of platelet precursors may be operating simultaneously.…”

Section: Discussionmentioning

confidence: 99%

Valproate‐induced thrombocytopenia: a prospective monotherapy study

2007

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SUMMARYPurpose: The frequency of valproate (VPA)-induced thrombocytopenia varied widely in previous studies, due to methodological differences. Our objective was to evaluate the relationship between trough VPA plasma levels and platelet counts and assess risk factors for the development of thrombocytopenia. Methods: Patients with refractory partial epilepsy were enrolled in this double-blind, multicenter, concentration-response trial that evaluated the efficacy and safety of high versus low trough plasma VPA concentrations following administration of divalproex sodium as monotherapy. Trough VPA concentrations and concomitant platelet counts were drawn at baseline and intermittently throughout the 24-week trial. Bivariate correlations and multivariate stepwise regression analysis were performed between platelet counts and multiple variables. A logistic regression analysis was done to determine the probability of developing thrombocytopenia at various VPA levels.Results: A total of 851 VPA levels and concomitant platelet counts were analyzed in 265 patients. Of these, 17.7% of patients experienced at least one episode of thrombocytopenia (platelet count ≤ 100,000/μl) after exposure to divalproex sodium. A significant negative correlation was found between VPA levels and platelet counts. Women were significantly more likely to develop thrombocytopenia. The probability of developing thrombocytopenia substantially increased at trough VPA levels above 100 μg/ml in women and above 130 μg/ml in men. Discussion: Our data strongly support a causal relationship between rising plasma VPA levels and reduced platelet counts, with additional risk factors including female gender and lower baseline platelet counts.

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“…[4][5][6] Our patient developed pancytopenia upon rechallenge with 1,000 mg/day VPA, which was within the allowed therapeutic limit. [4][5][6] Our patient developed pancytopenia upon rechallenge with 1,000 mg/day VPA, which was within the allowed therapeutic limit.…”

Section: Discussionmentioning

confidence: 74%