Fatal pancytopenia during high-dose valproate monotherapy

Rajantie, Jukka; Kajosaari, Merja; Ylitalo, V.

doi:10.1007/bf01957735

Cited by 14 publications

(10 citation statements)

References 8 publications

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“…The drug may have severe side-effects on bone marrow suggestive of a possible myelodysplastic syndrome. The marrow abnormalities are usually reversible after VPA withdrawal but a fatal case of bone marrow failure has been reported after high-dose VPA monotherapy [10].…”

Section: Discussionmentioning

confidence: 99%

“…Hepatotoxicity and rare fatal liver failures are the most well-known side-effects [2]. However, haematological alterations can also occur, notably transient immune thrombocytopenia and, less frequently, neutropenia, red cell aplasia or fatal bone marrow failure [1,5,8,10]. We report a patient who developed severe thrombocytopenia, macrocytic anaemia and extensive allergic dermatitis during continued VPA therapy.…”

Section: Introductionmentioning

confidence: 92%

See 1 more Smart Citation

Haematological disturbances during long-term valproate therapy

Brichard¹,

Vermylen²,

Scheiff³

et al. 1994

Eur J Pediatr

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A 14-year-old boy with mental retardation presented with severe thrombocytopenia, macrocytic anaemia and allergic dermatitis. He had been treated with valproate for seizures since the age of 2 years. Clinical examination showed severe purpura, mucous bleeding and extensive dermatitis. Tests to detect serum direct antiplatelet antibodies were positive and bone marrow examination revealed myelodysplastic abnormalities. Valproate was discontinued and both dermatitis and general condition of the child improved with normalization of the full blood count. This report suggests that valproate may produce both peripheral immune thrombocytopenia and severe bone marrow depression several years after the initiation of the therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Haematological disturbances during long-term valproate therapy

Brichard¹,

Vermylen²,

Scheiff³

et al. 1994

Eur J Pediatr

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“…Here, the plasma free fraction is only 10% of the dose. However, several cases of leukopenia ascribable to sodium valproate have been reported to date (Sato et al, 1982;Schnabel et al, 1984;Watts et al, 1990;Safa Kaya et al, 1991;Sungur et al, 1992;Rajantie et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

A cellular model for drug interactions on hematopoiesis: The use of human umbilical cord blood progenitors as a model for the study of drug-related myelosuppression of normal hematopoiesis

et al. 1996

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A cellular model of hematopoiesis which would be more convenient than bone marrow (BM) progenitors and directly relevant to human pathology is needed in order to investigate xenobiotic toxicity. Human umbilical cord blood (HCB), previously shown to be able to repopulate BM, provides a powerful in vitro model of normal human hematopoiesis. In order to validate the use of normal HCB progenitors as targets for dose-related myelosuppression, we used clonogenic assays and expansion in a liquid culture of progenitor-enriched cell suspensions from HCB. A series of 8 reference molecules, doxorubicin, cytosine-arabinoside, 5-fluorouracil, 3'-azido-3'-deoxythymidine, acetylsalicylic acid, sodium valproate and two cephalosporin antibiotics, were tested. In vitro 50% inhibition concentrations (IC50) were compared to those observed or reported with BM progenitors, and to the values of plasma concentrations from treated patients. HCB progenitors as in vitro targets for cytotoxic molecules were easy to access and handle, and their use was sensitive, specific and reproducible. They gave results similar to BM progenitors and allowed a qualitative approach to cellular metabolism and toxicity using morphological, flow cytometric and chromatographic methods.

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“…Although side effects from VPA therapy are generally considered mild and transient, serious medical problems (such as hepatatoxicity, hyperammonemia, pancreatitis, and coagulopathy) have occurred [2,43,44,59].…”

Section: What Occurs With Valproic Acid Toxicity?mentioning

confidence: 99%

“…Despite the controversies, reports of fatal subarachnoid hemorrhage, pulmonary hemorrhage, and pancytopenia from the therapeutic use of VPA have been documented. This has influenced many anesthesiologists and surgeons to stop VPA-treatment before surgery to avoid bleeding complications [35,59,77,78].…”

Section: What Occurs With Valproic Acid Toxicity?mentioning

confidence: 99%

Case files of the Children’s Hospital of Michigan Regional Poison Control Center: The use of carnitine for the management of acute valproic acid toxicity

Katiyar

Aaron

2007

J. Med. Toxicol.

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A 28-year-old African-American male was found unresponsive outside of his girlfriend's house around 7 o'clock in the morning. He spent the night at the girlfriend's house and was last witnessed to be awake about 12 hours earlier. The girlfriend and her family were unable to awaken the patient and called emergency medical services (EMS). There was no history of headache, dizziness, fever, chills, nausea, vomiting, seizures, trauma, depressive thoughts, or suicidal ideation. When EMS arrived, they administered 6 mg of naloxone intramuscularly without effect, and the patient was transported to the emergency department (ED).After arriving in the ED, the cardiac monitor displayed a narrow-complex rhythm with a rate of 85-90 per minute. His initial vital signs were: heart rate 91/min; blood pressure 148/80 mmHg; respiratory rate 24/min; temperature 35.1°C (95.1°F) rectally; and pulse oximetry 100% on non-rebreather face mask oxygen. A fingerstick glucose determination was 106 mg/dL.Physical examination revealed a well developed, well nourished individual who was obtunded and unresponsive. His pupils were 2 mm, unreactive to light, and without nystagmus. He had diffuse bilateral wheezing, regular heart rate without any murmurs, and decreased bowel sounds. The patient had warm skin with good distal pulses in all extremities and no cyanosis, erythema, or edema. There was no clonus or hyperreflexia, and the gag reflex was intact.His past medical history was only pertinent for an old gunshot wound to the head. He developed a seizure disorder and was taking divalproex, 500 mg BID. Reportedly, he was allergic to carbamazepine and phenytoin. The patient smoked cigarettes, but the family stated that he had no history of alcohol or illicit drug use.A 12-lead electrocardiogram showed a sinus rhythm with a rate of 92 bpm, a PR interval of 134 msec, a QRS duration of 90 msec, and a QTc of 601 msec. A head CT and chest radiograph were unremarkable. Laboratory tests were obtained.

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Fatal pancytopenia during high-dose valproate monotherapy

Cited by 14 publications

References 8 publications

Haematological disturbances during long-term valproate therapy

Haematological disturbances during long-term valproate therapy

A cellular model for drug interactions on hematopoiesis: The use of human umbilical cord blood progenitors as a model for the study of drug-related myelosuppression of normal hematopoiesis

Case files of the Children’s Hospital of Michigan Regional Poison Control Center: The use of carnitine for the management of acute valproic acid toxicity

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