Neonatal Afibrinogenaemia Due to Sodium Valproate

Majer, R.V.; Green, P.J.

doi:10.1016/s0140-6736(87)91098-1

Cited by 32 publications

(8 citation statements)

References 4 publications

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“…Routine coagulation tests may show pathologic PT, aPTT, and TT if decrease of concentration is relevant. Hypofibrinogenemia associated with VPA therapy has been reported several times (6,17,43,61,70–77). In VPA‐induced hypofibrinogenemia, no fibrin degradation products have been found (71,77).…”

Section: Discussionmentioning

confidence: 99%

Valproate‐associated Coagulopathies Are Frequent and Variable in Children

Gerstner¹,

Teich²,

Bell³

et al. 2006

Epilepsia

108

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Summary:Purpose: Valproic acid (VPA) is an antiepileptic drug (AED) commonly used for generalized and focal epilepsies. The clinical relevance of coagulopathies, known as side effects of VPA therapy, especially thrombocytopenia, von Willebrand disease, and a decrease of factor XIII, is still unclear.Methods: In our institute, we noticed a high incidence of clinically relevant coagulation problems related to VPA in eight patients within 1 year only and a further seven children with significant coagulopathy were identified in the context of planned surgery. Results:We provide an overview of these patients and all six VPA-induced coagulopathies.Conclusions: At this time, it cannot be recommended to control all hemostatic parameters in every patient. Whenever an increased bleeding tendency is observed, or before surgical procedures, a platelet count, thrombelastography, prothrombin time, activated partial thromboplastin time, TT, fibrinogen, von Willibrand factor, and factor XIII should be examined. With 385 VPAtreated patients per year and 15 cases of coagulation disorders in this period, we estimate the incidence of coagulation disorders related to VPA in children to be nearly 4%.

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Section: Discussionmentioning

confidence: 99%

Valproate‐associated Coagulopathies Are Frequent and Variable in Children

Gerstner¹,

Teich²,

Bell³

et al. 2006

Epilepsia

108

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“…This should not be difficult since conditions that result in marked reduction in plasma fibrinogen, such as advanced liver disease and disseminated intravascular coagulation are clinically apparent. Patients treated with sodium valproate [39,40] and L-asparaginase [41] may develop moderate to severe hypofibrinogenemia. While dysfibrinogenemia may initially be confused with congenital afibrinogenemia, measurement of plasma fibrinogen by immunologic methods will distinguish the two disorders.…”

Section: Differential Diagnosismentioning

confidence: 99%

Congenital afibrinogenemia

Al‐Mondhiry

Ehmann

1994

American J Hematol

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Congenital afibrinogenemia is a rare disorder with unusual clinical manifestations. The disease is inherited as an autosomal recessive trait and consanguinity is common among affected families. Clinical manifestations range from minimal bleeding to catastrophic hemorrhage. Congenitally afibrinogenemic patients seem to be peculiarly susceptible to spontaneous rupture of the spleen. Coagulation tests which depend on clot formation as an end point may be infinitely prolonged and abnormalities of platelet function are usually present. The diagnosis is established by demonstrating trace or no immunoreactive fibrinogen. The disease is caused by markedly reduced or absent synthesis of fibrinogen by liver cells, but the genetic defect remains unknown. Bleeding episodes can be effectively treated with cryoprecipitate. Purified virally inactivated fibrinogen concentrates have been used in Europe and may soon be widely available.

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“…There are only a few reports about this observation. [24][25][26][27][28] The mechanism is still unknown. Some authors have noted a direct hepatotoxic effect that might have an influence on the synthesis of coagulation factors.…”

Section: Factor VIImentioning

confidence: 99%

Valproate-Associated Coagulopathies in Children During Short-Term Treatment

Köse¹,

Arhan²,

Unal³

et al. 2009

J Child Neurol

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Valproic acid is one of the most frequently prescribed antiepileptic drugs for the therapy of generalized and focal epilepsies. Valproate induces a variety of hemostatic disorders such as thrombocytopenia, abnormal platelet function, hypofibrinogenemia, and decreased concentrations of von Willebrand factor, and it rarely causes serious bleeding complications. It may also lead to atherosclerosis and thrombosis. However, there is still lack of knowledge about the incidence and occurrence of these particular side effects. In this prospective systematic study, we assessed the early effects of sodium valproate on both pro- and anticoagulatory factors, homocysteine, and lipoprotein (a) in 24 newly diagnosed epileptic children treated with valproate. Valproate causes decreased factor VII levels, platelet count, factor VIII, Protein C, fibrinogen, and increased lipoprotein (a) levels. To the best of our knowledge, our report is the first in the medical literature, which describes that valproate significantly reduces factor VII levels even during short-term therapy.

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Neonatal Afibrinogenaemia Due to Sodium Valproate

Cited by 32 publications

References 4 publications

Valproate‐associated Coagulopathies Are Frequent and Variable in Children

Valproate‐associated Coagulopathies Are Frequent and Variable in Children

Congenital afibrinogenemia

Valproate-Associated Coagulopathies in Children During Short-Term Treatment

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