Factor XIII Deficiency Associated with Valproate Treatment

Abstract

Summary:Purpose: We present two children who developed a deficiency of factor XIII with valproate (VPA) treatment. This coagulation disorder has not been described in association with VPA treatment in children, and only very recently in one adult patient.Results: Both patients showed recurrent epistaxis as major clinical sign of a combination of decreased coagulation parameters (factor XIII deficiency with thrombocytopenia and decreased von Willebrand factor, respectively). A few days after reduction or withdrawal of VPA treatment, clinical symptoms disappeared, and laboratory findings were within normal range. Conclusions:VPA is known to influence the synthetic function of the liver and the number and function of megakaryocytes. Therefore an alteration of the factor XIII level by VPA is conceivable. Our case reports suggest that bleeding symptoms during VPA treatment may be caused or aggravated by a decreased factor XIII activity. A determination of factor XIII activity should be considered before surgical procedures during VPA treatment to minimize the risk of (severe) postsurgical bleeding complications.

Association of perioperative factor XIII activity levels and other haemostatic markers with the risk of postoperative intracranial haematoma in a selected cohort of neurosurgical patients

“…Gerlach et al [3] found the relative risk of developing a postoperative haematoma in neurosurgical patients with postoperative factor XIII activity under 60%. Another study by Teich et al [12], found that factor XIII activity of below 70% was associated with severe haemorrhage for epilepsy surgery.…”

Valproic acid-induced pancreatitis: 16 new cases and a review of the literature

“…We asked that severe side effects such as hepatopathy, pancreatitis, encephalopathy, and coagulation disorders, [4][5][6] and also minor side effects such as weight gain, fatigue, change in hair color, and hair loss, be reported. We tried to obtain the fi les of anonymous patients to analyze the clinical details whenever possible.…”

“…3 Most of the side effects are mild and transient. However, more serious adverse reactions can occur, such as hepatotoxicity, 4 hyperammonemic encephalopathy, 5 coagulation disorders, 6 and pancreatitis.…”

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

“…VPA has been reported to induce thrombocytopenia, abnormal platelet function, hypofibrinogemia, von Willebrandlike disorders, and a decrease in vitamin K-dependent factors [74][75][76]. Teich et al reported a case of two patients who developed spontaneous bleeding while being treated with VPA.…”

“…Teich et al reported a case of two patients who developed spontaneous bleeding while being treated with VPA. Laboratory findings attributed the coagulopathy to factor XIII deficiency which returned to baseline upon discontinuation of the drug [74]. Although this side effect has been known for approximately 30 years, there have been several disagreements with regards to the clinical relevance of VPA-associated changes in coagulation.…”