To determine the frequency and clinical relevance of acquired von Willebrand syndrome (aVWS) due to antiepileptic therapy by valproic acid, we investigated 50 consecutive children in three neuropediatric institutions. Coagulation factors were determined in local laboratories before and three times after starting therapy with valproic acid. Parameters of von Willebrand factor (VWF) were additionally investigated in a reference laboratory including multimeric analysis. Significant changes in the coagulation system were found concerning fibrinogen (decreased from 287 +/- 70 mg/dl to 222 +/- 67 mg/dl; p < 0.001) and platelet count. Changes of VWF parameters were also found but no patient developed laboratory defined aVWS. We conclude that the bleeding tendency observed in some children undergoing antiepileptic therapy with valproic acid is not due to aVWS.
6 Figures and Tables
Fig. 1 Age of investigated patients
Fig. 2 Parameters before and after start of valproic acid; mean, 25/75 quartile , standard deviation and range (boxplot) a) fibrinogen (mg/dl); b) VWF : Ag (%); c) VWF : CB/VWF : Ag ratio (%/%)
Fig. 3 Bleeding time (Ivy) in minutes before and after six months valproic acid (normal < 9,5 min)
Fig. 4 Change of VWF : Ag concentration (●) in percent of the individual start value (-), after one week (▲), three (■) and six months (×) ◆: absolute value (%); -: 100% of start value;
Fig. 5 Relationship between concentration of VWF : Ag and VWF : CB/ VWF : Ag ratio at start (●), after one week (▲), three months (■) and six months (×)
Fig. 6 Correlation of valproic acid (Vpa) serum concentration and VWF : Ag, r = 0,12, n.s.
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