[Three cases of hypofibrinogenemia induced by chemotherapy with a combination of synthetic ACTH and valproic acid].

Chemotherapy with a combination of synthetic ACTH (ACTH-Zn) and valproic acid (VPA) induced remarkable hypofibrinogenemia in three children (5 months, 8 months, and 5 years and 10 months old) with intractable epilepsy. The lowest blood fibrinogen (Fbg) levels by this combination therapy were 22, 51 and 64 mg/dl (mean 45.7 mg/dl), respectively. These levels occurred, when ACTH-Zn was administered at an average dose of 0.33 mg/day (0.03 mg/kg/day) and the mean blood concentration of VPA was 59.7 micrograms/ml. With the administration of VPA without ACTH-Zn, the lowest blood Fbg levels were 232, 108 and 170 mg/dl (mean 170 mg/dl), respectively. The mean blood concentration of VPA was 109.0 micrograms/ml. The inadvertent-effects associated with this combination therapy consisted of thrombocytopenia (59,000/microliters) in one case and a mild GPT increase (65-109 IU/l) in three cases. However, all these changes were transient. No bleeding tendency was detected clinically, when this hypo-Fbg-emia appeared. The concentration of VPA and the blood level of Fbg were found inversely correlated with a correlation coefficient of -0.22 (p < 0.01) in 150 serum samples from 91 patients with childhood epilepsy treated with VPA without ACTH-Zn. In the three cases presented, the combination with ACTH-Zn resulted in considerably lower blood Fbg levels than those predicted from the blood VPA concentrations. This indicates that the combination of ACTH-Zn and VPA induces a further decrease of Fbg in blood. The reason why hypo-Fbg-emia results from this combination therapy is unknown.(ABSTRACT TRUNCATED AT 250 WORDS)