THE INFLUENCE OF ISOTRETINOIN UPON FIBRINOLYSIS IN PATIENTS WITH ACNE

A patient with haemophilia A and acne was recently reported to have experienced increased bleeding during therapy with isotretinoin. (1)The aim of the present study was to investigate the influence of isotretinoin upon fibrinolysis, and more specifically upon tissue plasminogen activator (tPA) and tissue plasminogen activator inhibitor (PAI) levels, in haemostatically normal individuals. Thirteen patients with severe acne received a 4-month course of isotretinoin at a dose of 1 mg/kg per day. In all cases, the acne responded to therapy, and the patients did not show any evidence of unexpected bleeding or bruising throughout the study. Although all investigations remained within the normal range, tPA measurements rose significantly (P<0.001) after 3 months' therapy compared with pretreatment values. Retinoids have been shown to stimulate tPA production in vitro from human endothelial cells. (2) Our results confirm that this can be demonstrated in vivo. Prior to therapy with isotretinoin, when all patients had inflammatory acne, PAI measurements were elevated in 12 of 13 individuals. The mean measurement of PAI decreased from 98.38+/-63.30 ng/ml prior to treatment, to 24.63+/-15.2 ng/ml (P<0.01) in the eight patients who returned for blood tests 6 weeks after completing therapy. The decline in PAI levels appears to reflect the resolving cutaneous inflammation following treatment with isotretinoin, rather than a direct effect of isotretinoin on the synthesis or release of PAI. This study provides further evidence that tPA production is stimulated by isotretinoin, and that this, together with falling PAI levels, may accelerate fibrinolysis. There was no clinical evidence that haemostasis was impaired in these haematologically normal individuals, However, the influence of retinoids upon fibrinolysis in haemostatically compromised patients may be clinically relevant, and at the present time we would caution against the use of retinoids in patients with impaired haemostasis.