The role of drugs, particularly oral contraceptives, in triggering thrombosis in congenital defects of coagulation inhibitors: a study of six patients.

ABSTRACT

It is well established that pregnancy and puerperium, surgery and trauma may often trigger thrombotic events even in the normal population. On the other hand, patients with congenital deficiency of clotting inhibitors may develop spontaneous thrombotic episodes, although they become often symptomatic when one of the above-mentioned triggering factors is present. We found this to be true in 40 out of 81 symptomatic patients with congenital defects of coagulation inhibitors. In six (15%) of these cases medications (mainly oral contraceptives) triggered the thrombotic event. The incidence of pharmacological factors as a cause of thrombosis is commonly maintained to be low. This study indicates that this is not so and underlines the potential importance of drugs, particularly oral contraceptives, in the pathogenesis of thrombotic events in patients with congenital defects of clotting inhibitors.

ABSTRACT

PIP 6 patients with deep vein thrombosis triggered by drug therapy, that is oral contraceptives in 5 and the anticonvulsant tranexamic acid in 1, are described. These cases were among 40 symptomatic patients out of a total group of 81 with congenital coagulation inhibitor defects studied over 10 years at the Institute of Medical Semiotics, Padua, Italy. The 5 women with deep vein thrombosis ranged in age from 20-34, and had typically taken oral contraceptives containing 35 mcg ethinyl estradiol in combined or phasic preparations, for 1 to 8 cycles. One women, however, had been prescribed sequential pills containing 50 mcg mestranol. Another had taken oral contraceptives with impunity for 3 years, but developed deep vein thrombosis after taking tranexamic acid for 10 days. All recovered after heparin or oral anticoagulant therapy, except a 21 year old whose condition evolved into complete ileo-caval obstruction up to the renal veins, and was treated with urokinase. the congenital defects involved were 3 probable heterozygous true deficiencies of antithrombin III (low ATIII antigen and activity); a decreased protein C antigen to factor X antigen ratio; a heparin cofactor II deficiency; and a type I protein S deficiency (low free protein S, with normal total protein S and normal levels of C4B-bp.) While 5 of these 6 women had family histories of thromboembolic disease, the drug was prescribed without knowing that they were heterozygous for a coagulation inhibitor deficiency. The incidence of drug-induced thromboembolism was low in this series overall, where most of the events were triggered by surgery or trauma.