Plasma Hypercoagulability After Immuntherapy With Corynebacterium Parvum

Toxic side effects after i.v. application of co- rynebacterium (c.) parvum in the experimental immuntherapy of malignant disease are known. Since hypercoagulability is proven in cancer patients a controlled trial was carried out in 18 patients with metastatic breast cancer to investigate the influence of c. parvum i.v. on platelet count, blood coagulation and fibrinolysis.

Patients were allocated randomly to one of the three treatments:1)0.4mg c.parvum i.v. and cytostatic therapy (vincristine, adriblastin and en- doxan), 2) 0.4mg c.parvum i.v. and 0.9% saline infusion at day 15 of the cytostatic cycles and 3) only cytostatic therapy. Parameters were controlled before and 1, 2, 4, and 24 hrs after beginning of therapy. Platelet count decreased in a rate of 15% within 4 hrs.in all groups. Factor VIII, fibrinogen, prothrombin time, aPTT, thrombin clotting time, reptilase time, ethanol gelation test and AT III remained uneffected in all groups. Fibrinopeptide A (FPA) determined radioimmunological ly increased in group 1 from 1.1 to 18.6 ng/ml (median)two hrs after the application of c.parvum and in group 2 from 4.5 to 57.5 ng/ml (p 0.05). Within 24 hrs FPA declined to the initial values. In group 3 no changes were measured. The euglobulinlysis time, plasminogen, α-1-antitrypsin and α-2-macroglobulin were not influenced in all treatment groups.

The data indicate, that c.parvum i.v. enhances or initates even in small doses plasma hypercoagulability in patients with malignancy. This may contribute to development of thrombemblic complications in patients with increased risk factors.