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PLASMA HYPERCOAGULABILITY AFTER IMMUNTHERAPY WITH REBOUND PHENOMENON AFTER DISCONTINUATION OF ORAL CORYNEBACTERIUM PARVUM. A.Baumgartner,J .Harenberg, ANTICOAGULANT THERAPY? J.Harenberg,R.Haas and D.Fritze and R.Zimmermann. Internal Medicine, Uni­ R,Zimmermann. Internal Medicine, University of versity of Heidelberg, GFR Heidelberg, GFR Toxic side effects after i.v. application of co- Duration and discontinuation of oral anticoagu­ rynebacterium (c.) parvum in the experimental lant therapy in the prophylaxis of recurrent immuntherapy of malignant disease are known. Since thrombembolic diseases is often discussed. After hypercoagulability is proven in cancer patients stopping of the therapy an elevated incidence of a controlled trial was carried out in 18 patients rethromboses are observed. Therefore we determined with metastatic breast cancer to investigate the fibrinopeptide A (FPA) as the most sensitive para­ influence of c. parvum i.v. on count, meter of activity in vivo in patients blood and . treated with phenprocoumon in order to get infor­ Patients were allocated randomly to one of the mation on the effectivity of the oral anticoagu­ three treatments: 1)0 .4mg c.parvum i.v. and cyto­ lant therapy and on the rebound phenomenon after static therapy (vincristine, adriblastin and en- discontinuation of the treatment. doxan),2) 0.4mg c.parvum i.v. and 0.9% saline in­ In 136 outpatients a significant relation bet­ fusion at day 15 of the cytostatic cycles and 3) ween FPA and the effectivity of the anticoagulant only cytostatic therapy. Parameters were con­ therapy was observed: 2.7 ng/ml plasma (mean, trolled before and 1, 2, 4, and 24 hrs after be­ thrombotest values<5%), 3.5 ng/ml (5%—15%) and ginning of therapy. Platelet count decreased in a 4.1 ng/ml (>15%, p<0.01). Normal FPA were 1.4ng/ rate of 15% within 4 hrs.in all groups. Factor ml. In 11 patients with low FPA the oral anticoa­ VIII, , , aPTT, throm­ gulants were discontinued. FPA was determined in bin clotting time, reptilase time, ethanol gela­ weekly intervalls. Within four weeks a continous tion test and AT III remained uneffected in all increase of FPA from 1.6 ng/ml (median) to 3.8 ng/ groups. Fibrinopeptide A (FPA) determined radio­ ml was observed. After eight weeks FPA was 8.2 ng/ immunological ly increased in group 1 from 1.1 to ml (p<0.05). The in vitro release of FPA after 18.6 ng/ml (median)two hrs after the application 10 min incubation of blood increased from 3.4ng/faL of c.parvum and in group 2 from 4.5 to 57.5 ng/ml to 72 ng/ml after eight weeks (p< 0.05, normal (p 0.05). Within 24 hrs FPA declined to the ini­ release up to 5 ng/ml). tial values. In group 3 no changes were measured. The data indicate the clinical relevance and the The euglobulinlysis time, plasminogen, a-1-anti­ different therapeutic implications of the deter­ trypsin and a- 2-macroglobulin were not influenced mination of FPA in patients treated with phenpro­ in all treatment groups. coumon. They further give the first criterion, The data indicate, that c.parvum i.v. enhances which outlines the effectivity of an oral anti­ or initates even in small doses plasma hypercoagu­ coagulation therapy by reducing the thrombin ac­ lability in patients with malignancy. This may tivity in vivo. They give some evidence for a contribute to development of thrombemblic compli­ rebound like phenomenon after discontinuation of cations in patients with increased risk factors. the oral anticoagulant treatment. This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

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