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Fibrinolysis and inhibitors of coagulation in patients with subclinical renal failure undergoing chemotherapy for advanced cervical cancer

Paweł Derlatka1, Małgorzata Benke2, Mariusz Bidziński1

Affiliacja i adres do korespondencji
GIN ONKOL 2007, 5 (3), p. 159-177
Streszczenie

Background: Radiotherapy and chemotherapy increase the likelihood of development of thromboembolic complications. Activation of coagulation and inhibition of fibrinolysis may lead to formation of thrombi in microcirculation of several organs, compromising their function. Appearance of serum coagulation proteins in urine indicates a compromised renal function. Aims of the paper: 1) To assess changes of serum level of coagulation inhibitors and serum fibrinolytic activity in patients with renal failure undergoing treatment for advanced cervical cancer. 2) To develop methods of improving renal function in this clinical setting. Material and method: This was a prospective randomized study, including patients with a diagnosis of FIGO stage IIB-IIIB cervical cancer, with subclinical renal insufficiency. Treatment protocol consisted in radiotherapy (46-65 Gy; box technique), cisplatin (40 mg/m2 QW) in patients with normal serum creatinin level. Renal function was assessed using dynamic scintigraphy to determine glomerular filtration rate (GFR). Serum hemostatic system was assessed by determining levels of D-dimers, PAP, PAI-I, tPA, FDP and C protein. The same parameters were concomitantly assessed in urine. Only patients with GFR below normal range limit were included in the study. Lower limit of age-adjusted normal range was considered 100%. Half of the patients were irradiated without concomitant anticoagulant prophylaxis (group 1). The other half received a standard dose of nadroparin – 2850 IU aXa/0.3 ml. Results: The study revealed a decrease of GFR in the control and in the treatment group not receiving nadroparin. The treatment group receiving nadroparin experienced an increase of GFR. Significant differences were noticed in endpoints between the control group and the treatment group receiving nadroparin, as well as between treatment groups with and without nadroparin (p=0.0001). Lab tests of coagulation system revealed activation of fibrinolysis in patients receiving nadroparin and its further inhibition in the group without nadroparin. Similar alterations were noticed in urine. Conclusions: One of the causes of subclinical renal failure in patients with late-stage cervical cancer may be inhibition of fibrinolysis. Renal insufficiency deteriorates after termination of radiochemotherapy. Unfavorable alterations in the hemostatic system become more pronounced. Administration of low-molecular-weight heparins results in activation of fibrinolysis, unblocking of renal glomeruli and improvement of glomerular filtration.

Słowa kluczowe
fibrinolysis, coagulation inhibitors, cervical cancer, glomerular filtration rate, anticoagulation prophylaxis