Presentation Details
The Role of Fibrinogen in Changing the Hemostasis of Patients with Neoplasia and Their Influence on the Microcirculatory Bed of the Lungs and Control by Anticoagulants

Vira A.Barilka, Volodymyr L.Matlan, Sofia V.Prymak, Olha O.Shalay, Vasyl L.Novak.

SI "Institute of Blood Pathology and Transfusion Medicine of NAMS of Ukraine" Lviv Ukraine, Lviv, Ukrenia

Abstract


Introduction: Fibrinogen (Fib) is the first coagulation factor with a half-life of 4-5 days in peripheral blood, an important indicator for the assessment of hemostasis and inflammation. Proinflammatory cytokine tumor necrosis factor (TNF), antiinflammatory transforming growth factor beta 1 (TGFβ1), which are secreted by the tumor can stimulate the synthesis of procoagulants and fibrinogen. Elevated Fib are life-threatening in oncohematological patients (pts) due to thrombosis within 1-12 days after surgical removal of tumors without the use of low molecular weight heparin (LMWH). The LMWH pharmacokinetics determined by indicators of anti-Xa-factor activity of plasma, which is not always available, and the efficacy of treatment with LMWH is insufficiently studied. The aim of this study was to evaluate the Fib level in plasma of 81 patients (pts) with uterine, cervical, ovarian, lung cancer and non- Hodgkin's lymphoma (NHL) before and after surgical removal/treatment and to select the doses of LMWH to prevent thrombosis. Methods: The hemostatic parametrs were investigated in tumors outflowing blood, peripheral arterial and venous citrate blood by the hemostatic methods. TNF and TGFβ1 were detected by biological methods. The mediana age 52 (range 40 - 68 years). Pts had no signs of thrombosis at the time of examination. The median Fib before surgery - 6.4 mg / ml (range 5.69 - 13.02 ), after surgery - 8.4 mg / ml (range 4.1 - 14.97). Fib content was determined on the 3rd day before treatment and up to 10 days after surgery/treatment. The use of LMWH was performed according to the level of Fib. Results: We administered LMWH subcutaneously once a day in 10,000 anti-Xa IU / ml in the preoperative period when Fib was ≥ 5.0 to 7,8 mg/ml. In cases of Fib ≥ 7,8  mg / ml used LMWH 2 times a day in the concentration above. In the postoperative period (Fib ≥ 5.0 to 7.8 mg / ml) we used subcutaneous administration of LMWH once a day at a dose of 10,000 anti-Xa IU / ml for 3 days, followed by pentoxifylline, aspirin for 60 days. If the level of Fib exceeded 8 mg / ml (in 40.5% of pts) in the postoperative period we used LMWH two times a day at a dose  10,000 anti-Xa IU / ml for 3 to 10 days, for the reduction of Fib. A significant decrease in TNF, TGFβ1 in plasma was observed in pts on the 10-th day after treatment with LMWH (p˂0, 005; in both cases) . However, the level of TNF, TGFβ1  in pts plasma was significantly higher before and after treatment than in healthy individuals. Conclusions: The determination of Fib and the use of LMWH according to the level of Fib allows to avoid mortality in the postoperative period and after the first  line treatments of NHL. The cytokines from the tumors microenvironment determine the high procoagulant activity of the blood flowing from the tumor. 

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