gms | German Medical Science

Objective: Patients with malignant neoplasias often suffer from thromboembolic events that complicate the course of cancer disease and reduce the patients’ quality of life or shorten the survival time.

Methods: Twenty tumor samples of intracerebral metastases of clear-cell renal cell carcinomas, small cell carcinomas of the lung and malignant melanomas were investigated immunohistochemically for the expression of the coagulation factors II/IIa and X/Xa as well as for the expression of the protease-activated receptors type 1, 2, 3, and 4. In addition, 116 patients with intracranial tumors were prospectively included in a case-controlled study and correlated to 116 control patients with lumbar disc herniations. Their blood was collected one day before and one and four days after the cranial metastasis surgery and investigated for the activity of the coagulation factors II, V, VII, VIII, IX, X, XI, XII, and XIII as well as for the activity of antithrombin III, and the concentrations of the d-dimers and of fibrinogen.

Results: Here, we show that even patients without active peripheral tumor disease, but with symptomatic brain metastasis develop a systemic activation of multiple coagulation factors. The pro-coagulatory state is expressed preoperatively, but can also be observed in the early postoperative period. The activity of antithrombin III is enhanced in patients with brain metastases, whereas the concentrations of fibrinogen or d-dimers do not significantly differ from the control group. In addition, intracerebral metastases of clear-cell renal cell carcinomas, small cell carcinomas of the lung, and malignant melanomas express prothrombin, thrombin, the coagulation factor X, and the protease-activated receptors type 1, 2, 3, and 4.

Conclusions: This study shows for the first time that human brain metastases express coagulation factors and their receptors and patients with intracerebral brain metastases demonstrate a systemic activation of the coagulation system.