Thrombophilia in tumor patients D68.5

Paraneoplastic syndromes are diseases that occur in the wake of tumor diseases and are indirectly related to the tumor. They often involve inadequate expression of hormones, cytokines or immune disorders, which are caused by the tumor and cause corresponding disorders. A large part of the paraneoplastic effects affect the coagulation system. Autopsies revealed thromboses in 50% of tumour patients. In up to 15% of patients with deep vein thrombosis a malignancy develops.

In hematological systemic diseases, thrombopenia is frequently present, e.g. due to maturation disorders or bone marrow aplasia. In the case of promyelocytic leukemia, consumption coagulopathies frequently occur.
The reasons for the increased incidence of thrombosis in tumours are caused by the production and increased release of procoagulant substances, in particular tissue factor and a factor X activator specially synthesised by the tumour, Cancer-Pro-Coagulant-A. Furthermore, an increase in the plasminogen activator inhibitor, an increase in fibrinogen and factor VIII and thrombocytosis have been described. A further cause of thrombophilia is an increased thrombocyte activation.

The extrinsic system is mainly activated by extravascular tissue thromboplastin located in the tumor tissue. In addition, there is a permeability factor produced by the tumour, which enables the extra- and intravasal factors to be combined. Elevated concentrations of fibrin and secondary fibrinolysis markers, such as D-dimers and PAI-1, can be detected in the serum of tumors. These parameters normalize in response to therapy.

In acute-phase reactions in non-specific defense and wound healing processes, cytokines such as IL-1 are used to synthesize not only plasma proteins but also increased fibrinogen and the plasminogen activator PAI-1. Furthermore, e.g. the compression of veins by tumours must be considered a risk factor for thrombosis. Postoperatively, tumor patients should undergo a thrombosis prophylase with low-molecular heparin for at least four weeks.
The value of a long-term prophylactic administration of heparins is not certain, but it may be beneficial for patients with a good prognosis. In particular, the effect of warfarin and low-molecular-weight heparin on the endothelial growth factor, the modulation of TFPI and the influence on matrix enzymes justify large clinical studies.

It has been known since the 19th century that thrombosis and thromboembolism can also occur in the context of tumour diseases. This connection was first clinically described by Armand Trousseau.

1. HA Neumann (2014) The coagulation system. ABW-Wissenschaftsverlag GmbH Berlin S. 233ff.