The Link between Venous Thrombosis and Arterial Thrombosis

Historically two different types of thrombosis are distinguished that seem to share little: venous and arterial thrombosis. Large case-control and cohort studies of patients with a first thrombotic event showed that the risk for venous thrombosis is primarily determined by the capacity of the blood coagulation system to generate thrombin and by conditions that impair blood flow in the extremities, whereas arterial thrombotic risk is increased when the arterial vessel wall is atherosclerotic and inflamed. From a mechanistic point of view, venous thrombotic risk is determined by flexible combinations of acquired and genetic risk factors. The acquired risk factors are manifold and notable examples include surgery, prolonged bed rest, plaster casts, cancer, and oral contraceptives. Genetic risk factors are also manifold and notable examples either impair the anticoagulant potential of blood (protein C, protein S, or anti-thrombin deficiency) or enhance the procoagulant potential (ABO-blood group, factor V Leiden, factor II G20210A). Arterial thrombotic risk factors are either acquired or lifestyle related such as high blood pressure, smoking, unfavorable lipid profile et cetera. Genetic risk factors are mainly involved in lipid metabolism.
This perceived difference in arterial and venous thrombosis is also reflected in the recommended treatments. Vascular health is best maintained by an adjusted life style, lowering blood pressure, and correcting hyperlipidemia by statin therapy, whereas the thrombotic risk is lowered by anticoagulant treatment with platelet inhibitors, heparin or oral anticoagulants.

New data, however, suggest that the view that processes underlying the development of arterial and venous thrombosis are fully unrelated is incorrect. Increasing evidence indicates that inflammation does also play a role in the development of venous thrombosis, while arterial thrombosis is influenced by the state of the coagulation system.

Clinical and mechanistic data that undermine the traditional view are amongst others:
1. Patients with unprovoked thrombosis have a much higher recurrence risk than those with a provoked. Reasons for this should be found outside of the classical risk factors known within the venous system.
2. Patients with venous thrombosis have a 2- to 3-fold increased risk of arterial thrombosis in the first year of treatment with anticoagulants for unknown reasons.
3. Venous thrombotic recurrence is related to changes in lipid (HDL) metabolism.
4. Blood coagulation components have specific functions in atherosclerotic lesion progression.
5. Statin treatment may be effective in the prevention of (recurrent) venous thrombosis through effects on blood coagulation, endothelial function, and inflammatory processes.
6. Recent animal studies suggest a more complex cause of venous thrombosis. Besides individual concentrations of pro- and anticoagulant proteins, stasis and low oxygen tension-induced activation of the endothelium, activation of innate and acquired immunity (involving recruitment of (inflammatory) monocytes and neutrophils at the activated endothelium), and activation of blood platelets, all claim a role. The interaction between inflammatory cells and activated vessel wall thus determines both venous and arterial thrombotic risk.

Taken together, the findings point towards an intricate relationship between venous and arterial thrombosis.

The objective of this research line is to uncover mechanisms that control the relationship between venous thromboembolism (VTE), recurrent VTE, and arterial thrombosis. Hereto, the groups of Dr. Bart van Vlijmen (LUMC), with expertise on coagulation and venous thrombosis and Dr. Miranda van Eck (LACDR), with expertise in arterial wall inflammation, platelet function and atherosclerosis will join forces and bring together their unique expertise areas.
Together, Van Vlijmen and Van Eck aim at exploring 1. the role of inflammatory cells in the link between venous thrombosis and arterial thrombosis. 2. Determine the effect of anticoagulation on vascular function and susceptibility for thrombosis. 3. Study the thromboprotective effect of HDL both in venous and arterial system.
These studies will uncover mechanisms that control the relationship between VTE and arterial thrombosis, and will form the starting point for innovative treatment options that may lie outside traditional antithrombotic therapy.