**2.2 Mechanisms of venous thrombosis in patients with chronic kidney disease**

The individual risk of venous thromboembolism varies as a result of a complex interaction between congenital and transient or permanent acquired risk factors.

Virchow summarized the pathophysiology of venous thromboembolism in his famous triad: venous stasis, endothelial damage and hypercoagulability (Ageno 2006 as cited in Virchow, 1856)

Stasis predisposes to venous thrombosis by reducing the clearance of activated coagulation factors, the mixing of this activated coagulation factors and inhibitors and the dilution of activated coagulation factors.

Vessel wall damage is more important in the pathogenesis of arterial thrombus. Venous endothelial damage results in endothelial cell detachment and exposure of blood to tissue factor and other subendothelial components that activate coagulation.

Hypercoagulable states could be in several situations: increase thrombin production following surgery or decrease activity of endogenous anticoagulants.

On the whole, venous thromboembolism probably has understood as a multicausal disease in which more than one genetic or environmental condition coincides to produce clinically apparent thrombosis (Rosendaal,1999).

#### **2.2.1 Procoagulant markers**

To elucidate the mechanisms that could increase the risk of venous thromboembolism in patients with chronic kidney diseases, some studies had investigated the levels of the procoagulant markers.

Patients with end stage renal disease and predialysis renal failures, nephrotic syndrome and mildly chronic kidney disease had elevated level of C Reactive Protein, fibrinogen, d-dimer, Factor VIII, Factor VII, and Von Willebrand, these high levels are due to increase synthesis out of proportion to urinary loss while lower levels of coagulation factors like IX, XI, and XII due to increased urinary loss (Keller, 2008; Vaziri, 1980). On the other hand, an association between increased levels of coagulation factors VIII, FIX and F XI and an increased risk of venous thromboembolism has been reported, the mechanisms and clinical significance of such association are still unclear (Crowther, 2003).
