**2.2.4 Reduced fibrinolysis**

Pathophysiology and Clinical Aspects of 44 Venous Thromboembolism in Neonates, Renal Disease and Cancer Patients

patients were included, 33 with juvenile diabetes mellitus. The overall frequency of thrombosis was 24.1%, diabetes mellitus being a significant risk factor (Bergqvist, 1985). Epidemiological studies have attempted to define risk in terms of modifiable (drugs, dialysis modality, surgical procedure) and no modifiable (age, diabetes mellitus, vascular anomalies, factor or identify changes in coagulation or fibrinolysis) promoting a more thrombotic state. Most recently the evolution of thrombophilia research has established the potential for inherited hypercoagulability to predispose to acute allograft thrombosis. Inheritance of the factor V Leiden (FVL), prothrombin G20210A mutation, or the presence of antiphospholipid antibodies may increase the risk of renal allograft thrombosis certain 3 fold in selected patients. Patients with end-stage renal disease due to systemic lupus erythematosus appear at particularly high risk of thrombosis, especially if they have either

antiphospholipid antibodies or detectable β2-glycoprotein-1. (Irish, 2004).

between congenital and transient or permanent acquired risk factors.

factor and other subendothelial components that activate coagulation.

following surgery or decrease activity of endogenous anticoagulants.

1856)

activated coagulation factors.

apparent thrombosis (Rosendaal,1999).

such association are still unclear (Crowther, 2003).

**2.2.1 Procoagulant markers** 

procoagulant markers.

**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

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

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

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

Hypercoagulable states could be in several situations: increase thrombin production

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

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

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 Fibrin cloths with reduced permeability, increased clot stiffness and reduced fibrinolysis susceptibility may predispose to thrombosis. Using permeability and turbidity studies in 22 end stage renal disease patients and 24 healthy controls. Fibrin clots made from plasma of patients with chronic renal disease were found to be less permeable, less compactable and less susceptible to fibrinolysis than clots from controls (Siǿland, 2007).

Another study in 33 patiens in long term haemodialysis has demonstrated unfavorably altered clot properties that may be associated with increase cardiovascular mortality (Unaas, 2008) There are studies that demonstrates that individuals with reduced fibrinolytic potential as measured by plasma based assays , have an increased risk of developing a first venous thrombosis. Whether this hypofibrinolytic state determined by genetic or adquired factors or a combination of them and which proteins are evolved is at present unknow (Lisman, 2005).

In conclusion, chronic kidney disease patients presents a pro-thrombotic state that increases the risk of venous thromboembolism and comprises alteration of platelet functions, coagulation factors, endogenous anticoagulants and fibrinolytic system, many mechanism are still unknown and opens a potential field for investigation.
