Clot architecture is altered in patients with abdominal aortic aneurysm
MedWire News: Patients with abdominal aortic aneurysm (AAA) form denser, smaller-pored plasma clots that are more resistant to fibrinolysis than individuals without the condition, UK research shows.
Furthermore, these characteristics correlate with aneurysm size, report Robert Ariëns and colleagues from the University of Leeds.
The researchers explain that AAA is characterized by widening of the aorta, which can carry a 10% risk for death due to rupture if the aneurysm exceeds 5.5 cm in width.
Larger aneurysms are often distinguished by the presence of intraluminal thrombus.
In addition, patients with coronary artery disease have previously been shown to produce clots with increased number of shorter fibers, decreased permeability, and increased stiffness.
Based on the common role of thrombosis in cardiovascular disease and AAA, Ariëns and team investigated whether patients with AAA produce clots with altered structure, and whether clot structure is associated with aneurysm size.
The researchers collected plasma from 42 patients with large AAA (aortic diameter ≥5.5 cm), 40 patients with small AAA (3.0-5.4 cm), and 49 controls (<3.0 cm), and measured fibrin pore structure by permeation and clot lysis time with tissue plasminogen activator (tPA).
They report in the journal Arteriosclerosis, Thrombosis and Vascular Biology that fibrinogen, factor VII, and factor XIII levels did not differ significantly among the groups.
Thrombin-antithrombin - a marker of thrombin generation - was significantly higher among AAA patients than among controls, as were D-dimer levels. In contrast, AAA patients had a significantly lower endogenous thrombin potential than did controls.
Plasma clot pore area (Ks) decreased significantly with increasing aortic diameter; mean Ks was 4.7 x 10-9 in controls, compared with 4.0 x 10-9 and 3.4 x 10-9 in patients with small and large AAA, respectively.
"These results indicate that patients with AAA show a propensity to form clots with more densely packed fibers and smaller pores than controls and that this correlates with aneurysm size," Ariëns and co-authors remark.
To investigate whether differences in plasma clot structure influenced susceptibility to fibrinolysis, the team measured time to 50% lysis using turbidity with tPA.
They found that lysis times increased significantly with increasing aortic diameter, going from 1892 seconds in controls to 2101 and 2195 seconds in patients with small and large AAA, respectively.
Furthermore, when patients with cardiovascular disease were excluded, Ks was still significantly smaller, and lysis time significantly longer, in patients with AAA than in controls.
Of note, clots made from purified fibrinogen samples, rather than plasma, did not show any structural differences between AAA patients and controls.
Taken together with the thrombin-generation data, "these results suggest that the alterations in clot structure in AAA were not caused by changes in fibrinogen levels, thrombin generation, or modifications of the fibrinogen molecule itself but that they may be caused by another, unknown factor."
They add that their findings indicate that "clot structure may be involved in AAA development and progressive dilation of the aorta, however, prospective studies will be required to test this hypothesis further."
By Laura Dean