High von Willebrand factor concentration compensates a relative adhesion defect in uremic blood

Abstract

Uremia is associated with a bleeding diathesis. We investigated platelet adhesion as a cause for the impaired primary hemostasis and the role of von Willebrand factor (vWF) in this process in uremic patients. Perfusions with blood with standardized hematocrit, platelet count, and free Ca2+ ions were performed over inverted and deendothelialized artery segments from human umbilical cords in a modified Baumgartner perfusion chamber. Platelet adhesion in patient perfusates was comparable with control adhesion. However, the high vWF levels present in uremic whole blood did not increase adhesion above the adhesion in control blood with lower vWF levels. These results suggested that a relative adhesion defect was present in patient blood. Control blood in which vWF levels were raised to uremic levels showed the high adhesion that uremic whole blood failed to show. Additionally, in perfusions with uremic plasma in which the initially high vWF level was normalized by dilution with vWF-depleted uremic plasma, adhesion was clearly lower than in normal plasma. Washed patient platelets did not differ from normal platelets in their association with purified vWF, via their adhesion receptors glycoprotein Ib and IIb-IIIa. Patient platelets present in patient plasma showed a similar adhesion defect as control platelets, which were resuspended in the uremic plasma. Therefore, primary defects of uremic platelets were of minor importance for the observed adhesion defect in uremic whole blood. The adhesion defect was not dependent on the presence of uremic vWF; plasma of uremic patients depleted of vWF also inhibited adhesion, and the defect remained present when purified control vWF was added to vWF-depleted uremic plasma. The binding of uremic vWF to the vessel wall and its support of subsequent adhesion were not impaired. These results indicate that the observed adhesion defect was not due to abnormal vWF. Our current results suggest an unknown component present in uremic plasma that directly inhibits platelet interaction with artery segments; however, it has no effect on vWF binding to the vessel wall. High vWF levels in uremic plasma are able to compensate for the defect.

Pathophysiological Changes in the Hemostatic System and Antithrombotic Management in Kidney Transplant Recipients

“…Anemia, which is frequent in ESKD patients, increases the risk of bleeding because of diminished platelet function caused by reduced vessel–wall interaction (as a result of a decreased number of erythrocytes pushing platelets towards the vessel wall), an impaired release of ADP stimulated by erythrocytes, and less scavenging of NO by hemoglobin. 3 , 16 Higher VWF levels in uremic patients compensate the relative adhesion defect to some extent, 17 but altogether, these interactions result in thrombocytopathy and a subsequently impaired primary hemostasis. Additionally, it is important to note that, on top of these changes in platelet function, many ESKD patients experience volume overload associated with hypertension and cardiovascular disease and use antiplatelet therapy indicated for their primary disease or other (cardiovascular) comorbidities, which increase the risk of bleeding.…”