Abnormal VIII: von Willebrand factor patterns in the plasma of patients with the hemolytic-uremic syndrome

Abstract

Plasma VIII:von Willebrand factor antigen (VIII:vWF) levels were elevated approximately two- to eightfold in seven patients (three adults and four children) during acute episodes of thrombocytopenia, renal failure, and hemolytic anemia (the hemolytic-uremic syndrome, HUS). In all seven patients, there was an alteration in plasma VIII:vWF patterns during these acute HUS episodes, so that the largest VIII:vWF forms were relatively decreased. Plasma VIII:vWF multimer patterns returned to normal, or nearly to normal, as platelet counts returned to preexisting levels, even in the patients whose recovery of renal function was incomplete and whose plasma VIII:vWF antigen level remained above normal. The sister of one of the HUS patients had a similar clinical prodrome (gastroenteritis) that was not followed by thrombocytopenia or renal failure and was not accompanied by an elevated level or abnormal forms of plasma VIII:vWF. These results suggest that an alteration in VIII:vWF metabolism, distribution, or interaction with platelets is associated with acute HUS episodes. In contrast to patients with chronic relapsing thrombotic thrombocytopenic purpura, none of the HUS patients (either during or after the acute HUS episodes) had a defect in the conversion of unusually large VIII:vWF multimers derived from endothelial cells to the VIII:vWF forms found in normal plasma.

Predicting response to plasma exchange in patients with thrombotic thrombocytopenic purpura with measurement of vWF‐cleaving protease activity

“…Moake et al 7,29 and Charba et al 30 attributed enhanced intravascular platelet clumping at the site of high fluid shear stress in the microvasculature to the presence of UL-vWFMs; they believe that this phenomenon may play an important role in the pathogenesis of TTP. Systemic endothelial cell injury may lead to an excessive release of UL-vWFMs from endothelial cells.…”

Investigation of plasma von Willebrand factor and circulating platelet aggregating activity in mitomycin C‐related hemolytic‐uremic syndrome

“…Results arising from ristocetin-induced binding to formaldehyde-fixed platelets suggest that there was no increased affinity of the patients' circulating vWF for the platelet membrane glycoprotein Ib. The loss of highest molecular weight multimers found by others [8,16] possibly reflects their peripheric consumption by a previously triggered platelet activation [ 171. The absence of such multimers might be, therefore, an effect rather than a cause in the mechanism of this platelet aggregation in the small vessels.…”

Inflammatory mediators promote strong sickle cell adherence to endothelium under venular flow conditions

“…Washed sickle erythrocytes were suspended in endothelial cell supernatant containing unusually large von Willebrand factor (ULvWF) multimers to promote adherence via ULvWF [12]. Supernatants tested positive for vWF multimers with antigen levels varying from 2.5 to 18.3 U/dl and unusually large multimers were detected using agarose gel electrophoresis [12,35]. Adherence does not vary with vWF concentration within this range [12].…”