Platelet reactive conformation and multimeric pattern of von Willebrand factor in acquired thrombotic thrombocytopenic purpura during acute disease and remission

Abstract

Summary. Background: Binding of von Willebrand factor (VWF) multimers of ultra‐large size to platelets is considered the triggering mechanism of microvascular thrombosis in thrombotic thrombocytopenic purpura (TTP). Objective: To assess the potential of VWF‐related measurements as markers of disease activity and severity in TTP. Methods: VWF antigen (VWF:Ag), platelet glycoprotein‐Ib‐α binding‐conformation (GPIb‐α/BC) and multimeric pattern were investigated in 74 patients with acquired TTP during acute disease, remission or both and 73 healthy controls. In patients with both acute and remission samples available, VWF ristocetin co‐factor activity (VWF:RCo) and collagen binding (VWF:CB) were also measured. The relationships of study measurements with the presence of acute disease and remission and with markers of disease severity were assessed. Results: VWF:Ag and VWF‐GPIb‐α/BC were higher in TTP patients than controls (P < 0.001 and 0.004). However, there was no statistically significant difference in VWF‐GPIb‐α/BC between samples obtained during acute TTP and remission. Larger VWF multimers were frequently lacking in acute TTP patients, who displayed ultra‐large multimers at remission. The degree of loss of larger VWF multimers correlated with the degree of abnormality of hemoglobin, platelet counts and serum lactate dehydrogenase (LDH) and was associated with low levels of both VWF:RCo/Ag and VWF:CB/Ag ratios. Conclusions: In TTP the platelet‐binding conformation of VWF is not exclusively present in acute disease, nor is it associated with its clinical and laboratory severity. The loss of larger VWF multimers, accompanied by low VWF:RCo/Ag and VWF:CB/Ag ratio values, represents an index of disease activity and severity of acute TTP in patients with severe ADAMTS‐13 deficiency.

Biomarkers of terminal complement activation confirm the diagnosis of aHUS and differentiate aHUS from TTP

“…13,14 Additionally, our data confirm previous work that ULVWF multimers are not abnormally accumulated in all cases of acquired TTP at the time of acute presentation. 13 Conceivably, an early presentation of disease may exhibit the accumulation of ULVWF in the blood, whereas a fulminant TTP case may not demonstrate the presence of ULVWF multimers because of consumption related to the development of extensive platelet thromboses. Future studies using a larger TTP cohort with longitudinal sampling may allow for a more detailed study of the relationship between severity of ULVWF accumulation, laboratory data, and clinical outcome, in the context of the measured ADAMTS13 activity.…”

Prevalence of Disease and Relationships between Laboratory Phenotype and Bleeding Severity in Platelet Primary Secretion Defects

“…A copy of the questionnaire used to compile BSS is in Table S1. Patients also undergo blood collection for first level diagnostic tests, which include complete blood count, measurement of prothrombin time, activated thromboplastin time, von Willebrand factor (VWF) antigen, and VWF ristocetin cofactor activity [14]. Patient with elevated BSS (i.e.…”

ADAMTS‐13 activity and autoantibodies classes and subclasses as prognostic predictors in acquired thrombotic thrombocytopenic purpura

“…Patients were classified as in remission when they became free of symptoms and had normal laboratory values (except for ADAMTS‐13 levels) for at least 30 days from the conclusion of plasma therapy [22]. Acute episode severity was assessed in terms of platelet counts and the number of plasma exchanges required to achieve remission based on previous studies [38] and in light of the observation that lower platelet counts are associated with consumption of VWF multimers in acute TTP [39]. This would also facilitate comparison with previous studies evaluating the prognostic values of ADAMTS‐13‐related biomarkers [36].…”