Case Report: Von Willebrand Factor Abnormalities and Endothelial Cell Perturbation in a Patient with Acute Thrombotic Thrombocytopenic Purpura

Moake, Joel L.; Rudy, Christine K.; Troll, Joseph H.; Weinstein, Mark J.; Colannino, Noreen M.; Hong, Suchen L.; Koutcher, Jason A.; Melaragno, A J; Manner, Charles E.

doi:10.1097/00000441-198601000-00009

Cited by 26 publications

(17 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The lack of larger VWF multimers in patients with acute TTP was previously described in the frame of case reports and small case series [16][17][18][19]. In this study the observed correlation between the degree of defect of larger multimers of regular size and laboratory markers of TTP activity and severity suggests that the electrophoretic measurement of the ULVWF ratio is an index of disease activity and severity at presentation, at least in patients with ADAMTS-13 deficiency.…”

Section: Discussionsupporting

confidence: 67%

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

Lotta

Lombardi

Mariani

et al. 2011

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 67%

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

Lotta

Lombardi

Mariani

et al. 2011

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

show abstract

“…Protease deficiency leads to excessive binding of ULvWf to platelet glycoprotein Ib/IX/V and activated IIb/IIIa receptors leading to increased platelet aggregation [3]. Deficient protease activity has been demonstrated among patients with acute forms of TTP, relapsing TTP, and in the early stages of acute, non-relapsing TTP [5, 6, 7, 15, 16], resulting in high concentrations of ULvWf [4]. Furlan et al [7]described 6 patients with familial TTP with no protease activity.…”

Section: Discussionmentioning

confidence: 99%

<i>Mycoplasma-pneumoniae</i>-Induced Thrombotic Thrombocytopenic Purpura

Meir¹,

Amital²,

Levy³

et al. 2000

Acta Haematol

View full text Add to dashboard Cite

Thrombotic thrombocytopenic purpura (TTP) is a fatal disease characterized by widespread platelet aggregation, hemolytic anemia and fever with renal and neurological involvement. Different factors have been associated with the development of TTP, e.g. infections, pregnancy, chemotherapy, drug therapy and bone marrow transplantation. Recent data imply that all these different causes may induce the disease by decreasing the activity of the plasma von Willebrand factor-cleaving protease resulting in unusually large von Willbrand factor multimers that later on initiate the cascade of TTP. In this communication, we present a unique association between infection with Mycoplasma pneumoniae and TTP. We believe that the emergence of antibodies that cross-react with Mycoplasma and the protease might elucidate in this case the pathogenesis of TTP.

show abstract

“…This was followed by studies that established a role of ADAMTS13 in the processing of von Willebrand factor (VWF) multimers. Moake demonstrated that TTP was caused by abnormally high levels of ultralarge VWF multimers due to congenital or acquired reductions in ADAMTS13 activity (3,4). In 1998, Goodship confirmed a linkage of atypical HUS (aHUS) to the region on chromosome 1 that contained the genes for a number of complement regulatory proteins (5).…”

Section: Introductionmentioning

confidence: 99%