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VWF High-Molecular-Weight Multimer Deficiency Associated With Neurological Symptoms in TTP


Loss of von Willebrand factor (VWF) high-molecular-weight multimers (HMWM) in patients with acquired thrombotic thrombocytopenic purpura (TTP) may be associated with neurological symptoms and anti-ADAMTS13 immunoglobulin (Ig) G, according to results published in Thrombosis Research.

TTP is characterized by a deficiency in ADAMTS13, a protease that cleaves VWF. This deficiency leads to accumulation of VWF multimers, including VWF-HMWM; however, the amount of VWF-HMWM present in a patient’s plasma can vary widely. Researchers sought to assess whether VWF-HMWM levels were associated with morbidity in patients with acquired TTP.

The study included 114 patients with acquired TTP with varying VWF-HMWM levels and 9 control patients with hereditary TTP in remission who demonstrated a constant excess of VWF-HMWM. Both VWF-HMWM and VWF collagen binding activity (VWF:CB) were measured. The researchers set a cutoff VWF-HMWM value of 37.3 IU/dL based on multimeric analysis performed on normal pooled plasma. The cutoff value for VWF:CB was 70 IU/dL.

Median VWF-HMWM level in patients with acquired TTP was 36.9 IU/dL, and 50% of the cohort had VWF-HMWM levels below the cutoff. Median VWF-HMWM level in patients with hereditary TTP was 57.4 IU/dL. Median VWF:CB level was 74 IU/dL in the acquired TTP cohort and 116 IU/dL in the hereditary TTP cohort; 47.4% of patients with acquired TTP had VWF:CB levels below the cutoff.

More than half (59.6%) of patients experienced neurological symptoms, with 10.0% of patients experiencing more than 1 symptom. Symptoms included headache (33.9%), confusion (20.2%), focal deficiency (7.3%), coma (6.4%), and seizure (1.8%).

Patients with lower VWF:CB demonstrated increased neurological impairment (P <.05), with 70.6% of patients with VWF:CB less than 70 IU/dL and 50% of patients with VWF:CB greater than 70 IU/dL exhibiting neurological symptoms. Lower VWF:CB was additionally associated with deeper thrombocytopenia and anti-ADAMTS13 IgG positivity (P <.05 for both).

Low VWF-HMWM levels were also associated with neurological abnormalities (P <.05); 70.5% of patients with VWF-HMWM below 37.3 IU/dL had neurological symptoms compared with 50% of patients with VWF-HMWM above 37.3 IU/dL.

VWF-HMWM and VWF:CB showed a statistically significant linear correlation (r2 = .5979; P <.0001), suggesting the 2 measures overlap.

The researchers noted that assessing VWF-HMWM levels may not be a useful diagnostic or prognostic tool. However, they reported, “VWF:CB is indeed a good reflect of the multimeric distribution of VWF and…could replace satisfactorily the latter reference method” because it is easier to measure.


1. Béranger N, Benghezal S, Savigny S, et al. Loss of von Willebrand factor high-molecular-weight multimers at acute phase is associated with detectable anti-ADAMTS13 IgG and neurological symptoms in acquired thrombotic thrombocytopenia purpura [published online July 16, 2019]. Thromb Res. doi:10.1016/j.thromres.2019.07.012

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