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In patients with acquired autoimmune thrombotic thrombocytopenic purpura, elevated plasma levels of human neutrophil proteins 1-3 inhibit proteolytic cleavage of von Willebrand factor by ADAMTS13, Vikram G. Pillai, PhD, of the University of Alabama at Birmingham, and colleagues reported.
The finding may explain how inflammation triggers microvascular thrombosis in these patients and potentially others with immune thrombotic disorders, according to the researchers (Blood 2016;128:110-9).
They performed enzyme-linked immunosorbent assays and found markedly increased levels of plasma human neutrophil proteins (HNPs) 1-3 in most of the patients with acquired autoimmune thrombotic thrombocytopenic purpura (TTP). The median levels in the 19 patients were 170 ng/mL, compared with 23 ng/mL in 18 healthy controls, a statistically significant difference (P less than .0001).
Liquid chromatography plus tandem mass spectrometry similarly confirmed statistically significant increases in HNP1, HNP2, and HNP3 in patient samples (P less than .001).
Measures of HNPs 1-3 by both methods correlated well, and the researchers concluded that HNPs 1-3 likely inhibit ADAMTS13 activity by binding to the central A2 domain of von Willebrand factor and physically blocking ADAMTS13 binding.
The researchers had no relevant financial disclosures.
On Twitter @maryjodales
In patients with acquired autoimmune thrombotic thrombocytopenic purpura, elevated plasma levels of human neutrophil proteins 1-3 inhibit proteolytic cleavage of von Willebrand factor by ADAMTS13, Vikram G. Pillai, PhD, of the University of Alabama at Birmingham, and colleagues reported.
The finding may explain how inflammation triggers microvascular thrombosis in these patients and potentially others with immune thrombotic disorders, according to the researchers (Blood 2016;128:110-9).
They performed enzyme-linked immunosorbent assays and found markedly increased levels of plasma human neutrophil proteins (HNPs) 1-3 in most of the patients with acquired autoimmune thrombotic thrombocytopenic purpura (TTP). The median levels in the 19 patients were 170 ng/mL, compared with 23 ng/mL in 18 healthy controls, a statistically significant difference (P less than .0001).
Liquid chromatography plus tandem mass spectrometry similarly confirmed statistically significant increases in HNP1, HNP2, and HNP3 in patient samples (P less than .001).
Measures of HNPs 1-3 by both methods correlated well, and the researchers concluded that HNPs 1-3 likely inhibit ADAMTS13 activity by binding to the central A2 domain of von Willebrand factor and physically blocking ADAMTS13 binding.
The researchers had no relevant financial disclosures.
On Twitter @maryjodales
In patients with acquired autoimmune thrombotic thrombocytopenic purpura, elevated plasma levels of human neutrophil proteins 1-3 inhibit proteolytic cleavage of von Willebrand factor by ADAMTS13, Vikram G. Pillai, PhD, of the University of Alabama at Birmingham, and colleagues reported.
The finding may explain how inflammation triggers microvascular thrombosis in these patients and potentially others with immune thrombotic disorders, according to the researchers (Blood 2016;128:110-9).
They performed enzyme-linked immunosorbent assays and found markedly increased levels of plasma human neutrophil proteins (HNPs) 1-3 in most of the patients with acquired autoimmune thrombotic thrombocytopenic purpura (TTP). The median levels in the 19 patients were 170 ng/mL, compared with 23 ng/mL in 18 healthy controls, a statistically significant difference (P less than .0001).
Liquid chromatography plus tandem mass spectrometry similarly confirmed statistically significant increases in HNP1, HNP2, and HNP3 in patient samples (P less than .001).
Measures of HNPs 1-3 by both methods correlated well, and the researchers concluded that HNPs 1-3 likely inhibit ADAMTS13 activity by binding to the central A2 domain of von Willebrand factor and physically blocking ADAMTS13 binding.
The researchers had no relevant financial disclosures.
On Twitter @maryjodales
FROM BLOOD
Key clinical point: In patients with acquired autoimmune thrombotic thrombocytopenic purpura, elevated plasma levels of human neutrophil proteins 1-3 inhibit proteolytic cleavage of von Willebrand factor by ADAMTS13.
Major finding: The median levels of plasma human neutrophil proteins 1-3 in patients with acquired autoimmune TTP were 170 ng/mL, compared with 23 ng/mL in healthy controls, a statistically significant difference (P less than .0001).
Data source: Studies in 19 patients with TTP and 18 control subjects.
Disclosures: The researchers had no relevant financial disclosures.
