Evidence of Endothelial Activation in Asymptomatic Plasmodium falciparum Parasitemia and Effect of Blood Group on Levels of von Willebrand Factor in Malaria

Abstract Factor VIII (FVIII) pharmacokinetic (PK) properties show high interpatient variability in hemophilia A patients. Although previous studies have determined that age, body mass index, von Willebrand factor antigen (VWF:Ag) levels, and ABO blood group status can influence FVIII PK, they do not account for all observed variability. In this study, we aim to describe the genetic determinants that modify the FVIII PK profile in a population of 43 pediatric hemophilia A patients. We observed that VWF:Ag and VWF propeptide (VWFpp)/VWF:Ag, but not VWFpp, were associated with FVIII half-life. VWFpp/VWF:Ag negatively correlated with FVIII half-life in patients with non-O blood type, but no correlation was observed for type O patients, suggesting that von Willebrand factor (VWF) half-life, as modified by the ABO blood group, is a strong regulator of FVIII PK. The FVIII-binding activity of VWF positively correlated with FVIII half-life, and the rare or low-frequency nonsynonymous VWF variants p.(Arg826Lys) and p.(Arg852Glu) were identified in patients with reduced VWF:FVIIIB but not VWF:Ag. Common variants at the VWF, CLEC4M, and STAB2 loci, which have been previously associated with plasma levels of VWF and FVIII, were associated with the FVIII PK profile. Together, these studies characterize the mechanistic basis by which VWF clearance and ABO glycosylation modify FVIII PK in a pediatric population. Moreover, this study is the first to identify non-VWF and non-ABO variants that modify FVIII PK in pediatric hemophilia A patients.

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ABO Blood Group Genotype and Plasma von Willebrand Factor in Normal Individuals

Vox Sanguinis ◽

10.1159/000462939 ◽

1995 ◽

Vol 68 (4) ◽

pp. 236-240 ◽

Cited By ~ 6

Author(s):

Masayuki Shima ◽

Yoshihiro Fujimura ◽

Takayuki Nishiyama ◽

Tomomi Tsujiuchi ◽

Nobuhiro Narita ◽

...

Keyword(s):

Blood Group ◽

Von Willebrand Factor ◽

Abo Blood Group ◽

Normal Individuals ◽

Von Willebrand ◽

Willebrand Factor

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Effect of ABO blood group on the collagen-binding assay for von Willebrand factor

American Journal of Hematology ◽

10.1002/ajh.10238 ◽

2002 ◽

Vol 71 (3) ◽

pp. 229-231 ◽

Cited By ~ 6

Author(s):

Erin Haley ◽

Nadiya Babar ◽

Cory Ritter ◽

Katharine A. Downes ◽

Deana Green ◽

...

Keyword(s):

Blood Group ◽

Von Willebrand Factor ◽

Binding Assay ◽

Abo Blood Group ◽

Collagen Binding ◽

Von Willebrand ◽

Willebrand Factor

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Measurement of plasma von Willebrand factor in acute coronary syndromes and the influence of ABO blood group status

Journal of Thrombosis and Haemostasis ◽

10.1111/j.1538-7836.2004.00965.x ◽

2004 ◽

Vol 2 (11) ◽

pp. 2053-2054 ◽

Cited By ~ 5

Author(s):

K. K. Ray ◽

S. Francis ◽

D. C. Crossman

Keyword(s):

Blood Group ◽

Von Willebrand Factor ◽

Acute Coronary Syndromes ◽

Abo Blood Group ◽

Group Status ◽

Coronary Syndromes ◽

Von Willebrand ◽

Willebrand Factor

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BLEEDING TIME IN NORMAL SUBJECTS: ITS RELATIONSHIP WITH SEX, AGE, BLOOD GROUP, HEMATOCRIT, PLATELET COUNT AND PLASMA VON WILLEBRAND FACTOR LEVEL

10.1055/s-0038-1644848 ◽

1987 ◽

Author(s):

F Rodeghiero ◽

G Castaman ◽

E Di Bona ◽

M Ruggeri

Keyword(s):

Platelet Count ◽

Blood Group ◽

Von Willebrand Factor ◽

Bleeding Time ◽

Physiological Parameters ◽

Factor Level ◽

Significant Difference ◽

Von Willebrand ◽

Willebrand Factor

Bleeding time (BT) is the most important test for in "vivo" Vevaluation of primary hemostasis. Several physiological parameters namely sex, age, blood group, hematocrit, platelet count and von Willebrand factor level could exert a significant influenceIn this study, the relationships between BT (Simplate II,General Diagnostics)and these physiological parameters havebeen examined in 58 subjects aging 17-71 (32 males and 26 females; 26 of 0 and 32 of non-0 group). In all the subjects bleedingdiathesis was excluded by interview. They were not taking anvmedicament for at least 10 days and showed normal platelet aggregation by ADP and ArachidonateMean BT value (seconds) was 318± 65 (range 195-A95)Statistical analysis failed to show any significant difference realated to sex and blood group. There was no significant relationship with hematocrit (0.01), platelet count (−0.2A), age (−0.28) and von Willebrand factor level, mesured as ristocetin cofactor (−0.2A). In particular, our data indicate that higher von Willebrand factor levels found in non-0 group in comparison with O-group (113.3 vs 83.5, P < 0:001) do not exert any apparent influence on bleeding time

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Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13

Frontiers in Immunology ◽

10.3389/fimmu.2020.610696 ◽

2020 ◽

Vol 11 ◽

Author(s):

Junxian Yang ◽

Zhiwei Wu ◽

Quan Long ◽

Jiaqi Huang ◽

Tiantian Hong ◽

...

Keyword(s):

Von Willebrand Factor ◽

Therapeutic Strategy ◽

Endothelial Activation ◽

Endothelial Damage ◽

Neutrophil Extracellular Trap ◽

Activated Neutrophils ◽

A Disintegrin And Metalloproteinase ◽

Von Willebrand ◽

Willebrand Factor

Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. The adhesive activity of VWF multimers is regulated by a specific metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Increasing evidence indicates that the interaction between NETs and VWF contributes to arterial and venous thrombosis as well as inflammation. Furthermore, contents released from activated neutrophils or NETs induce the reduction of ADAMTS13 activity, which may occur in both thrombotic microangiopathies (TMAs) and acute ischemic stroke (AIS). Recently, NET is considered as a driver of endothelial damage and immunothrombosis in COVID-19. In addition, the levels of VWF and ADAMTS13 can predict the mortality of COVID-19. In this review, we summarize the biological characteristics and interactions of NETs, VWF, and ADAMTS13, and discuss their roles in TMAs, AIS, and COVID-19. Targeting the NET-VWF axis may be a novel therapeutic strategy for inflammation-associated TMAs, AIS, and COVID-19.

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von Willebrand Factor Antigen, von Willebrand Factor Propeptide, and ADAMTS13 in Carotid Stenosis and Their Relationship with Cerebral Microemboli

Thrombosis and Haemostasis ◽

10.1055/s-0040-1715440 ◽

2020 ◽

Author(s):

Stephen J. X. Murphy ◽

Soon Tjin Lim ◽

Fionnuala Hickey ◽

Justin A. Kinsella ◽

Deirdre R. Smith ◽

...

Keyword(s):

Ischemic Stroke ◽

Carotid Stenosis ◽

Blood Group ◽

Von Willebrand Factor ◽

Adamts13 Activity ◽

Von Willebrand Factor Antigen ◽

Asymptomatic Patients ◽

Von Willebrand ◽

Willebrand Factor ◽

Factor Antigen

Abstract Background The relationship between von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio, ADAMTS13 activity, and microembolic signal (MES) status in carotid stenosis is unknown. Methods This prospective, multicenter study simultaneously assessed plasma VWF:Ag levels, VWFpp levels and ADAMTS13 activity, and their relationship with MES in asymptomatic versus symptomatic moderate-to-severe (≥50–99%) carotid stenosis patients. One-hour transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES+ve or MES−ve. Results Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the “early phase” (≤4 weeks) and 37 patients in the “late phase” (≥3 months) after transient ischemic attack (TIA)/ischemic stroke. VWF:Ag levels were higher (p = 0.049) and VWFpp/VWF:Ag ratios lower (p = 0.006) in early symptomatic than in asymptomatic patients overall, and in early symptomatic versus asymptomatic MES−ve subgroups (p ≤0.02). There were no intergroup differences in VWFpp expression or ADAMTS13 activity (p ≥0.05). VWF:Ag levels and ADAMTS13 activity decreased (p ≤ 0.048) and VWFpp/VWF:Ag ratios increased (p = 0.03) in symptomatic patients followed up from the early to late phases after TIA/stroke. Although there were no differences in the proportions of symptomatic and asymptomatic patients with blood group O, a combined analysis of early symptomatic and asymptomatic patients revealed lower median VWF:Ag levels in patients with blood group O versus those without blood group O (9.59 vs. 12.32 µg/mL, p = 0.035). Discussion VWF:Ag expression, a marker of endothelial ± platelet activation, is enhanced in recently symptomatic versus asymptomatic carotid stenosis patients, including in MES−ve patients, and decreases with ADAMTS13 activity over time following atherosclerotic TIA/ischemic stroke.

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