The Influence of Inflammation on Fibrinogen Turnover and Redistribution of the Hemostatic Balance to a Prothrombotic State in High On-Treatment Platelet Reactivity-Dual Poor Responder (HTPR-DPR) Patients

Knowledge about the influence of inflammation on platelet function and relocation of hemostatic balance to hypercoagulable state is still unclear. We compared two groups of patients who suffer from acute vs. chronic inflammatory process and additionally present high on-treatment platelet reactivity-dual platelet resistance. We did not found any differences in platelet aggregation between both investigated groups, but patients who suffer from chronic inflammation presented stronger relocation of the hemostatic balance to the hypercoagulability. A high concentration of prothrombin fragment F1+2 together with higher activity of von Willebrand factor in critical limb ischemia shows more exaggerated fibrinogen turnover although the blood concentration of this factor was in normal range. We concluded that high on-treatment platelet reactivity-dual platelet resistance and intensified inflammation are linked with elevated platelet and fibrinogen turnover to counteract proper hemostatic balance in favor of a prothrombotic state.

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Combined effects of plasma von Willebrand factor and platelet measures on the risk of incident venous thromboembolism

Blood ◽

10.1182/blood.2021011494 ◽

2021 ◽

Author(s):

Magnus Sandvik Edvardsen ◽

Ellen-Sofie Hansen ◽

Kristian Hindberg ◽

Vânia Maris Morelli ◽

Thor Ueland ◽

...

Keyword(s):

Platelet Count ◽

Venous Thromboembolism ◽

Von Willebrand Factor ◽

Platelet Reactivity ◽

High Plasma ◽

Combined Effects ◽

Exposure Group ◽

Increased Risk ◽

Von Willebrand ◽

Willebrand Factor

Plasma von Willebrand factor (VWF) and platelet reactivity are both risk factors for venous thromboembolism (VTE), and VWF can promote hemostasis by interaction with platelets. In this study, we explored the combined effects of plasma VWF and platelet measures on the risk of incident VTE. A population-based nested case-control study with 403 cases and 816 controls was derived from the Tromsø Study. VWF, platelet count and mean platelet volume (MPV) were measured in blood samples drawn at baseline. Odds ratios (ORs) with 95% confidence intervals (CIs) for VTE were estimated across VWF tertiles, within predefined MPV (<8.5, 8.5-9.5, ≥9.5 fL) and platelet count (<230, 230-299, ≥300·109 L-1) strata. Here, participants with VWF levels in the highest tertile and MPV ≥9.5 fL had an OR of 1.98 (95% CI 1.17-3.36) for VTE compared with those in the lowest VWF tertile and with MPV <8.5 fL in the age- and sex-adjusted model. In the joint exposure group, 48% (95% CI 15% to 96%) of VTEs were attributable to the biological interaction between VWF and MPV. Similarly, individuals with VWF in the highest tertile and platelet count ≥300·109 L-1 had an OR of 2.91 (95% CI 1.49-5.67) compared with those with VWF in the lowest tertile and platelet count <230, and 39% (95% CI -2% to 97%) of VTEs in the joint exposure group were explained by the interaction. Our results suggest that both platelet reactivity and platelet count interact biologically with high plasma VWF, resulting in an increased risk of incident VTE.

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Assessment of Plasma von Willebrand factor antigen in non-metastatic Prostate Cancerpatients: across-sectional study of the Sudanese Population

Sudan Journal of Medical Sciences ◽

10.18502/sjms.v14i3.5209 ◽

2019 ◽

Author(s):

Mohammed Othman Hashim ◽

Gad Allah Modawe ◽

Ibrahim Khider Ibrahim

Keyword(s):

Prostate Cancer ◽

Von Willebrand Factor ◽

Enzyme Linked Immunosorbent Assay ◽

Sectional Study ◽

High Concentration ◽

Cross Sectional ◽

Von Willebrand Factor Antigen ◽

Von Willebrand ◽

Willebrand Factor ◽

Factor Antigen

Backgrounds: VonWillebrand disease (VWD) is reportedly the most common inherited bleeding disorder and can also arise as an acquired syndrome (AVWS). These disorders arise due to defects and/or deficiency of the plasma protein von Willebrand factor (VWF)..High plasma vWF concentrations have been reported in patients with various types of cancer, such as prostatic cancer.Metastasization may be associated with activation of haemostatic processes resulting in increased levels of circulating factor VIII-related antigen (FVIIIRAg) (von Willebrand factor antigen). Objective: To evaluate the status of VWF AginSudanese patients with Prostate Cancer attending RICK Methodology: This is a cross-sectional study carried out in Khartoum state at Khartoum oncology (RICK) hospital, during the period from April to June 2018, 45 samples were collected from patients with non-metastatic CA prostate, their ages ranged between 51 to 82 years. The vWF level was measured using Enzyme-linked immunosorbent assay (ELISA). Data were analyzed by the statistical package for social science (SPSS). Results: Serology for vWF antigen was done for 45 cases of prostate cancer. According to the age, 2(8%) of patients with age 51-66 had a high concentration of VWF while 24(92%) had normal vWF antigen concentration; of those with age 67-82 years, 4(21%) had high vWF antigen and 15(79%) had normal antigen. Conclusion: The study revealedthat more than 80% of Sudanese patients withnon-metastatic prostate cancer have anormal concentration of VWF. Keywords: vWF, Prostate cancer, Age, ELISA

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ABNORMAL vWF IN CONGENITAL CARDIAC DISEASE: EVIDENCE FOR FRAGMENTATION

10.1055/s-0038-1644086 ◽

1987 ◽

Author(s):

J C Gill ◽

S Baganz ◽

J Endres-Brooks ◽

R R Montgomery

Keyword(s):

Low Dose ◽

Von Willebrand Disease ◽

High Concentration ◽

Agarose Gels ◽

Crossed Immunoelectrophoresis ◽

Congenital Cardiac Disease ◽

Agarose Electrophoresis ◽

Cardiac Lesions ◽

Von Willebrand ◽

Willebrand Factor

We previously reported the presence of an acquired von Willebrand factor (vWF) abnormality characterized by absence of the highest molecular weight (raw) multimers in 12 children with non-cyanotic congenital cardiac lesions. In order to determine the prevalence and define the mechanism of the vWF defect, a prospective series of 17 children were studied at the time of cardiac catheterization. In addition to standard coagulation and vWF assays, vWF multimeric patterns were determined by SDS agarose electrophoresis using two agarose concentrations, low concentration (0.65%) and high concentration (3.0%). Nine of the 17 children had absence of high mw vWF multimers on 0.65% agarose gels as follows:Of 5 children with absence of high mw vWF multimers on 0.65% agarose gels, 4 had 3% agarose gel patterns similar to that seen in patients with Type IIA von Willebrand disease (vWd). Two of 3 studied had the presence of vWF:frag on crossed immunoelectrophoresis. The patterns were not different when samples were drawn into a "cocktail" of proteolytic inhibitors. There was no correlation of abnormal vWF multimers with elevated B thromboglobulin, low dose ristocetin induced platelet aggregation or abnormal platelet vWF subunits. Thus, abnormal vWF multimers are commonly associated with non-cyanotic congenital cardiac lesions, particularly VSD. The lack of abnormality in platelet vWF multimers, absent low dose ristocetin aggregation, and presence of vWF:frag suggests that these alterations may be secondary to fragmentation or are of endothelial cell origin.

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Multi-Cellular Activation In Vivo by Endotoxin in Humans – Limited Protection by Adenosine Infusion

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614032 ◽

2000 ◽

Vol 84 (09) ◽

pp. 381-387 ◽

Cited By ~ 19

Author(s):

Nailin Li ◽

Anne Soop ◽

Alf Sollevi ◽

Paul Hjemdahl

Keyword(s):

Von Willebrand Factor ◽

Thrombin Generation ◽

Platelet Reactivity ◽

Adenosine Infusion ◽

Cellular Activation ◽

Soluble P ◽

Von Willebrand ◽

Willebrand Factor ◽

Factor Secretion

SummaryThe influence of adenosine infusion (40 µg/kg/min for 4 h) on inflammatory and hemostatic parameters was investigated in healthy males without (n = 10) or with (n = 11) intravenous endotoxin injection (4 ng/kg). Without endotoxin, adenosine elevated circulating leukocytes and circulating platelet-leukocyte aggregates. Endotoxin activated platelets and leukocytes in vivo. Platelet activation was seen as slightly increased platelet P-selectin expression, decreased platelet counts, and elevated plasma soluble P-selectin (from 39.6 ± 3.4 to 68.9 ± 6.6 ng/ml; P <0.01). Leukocyte activation was evidenced by increased CD11b expression (from MFI of 0.54 ± 0.02 to 2.21 ± 0.17; P <0.01) and plasma elastase levels (from 25.3 ± 2.5 to 169.3 ± 22.5 ng/ml; P <0.01). Endotoxin also enhanced platelet and leukocyte responsiveness to in vitro stimulation. Endotoxin induced von Willebrand factor secretion (from 92 ± 8 units to 265 ± 19 units at 4 h; P <0.001) and enhanced thrombin generation in vivo. Endotoxin induced leukocytosis and thus increased circulating platelet-leukocyte, mainly platelet-neutrophil, aggregates. Adenosine caused slight attenuation of platelet reactivity to agonist stimulation, enhanced the endotoxin-induced leukocytosis, and detained more platelet-leukocyte aggregates in circulation, but did not attenuate endotoxin-induced neutrophil elastase secretion, von Willebrand factor secretion, or thrombin generation. Thus, endotoxemia induces multi-cellular activation in vivo. Adenosine inhibits leukocyte adhesion and extravasation, and mildly attenuates platelet responsiveness and soluble P-selectin release. Adenosine has the potential of becoming a therapeutic antiinflammatory drug, but an optimal treatment strategy needs to be developed.

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Influence of ABO Locus on PFA-100 Collagen-ADP Closure Time Is Not Totally Dependent on the Von Willebrand Factor. Results of a GWAS on GAIT-2 Project Phenotypes

International Journal of Molecular Sciences ◽

10.3390/ijms20133221 ◽

2019 ◽

Vol 20 (13) ◽

pp. 3221 ◽

Cited By ~ 4

Author(s):

Núria Pujol-Moix ◽

Angel Martinez-Perez ◽

Maria Sabater-Lleal ◽

Dolors Llobet ◽

Noèlia Vilalta ◽

...

Keyword(s):

Von Willebrand Factor ◽

Genome Wide Association Study ◽

Platelet Reactivity ◽

Coagulation Factor ◽

Nucleotide Polymorphisms ◽

Closure Time ◽

A Genome ◽

Abo Genotype ◽

Von Willebrand ◽

Willebrand Factor

(1) Background: In a previous study, we found that two phenotypes related to platelet reactivity, measured with the PFA-100 system, were highly heritable. The aim of the present study was to identify genetic determinants that influence the variability of these phenotypes: closure time of collagen-ADP (Col-ADP) and of collagen-epinephrine (Col-Epi). (2) Methods: As part of the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia (2) Project, 935 individuals from 35 large Spanish families were studied. A genome-wide association study (GWAS) with ≈ 10 M single nucleotide polymorphisms (SNPs) was carried out with Col-ADP and Col-Epi phenotypes. (3) Results: The study yielded significant genetic signals that mapped to the ABO locus. After adjusting both phenotypes for the ABO genotype, these signals disappeared. After adjusting for von Willebrand factor (VWF) or for coagulation factor VIII (FVIII), the significant signals disappeared totally for Col-Epi phenotype but only partially for Col-ADP phenotype. (4) Conclusion: Our results suggest that the ABO locus exerts the main genetic influence on PFA-100 phenotypes. However, while the effect of the ABO locus on Col-Epi phenotype is mediated through VWF and/or FVIII, the effect of the ABO locus on Col-ADP phenotype is partly produced through VWF and/or FVIII, and partly through other mechanisms.

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Ex Vivo Evaluation of the Effect of Plasma-Derived Factor VIII/Von Willebrand Factor in Patients with Severe Hemophilia_A on Prophylaxis with Emicizumab By Thrombin Generation Assay

Blood ◽

10.1182/blood-2021-147184 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4233-4233

Author(s):

Maria-Isabel Bravo ◽

Aida Raventós ◽

Alba Pérez ◽

Elena G Arias-Salgado ◽

María Teresa Alvarez Román ◽

...

Keyword(s):

Von Willebrand Factor ◽

Research Funding ◽

Thrombin Generation ◽

Ex Vivo ◽

Concomitant Treatment ◽

Healthy Controls ◽

Normal Range ◽

Von Willebrand ◽

Willebrand Factor

Abstract Introduction: Hemophilia A (HA) patients under emicizumab prophylaxis treatment may require the concomitant use of procoagulant factors for breakthrough bleedings or immune tolerance induction. Thromboembolic events have been described with the concomitant use of emicizumab and activated prothrombin complex concentrate (aPCC), but not with recombinant activated factor VII (rFVIIa). Previous studies showed that the in vitro combination of emicizumab and plasma-derived Factor VIII/Von Willebrand Factor (pdFVIII/VWF) had a non-additive effect on thrombin generation (TG)(Bravo M-I, et al J Thromb Haemost. 2020;18:1934-39). The aim of this study was to evaluate the TG resulting from ex vivo combination of plasma samples from HA patients treated with emicizumab, with a pdFVIII/VWF concentrate (Fanhdi ®, Grifols). Methods: Twelve adult patients with severe HA without inhibitors on prophylaxis with emicizumab and nine healthy controls were included in the study. Blood samples were drawn in citrate plus corn trypsin inhibitor tubes. Then, platelet poor plasma (PPP) was collected for the TG assay, which measures the whole kinetics of TG. Thrombin peak (TP) and endogenous thrombin potential (ETP) were calculated using calibrated automated thrombogram (Thrombinoscope ™ software, Stago) after in vitro activation of coagulation by trigger solution, PPP Reagent LOW TM (4 μM phospholipids/1 pM tissue factor), fluorogenic substrate and CaCl 2 (FLUKAkit TM) reagents (Diagnostica Stago). Fluorescence was read in a Fluoroskan Ascent reader (Thermo) equipped with a 390/460 filter set. Samples were spiked with increasing concentrations of pdFVIII/VWF (10 to 400 IU/dL), rFVIIa (0.9 µg/mL) or aPCC (0.5 U/mL). Results: TG from healthy control samples was measured to establish TP and ETP normal ranges. TP and ETP results obtained from HA plasma with emicizumab were lower than in healthy controls. The addition of pdFVIII/VWF as of 25 IU/kg (prophylaxis dose in HA w/o inhibitors) to samples from HA patients concomitantly treated with emicizumab restored TP and ETP levels within healthy controls normal range (Table 1). Increasing ex vivo concentrations of pdFVIII/VWF maintained TP and ETP similar to healthy controls. The highest concentration of concomitant treatment with pdFVIII/VWF (200 IU/kg) and emicizumab did not result in excessive TP and, importantly, ETP levels were always within the normal range. The combination with the bypassing agent rFVIIa moderately increased TP and ETP values up to normal range. However, when HA plasma was spiked with aPCC in the presence of emicizumab, TP and ETP dramatically increased above normal range resulting in a synergistic procoagulant profile. Conclusions: The concomitant use of pdFVIII/VWF in patients with prophylaxis with emicizumab did not trigger a multiplying effect on TG. These results were aligned with previous in vitro data and suggested the low risk of overdose and thrombotic events of concomitant treatment emicizumab with the pdFVIII/VWF concentrate in HA patients. Figure 1 Figure 1. Disclosures Bravo: Grifols: Current Employment, Other: Grifols is a manufacturer of the pdFVIII/VWF concentrate, Fanhdi®. Raventós: Grifols: Current Employment, Other: Grifols is a manufacturer of the pdFVIII/VWF concentrate, Fanhdi®. Pérez: Grifols: Current Employment, Other: Grifols is a manufacturer of the pdFVIII/VWF concentrate, Fanhdi®. Alvarez Román: Grifols: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novo-Nordisk: Consultancy, Honoraria, Research Funding; Sobi: Consultancy, Honoraria, Research Funding; Octapharma: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; CSL-Behring: Consultancy, Honoraria, Research Funding; Biomarin: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Butta: CSL-Behring: Research Funding; Roche: Speakers Bureau; Takeda: Research Funding, Speakers Bureau; Novo-Nordisk: Speakers Bureau. Jiménez-Yuste: Bayer: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; BioMarin: Consultancy; Sobi: Consultancy, Honoraria, Research Funding; Octapharma: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; NovoNordisk: Consultancy, Honoraria, Research Funding; Grifols: Consultancy, Honoraria, Research Funding. Costa: Grifols: Current Employment, Other: Grifols is a manufacturer of the pdFVIII/VWF concentrate, Fanhdi®. Willis: Grifols: Current Employment, Other: Grifols is a manufacturer of the pdFVIII/VWF concentrate, Fanhdi®.

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Plasma Fibrinogen Independently Predicts Hypofibrinolysis in Severe COVID-19

Metabolites ◽

10.3390/metabo11120826 ◽

2021 ◽

Vol 11 (12) ◽

pp. 826

Author(s):

Diana Schrick ◽

Margit Tőkés-Füzesi ◽

Barbara Réger ◽

Tihamér Molnár

Keyword(s):

Platelet Count ◽

Von Willebrand Factor ◽

Platelet Reactivity ◽

Aspirin Therapy ◽

Platelet Function Test ◽

Fraction H ◽

Immature Platelet Fraction ◽

Von Willebrand ◽

Willebrand Factor

High rates of thrombosis are present in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Deeper insight into the prothrombotic state is essential to provide the best thromboprophylaxis care. Here, we aimed to explore associations among platelet indices, conventional hemostasis parameters, and viscoelastometry data. This pilot study included patients with severe COVID-19 (n = 21) and age-matched controls (n = 21). Each patient received 100 mg aspirin therapy at the time of blood sampling. Total platelet count, high immature platelet fraction (H-IPF), fibrinogen, D-dimer, Activated Partial Thromboplastin Time, von Willebrand factor antigen and von Willebrand factor ristocetin cofactor activity, plasminogen, and alpha2-antiplasmin were measured. To monitor the aspirin therapy, a platelet function test from hirudin anticoagulated whole blood was performed using the ASPI test by Multiplate analyser. High on-aspirin platelet reactivity (n = 8) was defined with an AUC > 40 cut-off value by ASPI tests. In addition, in vitro viscoelastometric tests were carried out using a ClotPro analyser in COVID-associated thromboembolic events (n = 8) (p = 0.071) nor the survival rate (p = 0.854) showed associations with high on-aspirin platelet reactivity status. The platelet count (p = 0.03), all subjects. COVID-19 patients presented with higher levels of inflammatory markers, compared with the controls, along with evidence of hypercoagulability by ClotPro. H-IPF (%) was significantly higher among non-survivors (n = 18) compared to survivors (p = 0.011), and a negative correlation (p = 0.002) was found between H-IPF and plasminogen level in the total population. The platelet count was significantly higher among patients with high on-aspirin platelet reactivity (p = 0.03). Neither the ECA-A10 (p = 0.008), and ECA-MCF (p = 0.016) were significantly higher, while the tPA-CFT (p < 0.001) was significantly lower among patients with high on-aspirin platelet reactivity. However, only fibrinogen proved to be an independent predictor of hypofibrinolysis in severe COVID-19 patients. In conclusion, a faster developing, more solid clot formation was observed in aspirin ‘non-responder’ COVID-19 patients. Therefore, an individually tailored thromboprophylaxis is needed to prevent thrombotic complications, particularly in the hypofibrinolytic cluster.

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Coated-Platelet Levels May Explain Some Variability in Clinical Phenotype of Severe Hemophilia.

Blood ◽

10.1182/blood.v108.11.1018.1018 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1018-1018 ◽

Cited By ~ 1

Author(s):

Kapil Saxena ◽

Kalpana Pethe ◽

George L. Dale

Keyword(s):

Factor Viii ◽

Clinical Phenotype ◽

Factor V ◽

Healthy Controls ◽

Severe Hemophilia ◽

High Concentration ◽

Co Activation ◽

Bleeding Episodes ◽

Von Willebrand ◽

Willebrand Factor

Abstract Objective: To determine if variability in clinical phenotype of severe hemophilia patients is influenced by the percentage of coated-platelets. Background: Co-activation of platelets with thrombin and collagen results in a unique subset of platelets, with high levels of alpha granule proteins on their surface, such as Factor V, fibrinogen, von Willebrand factor, and thrombospondin. This subset of activated platelets is referred to as coated-platelets (J. Thromb. Haemostasis3:2185, 2005). The high concentration of adhesive and prohemostatic proteins observed on coated-platelets provides a unique procoagulant locus that may influence the number of bleeding episodes in patients with severe hemophilia. Methods: After informed consent, 3–5 ml of blood was drawn from patients with severe hemophilia (Factor VIII <1%) and healthy controls. The number of bleeding episodes reported in the last 6 months was taken as an indicator of clinical phenotype. Results: In 6 patients with more than 3 bleeds reported in the last 6 months (14 ± 4.9 bleeds; mean ± 1SD), the average coated-platelets percentage was 22.3 ± 11.2%. In 17 patients with 3 or less bleeds (1.6 ± 1.3) in the last 6 months, the average coated-platelets percentage was 37.6 ± 12.0%, a difference that was statistically significant (p=0.012). In healthy controls (n=12), the mean coated-platelets were 30.2 ± 9.5%. Conclusion: A higher percentage of coated-platelets may provide a better procoagulant locus for residual Factor VIII, thereby reducing the number of clinical bleeding episodes and partially explaining some variability observed in clinical phenotype of severe hemophilia.

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Abnormalities of von Willebrand factor are also part of the prothrombotic state of Cushing??s syndrome

Blood Coagulation & Fibrinolysis ◽

10.1097/00001721-199904000-00006 ◽

1999 ◽

Vol 10 (3) ◽

pp. 145-152 ◽

Cited By ~ 64

Author(s):

A. Casonato ◽

E. Pontara ◽

M. Boscaro ◽

N. Sonino ◽

F. Sartorello ◽

...

Keyword(s):

Von Willebrand Factor ◽

Prothrombotic State ◽

Von Willebrand ◽

Willebrand Factor

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The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis

Blood ◽

10.1182/blood-2007-08-108571 ◽

2008 ◽

Vol 111 (7) ◽

pp. 3452-3457 ◽

Cited By ~ 49

Author(s):

Anil K. Chauhan ◽

Meghan T. Walsh ◽

Guojing Zhu ◽

David Ginsburg ◽

Denisa D. Wagner ◽

...

Keyword(s):

Genetic Background ◽

Murine Models ◽

Prothrombotic State ◽

Complete Protection ◽

Absolute Requirement ◽

Adamts13 Deficiency ◽

Normal Hemostasis ◽

Von Willebrand ◽

Willebrand Factor ◽

Deficient Mice

Abstract Ultralarge von Willebrand factor (UL-VWF) multimers are thought to play a central role in pathogenesis of the disease thrombotic thrombocytopenic purpura (TTP); however, experimental evidence in support of this hypothesis has been difficult to establish. Therefore, to examine directly the requirement for VWF in TTP pathogenesis, we generated ADAMTS13-deficient mice on a TTP-susceptible genetic background that were also either haploinsufficient (Vwf+/−) or completely deficient (Vwf−/−) in VWF. Absence of VWF resulted in complete protection from shigatoxin (Stx)–induced thrombocytopenia, demonstrating an absolute requirement for VWF in this model (Stx has been shown previously to trigger TTP in ADAMTS13-deficient mice). We next investigated the requirements for ADAMTS13 and VWF in a murine model of endotoxemia. Unlike Stx-induced TTP findings, LPS-induced thrombocytopenia and mortality were not affected by either VWF or ADAMTS13 deficiency, suggesting divergent mechanisms of thrombocytopenia between these 2 disorders. Finally, we show that VWF deficiency abrogates the ADAMTS13-deficient prothrombotic state, suggesting VWF as the only relevant ADAMTS13 substrate under these conditions. Together, these findings shed new light on the potential roles played by ADAMTS13 and VWF in TTP, endotoxemia, and normal hemostasis.

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