scholarly journals Elevated von Willebrand Factor Antigen is an Early Predictor of Mortality and Prolonged Length of Stay for Coronavirus Disease 2019 (COVID-19) Inpatients

2021 ◽  
Author(s):  
Alexander H. Cotter ◽  
Su-Jau T. Yang ◽  
Hedyeh Shafi ◽  
Timothy M. Cotter ◽  
Darryl Erik Palmer-Toy
Keyword(s):  
Length Of Stay ◽  
Fold Increase ◽  
Prolonged Length ◽  
Risk Of Death ◽  
Increased Risk ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen ◽  
D Dimer ◽  
Increase In Risk

ABSTRACT Context: Coagulation factor and endothelial injury marker, von Willebrand factor antigen (vWF:Ag), is elevated in coronavirus disease 2019 (COVID-19). Objective: To assess prognostic value of vWF:Ag for COVID-19 inpatients. Design: Citrated plasma samples collected from COVID-19 inpatients for D-dimer measurement were tested for vWF:Ag. Measurements of vWF:Ag and common acute phase reactants (APRs) were correlated with clinical outcomes and length of stay (LOS). Results: We included 333 samples from a diverse group of 120 COVID-19 inpatients. There was a clear association of higher peak measurements of vWF:Ag and other APRs with adverse clinical outcomes. Peak vWF:Ag >300% was associated with a 5-fold increased risk of death (Odds Ratio 5.08, P<.001) and a 30-fold increased risk of prolonged (>4 days) LOS (OR 29.65, P =.001). Peak D-dimer >3.8 FEU mg/L was associated with a 15-fold increase in risk of death (OR 14.73, P <.001) and a 5-fold increased risk of prolonged LOS (OR 4.55, P=.02). Using the earliest paired measurements of vWF:Ag and D-dimer from each patient and the same cut-offs, vWF:Ag was associated with a 3.5-fold increase in risk of death (OR 3.54, P=.004) and a 20-fold risk of prolonged LOS (OR 20.19, P=.004). Yet D-dimer was not significantly associated with either death (OR 1.9, P=.29) or prolonged LOS (OR 1.02, P=.98). Conclusions: Both peak and early post-admission vWF:Ag >300% were highly predictive of death and prolonged length of stay among COVID-19 inpatients. Measurement of vWF:Ag may prove a valuable tool to guide escalation of COVID-19 treatment, particularly anticoagulation.

scholarly journals Post-Covid-19 Hemostatic Characteristics of Convalescent Patients: The Bergamo Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1054-1054
Author(s):  
Carmen Julia J Tartari ◽  
Giulia Milani ◽  
Francesco Salvetti ◽  
Marina Marchetti ◽  
Laura Russo ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Protein C ◽  
Severe Disease ◽  
Protein S ◽  
Demographic Characteristics ◽  
Increased Risk ◽  
Antibody Levels ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
D Dimer

Abstract Introduction: Severe COVID-19 patients present with a hypercoagulable state, complement activation and endothelial perturbation, which result from an excessive inflammatory response. Thromboinflammation is one important mechanism underlying the COVID-19-associated coagulopathy and the increased risk of thrombosis. Bergamo city is one of the first and most affected area by SARS-CoV-2 infection in the world. For this reason, since the beginning we were actively involved in recruiting convalescent COVID-19 patients, in a program of selection of candidates for convalescent plasma donation. In a large cohort of convalescent COVID-19 patients, we aimed to characterize markers of coagulation activation and endothelial perturbation, in order to explore whether the COVID-19-related hemostasis activation might persist afterwards and evaluate its possible association with the degree of severity of the previous infection, and/or with demographic characteristics, or anti-SARS-CoV-2 antibody levels. Methods: In 392 convalescent COVID-19 patients (216M/176F, median age: 46 years) plasma levels of fibrinogen, protein C, protein S, factor V, factor VIII, factor XIII, D-dimer, von Willebrand factor (vWF), prothrombin fragment F1+2 were measured at the recruitment, i.e. 1-5 months from recovery. Samples were tested for the anti-SARS-CoV-2 antibodies, including anti-S IgG (Anti-S Ab) and anti-N IgG (Anti-N Ab) antibodies at enrollment and at each scheduled subsequent visits. Results: Levels of fibrinogen, D-dimer, von Willebrand factor, protein S and protein C were significantly higher (p<0.05) in patients who were hospitalized for severe COVID-19 as compared to patients who were treated at home. There was no correlation between levels of coagulation biomarkers and days from end of symptoms. Male gender, age > 40 years, and severe form of COVID-19 were identified as independent predictors of high levels of both anti-S and anti-N Ab (p<0.001). Among hemostatic biomarkers, fibrinogen (p<0.01) and vWF (p<0.05) independently predict high levels of anti-S Ab. In particular, vWF levels positively correlated with anti-S Ab levels (vWF-antigen r=0.188; vWF-activity r=0.241 and vWF-RiCof r=0.223, p<0.01). Evaluation of anti-SARS-CoV2 antibody levels at different time points during follow up revealed that 30% of patients displayed high levels of anti-S Ab until more than 8 months from the end of symptoms. Conclusions: Convalescent patients, with a history of severe COVID-19 had a persistent endothelium activation, despite of disease clinical remission even after 9 months from end of symptoms. Furthermore, fibrinogen and vWF levels predicted high levels of Anti-S Ab. Among demographic characteristics, gender, age and severe disease can be predictors of increased antibody response. These findings suggest that inflammation, coagulation and endothelial dysfunction may persist after recovery and may explain the findings of persistent clinical symptoms reported in these patients after healing from COVID-19. Disclosures Falanga: Bayer: Honoraria; Leo Pharma: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria.

von Willebrand Factor and Factor VIII: C in Acute Cerebrovascular Disease

1997 ◽  
Vol 77 (06) ◽  
pp. 1104-1108 ◽  
Author(s):  
Andrew J Catto ◽  
Angela M Carter ◽  
Jennifer H Barrett ◽  
John Bamford ◽  
Penny J Rice ◽  
...  
Keyword(s):  
Cerebrovascular Disease ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Case Fatality ◽  
Cranial Computed Tomography ◽  
Risk Of Death ◽  
Vessel Disease ◽  
Increased Risk ◽  
Von Willebrand ◽  
Willebrand Factor

Summary Background. Elevated von Willebrand factor (vWF) is a risk factor in the development of acute myocardial infarction. The importance of vWF and factor VIII :C in the pathogenesis of cerebrovascular disease (CVD) is poorly defined. Methods and results. We studied 208 cases of stroke whose pathological type was defined by cranial computed tomography. Cerebral infarcts were grouped according to the Oxfordshire Community Stroke Project (OCSP) clinical classification. The results in patients were compared with 184 healthy reference subjects. In patients, vWF and FVIII: C levels were determined initially and after three months. Patients were followed prospectively for six months or until death.Levels of vWF and FVIII :C were elevated initially (1.86 IU/ml and 2.20 U/ml respectively) and after 3 months (1.51 IU/ml and 1.90 U/ml) compared with a healthy reference population (1.26 IU/ml and 1.49 U/ml p = 0.0001). In the initial sample, vWF was associated with age (p = 0.01). FVIII: C was related to age (p = 0.04), gender (p = 0.007 higher for females) and a history of diabetes mellitus (2.56 U/ml vs. 2.16 U/ml in non-diabetics, p = 0.008).Initial vWF levels were higher in subjects with large vessel disease (TACI/PACI) group compared with the small vessel disease (LACI) group [2.12 IU/ml, (n = 112) vs. 1.48 IU/ml (n = 59) respectively, p = 0.0001] and similarly in initial FVIII :C levels (2.43 U/ml vs. 1.87 U/ml, p = 0.0001).Analysis of six-month case fatality, vWF levels were associated with risk of death [p = 0.01, OR 1.73 (1.12,2.66) for an increase of 1 U/ml], even after allowing for stroke type. Conclusion. The relationship of vWF with stroke mortality has not previously been described. Although we have not demonstrated a causal role for vWF in the pathogenesis of CVD, elevated circulating levels of vWF may be associated with increased risk of death following stroke. A prospective study would be required to establish whether vWF is predictive for the development of CVD.

Prolonged length of stay in the emergency department and increased risk of hospital mortality in patients with sepsis requiring ICU admission

2018 ◽  
pp. emermed-2018-208032 ◽  
Author(s):  
Zhongheng Zhang ◽  
Faran Bokhari ◽  
Yizhan Guo ◽  
Hemant Goyal
Keyword(s):  
Length Of Stay ◽  
Hospital Mortality ◽  
Prolonged Length ◽  
Icu Admission ◽  
Risk Of Death ◽  
Crude Mortality Rate ◽  
Crude Mortality ◽  
Increased Risk ◽  
Multivariable Regression Model ◽  
Multivariable Regression

Background and objectivesDelayed patient admission to the intensive care unit (ICU) from the ED is common in China. Patients with severe sepsis or septic shock requiring ICU admission are in need of specialised monitoring and tailored treatment. Delayed admission to the ICU might be associated with adverse clinical outcomes for patients with sepsis.MethodsPatients with sepsis admitted to the ICU from the ED from January 2010 to April 2018 were retrospectively identified from a clinical data warehouse. The primary endpoint was in-hospital mortality. Length of stay in ED (EDLOS) was compared between survivors and non-survivors. A multivariable regression model was employed to adjust for potential confounding due to patient clinical condition.ResultsA total of 1997 patients, including 473 non-survivors and 1524 survivors, were included. The crude mortality rate for patients with EDLOS <6 hours was 21.4%, which was significantly lower than patients with EDLOS of 12–24 hours (31.9%), and those with EDLOS >24 hours (31.8%). After adjusting for PaO2/FiO2, serum creatinine, age, Sequential Organ Failure Assessment, body mass index, lactate, comorbidities and infection site, EDLOS continued to be independently associated with increased risk of hospital mortality. Compared with the group with EDLOS <6 hours, those with EDLOS between 12and24 hours (OR 1.82, 95% CI 1.28 to 2.58) and EDLOS >24 hours (OR 1.79, 95% CI 1.27 to 2.52) showed a significantly increased risk of death.ConclusionsOur study shows that prolonged EDLOS is independently associated with increased risk of hospital mortality in patients with sepsis requiring ICU admission.

Significance of Platelet β-Adrenoceptors for Platelet Responses In Vivo and In Vitro

1992 ◽  
Vol 68 (06) ◽  
pp. 687-693 ◽  
Author(s):  
P T Larsson ◽  
N H Wallén ◽  
A Martinsson ◽  
N Egberg ◽  
P Hjemdahl
Keyword(s):  
Ex Vivo ◽  
High Dose ◽  
Platelet Aggregability ◽  
Adrenoceptor Agonist ◽  
Dose Infusion ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryThe significance of platelet β-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the β-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed α- and β-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma β-thromboglobulin levels. Adrenaline levels were 3–4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels β-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that β-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an α-adrenoceptor mediated proaggregatory action.

The Effect of n-3 Fatty Acids on Lipids and Haemostasis in Patients with Type lla and Type IV Hyperlipidaemia

1989 ◽  
Vol 62 (02) ◽  
pp. 797-801 ◽  
Author(s):  
E Berg Schmidt ◽  
E Ernst ◽  
K Varming ◽  
J O Pedersen ◽  
J Dyerberg
Keyword(s):  
Fatty Acids ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Hdl Cholesterol ◽  
Apolipoprotein A1 ◽  
Type Iv ◽  
Before And After ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryPlasma lipids and haemostasis were investigated in 17 patients with hyperlipidaemia before and after 6 weeks supplementation with 6 g n-3 fatty acids. Nine of the patients had type IIa and 8 had type IV hyperlipidaemia. No effect on plasma cholesterol, LDL- or HDL-cholesterol were seen, but plasma triglycerides decreased after n-3 supplementation. Apolipoprotein B increased and apolipoprotein A1 decreased after the oil supplement. The bleeding time was prolonged, but platelet aggregation was unaltered by n-3 fatty acids. Protein C activity increased in type II a and decreased in type IV after the supplement. Fibrinolysis was markedly depressed while von Willebrand factor antigen was reduced after intake of n-3 fatty acids.

Transmembrane Calcium Influx Associated with von Willebrand Factor Binding to GP Ib in the Initiation of Shear-Induced Platelet Aggregation

1993 ◽  
Vol 69 (05) ◽  
pp. 496-502 ◽  
Author(s):  
Yasuo Ikeda ◽  
Makoto Handa ◽  
Tetsuji Kamata ◽  
Koichi Kawano ◽  
Yohko Kawai ◽  
...  
Keyword(s):  
Shear Force ◽  
Calcium Influx ◽  
Fold Increase ◽  
Intracellular Camp ◽  
Recombinant Fragment ◽  
Transmembrane Flux ◽  
Irreversible Aggregation ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Camp Levels

SummaryWe found that the binding of multimeric vWF to GP Ib under a shear force of 108 dynes/cm2 resulted in the transmembrane flux of Ca2+ ions with a two-to three-fold increase in their intracellular concentration ([Ca2+]i). The blockage of this event, obtained by inhibiting the vWF-GP Ib interaction, suppressed aggregation. In contrast, the blockage of vWF binding to GP IIb-IIIa, as well as the prevention of activation caused by increased intracellular cAMP levels, inhibited aggregation but had no significant effect on [Ca2+]i increase. A monomeric recombinant fragment of vWF containing the GP Ib-binding domain of the molecule (residues 445-733) prevented all effects mediated by multimeric vWF but, by itself, failed to support the increase in [Ca2+]i and aggregation. These results suggest that the binding of multimeric vWF to GP Ib initiates platelets aggregation induced by high shear stress by mediating a transmembrane flux of Ca2+ ions, perhaps through a receptor-dependent calcium channel. The increase in [Ca2+]i may act as an intracellular message and cause the activation of GP IIb-IIIa; the latter receptor then binds vWF and mediates irreversible aggregation.

Comparative Study of Intranasal, Subcutaneous and Intravenous Administration of Desamino-D-Arginine Vasopressin (DDAVP)

1986 ◽  
Vol 55 (01) ◽  
pp. 108-111 ◽  
Author(s):  
M Köhler ◽  
P Hellstern ◽  
C Miyashita ◽  
G von Blohn ◽  
E Wenzel
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Factor Xii ◽  
Additional Advantage ◽  
Mean Values ◽  
Routes Of Administration ◽  
The Mean ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryThis study was performed to evaluate the influence of different routes of administration on the efficacy of DDAVP treatment. Ten healthy volunteers received DDAVP intranasally (i.n.), subcutaneously (s.c.) and intravenously (i.v.) in a randomized cross-over trial. Factor XII and high molecular weight (HMW)-kininogen levels increased only slightly after DDAVP administration. The mean increase of factor VIII: C was 3.1 (i. v.), 2.3 (s. c.), and 1.3 (i.n.) - fold over baseline. Ristocetin cofactor (von Willebrand factor antigen) increased 3.1 (2.5), 2.0 (2.3) and 1.2 (1.2) - fold over baseline mean values after i.v., s.c. and i.n. DDAVP, respectively. The half-disappearance time of factor VIII and von Willebrand factor (vWF) after DDAVP ranged from five (factor VIII: C) to eight hours (vWF). The mean increase of fibrinolytic activity was more pronounced after i.v. DDAVP. The antidiuretic effect was moderate with no apparent differences between the routes of application. This study provides further evidence that both i.v. and s.c. DDAVP administration result in an appropriate and reliable stimulation of haemostasis. An additional advantage of s. c. administration is its suitability for home treatment.

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